UPDATED 2021 Medications for Opioid Use Disorder For Healthcare and Addiction Professionals, Policymakers, Patients, and Families TREATMENT IMPROVEMENT PROTOCOL TIP 63 Please share your thoughts about this publication by completing a brief online survey at: https://www.surveymonkey.com/r/KAPPFS The survey takes about 7 minutes to complete and is anonymous. Your feedback will help SAMHSA develop future products. MEDICATIONS FOR OPIOID USE DISORDERTIP 63 Treatment Improvement Protocol 63 For Healthcare and Addiction Professionals, Policymakers, Patients, and Families This TIP reviews three Food and Drug Administration-approved medications for opioid use disorder treatment—methadone, naltrexone, and buprenorphine—and the other strategies and services needed to support people in recovery. TIP Navigation Executive Summary For healthcare and addiction professionals, policymakers, patients, and families Part 1: Introduction to Medications for Opioid Use Disorder Treatment For healthcare and addiction professionals, policymakers, patients, and families Part 2: Addressing Opioid Use Disorder in General Medical Settings For healthcare professionals Part 3: Medications for Opioid Use Disorder For healthcare professionals Part 4: Bringing Together Addiction Treatment Counselors, Clients, and Healthcare Professionals For healthcare and addiction professionals Part 5: Resources Related to Medications for Opioid Use Disorder For healthcare and addiction professionals, policymakers, patients, and families ii TIP 63 MEDICATIONS FOR OPIOID USE DISORDER PART 1: INTRODUCTION TO MEDICATIONS FOR OPIOID USE DISORDER TREATMENT Contents EXECUTIVE SUMMARY Foreword . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ES-iii TIP 63 Update . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ES-iii Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ES-1 Overall Key Messages . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ES-1 Content Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ES-3 Notes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ES-7 TIP Development Participants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ES-9 Publication Information . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ES-12 The Approach to OUD Care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1-1 Overview of Medications for OUD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1-3 Duration of Treatment With OUD Medication. . . . . . . . . . . . . . . . . . . . . . . . . . . 1-8 Treatment Settings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1-9 Challenges to Expanding Access to OUD Medication. . . . . . . . . . . . . . . . . . . 1-10 Resources . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1-10 Notes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1-11 PART 2: ADDRESSING OPIOID USE DISORDER IN GENERAL MEDICAL SETTINGS Scope of the Problem . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-1 Screening . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-1 Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-8 Treatment Planning or Referral . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-17 Resources . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-28 Appendix . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-32 Notes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-39 iii MEDICATIONS FOR OPIOID USE DISORDER TIP 63 PART 3: MEDICATIONS FOR OPIOID USE DISORDER Scope of the Problem . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3-1 Chapter 3A: Overview of Medications for Opioid Use Disorder . . . . . . . . . 3-5 Chapter 3B: Methadone. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3-17 Chapter 3C: Naltrexone . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3-37 Chapter 3D: Buprenorphine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3-51 Chapter 3E: Medical Management Strategies for Patients Taking OUD Medications in Ofce-Based Settings. . . . . . . . . . . . . . . . . . . . . . 3-83 Chapter 3F: Medical Management of Patients Taking OUD Medications in Hospital Settings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3-103 Notes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3-109 PART 4: BRINGING TOGETHER ADDICTION TREATMENT COUNSELORS, CLIENTS, AND HEALTHCARE PROFESSIONALS Overview and Context . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-1 Quick Guide to Medications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-12 Counselor–Prescriber Communications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-18 Creation of a Supportive Counseling Experience . . . . . . . . . . . . . . . . . . . . . . . 4-20 Other Common Counseling Concerns . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-34 Notes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-37 PART 5: RESOURCES RELATED TO MEDICATIONS FOR OPIOID USE DISORDER General Resources . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5-1 Resources for Counselors and Peer Providers . . . . . . . . . . . . . . . . . . . . . . . . . . 5-10 Resources for Clients and Families . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5-12 Provider Tools and Sample Forms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5-16 Glossary of TIP Terminology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5-56 Notes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5-59 This page intentionally left blank. MEDICATIONS FOR OPIOID USE DISORDERTIP 63 Substance Abuse and Mental Health Services Administration Executive Summary For Healthcare and Addiction Professionals, Policymakers, Patients, and Families The Executive Summary of this Treatment Improvement Protocol provides an overview on the use of the three Food and Drug Administration-approved medications used to treat opioid use disorder—methadone, naltrexone, and buprenorphine—and the other strategies and services needed to support recovery. TIP Navigation Executive Summary For healthcare and addiction professionals, policymakers, patients, and families Part 1: Introduction to Medications for Opioid Use Disorder Treatment For healthcare and addiction professionals, policymakers, patients, and families Part 2: Addressing Opioid Use Disorder in General Medical Settings For healthcare professionals Part 3: Medications for Opioid Use Disorder For healthcare professionals Part 4: Bringing Together Addiction Treatment Counselors, Clients, and Healthcare Professionals For healthcare and addiction professionals Part 5: Resources Related to Medications for Opioid Use Disorder For healthcare and addiction professionals, policymakers, patients, and families ES-ii TIP 63 MEDICATIONS FOR OPIOID USE DISORDER—Executive Summary Contents Foreword . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ES-iii TIP 63 Update . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ES-iii Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ES-1 Overall Key Messages . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ES-1 Content Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ES-3 Part 1: Introduction to Medications for Opioid Use Disorder Treatment . . . . . . . . . . . . . ES-3 Part 2: Addressing Opioid Use Disorder in General Medical Settings . . . . . . . . . . . . . . . . ES-4 Part 3: Medications for Opioid Use Disorder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ES-4 Part 4: Bringing Together Addiction Treatment Counselors, Clients, and Healthcare Professionals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ES-5 Part 5: Resources Related to Medications for Opioid Use Disorder . . . . . . . . . . . . . . . . . . ES-5 Notes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ES-7 TIP Development Participants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ES-9 Expert Panelists . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ES-9 Scientific Reviewers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ES-10 Field Reviewers. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ES-10 Publication Information . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ES-12 ES-iii TIP 63Executive Summary Foreword The Substance Abuse and Mental Health Services Administration (SAMHSA) is the U.S. Department of Health and Human Services agency that leads public health efforts to reduce the impact of substance abuse and mental illness on America’s communities. An important component of SAMHSA’s work is focused on dissemination of evidence-based practices and providing training and technical assistance to healthcare practitioners on implementation of these best practices. The Treatment Improvement Protocol (TIP) series contributes to SAMHSA’s mission by providing science-based, best-practice guidance to the behavioral health field. TIPs reflect careful consideration of all relevant clinical and health services research, demonstrated experience, and implementation requirements. Select nonfederal clinical researchers, service providers, program administrators, and patient advocates comprising each TIP’s consensus panel discuss these factors, offering input on the TIP’s specific topics in their areas of expertise to reach consensus on best practices. Field reviewers then assess draft content and the TIP is finalized. The talent, dedication, and hard work that TIP panelists and reviewers bring to this highly participatory process have helped bridge the gap between the promise of research and the needs of practicing clinicians and administrators to serve, in the most scientifically sound and effective ways, people in need of care and treatment of mental and substance use disorders. U.S. Department of Health and Human Services Substance Abuse and Mental Health Services Administration TIP 63 Update As a reflection of SAMHSA’s commitment to ensuring that people with substance use disorders receive timely, relevant, high-quality care, SAMHSA in May 2021 revised certain areas of all five parts of this TIP to bring the content up to date and make it as useful to readers as possible. These changes will help provide readers with the latest information needed to understand medications for opioid use disorder. These changes include the following: • Updating statistics from SAMHSA, the Centers for Disease Control and Prevention, and other health authorities on opioid-related deaths, overdoses, accidents, and hospitalizations. • Updating the qualifications of practitioners who are eligible to apply for a waiver to prescribe buprenorphine (i.e., clinical nurse specialists, certified registered nurse anesthetists, and certified nurse midwives) to include exceptions under the latest buprenorphine practice guidelines on obtaining a waiver. • Where needed, clarifying whether references to naltrexone refer to the oral formulation or the extended-release injectable formulation. • Adding recent citations that support induction onto extended-release naltrexone of people with positive urine tests for opioids so long as they pass the naloxone challenge. • Clarifying that naltrexone can result in decreased opioid cravings. • Removing or replacing broken hyperlinks to online resources. This page intentionally left blank. ES-1 MEDICATIONS FOR OPIOID USE DISORDERTIP 63 Executive Summary The goal of treatment for opioid addiction or opioid use disorder (OUD) is remission of the disorder leading to lasting recovery. Recovery is a process of change through which individ- uals improve their health and wellness, live self-directed lives, and strive to reach their full potential.1 This Treatment Improvement Protocol (TIP) reviews the use of the three Food and Drug Administration (FDA)-approved medications used to treat OUD—methadone, naltrexone, and buprenorphine—and the other strategies and services needed to support recovery for people with OUD. Introduction Our nation faces a crisis of overdose deaths from opioids, including heroin, illicit fentanyl, and prescription opioids. These deaths represent a mere fraction of the total number of Americans harmed by opioid misuse and addiction. Many Americans now suffer daily from a chronic medical illness called “opioid addiction” or OUD (see the Glossary in Part 5 of this TIP for definitions). Healthcare professionals, treatment providers, and policymakers have a responsibility to expand access to evidence-based, effective care for people with OUD. Estimated cost of the OPIOID EPIDEMIC was $504 B I L L I O N in 2015.2 An expert panel developed the TIP’s content based on a review of the literature and on their extensive experience in the field of addiction treatment. Other professionals also generously contributed their time and commitment to this project. An estimated 1.4M AMERICANS have OUD related to opioid painkillers; 438K have heroin- related OUD.3 The TIP is divided into parts so that readers can easily find the material they need. Part 1 is a general introduction to providing medications for OUD and issues related to providing that treatment. Some readers may prefer to go directly to those parts most relevant to their areas of interest, but everyone is encouraged to read Part 1 to establish a shared understanding of key facts and issues covered in detail in this TIP. Following is a summary of the TIP’s overall main points and brief summaries of each of the five TIP parts. Overall Key Messages Addiction is a chronic, treatable illness. Opioid addiction, which generally corresponds with moderate to severe forms of OUD, often requires continuing care for effective treatment rather than an episodic, acute-care treatment approach. ES-2 Medications for Opioid Use Disorder TIP 63 Opioid overdose caused 49,860 DEATHS nationwide in 2019— this exceeded the # caused by motor vehicle crashes.4,5 General principles of good care for chronic diseases can guide OUD treatment. Approaching OUD as a chronic illness can help providers deliver care that helps patients stabilize, achieve remission of symptoms, and establish and maintain recovery. Patient-centered care empowers patients with information that helps them make better treatment decisions with the healthcare professionals involved in their care. Patients should receive information from their healthcare team that will help them understand OUD and the options for treating it, including treatment with FDA-approved medication. Patients with OUD should have access to mental health services as needed, medical care, and addiction counseling, as well as recovery support services, to supplement treatment with medication. The words you use to describe OUD and an individual with OUD are powerful. This TIP defines, uses, and encourages providers to adopt terminology that will not reinforce prejudice, negative attitudes, or discrimination. There is no “one size fits all” approach to OUD treatment. Many people with OUD benefit from treatment with medication for varying lengths of time, including lifelong treatment. Ongoing outpatient medication treatment for OUD is linked to better retention and outcomes than treatment without medication. Even so, some people stop using opioids on their own; others recover through support groups or specialty treatment with or without medication. The science demonstrating the effectiveness of medication for OUD is strong. For example, methadone, extended-release injectable naltrex- one (XR-NTX), and buprenorphine were each found to be more effective in reducing illicit opioid use than no medication in randomized clinical trials, which are the gold standard for demonstrating efficacy in clinical medicine.6,7,8,9,10 Methadone and buprenorphine treatment have also been associated with reduced risk of overdose death.11,12,13,14,15 This doesn’t mean that remission and recovery occur only through medication. Some people achieve remission without OUD medication, just as some people can manage type 2 diabetes with exercise and diet alone. But just as it is inadvisable to deny people with diabetes the medication they need to help manage their illness, it is also not sound medical practice to deny people with OUD access to FDA-approved medications for their illness. Medication for OUD should be successfully integrated with outpatient and residential treatment. Some patients may benefit from different levels of care at different points in their lives, such as outpatient counseling, intensive outpatient treatment, inpatient treatment, or long-term therapeutic communities. Patients treated in these settings should have access to OUD medications. 1.6 MILLION people in the U.S., ages 12 and older, had OUD involving PRESCRIPTION OPIOIDS, HEROIN, or both in 2019.16 ES-3 TIP 63Executive Summary Patients treated with medications for OUD can benefit from individualized psychosocial supports. These can be offered by patients’ healthcare providers in the form of medication management and supportive counseling and/or by other providers offering adjunctive addiction counseling, recovery coaching, mental health services, and other services that may be needed by particular patients. Expanding access to OUD medications is an important public health strategy.17 The gap between the number of people needing opioid addiction treatment and the capacity to treat them with OUD medication is substantial. In 2012, the gap was estimated at nearly 1 million people, with about 80 percent of opioid treatment programs (OTPs) nationally operating at 80 percent capacity or greater.18 Improving access to treatment with OUD medications is crucial to closing the wide gap between treatment need and treatment availability, given the strong evidence of effectiveness for such treatments.19 Data indicate that medications for OUD are cost effective and cost beneficial.20,21 Content Overview The TIP is divided into parts to make the material more accessible according to the reader’s interests. Part 1: Introduction to Medications for Opioid Use Disorder Treatment This part lays the groundwork for understanding treatment concepts discussed later in this TIP. The intended audience includes: • Healthcare professionals (physicians, nurse practitioners, physician assistants, and, until October 1, 2023, clinical nurse specialists, certified registered nurse anesthetists, and certified nurse midwives). • Professionals who offer addiction counseling or mental health services. O P I O I D - R E L AT E D EMERGENCY DEPARTMENT visits more than tripled from 2005 to 2017.22,23. • Peer support specialists. • People needing treatment and their families. • People in remission or recovery and their families. • Hospital administrators. • Policymakers. In Part 1, readers will learn that: • Increasing opioid overdose deaths, illicit opioid use, and prescription opioid misuse constitute a public health crisis. • OUD medications reduce illicit opioid use, retain people in treatment, and reduce risk of opioid overdose death better than treatment with placebo or no medication. • Only physicians; nurse practitioners; physician assistants; and, until October 1, 2023, clinical nurse specialists, certified registered nurse anesthetists, and certified nurse midwives can prescribe buprenorphine for OUD. They must get a federal waiver to do so. • Only federally certified, accredited OTPs can dispense methadone to treat OUD. OTPs can administer and dispense buprenorphine without a federal waiver. • Any prescriber can offer naltrexone. • OUD medication can be taken on a short- or long-term basis, including as part of medically supervised withdrawal and as maintenance treatment. • Patients taking medication for OUD are considered to be in recovery. • Several barriers contribute to the underuse of medication for OUD. ES-4 Medications for Opioid Use Disorder TIP 63 EVERYONE AGES 15 TO 65 should be tested at least ONCE for HIV . Persons at HIGHER RISK, such as people who use DRUGS by injection, should be tested ANNUALLY. HIV Hep C Anyone who is injecting or has ever INJECTED DRUGS, even ONCE, no matter how long ago, should be TESTED for HEPATITIS C, r e g a r d l e s s o f t h e i r i n t e n t i o n t o s e e k TREATMENT for SUD.24,25 Part 2: Addressing Opioid Use Disorder in General Medical Settings This part offers guidance on OUD screening, assessment, treatment, and referral. Part 2 is for healthcare professionals working in general medical settings with patients who have or are at risk for OUD. In Part 2, readers will learn that: • All healthcare practices should screen for alcohol, tobacco, and other substance misuse (including opioid misuse). • Validated screening tools, symptom surveys, and other resources are readily available; this part lists many of them. • When patients screen positive for risk of harm from substance use, practitioners should assess them using tools that determine whether substance use meets diagnostic criteria for a substance use disorder (SUD). • Thorough assessment should address patients’ medical, social, SUD, and family histories. • Laboratory tests can inform treatment planning. • Practitioners should develop treatment plans or referral strategies (if onsite SUD treatment is unavailable) for patients who need SUD treatment. Part 3: Medications for Opioid Use Disorder This part offers information and tools for health- care professionals who prescribe, administer, or dispense OUD medications or treat other illnesses in patients who take these medications. It provides guidance on the use of buprenorphine, methadone, and naltrexone by healthcare professionals in: • General medical settings, including hospitals. • Office-based opioid treatment settings. • Specialty addiction treatment programs, including OTPs. In Part 3, readers will learn that: • OUD medications are safe and effective when used appropriately. OPIOID-RELATED inpatient hospital stays INCREASED 119% nationally from 2005 to 2017.26,27 ES-5 TIP 63Executive Summary • OUD medications can help patients reduce or stop illicit opioid use and improve their health and functioning. • Medications should be considered for all patients with OUD. Opioid medications should be reserved for those with moderate- to-severe OUD with physical dependence. • Patients with OUD should be informed of the risks and benefits of medications to treat OUD, treatment without medication, and no treatment. • Patients should be advised on where and how to get treatment with OUD medication. • Doses and schedules of medications must be individualized. Part 4: Bringing Together Addiction Treatment Counselors, Clients, and Healthcare Professionals This part recommends ways that addiction treatment counselors can collaborate with healthcare professionals to support client- centered, trauma-informed OUD treatment and recovery. It also serves as a quick guide to medications that can treat OUD and presents strategies for clear communication with pre- scribers, creation of supportive environments for clients who take OUD medication, and ways to address other common counseling concerns when working with this population. In Part 4, readers will learn that: • Many patients taking OUD medication benefit from counseling as part of treatment. • Counselors play the same role for clients with OUD who take medication as for clients with any other SUD. • Counselors help clients recover by addressing the challenges and consequences of addiction. • OUD is often a chronic illness requiring ongoing communication among patients and providers to ensure that patients fully benefit from both medication and psychosocial treatment and support. OPIOID ADDICTION is linked with high rates of ILLEGAL ACTIVITY and INCARCERATION.28,29 • OUD medications are safe and effective when prescribed and taken appropriately. • Medication is integral to recovery for many people with OUD. Medication usually produces better treatment outcomes than outpatient treatment without medication. • Supportive counseling environments for clients who take OUD medication can promote treatment and help build recovery capital. Part 5: Resources Related to Medications for Opioid Use Disorder This part has a glossary and audience-segmented resource lists to help medical and behavioral health service providers better understand how to use OUD medications with their patients and to help patients better understand how OUD medications work. It is for all interested readers. In Part 5, readers will learn that: • Practice guidelines and decision-making tools can help healthcare professionals with OUD screening, assessment, diagnosis, treatment planning, and referral. • Patient- and family-oriented resources provide information about opioid addiction in general; the role of medication, behavioral and sup- portive services, and mutual-help groups in the treatment of OUD; how-tos for identifying recovery support services; and how-tos for locating medical and behavioral health service providers who specialize in treating OUD or other SUDs. ES-6 Medications for Opioid Use Disorder TIP 63 PRESCRIBING CONSIDERATIONS METHADONE NALTREXONE BUPRENORPHINE Mechanism of Action at mu- Opioid Receptor Agonist Antagonist Partial agonist Phase of Treatment Medically supervised withdrawal, maintenance Prevention of relapse to opioid misuse, following medically supervised withdrawal Medically supervised withdrawal, maintenance Route of Administration Oral Oral, intramuscular extended-release Sublingual, buccal, subdermal implant, subcutaneous extended release injection Possible Adverse Effects Constipation, hyperhidrosis, respiratory depression, sedation, QT prolongation, sexual dysfunction, severe hypotension including orthostatic hypotension and syncope, misuse potential, neonatal abstinence syndrome Nausea, anxiety, insomnia, precipitated opioid withdrawal, hepatotoxicity, vulnerability to opioid overdose, depression, suicidality, muscle cramps, dizziness or syncope, somnolence or sedation, anorexia, decreased appetite or other appetite disorders Intramuscular: Pain, swelling, induration (including some cases requiring surgical intervention) Constipation, nausea, precipitated opioid withdrawal, excessive sweating, insomnia, pain, peripheral edema, respiratory depression (particularly combined with benzodiazepines or other CNS depressants), misuse potential, neonatal abstinence syndrome Implant: Nerve damage during insertion/removal, accidental overdose or misuse if extruded, local migration or protrusion Subcutaneous Injection: Injection site itching or pain, death from intravenous injection Regulations and Availability Schedule II; only available at federally certified OTPs and the acute inpatient hospital setting for OUD treatment Not a scheduled medication; not included in OTP regulations; requires prescription; office-based treatment or specialty substance use treatment programs, including OTPs Schedule III; requires waiver to prescribe outside OTPs Implant: Prescribers must be certified in the Probuphine Risk Evaluation and Mitigation Strategy (REMS) Program. Providers who wish to insert/ remove implants are required to obtain special training and certification in the REMS Program Subcutaneous Injection: Healthcare settings and pharmacies must be certified in the Sublocade REMS Program and only dispense the medication directly to a provider for administration Adapted with permission.30 Copyrighted 2017. UBM Medica. 131265:0917SH EXHIBIT ES.1. Comparison of Medications for OUD ES-7 TIP 63Executive Summary Notes 1 Substance Abuse and Mental Health Services Administration. (2017). Recovery and recovery support [Webpage]. Retrieved November 17, 2017, from www.samhsa.gov/recovery 2 Council of Economic Advisers. (2017, November). The underestimated cost of the opioid crisis. Washington, DC: Executive Office of the President of the United States. 3 Center for Behavioral Health Statistics and Quality. (2020). Results from the 2019 National Survey on Drug Use and Health: Detailed tables. Rockville, MD: Substance Abuse and Mental Health Services Administration. Retrieved May 21, 2021, from www.samhsa.gov/data/ 4 Centers for Disease Control and Prevention, National Center for Health Statistics. (2020). Multiple Cause of Death 2018-2019 on CDC WONDER Online Database, released in 2020. Retrieved April 29, 2021, from http:// wonder.cdc.gov/mcd-icd10.html 5 National Highway Traffic Safety Administration. (2020). NHTSA Releases 2019 Crash Fatality Data. Retrieved April 29, 2021, from www.nhtsa.gov/press-releases/ nhtsa-releases-2019-crash-fatality-data 6 Johnson, R. E., Chutuape, M. A., Strain, E. C., Walsh, S. L., Stitzer, M. L., & Bigelow, G. E. (2000). A comparison of levomethadyl acetate, buprenorphine, and methadone for opioid dependence. New England Journal of Medicine, 343(18), 1290–1297. 7 Krupitsky, E., Nunes, E. V., Ling, W., Illeperuma, A., Gastfriend, D. R., & Silverman, B. L. (2011, April 30). Injectable extended-release naltrexone for opioid dependence: A double-blind, placebo-controlled, multicentre randomised trial. Lancet, 377(9776), 1506–1513. 8 Lee, J. D., Friedmann, P. D., Kinlock, T. W., Nunes, E. V., Boney, T. Y., Hoskinson, R. A., Jr., … O’Brien, C. P. (2016). Extended-release naltrexone to prevent opioid relapse in criminal justice offenders. New England Journal of Medicine, 374(13), 1232–1242. 9 Mattick, R. P., Breen, C., Kimber, J., & Davoli, M. (2009). Methadone maintenance therapy versus no opioid replacement therapy for opioid dependence. Cochrane Database of Systematic Reviews, 2009(3), 1–19. 10 Mattick, R. P., Breen, C., Kimber, J., & Davoli, M. (2014). Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. Cochrane Database of Systematic Reviews, 2014(2), 1–84. 11 Auriacombe, M., Fatséas, M., Dubernet, J., Daulouède, J. P., & Tignol, J. (2004). French field experience with buprenorphine. American Journal on Addictions, 13(Suppl. 1), S17–S28. 12 Degenhardt, L., Randall, D., Hall, W., Law, M., Butler, T., & Burns, L. (2009). Mortality among clients of a state-wide opioid pharmacotherapy program over 20 years: Risk factors and lives saved. Drug and Alcohol Dependence, 105(1–2), 9–15. 13 Gibson, A., Degenhardt, L., Mattick, R. P., Ali, R., White, J., & O’Brien, S. (2008). Exposure to opioid maintenance treatment reduces long-term mortality. Addiction, 103(3), 462–468. 14 Schwartz, R. P., Gryczynski, J., O’Grady, K. E., Sharfstein, J. M., Warren, G., Olsen, Y., … Jaffe, J. H. (2013). Opioid agonist treatments and heroin overdose deaths in Baltimore, Maryland, 1995–2009. American Journal of Public Health, 103(5), 917–922. 15 World Health Organization. (2009). Guidelines for the psychosocially assisted pharmacological treatment of opioid dependence. Geneva, Switzerland: WHO Press. 16 Center for Behavioral Health Statistics and Quality. (2020). Results from the 2019 National Survey on Drug Use and Health: Detailed tables. Rockville, MD: Substance Abuse and Mental Health Services Administration. Retrieved May 21, 2021, from www.samhsa.gov/data/ 17 Department of Health and Human Services, Office of the Surgeon General. (2016). Facing addiction in America: The Surgeon General’s report on alcohol, drugs, and health. Washington, DC: Department of Health and Human Services. 18 Jones, C. M., Campopiano, M., Baldwin, G., & McCance- Katz, E. (2015). National and state treatment need and capacity for opioid agonist medication-assisted treatment. American Journal of Public Health, 105(8), e55–e63. 19 Jones, C. M., Campopiano, M., Baldwin, G., & McCance- Katz, E. (2015). National and state treatment need and capacity for opioid agonist medication-assisted treatment. American Journal of Public Health, 105(8), e55–e63. 20 Cartwright, W. S. (2000). Cost-benefit analysis of drug treatment services: Review of the literature. Journal of Mental Health Policy and Economics, 3(1), 11–26. 21 McCollister, K. E., & French, M. T. (2003). The relative contribution of outcome domains in the total economic benefit of addiction interventions: A review of first findings. Addiction, 98(12), 1647–1659. 22 Weiss, A. J., Elixhauser, A., Barrett, M. L., Steiner, C. A., Bailey, M. K., & O’Malley, L. (2017, January). Opioid- related inpatient stays and emergency department visits by state, 2009–2014. HCUP Statistical Brief No. 219. Rockville, MD: Agency for Healthcare Research and Quality. ES-8 Medications for Opioid Use Disorder TIP 63 23 Agency for Healthcare Research and Quality. (2020). Rate of opioid-related ED visits per 100,000 population. Retrieved April 29, 2021, from www.hcup-us.ahrq.gov/ faststats/OpioidUseMap?setting=ED 24 U.S. Preventive Services Task Force. (2013). Archived Final Recommendation Statement on Human Immunodeficiency Virus (HIV) Infection: Screening. December 30, 2013. Retrieved January 11, 2020, from www.uspreventiveservicestaskforce.org/Page/ Document/RecommendationStatementFinal/human- immunodeficiency-virus-hiv-infection-screening#consider 25 Centers for Disease Control and Prevention. (2015). Testing recommendations for hepatitis C virus infection. October 15, 2015. Retrieved January 11, 2020, from www.cdc.gov/hepatitis/hcv/guidelinesc.htm 26 Weiss, A. J., Elixhauser, A., Barrett, M. L., Steiner, C. A., Bailey, M. K., & O’Malley, L. (2017, January). Opioid- related inpatient stays and emergency department visits by state, 2009–2014. HCUP Statistical Brief No.219. Rockville, MD: Agency for Healthcare Research and Quality. 27 Agency for Healthcare Research and Quality. (2020). Rate of opioid-related inpatient stays per 100,000 population. Retrieved April 29, 2021, from www.hcup-us.ahrq.gov/ faststats/OpioidUseMap?setting=IP 28 World Health Organization. (2009). Guidelines for the psychosocially assisted pharmacological treatment of opioid dependence. Geneva, Switzerland: WHO Press. 29 Soyka, M., Träder, A., Klotsche, J., Haberthür, A., Bühringer, G., Rehm, J., & Wittchen, H. U. (2012). Criminal behavior in opioid-dependent patients before and during maintenance therapy: 6-year follow-up of a nationally representative cohort sample. Journal of Forensic Sciences, 57(6), 1524–1530. 30 Brezing, C., & Bisaga, A. (2015, April 30). Opioid use disorder: Update on diagnosis and treatment. Psychiatric Times, 32(4) 1–4. ES-9 TIP 63Executive Summary TIP Development Participants Expert Panelists Each Treatment Improvement Protocol’s (TIP’s) expert panel is a group of primarily nonfederal addiction-focused clinical, research, administrative, and recovery support experts with deep knowledge of the TIP’s topic. With the Substance Abuse and Mental Health Services Administration’s (SAMHSA’s) Knowledge Application Program (KAP) team, they develop each TIP via a consensus- driven, collaborative process that blends evidence-based, best, and promising practices with the panel’s expertise and combined wealth of experience. (Note that affiliations reflect those relevant at the time of the individual’s review.) TIP Chair Robert P. Schwartz, M.D.—TIP Chair Medical Director/Senior Research Scientist Friends Research Institute Baltimore, MD TIP Expert Panelists Sarah Church, Ph.D. Executive Director Montefiore Medical Center Wellness Center at Waters Place Bronx, NY Diana Coffa, M.D., FM Associate Professor University of California School of Medicine Family Community Medicine San Francisco, CA Zwaantje Hamming, M.S.N., FNP-C, CARN-AP La Familia Medical Center Santa Fe, NM Ron Jackson, M.S.W., LICSW Affiliate Professor University of Washington School of Social Work Seattle, WA Hendree Jones, Ph.D. Professor and Executive Director Horizons Program Chapel Hill, NC Michelle Lofwall, M.D., DFASAM Medical Director University of Kentucky College of Medicine— Straus Clinic Associate Professor of Behavioral Science and Psychiatry Faculty in UK Center on Drug and Alcohol Research Lexington, KY Shannon C. Miller, M.D., DFASAM, DFAPA (ad hoc panelist) Director, Addiction Services Veterans Affairs Medical Center Cincinnati, OH Charles Schauberger, M.D. Obstetrician-Gynecologist Gundersen Health System La Crosse, WI Joycelyn Woods, M.A., CMA Executive Director National Alliance for Medication Assisted Recovery New York, NY SAMHSA’s TIP Champion Melinda Campopiano von Klimo, M.D. Senior Medical Advisor Center for Substance Abuse Treatment SAMHSA Rockville, MD ES-10 Medications for Opioid Use Disorder TIP 63 Scientific Reviewers This TIP’s scientific reviewers are among the foremost experts on the three medications discussed in this TIP to treat opioid use disorder. Their role in the collaborative TIP development process was to help the KAP team include current, accurate, and comprehensive information and instructions about the use of each of these medications. (Note that affiliations reflect those relevant at the time of the individual’s review.) Buprenorphine David A. Fiellin, M.D. Professor of Investigative Medicine and Public Health Yale University School of Medicine New Haven, CT Methadone Andrew J. Saxon, M.D. Professor Department of Psychiatry and Behavioral Sciences University of Washington School of Medicine Director Center of Excellence in Substance Abuse Treatment and Education Veterans Affairs Puget Sound Health Care System Seattle, WA Naltrexone Joshua D. Lee, M.D., M.Sc. Associate Professor Department of Population Health Division of General Medicine and Clinical Innovation NYU Langone Health New York, NY Field Reviewers Field reviewers represent each TIP’s intended target audiences. They work in addiction, mental health, primary care, and adjacent fields. Their direct front-line experience related to the TIP’s topic allows them to provide valuable input on a TIP’s relevance, utility, accuracy, and accessibility. (Note that affiliations reflect those relevant at the time of the individual’s review.) William Bograkos, M.A., D.O., FACOEP, FACOFP Adjunct Professor Center for Excellence in the Neurosciences University of New England (UNE) Clinical Professor of Medical Military Science Family Practice and Emergency Medicine, UNE Biddeford, ME Meg Brunner, M.L.I.S. Librarian, Alcohol and Drug Abuse Institute University of Washington Seattle, WA Kathryn Cates-Wessell Chief Executive Officer American Academy of Addiction Psychiatry East Providence, RI Mary Catlin, BSN, M.P.H., CIC Public Health Nurse Alcohol and Drug Abuse Institute University of Washington Seattle, WA Kelly J. Clark, M.D., M.B.A., DFASAM President American Society of Addiction Medicine Rockville, MD Marc Fishman, M.D. Assistant Professor Johns Hopkins University School of Medicine, Psychiatry/Behavioral Sciences Expert Team Baltimore, MD Katherine Fornili, D.N.P., M.P.H., RN, CARN Assistant Professor University of Maryland School of Nursing Baltimore, MD ES-11 TIP 63Executive Summary Adam Gordon, M.D., M.P.H., FACP, FASAM, CMRO Associate Professor of Medicine and Advisory Dean University of Pittsburgh School of Medicine Pittsburgh, PA Ellie Grossman, M.D. Instructor in Medicine Cambridge Health Alliance Somerville Hospital Primary Care Somerville, MA Kyle Kampman, M.D. Professor, Department of Psychiatry Perelman School of Medicine University of Pennsylvania Center for Studies of Addiction Philadelphia, PA Janice Kauffman, M.P.H., RN, CAS, CADC-1 Vice President of Addiction Treatment Services, North Charles Foundation, Inc. Director of Addictions Consultation, Department of Psychiatry, Cambridge Health Alliance Assistant Professor of Psychiatry, Harvard Medical School, the Cambridge Hospital Cambridge, MA Jason Kletter, Ph.D. President, Bay Area Addiction Research and Treatment President, California Opioid Maintenance Providers San Francisco, CA William J. Lorman, J.D., Ph.D., MSN, PMHNP-BC, CARN-AP Vice President and Chief Clinical Officer Livengrin Foundation, Inc. Bensalem, PA Megan Marx-Varela, M.P.A. Associate Director The Joint Commission—Behavioral Health Care Accreditation Oakbrook Terrace, IL Alison Newman, M.P.H. Continuing Education Specialist Alcohol and Drug Abuse Institute University of Washington Seattle, WA David O’Gurek, M.D., FAAFP Assistant Professor Family and Community Medicine, Lewis Katz School of Medicine Temple University Philadelphia, PA Yngvild Olsen, M.D., M.P.H, FASAM Medical Director Institutes for Behavior Resources, Inc./Recovery Enhanced by Access to Comprehensive Healthcare (REACH) Health Services Baltimore, MD Shawn A. Ryan, M.D., M.B.A., ABEM, FASAM President & Chief Medical Officer BrightView Cincinnati, OH Paul Stasiewicz, Ph.D. Senior Research Scientist Research Institute on Addictions State University of New York-Buffalo Buffalo, NY Kenneth Stoller, M.D. Director Broadway Center for Addiction at the Johns Hopkins Hospital Assistant Professor of Psychiatry and Behavioral Sciences Johns Hopkins University Baltimore, MD Mishka Terplan, M.D., M.P.H., FACOG Professor Department of Obstetrics and Gynecology, Division of General Obstetrics and Gynecology Virginia Commonwealth University Richmond, VA Christopher Welsh, M.D. Associate Professor of Psychiatry University of Maryland Medical Center Baltimore, MD George E. Woody, M.D. Professor of Psychiatry Department of Psychiatry Center for Studies of Addiction University of Pennsylvania’s Perelman School of Medicine Philadelphia, PA ES-12 Medications for Opioid Use Disorder TIP 63 Publication Information Acknowledgments This publication was prepared under contract numbers 270-14-0445 and 283-17-4901 by the Knowledge Application Program (KAP) for the Center for Substance Abuse Treatment, Substance Abuse and Mental Health Services Administration (SAMHSA), U.S. Department of Health and Human Services (HHS). Suzanne Wise served as the Contracting Officer’s Representative, and Candi Byrne served as KAP Project Coordinator. Disclaimer The views, opinions, and content expressed herein are the views of the consensus panel members and do not necessarily reflect the official position of SAMHSA or HHS. No official support of or endorse- ment by SAMHSA or HHS for these opinions or for the instruments or resources described is intended or should be inferred. The guidelines presented should not be considered substitutes for individual- ized client care and treatment decisions. Public Domain Notice All materials appearing in this publication except those taken directly from copyrighted sources are in the public domain and may be reproduced or copied without permission from SAMHSA or the authors. Citation of the source is appreciated. However, this publication may not be reproduced or distributed for a fee without the specific, written authorization of the Office of Communications, SAMHSA, HHS. Electronic Access and Copies of Publication This publication may be ordered or downloaded from SAMHSA’s Publications Ordering webpage at https://store.samhsa.gov. Or, please call SAMHSA at 1-877-SAMHSA-7 (1-877-726-4727) (English and Español). Recommended Citation Substance Abuse and Mental Health Services Administration. Medications for Opioid Use Disorder. Treatment Improvement Protocol (TIP) Series 63 Publication No. PEP21-02-01-002. Rockville, MD: Substance Abuse and Mental Health Services Administration, 2021. Originating Office Quality Improvement and Workforce Development Branch, Division of Services Improvement, Center for Substance Abuse Treatment, Substance Abuse and Mental Health Services Administration, 5600 Fishers Lane, Rockville, MD 20857. Nondiscrimination Notice SAMHSA complies with applicable federal civil rights laws and does not discriminate on the basis of race, color, national origin, age, disability, or sex. SAMHSA cumple con las leyes federales de derechos civiles aplicables y no discrimina por motivos de raza, color, nacionalidad, edad, discapacidad, o sexo. Publication No. PEP21-02-01-002 First released 2018. Revised 2019, 2020, and 2021. MEDICATIONS FOR OPIOID USE DISORDERTIP 63 Substance Abuse and Mental Health Services Administration Part 1: Introduction to Medications for Opioid Use Disorder Treatment For Healthcare and Addiction Professionals, Policymakers, Patients, and Families Part 1 of this Treatment Improvement Protocol (TIP) will help readers understand key facts and issues related to providing Food and Drug Administration (FDA)-approved medications used to treat opioid use disorder (OUD). TIP Navigation Executive Summary For healthcare and addiction professionals, policymakers, patients, and families Part 1: Introduction to Medications for Opioid Use Disorder Treatment For healthcare and addiction professionals, policymakers, patients, and families Part 2: Addressing Opioid Use Disorder in General Medical Settings For healthcare professionals Part 3: Medications for Opioid Use Disorder For healthcare professionals Part 4: Bringing Together Addiction Treatment Counselors, Clients, and Healthcare Professionals For healthcare and addiction professionals Part 5: Resources Related to Medications for Opioid Use Disorder For healthcare and addiction professionals, policymakers, patients, and families KEY MESSAGES • Increasing opioid overdose deaths, illicit opioid use, and prescription opioid misuse constitute a public health crisis. • OUD medications reduce illicit opioid use, retain people in treatment, and reduce risk of opioid overdose death better than treatment with placebo or no medication. • Only physicians; nurse practitioners; physician assistants; and, until October 1, 2023, clinical nurse specialists, certifed registered nurse anesthetists, and certifed nurse midwives can prescribe buprenorphine for OUD. They must get a federal waiver to do so. • Only federally certifed, accredited opioid treatment programs (OTPs) can dispense methadone to treat OUD. OTPs can administer and dispense buprenorphine without a federal waiver. • Any prescriber can offer naltrexone. • OUD medication can be taken on a short- or long-term basis, including as part of medically supervised withdrawal and as maintenance treatment. • Patients taking medication for OUD are considered to be in recovery. • Several barriers contribute to the underuse of medication for OUD. 1-ii TIP 63 MEDICATIONS FOR OPIOID USE DISORDER—Part 1 of 5 Contents The Approach to OUD Care 1-1 Overview of Medications for OUD 1-3 Benefts 1-3 Efectiveness 1-3 Cost Efectiveness and Cost Benefts 1-7 Requirements and Regulations 1-7 Duration of Treatment With OUD Medication 1-8 Maintenance Treatment 1-8 Medication Taper 1-9 Medically Supervised Withdrawal 1-9 Treatment Settings 1-9 Challenges to Expanding Access to OUD Medication 1-10 Resources 1-10 Notes 1-11 1-1 MEDICATIONS FOR OPIOID USE DISORDERTIP 63 PART 1 of 5 Introduction to Medications for Opioid Use Disorder Treatment Part 1 of this TIP offers a general introduction to providing medications to address opioid use disorder (OUD). It is for all audiences. Part 1 will help readers understand key facts and issues related to providing FDA-approved medications used to treat OUD. TIP Parts 2 through 5 cover these issues in more detail. The Approach to OUD Care According to the Substance Abuse and Mental Health Services Administration (SAMHSA) and the National Institute on Drug Abuse, addiction is a chronic, treatable illness. Opioid addiction, which generally corresponds with moderate to severe forms of OUD (Exhibit 1.1), often requires continuing care for effective treatment rather than an episodic, acute-care treatment approach. The World Health Organization’s (WHO’s) principles of good care for chronic diseases can guide OUD care:1 • Develop a treatment partnership with patients. • Focus on patients’ concerns and priorities. • Support patient self-management of illness. • Use the fve A’s at every visit (assess, advise, agree, assist, and arrange). • Organize proactive follow-up. • Link patients to community resources/support. • Work as a clinical team. • Involve “expert patients,” peer educators, and support staff in the health facility. • Ensure continuity of care. Chronic care management is effective for many long-term medical conditions, such as diabetes and cardiovascular disease, and it can offer Estimated cost of the OPIOID EPIDEMIC was $504 B I L L I O N in 2015.2 similar benefts to patients with substance use disorders (SUDs); for example, it can help them stabilize, achieve remission of symptoms, and establish and maintain recovery. Good con- tinuing care also provides, and links to, other medical, behavioral health, and community and recovery support services. A noticeable theme in chronic disease management is patient-centered care. Patient-centered care empowers patients with information that helps them make better treatment decisions with the healthcare profes- sionals involved in their care. Patients should receive information from their healthcare team that will help them understand OUD and the options for treating it, including treatment with FDA-approved medications. Healthcare professionals should also make patients aware of available, appropriate recovery support and behavioral health services. 1-2 Medications for Opioid Use Disorder TIP 63 EXHIBIT 1.1. Key Terms Addiction: As defned by the American Society of Addiction Medicine, “a primary, chronic disease of brain reward, motivation, memory, and related circuitry.”3 It is characterized by inability to consistently abstain, impairment in behavioral control, craving, diminished recognition of signifcant problems with one’s behaviors and interpersonal relationships, and a dysfunctional emotional response. Like other chronic diseases, addiction often involves cycles of relapse and remission. The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition4 (DSM-5), does not use the term for diagnostic purposes, but it commonly describes the more severe forms of OUD. Medically supervised withdrawal (formerly called detoxifcation): Using an opioid agonist (or an alpha-2 adrenergic agonist if an opioid agonist is not available) in tapering doses or other medications to help a patient discontinue illicit or prescription opioids. Opioid misuse: The use of prescription opioids in any way other than as directed by a prescriber; the use of any opioid in a manner, situation, amount, or frequency that can cause harm to self or others.5 Opioid receptor agonist: A substance that has an affnity for and stimulates physiological activity at cell receptors in the central nervous system (CNS) that are normally stimulated by opioids. Mu-opioid receptor full agonists (e.g., methadone) bind to the mu-opioid receptor and produce actions similar to those produced by the endogenous opioid beta-endorphin. Increasing the dose increases the effect. Mu-opioid receptor partial agonists (e.g., buprenorphine) bind to the mu-opioid receptor. Unlike with full agonists, increasing their dose may not produce additional effects once they have reached their maximal effect. At low doses, partial agonists may produce effects similar to those of full agonists. Opioid receptor antagonist: A substance that has affnity for opioid receptors in the CNS without producing the physiological effects of opioid agonists. Mu-opioid receptor antagonists (e.g., naltrexone) can block the effects of exogenously administered opioids. Opioids: All natural, synthetic, and semisynthetic substances that have effects similar to morphine. They can be used as medications having such effects (e.g., methadone, buprenorphine, oxycodone). Opioid treatment program (OTP): An accredited treatment program with SAMHSA certifcation and Drug Enforcement Administration registration to administer and dispense opioid agonist medications that are approved by FDA to treat opioid addiction. Currently, these include methadone and buprenorphine products. Other pharmacotherapies, such as naltrexone, may be provided but are not subject to these regulations. OTPs must provide adequate medical, counseling, vocational, educational, and other assessment and treatment services either onsite or by referral to an outside agency or practitioner through a formal agreement.6 Opioid use disorder (OUD): Per DSM-5, a disorder characterized by loss of control of opioid use, risky opioid use, impaired social functioning, tolerance, and withdrawal. Tolerance and withdrawal do not count toward the diagnosis in people experiencing these symptoms when using opioids under appropriate medical supervision. OUD covers a range of severity and replaces what DSM-IV termed “opioid abuse” and “opioid dependence.” An OUD diagnosis is applicable to a person who uses opioids and experiences at least 2 of the 11 symptoms in a 12-month period. (See Exhibit 2.13 in Part 2 for full DSM-5 diagnostic criteria for OUD.) Recovery: A process of change through which individuals improve their health and wellness, live self- directed lives, and strive to reach their full potential. Even individuals with severe and chronic SUDs can, with help, overcome their SUDs and regain health and social function. Although abstinence from all substance misuse is a cardinal feature of a recovery lifestyle, it is not the only healthy, prosocial feature. Patients taking FDA-approved medication to treat OUD can be considered in recovery. Relapse: A process in which a person with OUD who has been in remission experiences a return of symptoms or loss of remission. A relapse is different from a return to opioid use in that it involves more than a single incident of use. Relapses occur over a period of time and can be interrupted. Relapse need not be long lasting. The TIP uses relapse to describe relapse prevention, a common treatment modality. Remission: A medical term meaning a disappearance of signs and symptoms of the disease.7 DSM-5 defnes remission as present in people who previously met OUD criteria but no longer meet any OUD criteria (with the possible exception of craving).8 Remission is an essential element of recovery. Return to opioid use: One or more instances of opioid misuse without a return of symptoms of OUD. A return to opioid use may lead to relapse. 1-3 TIP 63Part 1 of 5—Introduction to Medications for Opioid Use Disorder Treatment As is true for patients undergoing treatment for any chronic medical condition, patients with OUD should have access to medical, mental health, addiction counseling, and recovery support services that they may need to supplement treatment with medication. Medical care should include preventive services and disease management. Patients with OUD who have mental disorders should have access to mental health services. Treatment and support services should refect each patient’s individual needs and preferences. Some patients, particularly those with co- occurring disorders, may require these treatments and services to achieve sustained remission and recovery. The words you use to describe both OUD and an individual with OUD are powerful and can reinforce prejudice, negative attitudes, and discrimination. Negative attitudes held by the public and healthcare professionals can deter people from seeking treatment, make patients leave treatment prematurely, and contribute to worse treatment outcomes. The TIP expert panel recommends that providers always use medical terms when discussing SUDs (e.g., positive or negative urine sample, not dirty or clean sample) and use person-frst language (e.g., a person with an SUD, not a user, alcoholic, or addict). Exhibit 1.1 defnes some key terms. A full glossary is in Part 5 of this TIP. RESOURCE ALERT Shared Decision Making SAMHSA’s shared decision-making resource page is helpful for educating patients and their families about OUD. The information provided can help patients make informed decisions about their care (www.samhsa.gov/brss-tacs/ recovery-support-tools/shared-decision- making). Overview of Medications for OUD There is no “one size fts all” approach to OUD treatment. Many people with OUD beneft from treatment with medication for varying lengths of time, including lifelong treatment. Ongoing outpatient medication treatment for OUD is linked to better retention and outcomes than treatment without medication. Even so, some people stop using opioids on their own; others recover through support groups or specialty outpatient or residential treatment with or without medication. Still, FDA-approved medication should be considered and offered to patients with OUD as part of their treatment. Benefts The three FDA-approved medications used to treat OUD improve patients’ health and wellness by: • Reducing or eliminating withdrawal symptoms: methadone, buprenorphine. • Blunting or blocking the effects of illicit opioids: methadone, naltrexone, buprenorphine. • Reducing or eliminating cravings to use opioids: methadone, naltrexone, buprenorphine. See Exhibit 1.2 for further comparison between these medications. Efectiveness The science demonstrating the effectiveness of medication for OUD is strong. For example, methadone, extended-release injectable naltrex- one (XR-NTX), and buprenorphine were each found to be more effective in reducing illicit opioid use than no medication in randomized clinical trials,9,10,11,12 which are the gold standard for demonstrating effcacy in clinical medicine. Methadone and buprenorphine treatment have also been associated with reduced risk of overdose death.13,14,15,16,17 1-4 Medications for Opioid Use Disorder TIP 63 EXHIBIT 1.2. Comparison of Medications for OUD PRESCRIBING CONSIDERATIONS METHADONE NALTREXONE BUPRENORPHINE Mechanism of Action at mu- Opioid Receptor Agonist Antagonist Partial agonist Phase of Treatment Medically supervised withdrawal, maintenance Prevention of relapse to opioid misuse, following medically supervised withdrawal Medically supervised withdrawal, maintenance Route of Administration Oral Oral, intramuscular extended-release Sublingual, buccal, subdermal implant, subcutaneous extended release injection Possible Adverse Effects Constipation, hyperhidrosis, respiratory depression, sedation, QT prolongation, sexual dysfunction, severe hypotension including orthostatic hypotension and syncope, misuse potential, neonatal abstinence syndrome Nausea, anxiety, insomnia, precipitated opioid withdrawal, hepatotoxicity, vulnerability to opioid overdose, depression, suicidality, muscle cramps, dizziness or syncope, somnolence or sedation, anorexia, decreased appetite or other appetite disorders Intramuscular: Pain, swelling, induration (including some cases requiring surgical intervention) Constipation, nausea, precipitated opioid withdrawal, excessive sweating, insomnia, pain, peripheral edema, respiratory depression (particularly combined with benzodiazepines or other CNS depressants), misuse potential, neonatal abstinence syndrome Implant: Nerve damage during insertion/removal, accidental overdose or misuse if extruded, local migration or protrusion Subcutaneous Injection: Injection site itching or pain, death from intravenous injection Regulations and Availability Schedule II; only available at federally certifed OTPs and the acute inpatient hospital setting for OUD treatment Not a scheduled medication; not included in OTP regulations; requires prescription; offce-based treatment or specialty substance use treatment programs, including OTPs Schedule III; requires waiver to prescribe outside OTPs Implant: Prescribers must be certifed in the Probuphine Risk Evaluation and Mitigation Strategy (REMS) Program. Providers who wish to insert/ remove implants are required to obtain special training and certifcation in the REMS Program Subcutaneous Injection: Healthcare settings and pharmacies must be certifed in the Sublocade REMS Program and only dispense the medication directly to a provider for administration Adapted with permission.18 Copyrighted 2017. UBM Medica. 131265:0917SH 1-5 TIP 63Part 1 of 5—Introduction to Medications for Opioid Use Disorder Treatment This doesn’t mean that remission and recovery occur only through medication. Some people achieve remission without OUD medication, just as some people can manage type 2 diabetes with exercise and diet alone. But just as it is inadvisable to deny people with diabetes the medication they need to help manage their illness, it is also not sound medical practice to deny people with OUD access to FDA-approved medications for their illness. Medication for OUD should be successfully integrated with outpatient and residential treatment. Some patients may beneft from different levels of care during the course of their lives. These different levels include outpatient counseling, intensive outpatient treatment, inpatient treatment, or long-term therapeutic communities. Patients receiving treatment in these settings should have access to FDA- approved medications for OUD. Patients treated with OUD medications can beneft from individualized psychosocial supports. These can be offered by patients’ healthcare providers in the form of medication management and supportive counseling and/or by other providers offering adjunctive addiction counseling, contingency management, recovery coaching, mental health services, and other services (e.g., housing supports) that particular patients may need. The TIP expert panel strongly recommends informing all patients with OUD about the risks and benefts of treatment of OUD with all FDA- approved medications. Alternatives to these treatments and their risks and benefts should be discussed. Patients should receive access to such medications if clinically appropriate and desired by the patients. Expanding access to FDA-approved medica- tions is an important public health strategy.19 A substantial gap exists between the number of people needing OUD treatment and the capacity to treat those individuals with OUD medication. In 2012, the gap was estimated at nearly 1 million people, with approximately 80 percent of OTPs nationally operating at 80 percent capacity or greater.20 Blue Cross Blue Shield reported a 493 percent increase in members diagnosed with OUD from 2010 to 2016 but only a 65 percent increase in the use of medication for OUD.21 Improving access is crucial to closing the wide gap between the need for treatment with OUD medications and the availability of such treatment, given the strong evidence of OUD medications’ effectiveness.22 Methadone Methadone retains patients in treatment and reduces illicit opioid use more effectively than placebo, medically supervised withdrawal, or no treatment, as numerous clinical trials and meta-analyses of studies conducted in many countries show.23,24,25 Higher methadone doses are associated with superior outcomes.26,27 Given the evidence of methadone’s effectiveness, WHO lists it as an essential medication.28 Methadone treatment has by far the largest, oldest evidence base of all treatment ap- proaches to opioid addiction. Large multisite longitudinal studies from the world over support methadone maintenance’s effectiveness.29,30,31 Longitudinal studies have also found that it is associated with:32,33,34,35,36,37,38,39,40 • Reduced risk of overdose-related deaths. • Reduced risk of HIV and hepatitis C infection. • Lower rates of cellulitis. • Lower rates of HIV risk behavior. • Reduced criminal behavior. 1-6 Medications for Opioid Use Disorder TIP 63 Naltrexone XR-NTX reduces illicit opioid use and retains patients in treatment more effectively than placebo and no medication, according to fndings from randomized controlled trials.41,42,43 In a two-group random assignment study of adults who were opioid dependent and involved in the justice system, all participants received brief counseling and community treatment referrals. One group received no medication, and the other group received XR-NTX. During the 6-month follow-up period, compared with the no-medication group, the group that received the medication demonstrated:44 • Longer time to return to substance use (10.5 weeks versus 5.0 weeks). • A lower rate of return to use (43 percent versus 64 percent). • A higher percentage of negative urine screens (74 percent versus 56 percent). There are two studies comparing XR-NTX to sublingual buprenorphine. A multisite random- ized trial assigned adult residential treatment patients with OUD to either XR-NTX or bu- prenorphine. Patients randomly assigned to buprenorphine had signifcantly lower relapse rates during 24 weeks of outpatient treatment than patients assigned to XR-NTX.45 This fnding resulted from challenges in completing XR-NTX induction, such that a signifcant proportion of patients did not actually receive XR-NTX. However, when comparing only those partici- pants who started their assigned medication, no signifcant between-group differences in relapse rates were observed. Because dose induction was conducted with inpatients, fndings may not be generalizable to dose induction in outpatient settings, where most patients initiate treatment. A 12-week trial among adults with opioid de- pendence in Norway who were opioid abstinent at the time of random assignment found that XR-NTX was as effective as buprenorphine in retaining patients in treatment and in reducing illicit opioid use.46 Oral naltrexone is also available, but it has not been found to be superior to placebo or to no medication in clinical trials.47 Nonadherence limits its use. Buprenorphine Buprenorphine in its sublingual form retains patients in treatment and reduces illicit opioid use more effectively than placebo.48 It also reduces HIV risk behaviors.49,50 A multisite randomized trial with individuals addicted to prescription opioids showed that continued buprenorphine was superior to buprenorphine dose taper in reducing illicit opioid use.51 Another randomized trial showed that continued buprenorphine also improved treatment retention and reduced illicit prescription opioid use compared with buprenorphine dose taper.52 Long-term studies of buprenorphine show its effectiveness outside of clinical research proto- cols.53,54 Naloxone, a short-acting opioid antago- nist, is also often included in the buprenorphine formulation to help prevent diversion to injected misuse. Because of the evidence of buprenor- phine’s effectiveness, WHO lists it as an essential medication.55 Buprenorphine is available in “transmucosal” (i.e., sublingual or buccal) formulations. Buprenorphine implants can be effective in stable patients. FDA approved implants (Probuphine) after a clinical trial showed them to be as effective as relatively low-dose (i.e., 8 mg or less daily) sublingual buprenorphine (Suboxone equivalents) for patients who are already clinically stable.56 More research is needed to establish implants’ effectiveness outside of research studies, but fndings to date are promising.57,58 FDA approved buprenorphine extended- release injection (Sublocade) in November 2017 to treat patients with moderate or severe OUD who have frst received treatment with transmucosal buprenorphine for at least 1 week. This buprenorphine formu- lation is a monthly subcutaneous injection. Exhibit 1.2 compares medications for OUD. 1-7 TIP 63Part 1 of 5—Introduction to Medications for Opioid Use Disorder Treatment Cost Efectiveness and Cost Benefts Cost-effectiveness and cost-beneft analyses can further our understanding of OUD medications’ effectiveness. Data indicate that medications for OUD are cost effective. Cost-effectiveness analyses compare the cost of different treatments with their associated outcomes (e.g., negative opioid urine tests). Such analyses have found that: • Methadone and buprenorphine are more cost effective than OUD treatment without medication.59 • Counseling plus buprenorphine leads to signifcantly lower healthcare costs than little or no treatment among commercially insured patients with OUD.60 • Treatment with any of the three OUD medi- cations this TIP covers led to lower healthcare usage and costs than treatment without medication in a study conducted in a large health plan.61 Relatively few cost-beneft analyses have examined addiction treatment with medi- cation separately from addiction treatment in general.62 Cost-beneft studies compare a treatment’s cost with its benefts. The treatment is cost benefcial if its benefts outweigh its cost. These benefts can include: • Reduced expenditures because of decreased crime. • Reduced expenditures related to decreases in the use of the justice system. • Improved quality of life. • Reduced healthcare spending. • Greater earned income. Methadone treatment in OTPs can reduce justice system and healthcare costs.63,64 Requirements and Regulations Following is a summary of regulations and requirements that apply to the three OUD medications. Part 3 of this TIP discusses the pharmacology and dosing of these medications. Only federally certifed and accredited OTPs can dispense methadone for the treatment of OUD. Methadone is typically given orally as a liquid.65 OTPs can dispense buprenorphine under OTP regulations without using a federal waiver. Individual healthcare practitioners can prescribe buprenorphine in any medical setting, as long as they apply for and receive waivers of the special registration requirements defned in the Controlled Substances Act. Several laws and regulations contain information about which healthcare practitioners are eligible to apply for a waiver and how to qualify (www.samhsa.gov/medication-assisted-treat- ment/training-materials-resources/apply-for- practitioner-waiver). This information is summarized below. • Eligible physicians, nurse practitioners, physician assistants, and other qualifying practitioners (clinical nurse specialists, certifed registered nurse anesthetists, and certifed nurse midwives) can apply for a waiver. • At present, clinical nurse specialists, certifed registered nurse anesthetists, and certifed nurse midwives are only eligible to apply for a waiver until October 1, 2023. • For the frst year of waiver use, all providers can treat up to 30 patients at one time. However, providers who satisfy additional practice and reporting requirements, and physicians who are board certifed in addiction psychiatry or addiction medicine, may request to treat up to 100 patients at a time in the frst year of waiver use. Additionally, practitioners who provide MAT in “qualifed practice settings,” as defned in title 42, section 8.615 of the Code of Federal Regulations, may also request to treat up to 100 patients within the frst year. • After the frst year of waiver use, all providers may request to increase their patient limit to 100. 1-8 Medications for Opioid Use Disorder TIP 63 • Physicians and other qualifed providers who are board certifed in addiction psychiatry or addiction medicine or who satisfy additional practice and reporting requirements may apply to increase their patient limit to 275 after a year at the 100-patient limit. Prescribing buprenorphine implants requires Probuphine REMS Program certifcation. Providers who wish to insert or remove implants must obtain live training and certif- cation in the REMS Program. Healthcare settings and pharmacies must get Sublocade REMS Program certifcation to dispense this medication and can only dispense it directly to healthcare providers for subcutane- ous administration. RESOURCE ALERT OUD Medication Treatment Limits and Reporting Requirements The following websites provide information about the Department of Health and Human Services' (1) fnal rule to increase patient access to medication for OUD, (2) notice on Practice Guidelines for the Administration of Buprenorphine for Treating Opioid Use Disorder, and (3) associated reporting requirements: www.federalregister.gov/documents/2016/ 07/08/2016-16120/medication-assisted- treatment-for-opioid-use-disorders www.federalregister.gov/documents/ 2021/04/28/2021-08961/practice-guidelines- for-the-administration-of-buprenorphine- for-treating-opioid-use-disorder www.samhsa.gov/sites/default/fles/ programs_campaigns/medication_assisted/ understanding-patient-limit275.pdf Naltrexone has no regulations beyond those that apply to any prescription pharmaceuti- cal. Any healthcare provider with prescribing authority, including those practicing in OTPs, can prescribe its oral formulation and administer its long-acting injectable formulation. The Controlled Substances Act contains a few exceptions from the requirement to provide methadone through an OTP or buprenorphine through an OTP or a waivered practitioner. These include (1) administering (not prescribing) an opioid for no more than 3 days to a patient in acute opioid withdrawal while preparations are made for ongoing care and (2) administering opioid medications in a hospital to maintain or detoxify a patient as an “incidental adjunct to medical or surgical treatment of conditions other than addiction.”66 Duration of Treatment With OUD Medication Patients can take medication for OUD on a short-term or long-term basis. However, patients who discontinue OUD medication generally return to illicit opioid use. Why is this so, even when discontinuation occurs slowly and carefully? Because the more severe form of OUD (i.e., addiction) is more than physical depen- dence. Addiction changes the reward circuitry of the brain, affecting cognition, emotions, and behavior. Providers and their patients should base decisions about discontinuing OUD medication on knowledge of the evidence base for the use of these medications, individualized assessments, and an individualized treatment plan they collaboratively develop and agree upon. Arbitrary time limits on the duration of treatment with OUD medication are inadvisable. Maintenance Treatment The best results occur when a patient receives medication for as long as it provides a beneft. This approach is often called “maintenance treatment.”67,68 Once stabilized on OUD med- ication, many patients stop using illicit opioids completely. Others continue to use for some 1-9 TIP 63Part 1 of 5—Introduction to Medications for Opioid Use Disorder Treatment time, but less frequently and in smaller amounts, which reduces their risk of morbidity and overdose death. OUD medication gives people the time and ability to make necessary life changes associated with long-term remission and recovery (e.g., changing the people, places, and things connected with their drug use), and to do so more safely. Maintenance treatment also minimizes cravings and withdrawal symptoms. And it lets people better manage other aspects of their life, such as parenting, attending school, or working. Medication Taper After some time, patients may want to stop opioid agonist therapy for OUD through gradually tapering doses of the medication. Their outcomes will vary based on factors such as the length of their treatment, abstinence from illicit drugs, fnancial and social stability, and motivation to discontinue medication.69 Longitudinal studies show that most patients who try to stop methadone treatment relapse during or after completing the taper.70,71 For example, in a large, population-based retrospective study, only 13 percent of patients who tapered from methadone had successful outcomes (no treatment reentry, death, or opioid-related hospitalization within 18 months after taper).72 A clinical trial of XR-NTX versus treatment without medication also found increased risk of returning to illicit opioid use after discontinuing medication.73 Adding psychosocial treatments to taper regimens may not signifcantly improve outcomes compared with remaining on med- ication. One study randomly assigned partici- pants to methadone maintenance or to 6 months of methadone treatment with a dose taper plus intensive psychosocial treatment. The mainte- nance group had more days in treatment and lower rates of heroin use and HIV risk behavior at 12-month follow-up.74 Patients wishing to taper their opioid agonist medication should be offered psychosocial and recovery support Primary care physicians are on the front lines of providing offce-based treatment with medication for OUD. services. They should be monitored during and after dose taper, offered XR-NTX, and encouraged to resume treatment with medication quickly if they return to opioid use. Medically Supervised Withdrawal Medically supervised withdrawal is a process in which providers offer methadone or buprenor- phine on a short-term basis to reduce physical withdrawal signs and symptoms. Formerly called detoxifcation, this process gradually decreases the dose until the medication is discontinued, typically over a period of days or weeks. Studies show that most patients with OUD who undergo medically supervised withdrawal will start using opioids again and won’t continue in recom- mended care.75, 76, 77, 78, 79, 80, 81, 82, 83 Psychosocial treatment strategies, such as contingency management, can reduce dropout from medically supervised withdrawal, opioid use during with- drawal, and opioid use following completion of withdrawal.84 Medically supervised withdrawal is necessary for patients starting naltrexone, which requires at least 7 days without short-acting opioids and 10 to 14 days without long-acting opioids. Patients who complete medically supervised withdrawal are at risk of opioid overdose. Treatment Settings Almost all healthcare settings are appropriate for screening and assessing for OUD and offering medication onsite or by referral. Settings that offer OUD treatment have expanded from specialty sites (certifed OTPs, residential fa- cilities, outpatient addiction treatment programs, and addiction specialist physicians’ offces) to general primary care practices, health centers, emergency departments, inpatient medical and psychiatric units, jails and prisons, and other settings. 1-10 Medications for Opioid Use Disorder TIP 63 Sustained public health efforts are essential to address the urgent need for OUD treatment and the risk of related overdose, HIV, and hepatitis C virus epidemics. These efforts must remove barriers and increase access to OUD medication. OUD medications should be available to patients across all settings and at all levels of care—as a tool for remission and recovery. Because of the strength of the science, a 2016 report from the Surgeon General85 urged adoption of medication for OUD along with recovery supports and other behavioral health services throughout the healthcare system. Challenges to Expanding Access to OUD Medication Despite the urgent need for treatment throughout the United States, only about 21.5 percent of people with OUD received treatment from 2009 to 2013.86 The Centers for Disease Control and Prevention lists more than 200 U.S. counties as at risk for an HIV or a hepatitis C virus outbreak related to injection drug use.87 Resources Patient success stories are inspirational. They highlight the power of OUD medication to help people achieve remission and recovery. See the “Patient Success Stories” section in Part 5 of this TIP. Part 5 of this TIP also contains community resources and advocacy resources. The community resources are for OTP, addiction treatment, and offce-based providers. The advocacy resources can help patients and others advocate for OUD medication for themselves and in their communities. 1-11 TIP 63Part 1 of 5—Introduction to Medications for Opioid Use Disorder Treatment Notes 1 World Health Organization. (2009). Guidelines for the psychosocially assisted pharmacological treatment of opioid dependence. Geneva, Switzerland: WHO Press. 2 Council of Economic Advisers. (2017). The underestimated cost of the opioid crisis. Washington, DC: Executive Offce of the President of the United States. 3 American Society of Addiction Medicine. (2011). Defnition of addiction. Retrieved January 9, 2018, from www.asam.org/resources/defnition-of-addiction 4 American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Arlington, VA: American Psychiatric Publishing. 5 Department of Health and Human Services, Offce of the Surgeon General. (2016). Facing addiction in America: The Surgeon General’s report on alcohol, drugs, and health. Washington, DC: Department of Health and Human Services. 6 Substance Abuse and Mental Health Services Administration. (2015). Federal guidelines for opioid treatment programs. HHS Publication No. (SMA) PEP15- FEDGUIDEOTP. Rockville, MD: Substance Abuse and Mental Health Services Administration. 7 National Cancer Institute. (n.d.). Remission. In NCI dictionary of cancer terms. Retrieved November 22, 2017, from www.cancer.gov/publications/dictionaries /cancer-terms?cdrid=45867 8 American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Arlington, VA: American Psychiatric Publishing. 9 Krupitsky, E., Nunes, E. V., Ling, W., Illeperuma, A., Gastfriend, D. R., & Silverman, B. L. (2011, April 30). Injectable extended-release naltrexone for opioid dependence: A double-blind, placebo-controlled, multicentre randomised trial. Lancet, 377(9776), 1506–1513. 10 Lee, J. D., Friedmann, P. D., Kinlock, T. W., Nunes, E. V., Boney, T. Y., Hoskinson, R. A., Jr., … O’Brien, C. P. (2016). Extended-release naltrexone to prevent opioid relapse in criminal justice offenders. New England Journal of Medicine, 374(13), 1232–1242. 11 Mattick, R. P., Breen, C., Kimber, J., & Davoli, M. (2009). Methadone maintenance therapy versus no opioid replacement therapy for opioid dependence. Cochrane Database of Systematic Reviews, 2009(3), 1–19. 12 Mattick, R. P., Breen, C., Kimber, J., & Davoli, M. (2014). Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. Cochrane Database of Systematic Reviews, 2014(2), 1–84. 13 Auriacombe, M., Fatséas, M., Dubernet, J., Daulouède, J. P., & Tignol, J. (2004). French feld experience with buprenorphine. American Journal on Addictions, 13(Suppl. 1), S17–S28. 14 Degenhardt, L., Randall, D., Hall, W., Law, M., Butler, T., & Burns, L. (2009). Mortality among clients of a state-wide opioid pharmacotherapy program over 20 years: Risk factors and lives saved. Drug and Alcohol Dependence, 105(1–2), 9–15. 15 Gibson, A., Degenhardt, L., Mattick, R. P., Ali, R., White, J., & O’Brien, S. (2008). Exposure to opioid maintenance treatment reduces long-term mortality. Addiction, 103(3), 462–468. 16 Schwartz, R. P., Gryczynski, J., O’Grady, K. E., Sharfstein, J. M., Warren, G., Olsen, Y., … Jaffe, J. H. (2013). Opioid agonist treatments and heroin overdose deaths in Baltimore, Maryland, 1995–2009. American Journal of Public Health, 103(5), 917–922. 17 World Health Organization. (2009). Guidelines for the psychosocially assisted pharmacological treatment of opioid dependence. Geneva, Switzerland: WHO Press. 18 Brezing, C., & Bisaga, A. (2015, April 30). Opioid use disorder: Update on diagnosis and treatment. Psychiatric Times, 32(4) 1–4. 19 Department of Health and Human Services, Offce of the Surgeon General. (2016). Facing addiction in America: The Surgeon General’s report on alcohol, drugs, and health. Washington, DC: Department of Health and Human Services. 20 Jones, C. M., Campopiano, M., Baldwin, G., & McCance- Katz, E. (2015). National and state treatment need and capacity for opioid agonist medication-assisted treatment. American Journal of Public Health, 105(8), e55–e63. 21 Blue Cross Blue Shield. (2017). America’s opioid epidemic and its effect on the nation’s commercially insured population. Washington, DC: Blue Cross Blue Shield Association. 22 Jones, C. M., Campopiano, M., Baldwin, G., & McCance- Katz, E. (2015). National and state treatment need and capacity for opioid agonist medication-assisted treatment. American Journal of Public Health, 105(8), e55–e63. 23 Mattick, R. P., Breen, C., Kimber, J., & Davoli, M. (2014). Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. Cochrane Database of Systematic Reviews, 2014(2), 1–84. 24 Sees, K. L., Delucchi, K. L., Masson, C., Rosen, A., Clark, H. W., Robillard, H., … Hall, S. M. (2000). Methadone maintenance vs 180-day psychosocially enriched detoxifcation for treatment of opioid dependence: A randomized controlled trial. JAMA, 283(10), 1303–1310. 1-12 Medications for Opioid Use Disorder TIP 63 25 Nielsen, S., Larance, B., Degenhardt, L., Gowing, L., Kehler, C., & Lintzeris, N. (2016). Opioid agonist treatment for pharmaceutical opioid dependent people. Cochrane Database of Systematic Reviews, 2016(5), 1–61. 26 Amato, L., Davoli, M., Perucci, C. A., Ferri, M., Faggiano, F., & Mattick, R. P. (2005). An overview of systematic reviews of the effectiveness of opiate maintenance therapies: Available evidence to inform clinical practice and research. Journal of Substance Abuse Treatment, 28(4), 321–329. 27 Faggiano, F., Vigna-Taglianti, F., Versino, E., & Lemma, P. (2003). Methadone maintenance at different dosages for opioid dependence. Cochrane Database of Systematic Reviews, 2003(3), 1–45. 28 Herget, G. (2005). Methadone and buprenorphine added to the WHO list of essential medicines. HIV/AIDS Policy and Law Review, 10(3), 23–24. 29 Gossop, M., Marsden, J., Stewart, D., & Kidd, T. (2003). The National Treatment Outcome Research Study (NTORS): 4–5 year follow-up results. Addiction, 98(3), 291–303. 30 Lawrinson, P., Ali, R., Buavirat, A., Chiamwongpaet, S., Dvoryak, S., Habrat, B., … Zhao, C. (2008). Key fndings from the WHO collaborative study on substitution therapy for opioid dependence and HIV/AIDS. Addiction, 103(9), 1484–1492. 31 Teesson, M., Ross, J., Darke, S., Lynskey, M., Ali, R., Ritter, A., & Cooke, R. (2006). One year outcomes for heroin dependence: Findings from the Australian Treatment Outcome Study (ATOS). Drug and Alcohol Dependence, 83(2), 174–180. 32 Bruce, R. D. (2010). Methadone as HIV prevention: High volume methadone sites to decrease HIV incidence rates in resource limited settings. International Journal on Drug Policy, 21(2), 122–124. 33 Fullerton, C. A., Kim, M., Thomas, C. P., Lyman, D. R., Montejano, L. B., Dougherty, R. H., … Delphin-Rittmon, M. E. (2014). Medication-assisted treatment with methadone: Assessing the evidence. Psychiatric Services, 65(2), 146–157. 34 Gowing, L., Farrell, M. F., Bornemann, R., Sullivan, L. E., & Ali, R. (2011). Oral substitution treatment of injecting opioid users for prevention of HIV infection. Cochrane Database of Systematic Reviews, 2011(8), 1–117. 35 MacArthur, G. J., Minozzi, S., Martin, N., Vickerman, P., Deren, S., Bruneau, J., … Hickman, M. (2012). Opiate substitution treatment and HIV transmission in people who inject drugs: Systematic review and meta-analysis. BMJ, 345, e5945. 36 Mattick, R. P., Breen, C., Kimber, J., & Davoli, M. (2009). Methadone maintenance therapy versus no opioid replacement therapy for opioid dependence. Cochrane Database of Systematic Reviews, 2009(3), 1–19. 37 Metzger, D. S., & Zhang, Y. (2010). Drug treatment as HIV prevention: Expanding treatment options. Current HIV/ AIDS Reports, 7(4), 220–225. 38 Woody, G. E., Bruce, D., Korthuis, P. T., Chhatre, S., Poole, S., Hillhouse, M., … Ling, W. (2014). HIV risk reduction with buprenorphine-naloxone or methadone: Findings from a randomized trial. Journal of Acquired Immune Defciency Syndromes, 66(3), 288–293. 39 Fullerton, C. A., Kim, M., Thomas, C. P., Lyman, D. R., Montejano, L. B., Dougherty, R. H., … Delphin-Rittmon, M. E. (2014). Medication-assisted treatment with methadone: Assessing the evidence. Psychiatric Services, 65(2), 146–157. 40 Schwartz, R. P., Jaffe, J. H., O’Grady, K. E., Kinlock, T. W., Gordon, M. S., Kelly, S. M., … Ahmed, A. (2009). Interim methadone treatment: Impact on arrests. Drug and Alcohol Dependence, 103(3), 148–154. 41 Lee, J. D., Friedmann, P. D., Kinlock, T. W., Nunes, E. V., Boney, T. Y., Hoskinson, R. A., Jr., … O’Brien, C. P. (2016). Extended-release naltrexone to prevent opioid relapse in criminal justice offenders. New England Journal of Medicine, 374(13), 1232–1242. 42 Comer, S. D., Sullivan, M. A., Yu, E., Rothenberg, J. L., Kleber, H. D., Kampman, K., … O’Brien, C. P. (2006). Injectable, sustained-release naltrexone for the treatment of opioid dependence: A randomized, placebo- controlled trial. Archives of General Psychiatry, 63(2), 210–218. 43 Krupitsky, E., Nunes, E. V., Ling, W., Illeperuma, A., Gastfriend, D. R., & Silverman, B. L. (2011, April 30). Injectable extended-release naltrexone for opioid dependence: A double-blind, placebo-controlled, multicentre randomised trial. Lancet, 377(9776), 1506–1513. 44 Lee, J. D., Friedmann, P. D., Kinlock, T. W., Nunes, E. V., Boney, T. Y., Hoskinson, R. A., Jr., … O’Brien, C. P. (2016). Extended-release naltrexone to prevent opioid relapse in criminal justice offenders. New England Journal of Medicine, 374(13), 1232–1242. 45 Lee, J. D., Nunes, E. V., Jr., Novo, P., Bachrach, K., Bailey, G. L., Bhatt, S., … Rotrosen, J. (2018). Comparative effectiveness of extended-release naltrexone versus buprenorphine-naloxone for opioid relapse prevention (X:BOT): A multicentre, open-label, randomised controlled trial. Lancet, 391(10118), 309–318. 46 Tanum, L., Solli, K. K., Latif, Z. E., Benth, J. Š., Opheim, A., Sharma-Haase, K., … Kunøe, N. (2017). Effectiveness of injectable extended-release naltrexone vs daily buprenorphine-naloxone for opioid dependence: A randomized clinical noninferiority trial. JAMA Psychiatry, 74(12), 1197–1205. 1-13 TIP 63Part 1 of 5—Introduction to Medications for Opioid Use Disorder Treatment 47 Minozzi, S., Amato, L., Vecchi, S., Davoli, M., Kirchmayer, U., & Verster, A. (2011). Oral naltrexone maintenance treatment for opioid dependence. Cochrane Database of Systematic Reviews, 2011(2), 1–45. 48 Mattick, R. P., Breen, C., Kimber, J., & Davoli, M. (2014). Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. Cochrane Database of Systematic Reviews, 2014(2), 1–84. 49 Edelman, E. J., Chantarat, T., Caffrey, S., Chaudhry, A., O’Connor, P. G., Weiss, L., … Fiellin, L. E. (2014). The impact of buprenorphine/naloxone treatment on HIV risk behaviors among HIV-infected, opioid-dependent patients. Drug and Alcohol Dependence, 139, 79–85. 50 Sullivan, L. E., Moore, B. A., Chawarski, M. C., Pantalon, M. V., Barry, D., O’Connor, P. G., … Fiellin, D. A. (2008). Buprenorphine/naloxone treatment in primary care is associated with decreased human immunodefciency virus risk behaviors. Journal of Substance Abuse Treatment, 35(1), 87–92. 51 Weiss, R. D., Potter, J. S., Fiellin, D. A., Byrne, M., Connery, H. S., Dickinson, W., … Ling, W. (2011). Adjunctive counseling during brief and extended buprenorphine-naloxone treatment for prescription opioid dependence: A 2-phase randomized controlled trial. Archives of General Psychiatry, 68(12), 1238–1246. 52 Fiellin, D. A., Schottenfeld, R. S., Cutter, C. J., Moore, B. A., Barry, D. T., & O’Connor, P. G. (2014). Primary care- based buprenorphine taper vs maintenance therapy for prescription opioid dependence: A randomized clinical trial. JAMA Internal Medicine, 174(12), 1947–1954. 53 Fiellin, D. A., Moore, B. A., Sullivan, L. E., Becker, W. C., Pantalon, M. V., Chawarski, M. C., … Schottenfeld, R. S. (2008). Long-term treatment with buprenorphine/ naloxone in primary care: Results at 2–5 years. American Journal on Addictions, 17(2), 116–120. 54 Soeffng, J. M., Martin, L. D., Fingerhood, M. I., Jasinski, D. R., & Rastegar, D. A. (2009). Buprenorphine maintenance treatment in a primary care setting: Outcomes at 1 year. Journal of Substance Abuse Treatment, 37(4), 426–430. 55 Herget, G. (2005). Methadone and buprenorphine added to the WHO list of essential medicines. HIV/AIDS Policy and Law Review, 10(3), 23–24. 56 Rosenthal, R. N., Lofwall, M. R., Kim, S., Chen, M., Beebe, K. L., Vocci, F. J., & PRO-814 Study Group. (2016). Effect of buprenorphine implants on illicit opioid use among abstinent adults with opioid dependence treated with sublingual buprenorphine: A randomized clinical trial. Journal of the American Medical Association, 316(3), 282–290. 57 Rosenthal, R. N., Lofwall, M. R., Kim, S., Chen, M., Beebe, K. L., & Vocci, F. J. (2016). Effect of buprenorphine implants on illicit opioid use among abstinent adults with opioid dependence treated with sublingual buprenorphine: A randomized clinical trial. JAMA, 316(3), 282–290. 58 Barnwal, P., Das, S., Mondal, S., Ramasamy, A., Maiti, T., & Saha, A. (2017). Probuphine® (buprenorphine implant): Promising candidate in opioid dependence. Therapeutic Advances in Psychopharmacology, 7(3), 119–134. 59 Connock, M., Juarez-Garcia, A., Jowett, S., Frew, E., Liu, Z., Taylor, R. J., … Taylor, R. S. (2007, March). Methadone and buprenorphine for the management of opioid dependence: A systematic review and economic evaluation. Health Technology Assessment, 11(9), 1–171, iii–iv. 60 Lynch, F. L., McCarty, D., Mertens, J., Perrin, N. A., Green, C. A., Parthasarathy, S., … Pating, D. (2014). Costs of care for persons with opioid dependence in commercial integrated health systems. Addiction Science and Clinical Practice, 9, 16. 61 Baser, O., Chalk, M., Fiellin, D. A., & Gastfriend, D. R. (2011). Cost and utilization outcomes of opioid- dependence treatments. American Journal of Managed Care, 17(Suppl. 8), S235–S248. 62 Schwartz, R. P., Alexandre, P. K., Kelly, S. M., O’Grady, K. E., Gryczynski, J., & Jaffe, J. H. (2014). Interim versus standard methadone treatment: A beneft-cost analysis. Journal of Substance Abuse Treatment, 46(3), 306–314. 63 Cartwright, W. S. (2000). Cost-beneft analysis of drug treatment services: Review of the literature. Journal of Mental Health Policy and Economics, 3(1), 11–26. 64 McCollister, K. E., & French, M. T. (2003). The relative contribution of outcome domains in the total economic beneft of addiction interventions: A review of frst fndings. Addiction, 98(12), 1647–1659. 65 Substance Abuse and Mental Health Services Administration. (2015). Federal guidelines for opioid treatment programs. HHS Publication No. (SMA) PEP15- FEDGUIDEOTP. Rockville, MD: Substance Abuse and Mental Health Services Administration. 66 Drug Enforcement Administration. (n.d.). Title 21 Code of Federal Regulations. Part 1306—Prescriptions. §1306.07 Administering or dispensing of narcotic drugs. Retrieved November 22, 2017, from www .deadiversion.usdoj.gov/21cfr/cfr/1306/1306_07.htm 67 Mattick, R. P., Breen, C., Kimber, J., & Davoli, M. (2009). Methadone maintenance therapy versus no opioid replacement therapy for opioid dependence. Cochrane Database of Systematic Reviews, 2009(3), 1–19. 68 Mattick, R. P., Breen, C., Kimber, J., & Davoli, M. (2014). Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. Cochrane Database of Systematic Reviews, 2014(2), 1–84. 1-14 Medications for Opioid Use Disorder TIP 63 69 Calsyn, D. A., Malcy, J. A., & Saxon, A. J. (2006). Slow tapering from methadone maintenance in a program encouraging indefnite maintenance. Journal of Substance Abuse Treatment, 30, 159–163. 70 Stimmel, B., Goldberg, J., Rotkopf, E., & Cohen, M. (1977). Ability to remain abstinent after methadone detoxifcation. JAMA, 237, 1216–1220. 71 Cushman, P. (1978). Abstinence following detoxifcation and methadone maintenance treatment. American Journal of Medicine, 65, 46–52. 72 Nosyk, B., Sun, H., Evans, E., Marsh, D. C., Anglin, M. D., Hser, Y. I., & Anis, A. H. (2012). Defning dosing pattern characteristics of successful tapers following methadone maintenance treatment: Results from a population-based retrospective cohort study. Addiction, 107(9), 1621–1629. 73 Lee, J. D., Friedmann, P. D., Kinlock, T. W., Nunes, E. V., Boney, T. Y., Hoskinson, R. A., Jr., … O’Brien, C. P. (2016). Extended-release naltrexone to prevent opioid relapse in criminal justice offenders. New England Journal of Medicine, 374(13), 1232–1242. 74 Sees, K. L., Delucchi, K. L., Masson, C., Rosen, A., Clark, H. W., Robillard, H., … Hall, S. M. (2000). Methadone maintenance vs 180-day psychosocially enriched detoxifcation for treatment of opioid dependence: A randomized controlled trial. JAMA, 283(10), 1303–1310. 75 Wines, J. D., Jr., Saitz, R., Horton, N. J., Lloyd-Travaglini, C., & Samet, J. H. (2007). Overdose after detoxifcation: A prospective study. Drug and Alcohol Dependence, 89(2–3), 161–169. 76 Strang, J., McCambridge, J., Best, D., Beswick, T., Bearn, J., Rees, S., & Gossop, M. (2003). Loss of tolerance and overdose mortality after inpatient opiate detoxifcation: Follow up study. British Medical Journal, 326(7396), 959–960. 77 Weiss, R. D., Potter, J. S., Fiellin, D. A., Byrne, M., Connery, H. S., Dickinson, W., … Ling, W. (2011). Adjunctive counseling during brief and extended buprenorphine-naloxone treatment for prescription opioid dependence: A 2-phase randomized controlled trial. Archives of General Psychiatry, 68(12), 1238–1246. 78 Ling, W., Amass, L., Shoptaw, S., Annon, J. J., Hillhouse, M., Babcock, D., … Ziedonis, D. (2005). A multi-center randomized trial of buprenorphine-naloxone versus clonidine for opioid detoxifcation: Findings from the National Institute on Drug Abuse Clinical Trials Network. Addiction, 100(8), 1090–1100. 79 McCusker, J., Bigelow, C., Luippold, R., Zorn, M., & Lewis, B. F. (1995). Outcomes of a 21-day drug detoxifcation program: Retention, transfer to further treatment, and HIV risk reduction. American Journal of Drug and Alcohol Abuse, 21(1), 1–16. 80 Fiellin, D., Schottenfeld, R., Cutter, C., Moore, A., Barry, D., & O’Connor, P. (2014). Primary care based buprenorphine taper vs maintenance therapy for prescription opioid dependence: A randomized clinical trial. JAMA Internal Medicine, 174(12), 1947–1954. 81 Gruber, V., Delucchi, K., Kielstein, A., & Batki, S. (2008). A randomized trial of six-month methadone maintenance with standard or minimal counseling versus 21-day methadone detoxifcation. Drug and Alcohol Dependence, 94, 199. 82 Ling, W., Hillhouse, M., Domier, C., Doraimani, G., Hunter, J., Thomas, C., … Bilangi, R. (2009). Buprenorphine tapering schedule and illicit opioid use. Addiction, 104(2), 256–265. 83 Smyth, B. P., Barry, J., Keenan, E., & Ducray, K. (2010). Lapse and relapse following inpatient treatment of opiate dependence. Irish Medical Journal, 103(6), 176–179. 84 Amato, L., Minozzi, S., Davoli, M., & Vecchi, S. (2011). Psychosocial and pharmacological treatments versus pharmacological treatments for opioid detoxifcation. Cochrane Database of Systematic Reviews, 2011(9), 1–55. 85 Department of Health and Human Services, Offce of the Surgeon General. (2016). Facing addiction in America: The Surgeon General’s report on alcohol, drugs, and health. Washington, DC: Department of Health and Human Services. 86 Saloner, B., & Karthikeyan, S. (2015). Changes in substance abuse treatment use among individuals with opioid use disorders in the United States, 2004–2013. JAMA, 314(14), 1515–1517. 87 Van Handel, M. M., Rose, C. E., Hallisey, E. J., Kolling, J. L., Zibbell, J. E., Lewis, B., … Brooks, J. T. (2016). County- level vulnerability assessment for rapid dissemination of HIV or HCV infections among persons who inject drugs, United States. Journal of Acquired Immune Defciency Syndromes, 73(3), 323–331. MEDICATIONS FOR OPIOID USE DISORDERTIP 63 Substance Abuse and Mental Health Services Administration Part 2: Addressing Opioid Use Disorder in General Medical Settings For Healthcare Professionals Part 2 of this Treatment Improvement Protocol (TIP) will guide practitioners’ efforts to identify, assess, and treat or refer patients with opioid use disorder (OUD) in general medical settings. TIP Navigation Executive Summary For healthcare and addiction professionals, policymakers, patients, and families Part 1: Introduction to Medications for Opioid Use Disorder Treatment For healthcare and addiction professionals, policymakers, patients, and families Part 2: Addressing Opioid Use Disorder in General Medical Settings For healthcare professionals Part 3: Medications for Opioid Use Disorder For healthcare professionals Part 4: Bringing Together Addiction Treatment Counselors, Clients, and Healthcare Professionals For healthcare and addiction professionals Part 5: Resources Related to Medication for Opioid Use Disorder For healthcare and addiction professionals, policymakers, patients, and families KEY MESSAGES • All healthcare practices should screen for alcohol, tobacco, and other substance misuse (including opioid misuse). • Validated screening tools, symptom surveys, and other resources are readily available; this part lists many of them. • When patients screen positive for risk of harm from substance use, practitioners should assess them using tools that determine whether substance use meets diagnostic criteria for a substance use disorder (SUD). • Thorough assessment should address patients’ medical, social, SUD, and family histories. • Laboratory tests can inform treatment planning. • Practitioners should develop treatment plans or referral strategies (if onsite SUD treatment is unavailable) for patients who need SUD treatment. 2-ii TIP 63 MEDICATIONS FOR OPIOID USE DISORDER—Part 2 of 5 Contents Scope of the Problem . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-1 Screening . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-1 Alcohol Screening . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-3 Tobacco Screening . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-5 Drug Screening. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-5 Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-8 Determine the Need for and Extent of Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-8 Set the Stage for Successful Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-8 Take a Complete History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-9 Conduct a Physical Examination . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-12 Obtain Appropriate Laboratory Tests. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-13 Review the PDMP. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-16 Determine Diagnosis and Severity of OUD. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-17 Treatment Planning or Referral . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-17 Making Decisions About Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-17 Understanding Treatment Settings and Services. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-18 Outpatient OUD Treatment Settings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-18 Determining OUD Service Intensity and Ensuring Follow-Through . . . . . . . . . . . . . . . . . . 2-23 Preventing Opioid-Related Overdose . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-26 Resources . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-28 Alcohol and Drug Use Screening. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-28 Tobacco Screening . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-28 Buprenorphine Treatment Locator . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-28 Buprenorphine Training, Mentorship, and Waivers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-28 Medication Treatment for OUD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-29 Syringe Exchange . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-29 Opioid-Related Overdose Prevention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-29 Opioid Withdrawal Scales . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-30 Patient and Family Education on Medications To Treat OUD . . . . . . . . . . . . . . . . . . . . . . . 2-30 Referral and Treatment Locators . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-30 Screening, Assessment, and Drug Testing Resources . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-30 Treatment Planning . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-31 2-iii TIP 63MEDICATIONS FOR OPIOID USE DISORDER—Part 2 of 5 Part 2 Appendix. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-32 Stable Resource Toolkit . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-32 Drug Abuse Screening Test (DAST-10) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-34 DSM-5 Opioid Use Disorder Checklist . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-35 TAPS Tool Part I . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-36 TAPS Tool Part 2 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-37 Notes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2-39 This page intentionally left blank. 2-1 MEDICATIONS FOR OPIOID USE DISORDERTIP 63 PART 2 of 5 Addressing Opioid Use Disorder in General Medical Settings Part 2 of this TIP is for healthcare professionals who work in general medical settings* and care for patients who misuse opioids or have OUD. Healthcare professionals in such settings address most personal healthcare needs, develop sustained partnerships with patients, and practice in the context of family and community. Thus, they have a good basis from which to understand patients’ needs related to OUD screening, assessment, and treatment (or referral to specialty treatment). Scope of the Problem The number of patients presenting with OUD in medical clinics, community health centers, and private practices is increasing. Healthcare professionals in these general settings are in an important position to identify, assess, and treat OUD or to refer patients for treatment. Moreover, patients who are medically and mentally stable can beneft from receiving OUD medications in integrated care settings, where they often have already established therapeutic relationships with their healthcare providers. Exhibit 2.1 defnes key terms in Part 2. For more defnitions, see the glossary in Part 5 of this TIP. Screening Screening can identify patients who may have diseases or conditions related to their substance use. Health care in general medical settings routinely includes screening for common, treatable conditions such as cancer that are associated with signifcant morbidity and mortality. Screening for SUDs is important, as misuse of alcohol, tobacco, and other substances is common among patients in medical settings (Exhibit 2.2).1 An estimated 1.4M AMERICANS have OUD related to opioid painkillers; 438K have heroin- related OUD.2 Screening can identify substance misuse in patients who wouldn’t otherwise discuss it or connect it with the negative consequences they’re experiencing. Some patients may spontaneously reveal their substance use and ask for help. This is more likely when they’re experiencing harmful consequences of substance use. However, screening may identify unhealthy substance use (e.g., binge drinking) and SUDs The TIP expert panel recommends that healthcare professionals screen patients for alcohol, tobacco, prescription drug, and illicit drug use at least annually. *In this TIP, the term “general medical setting” includes medical clinics, community health centers, and private practices. 2-2 Medications for Opioid Use Disorder TIP 63 EXHIBIT 2.1. Key Terms Addiction: As defned by the American Society of Addiction Medicine (ASAM),3 “a primary, chronic disease of brain reward, motivation, memory, and related circuitry.” It is characterized by inability to consistently abstain, impairment in behavioral control, craving, diminished recognition of signifcant problems with one’s behaviors and interpersonal relationships, and a dysfunctional emotional response. Like other chronic diseases, addiction often involves cycles of relapse and remission. The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition4 (DSM-5), does not use the term for diagnostic purposes, but it commonly describes the more severe forms of OUD. Healthcare professionals: Physicians, nurse practitioners (NPs), physician assistants (PAs), and other medical service professionals who are eligible to prescribe medications for and treat patients with OUD (i.e., until October 1, 2023, clinical nurse specialists, certifed registered nurse anesthetists, certifed nurse midwives). The term “prescribers” also refers to these healthcare professionals. Maintenance treatment: Providing medications to achieve and sustain clinical remission of signs and symptoms of OUD and support the individual process of recovery without a specifc endpoint (as with the typical standard of care in medical and psychiatric treatment of other chronic illnesses). Medically supervised withdrawal (formerly called detoxifcation): Using an opioid agonist (or an alpha-2 adrenergic agonist if an opioid agonist is not available) in tapering doses or other medications to help a patient discontinue illicit or prescription opioids. Medical management: Process whereby healthcare professionals provide medication, basic brief supportive counseling, monitoring of drug use and medication adherence, and referrals, when necessary, to addiction counseling and other services to address the patient’s medical, mental health, comorbid addiction, and psychosocial needs. Offce-based opioid treatment (OBOT): Providing medication for OUD in outpatient settings other than certifed opioid treatment programs (OTPs). Opioid misuse: The use of prescription opioids in any way other than as directed by a prescriber; the use of any opioid in a manner, situation, amount, or frequency that can cause harm to self or others.5 Opioid receptor agonist: A substance that has an affnity for and stimulates physiological activity at cell receptors in the central nervous system that are normally stimulated by opioids. Mu-opioid receptor full agonists (e.g., methadone) bind to the mu-opioid receptor and produce actions similar to those produced by the endogenous opioid beta-endorphin. Increasing the dose increases the effect. Mu-opioid receptor partial agonists (e.g., buprenorphine) bind to the mu-opioid receptor. Unlike with full agonists, increasing their dose may not produce additional effects once they have reached their maximal effect. At low doses, partial agonists may produce effects similar to those of full agonists. Opioid receptor antagonist: A substance that has an affnity for opioid receptors in the central nervous system without producing the physiological effects of opioid agonists. Mu-opioid receptor antagonists (e.g., naltrexone) can block the effects of exogenously administered opioids. Opioid treatment program (OTP): An accredited treatment program with Substance Abuse and Mental Health Services Administration (SAMHSA) certifcation and Drug Enforcement Administration (DEA) registration to administer and dispense opioid agonist medications that are approved by the Food and Drug Administration (FDA) to treat opioid addiction. Currently, these include methadone and buprenorphine products. Other pharmacotherapies, such as naltrexone, may be provided but are not subject to these regulations. OTPs must provide adequate medical, counseling, vocational, educational, and other assessment and treatment services either onsite or by referral to an outside agency or practitioner through a formal agreement.6 Continued on next page 2-3 TIP 63Part 2 of 5—Addressing Opioid Use Disorder in General Medical Settings EXHIBIT 2.1. Key Terms (continued) Opioid use disorder (OUD): Per DSM-5,7 a disorder characterized by loss of control of opioid use, risky opioid use, impaired social functioning, tolerance, and withdrawal. Tolerance and withdrawal do not count toward the diagnosis in people experiencing these symptoms when using opioids under appropriate medical supervision. OUD covers a range of severity and replaces what the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, termed “opioid abuse” and “opioid dependence.” An OUD diagnosis is applicable to a person who uses opioids and experiences at least 2 of the 11 symptoms in a 12-month period. (See Exhibit 2.13 and the Appendix in Part 2 for full DSM-5 diagnostic criteria for OUD.) Recovery: A process of change through which individuals improve their health and wellness, live a self-directed life, and strive to reach their full potential. Even individuals with severe and chronic SUDs can, with help, overcome their SUDs and regain health and social function. Although abstinence from all substance misuse is a cardinal feature of a recovery lifestyle, it is not the only healthy, prosocial feature. Patients taking FDA-approved medication to treat OUD can be considered in recovery. Relapse: A process in which a person with OUD who has been in remission experiences a return of symptoms or loss of remission. A relapse is different from a return to opioid use in that it involves more than a single incident of use. Relapses occur over a period of time and can be interrupted. Relapse need not be long lasting. The TIP uses relapse to describe relapse prevention, a common treatment modality. Remission: A medical term meaning a disappearance of signs and symptoms of the disease.8 DSM-5 defnes remission as present in people who previously met OUD criteria but no longer meet any OUD criteria (with the possible exception of craving).9 Remission is an essential element of recovery. Return to opioid use: One or more instances of opioid misuse without a return of symptoms of OUD. A return to opioid use may lead to relapse. Tolerance: Alteration of the body’s responsiveness to alcohol or other drugs (including opioids) such that higher doses are required to produce the same effect achieved during initial use. See also medically supervised withdrawal. before patients connect their substance use with their presenting complaint. Screening is also helpful when patients feel ashamed or afraid to reveal their concerns spontaneously. Every medical practice should determine which screening tools to use and when, how, and by whom they will be administered. Each practice should also identify steps to take when a patient screens positive. One effcient workfow strategy is to have clinical assistants or nurses administer the screening instrument in an interview or provide patients with a paper or computer tablet version for self-administration. (Self-administration is generally as reliable as interviewer administration.)10 Providers should be nonjudgmental and rely on established rapport when discussing screening results with patients. The following sections summarize reliable screening tools. (See Part 5 for more resources.) Alcohol Screening Screening for alcohol misuse can identify patients at increased risk for opioid use. When screening patients for opioid misuse, providers should also screen for alcohol misuse and alcohol use disorder (AUD), which cause considerable morbidity and mortality.11 Providers should warn patients who use opioids that alcohol may increase opioid overdose risk.12 The U.S. Preventive Services Task Force (USPSTF) recommends screening adults for alcohol misuse, including risky drinking and AUD. USPSTF also recommends brief counseling for patients with risky drinking.13,14 2-4 Medications for Opioid Use Disorder TIP 63 EXHIBIT 2.2. Substance Misuse and SUD Screening Substance misuse screening Negative Positive Reinforce healthy behavior Assess substance use and comorbidities Substance misuse Substance use disorder Brief counseling Brief counseling and treatment referral Monitoring/follow up - Consider medication If misuse continues, negotiate a plan and refer to treatment Ongoing assessment and support Adapted with permission.15 USPSTF recommends the following alcohol screeners: • The single-item National Institute on Alcohol Abuse and Alcoholism (NIAAA) Screener is the briefest tool available (Exhibit 2.3). It can help distinguish at-risk patients who require further screening from those not at risk for AUD. Encourage patients in the latter category to maintain healthy behavior. • The Alcohol Use Disorders Identifcation Test (AUDIT)16 or its briefer version, the AUDIT-Consumption,17 can elicit more in- formation from patients who screen positive on the single-item screener. The full AUDIT tool (Exhibit 2.4) and its briefer version have demonstrated acceptable reliability in AUD screening.18 Assess patients with positive screens for AUD. Practitioners should consider medication and referral to counseling for people with AUD. The three FDA-approved medications to treat AUD—acamprosate, disulfram, and naltrexone (oral and extended-release injectable naltrex- one [XR-NTX])—can be prescribed in general medical and specialty SUD treatment settings. (For more information on AUD treatment, see the SAMHSA/NIAAA publication Medication for the Treatment of Alcohol Use Disorder: A Brief Guide.)19 2-5 TIP 63Part 2 of 5—Addressing Opioid Use Disorder in General Medical Settings EXHIBIT 2.3. NIAAA Single-Item Screener How many times in the past year have you had fve or more drinks in a day (four drinks for women and all adults older than age 65)? One or more times constitutes a positive screen. Patients who screen positive should have an assessment for AUD. Adapted with permission.20 Tobacco Screening More than 80 percent of patients who are opioid dependent smoke cigarettes.21 Understanding of the major health conse- quences and risks associated with tobacco use has grown signifcantly over the past 50 years. Among preventable causes of premature death, smoking remains most prevalent, with more than 480,000 deaths per year in the United States.22 In addition, more than 40 percent of all people who smoke are mentally ill or have SUDs.23,24 USPSTF recommends that primary care providers screen for tobacco use, advise patients to quit, and provide counseling and FDA-approved medications for tobacco cessation.25 The six-item Fagerström Test for Nicotine Dependence26 assesses cigarette use and nicotine dependence. The maximum score is 10; the higher the total score, the more severe the patient’s nicotine dependence. The two-item Heaviness of Smoking Index (Exhibit 2.5) is also useful.27 Drug Screening Screening for illicit drug use and prescription medication misuse is clinically advantageous. USPSTF’s position is that adults ages 18 and older (including those who are pregnant) should be routinely screened in primary care for illicit drug use and prescription medication misuse when services for accurate diagnosis, effective treatment, and appropriate care can be offered or referral can be provided.28 Identifying misuse of prescription or illegal drugs can prevent harmful drug interactions, lead to adjustments in prescribing practices, improve medical care adherence, and increase the odds of patients getting needed interventions or treatment.29 Brief screening instruments for drug use can determine which patients need further assessment. Providers should reinforce healthy behaviors among patients who report “no use” and direct those who report “some use” for further screening and assessment to obtain a diagnosis. Several brief screening instruments for drug use can help primary care practitioners identify patients who use drugs.30,31 For example, a single-item screen is available for the general public (Exhibit 2.6).32 A two-item valid screener is available for use with U.S. veterans (Exhibit 2.7).33 Brief drug screens don’t indicate specifc types of drugs used (nor does the longer Drug Abuse Screening Test; see the Part 2 Appendix).34 If providers use nonspecifc screens, they need to assess further which substances patients use and to what degree. The TIP expert panel recommends universal OUD screening. Given the high prevalence of SUDs in patients visiting primary care settings and the effectiveness of medications to treat OUD specifcally, the TIP expert panel recommends screening all patients for opioid misuse. 2-6 Medications for Opioid Use Disorder TIP 63 EXHIBIT 2.4. AUDIT Screener 1. How often do you have a drink containing alcohol? (0) Never [Skip to Questions 9–10] (1) Monthly or less (2) 2 to 4 times a month (3) 2 to 3 times a week (4) 4 or more times a week 6. How often during the last year have you needed an alcoholic drink frst thing in the morning to get yourself going after a night of heavy drinking? (0) Never (1) Less than monthly (2) Monthly (3) Weekly (4) Daily or almost daily 2. How many drinks containing alcohol do you have on a typical day when you are drinking? (0) 1 or 2 (1) 3 or 4 (2) 5 or 6 (3) 7, 8, or 9 (4) 10 or more 7. How often during the last year have you had a feeling of guilt or remorse after drinking? (0) Never (1) Less than monthly (2) Monthly (3) Weekly (4) Daily or almost daily 3. How often do you have six or more drinks on one occasion? (0) Never (1) Less than monthly (2) Monthly (3) Weekly (4) Daily or almost daily Skip to Questions 9 and 10 if total score for Questions 2 and 3 = 0 8. How often during the last year have you been unable to remember what happened the night before because you had been drinking? (0) Never (1) Less than monthly (2) Monthly (3) Weekly (4) Daily or almost daily 4. How often during the last year have you found that you were not able to stop drinking once you had started? (0) Never (1) Less than monthly (2) Monthly (3) Weekly (4) Daily or almost daily 9. Have you or someone else been injured as a result of your drinking? (0) No (2) Yes, but not in the last year (4) Yes, during the last year 5. How often during the last year have you failed to do what was normally expected from you because of drinking? (0) Never (1) Less than monthly (2) Monthly (3) Weekly (4) Daily or almost daily 10. Has a relative, friend, doctor, or another health professional expressed concern about your drinking or suggested you cut down? (0) No (2) Yes, but not in the last year (4) Yes, during the last year Note: Add up the points associated with answers. A score of 8 or more is considered a positive test for unhealthy drinking. Adapted from material in the public domain.35 Available online (http://auditscreen.org). 2-7 TIP 63Part 2 of 5—Addressing Opioid Use Disorder in General Medical Settings EXHIBIT 2.5. Heaviness of Smoking Index Ask these two questions of current or recent smokers: 1. How soon after waking do you smoke your frst cigarette? • Within 5 minutes (3 points) • 5–30 minutes (2 points) • 31–60 minutes (1 point) • 61 or more minutes (no points) 2. How many cigarettes a day do you smoke? • 10 or less (no points) • 11–20 (1 point) • 21–30 (2 points) • 31 or more (3 points) Total score: 1–2 points = very low dependence 3 points = low to moderate dependence 4 points = moderate dependence 5 or more points = high dependence Adapted with permission.36 The Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST) screens patients for all categories of substance misuse, including alcohol and tobacco. This World Health Organization (WHO) screener also assesses substance-specifc risk. The ASSIST’s length and rather complex scoring system have hindered its adoption, but a computerized version and a briefer hard copy version (ASSIST- lite) make its use more effcient.37,38 The TIP expert panel does not recommend routine universal drug testing with urine, blood, or oral fuids in primary care. Still, drug testing can confrm recent drug use in patients receiving diagnostic workups for changes in mental status, seizures, or other disorders. Conduct drug testing before patients start OUD medication and during treatment for monitoring. EXHIBIT 2.6. Single-Item Drug Screener How many times in the past year have you used an illegal drug or a prescription medication for nonmedical reasons? (A positive screen is 1 or more days.) Reprinted with permission.39 EXHIBIT 2.7. Two-Item Drug Use Disorder Screener for Primary Care Clinics Serving U.S. Veterans Question 1: How many days in the past 12 months have you used drugs other than alcohol? (A positive screen is 7 or more days.) If fewer than 7, proceed with Question 2. Question 2: How many days in the past 12 months have you used drugs more than you meant to? (A positive screen is 2 or more days.) Adapted with permission.40 (See the “Screening, Assessment, and Drug Testing Resources” section for a link to a modifed version of the ASSIST.) Follow up any positive one-question screen with a brief assessment. An example of a two-step screening and brief assessment is the Tobacco, Alcohol, Prescription Medications, and Other Substance Use (TAPS Tool; see Part 2 Appendix), developed and tested in primary care settings.41 This tool is based on the National Institute on Drug Abuse (NIDA) Quick Screen V1.042,43 and a modifed WHO ASSIST-lite.44 The TAPS Tool screens for clinically relevant heroin and prescription opioid misuse (meeting one or more DSM-5 SUD criteria) and misuse of an array of other substances in primary care patients. However, it may also detect SUDs only for the most often-used substances (i.e., alcohol, tobacco, and marijuana). Patients with positive screens for heroin or prescription opioid misuse need more indepth assessment.45 2-8 Medications for Opioid Use Disorder TIP 63 Assessment Determine the Need for and Extent of Assessment Assess patients for OUD if: • They screen positive for opioid misuse. • They disclose opioid misuse. • Signs or symptoms of opioid misuse are present. The extent of assessment depends on a provider’s ability to treat patients directly. If a provider does not offer medication, the focus should be on medical assessment, making a diagnosis of OUD, and patient safety. This allows the provider to refer patients to the appropriate level of treatment. The provider can also conduct: • Assessment and treatment for co-occurring medical conditions or mental disorders (including HIV and hepatitis C [anti-HCV]). • Motivational brief interventions to promote safer behavior and foster effective treatment engagement. • Overdose prevention education and provide a naloxone prescription. • Education for patients who inject drugs on how to access sterile injecting equipment. • An in-person follow-up, regardless of referral to specialty treatment. If the provider offers medication, the patient needs more comprehensive assessment, including: • A review of the prescription drug monitoring program (PDMP). • A history, including a review of systems. • A targeted physical exam for signs of opioid withdrawal, intoxication, injection, and other medical consequences of misuse. • Determination of OUD diagnosis and severity. • Appropriate laboratory tests in addition to those recommended by the nontreating provider (e.g., urine or oral fuid drug tests, liver function tests, hepatitis B test).46 EVERYONE AGES 15 TO 65 should be tested at least ONCE for HIV . Persons at HIGHER RISK, such as people who useDRUGS by injection, should be tested ANNUALLY. HIV Hep C Anyone who is injecting or has ever INJECTED DRUGS, even ONCE, no matter how long ago, should be TESTED for HEPATITIS C, r e g a r d l e s s o f t h e i r i n t e n t i o n t o s e e k TREATMENT for SUD .47,48 A comprehensive assessment is intended to: • Establish the diagnosis of OUD. • Determine the severity of OUD. • Identify contraindicated medications. • Indicate other medical conditions to address during treatment. • Identify mental and social issues to address. Set the Stage for Successful Assessment The medical setting should create a welcoming environment that is nonjudgmental, respect- ful, and empathetic. Many patients with OUD are reluctant to discuss their opioid use in medical settings.49 A welcoming environment can 2-9 TIP 63Part 2 of 5—Addressing Opioid Use Disorder in General Medical Settings Open-ended, thought-provoking questions encourage patients to explore their own experiences. Ask questions like “In what ways has oxycodone affected your life?” or “What could you do to prevent infections like this in the future?” Closed-ended questions with yes/no answers—like “Has oxycodone caused your family trouble?”—can seem judgmental to patients who already feel ashamed and defensive. Closed-ended questions don’t help patients become aware of and express their own circumstances and motivations, nor do they encourage patients to identify what they see as the consequences of their substance use. help patients feel safe disclosing facts they may fnd embarrassing.50 Motivational interviewing strategies, such as asking open-ended questions, foster successful assessment.51 (Refer to TIP 34, Brief Interventions and Brief Therapies for Substance Abuse, for more specifc examples of interview questions and responses.)52 Staff should explore patients’ ambivalence and highlight problem areas to help them fnd motivations for change. Almost all patients have some ambivalence about their opioid use. They will fnd some aspects pleasant and benefcial, but others problematic, painful, or destructive. By exploring that ambivalence and highlighting problem areas, providers can help patients discover their own motivations for change. Motivational Interviewing: Helping People Change53 discusses specifc applications of motivational interviewing in health care. Take a Complete History Staff should prioritize medical, mental health, substance use, and SUD treatment histories. When obtaining patient histories, staff should address these domains before starting treatment. As providers and staff build trust over future visits, they can get into more detailed elements of the assessment. Medical history Taking a complete medical history of patients with OUD is critical, as it is for patients with any other medical condition treatable with medi- cation. Asking about patients’ medical/surgical history can: • Reveal medical effects of substance use (e.g., endocarditis, soft tissue infection, hepatitis B or C, HIV infection) that may need treatment. • Highlight consequences that motivate change. • Identify medical issues (e.g., severe liver disease) that contraindicate or alter dosing approaches for OUD pharmacotherapies. • Reveal chronic pain issues. • Help providers consider interactions among various medications and other substances. Exhibit 2.8 lists medical problems associated with opioid misuse. Mental health history Assessing for comorbid mental illness is critical. Mental illness is prevalent among people with SUDs; it can complicate their treatment and worsen their prognosis. In one study, nearly 20 percent of primary care patients with OUD had major depression.54 SUDs can also mimic or induce depression and anxiety disorders. Although substance-induced depression and anxiety disorders may improve with abstinence, they may still require treatment in their own right after a period of careful observation.55 Take a history of the relationship between a patient’s psychiatric symptoms and periods of substance use and abstinence. Treatment for mental disorders and SUDs can occur concurrently. Substance use history Substance use histories can help gauge OUD severity, inform treatment planning, clarify potential drug interactions, and highlight the negative consequences of patients’ opioid use. 2-10 Medications for Opioid Use Disorder TIP 63 • • • To help determine the severity of patients’ substance use, explore historical features of their use, like: Histories should also explore current patterns of use,56 which inform treatment planning and include: • Age at frst use. Which drugs patients use. Comorbid alcohol and tobacco use. Frequency, recency, and intensity of use. • Routes of ingestion (e.g., injection). • History of tolerance, withdrawal, drug mixing, and overdose. EXHIBIT 2.8. Medical Problems Associated With Opioid Misuse57 CATEGORY POSSIBLE COMPLICATIONS Cancer Injection drug use: Hepatocellular carcinoma related to hepatitis C Cardiovascular Injection drug use: Endocarditis, septic thrombophlebitis Endocrine/metabolic Opioids: Osteopenia, hypogonadism, erectile dysfunction, decreased sperm motility, menstrual irregularity including amenorrhea, infertility Hematologic Injection drug use/sharing intranasal use equipment: Hematologic consequences of liver disease from hepatitis C, hepatitis C‐related cryoglobulinemia and purpura Hepatic Injection drug use/sharing intranasal use equipment: Hepatitis B, C, D; infectious and toxic hepatitis Infectious Opioids: Aspiration pneumonia, sexually transmitted infections Injection drug use: Endocarditis, cellulitis, necrotizing fasciitis, pneumonia, septic thrombophlebitis, mycotic aneurysm, septic arthritis (unusual joints, such as sternoclavicular), osteomyelitis (including vertebral), epidural and brain abscess, abscesses and soft tissue infections, mediastinitis, malaria, tetanus, hepatitis B, hepatitis C, hepatitis D, HIV, botulism Neurologic Opioids: Seizure (overdose and hypoxia), compression neuropathy (following overdose), sleep disturbances Nutritional Opioids: Protein malnutrition Other gastrointestinal Opioids: Constipation, ileus, intestinal pseudo‐obstruction, sphincter of Oddi spasm, nausea Pulmonary Opioids: Respiratory depression/failure, bronchospasm, exacerbation of sleep apnea, noncardiogenic pulmonary edema, bullae Injection drug use: Pulmonary hypertension, talc granulomatosis, septic pulmonary embolism, pneumothorax, emphysema, needle embolization Renal Opioids: Rhabdomyolysis, acute renal failure (not direct toxic effect of opioids but secondary to central nervous system depression and resulting complications), factitious hematuria Injection drug use: Focal glomerular sclerosis (HIV, heroin), glomerulonephritis from hepatitis or endocarditis, chronic renal failure, amyloidosis, nephrotic syndrome (hepatitis C) 2-11 TIP 63Part 2 of 5—Addressing Opioid Use Disorder in General Medical Settings To diagnose an SUD, assess patients’ negative consequences of use, which can affect: • Physical health. • Mental health. • Family relationships. • Work/career status. • Legal involvement. • Housing status. Buprenorphine and methadone can cause complications for patients who misuse or have SUDs involving alcohol or benzodiazepines. Providers should take specifc histories on the use of these substances. SUD treatment history Information about a patient’s past efforts to get treatment or quit independently can inform treatment planning. The same is true for details about the events and behaviors that led to a patient’s return to substance use after periods of abstinence and remission of SUD. Similarly, identifying the features of successful quit attempts can help guide treatment plan decisions. Such features may involve: • Specifc treatment settings. • Use of support groups. • Previous responses to OUD medications. Social history Information about a patient’s social environ- ments and relationships can aid treatment planning. Social factors that may infuence treatment engagement and retention, guide treatment planning, and affect prognosis include: • Transportation and child care needs. • Adequacy and stability of housing. • Criminal justice involvement. • Employment status and quality of work environment. • Close/ongoing relationships with people with SUDs. • Details about drug use from people the patient lives or spends time with (obtained with patient’s consent). Understanding patients’ motivations for change can be more useful than assessing “readiness” for change. Patients coerced into treatment—such as through parole and probation or drug courts—are as likely to succeed in treatment as patients engaging voluntarily. Readiness fuctuates and depends on context. Helping patients explore why they want to change their drug use can motivate them and prepare their providers to support them during assessment and treatment. • Sexual orientation, identity, and history, including risk factors for HIV/sexually transmit- ted infections. • Safety of the home environment. Substance misuse substantially increases the risk of intimate partner violence; screen all women presenting for treatment for domestic violence.58 Family history Learn the substance use histories of patients’ parents, siblings, partners, and children. One of the strongest risk factors for developing SUDs is having a parent with an SUD. Genetic factors, exposure to substance use in the household during childhood, or both can contribute to the development of SUDs.59 EXHIBIT 2.9. Signs of Opioid Intoxication Physical fndings Drowsy but arousable Sleeping intermittently (“nodding off”) Constricted pupils Mental status fndings Slurred speech Impaired memory or concentration Normal to euphoric mood 2-12 Medications for Opioid Use Disorder TIP 63 PATIENT TESTIMONY Opioid Withdrawal “Severe opioid withdrawal isn’t something I’d wish on my worst enemy. The last time I went cold turkey, I was determined to come off all the way. The physical symptoms were just the tip of the iceberg. My mind was a nightmare that I thought I would never wake up from. There were times when I was almost convinced that dying would be better than what I was feeling. I did not experience a moment of ease for the frst 3 months, and it was 6 months until I started to feel normal.” EXHIBIT 2.10. Physical Signs of Opioid Withdrawal and Time to Onset STAGE GRADE PHYSICAL SIGNS/ SYMPTOMS Conduct a Physical Examination Perform a physical exam as soon as possible if recent exam records aren’t accessible. Assess for: • Opioid intoxication or withdrawal. • Physical signs of opioid use. • Medical consequences of opioid use. Exhibit 2.9 provides an overview of physical and mental status fndings for opioid intoxication. Opioid withdrawal Opioid withdrawal can be extremely uncom- fortable. Symptoms are similar to experiencing gastroenteritis, severe infuenza, anxiety, and dysphoria concurrently. Severity of withdrawal can indicate a patient’s level of physical dependence and can inform medication choices and dosing decisions. The duration of withdrawal depends on the specifc opioid from which the patient is withdrawing and Early withdrawal Short-acting opioids: 8–24 hours after last use Long-acting opioids: Up to 36 hours after last use Grade 1 Lacrimation, rhinorrhea, or both Diaphoresis Yawning Restlessness Insomnia Early withdrawal Grade Dilated pupils Short-acting opioids: 2 Piloerection 8–24 hours after last Muscle use twitching Long-acting opioids: Up to 36 hours after last use Myalgia Arthralgia Abdominal pain Fully developed Grade Tachycardia withdrawal 3 Hypertension Short-acting opioids: Tachypnea 1–3 days after last use Fever Long-acting opioids: Anorexia or 72–96 hours after last use nausea Extreme restlessness Fully developed Grade Diarrhea, withdrawal 4 vomiting, or Short-acting opioids: both 1–3 days after last use Dehydration Long-acting opioids: 72–96 hours after last Hyperglycemia Hypotension Curled-up use position Total duration of withdrawal: • Short-acting opioids: 7–10 days • Long-acting opioids: 14 days or more can last 1 to 4 weeks. After the initial withdrawal phase is complete, many patients experience a prolonged phase of dysphoria, craving, insomnia, and hyperalgesia that can last for weeks or months. Assess opioid withdrawal in the physical exam by noting physical signs and symptoms (Exhibit 2.10). Structured measures (e.g., Clinical Opiate Withdrawal Scale [COWS]; Clinical Institute 2-13 TIP 63Part 2 of 5—Addressing Opioid Use Disorder in General Medical Settings Narcotic Assessment Scale for Withdrawal Symptoms) can help standardize documentation of signs and symptoms to support diagnosis, initial management, and treatment planning. See the “Resources” section for links to standardized scales. Part 3 of this TIP covers withdrawal symptom documentation for medication initiation. − − − Abscesses or cellulitis. The physical signs of opioid misuse vary depending on the route of ingestion: • Patients who primarily smoke or sniff (“snort”) opioids or take them orally often have few physical signs of use other than signs of intoxication and withdrawal. However, snorting can cause congestion and damage nasal mucosa. • Patients who inject opioids may develop: − Sclerosis or scarring of the veins and needle marks, or “track marks,” in the arms, legs, hands, neck, or feet (intravenous use). − Edema in the foot, hand, or both (common in injection use, but may occur in oral use). Jaundice, caput medusa, palmar erythema, spider angiomata, or an enlarged or hardened liver secondary to liver disease. Heart murmur secondary to endocarditis. Obtain Appropriate Laboratory Tests Urine or oral fuid drug testing Urine or oral fuid drug testing is useful before initiating OUD medication. Testing establishes a baseline of substances the patient has used so that the provider can monitor the patient’s response to treatment over time. Testing for a range of commonly used substances helps confrm patient histories, facilitates discussion of recent drug use and symptoms, and aids in diagnosing and determining severity of SUDs. Drug testing is an important tool in the diagnosis and treatment of addiction. During ongoing medication for OUD with buprenorphine or methadone, drug testing can confrm medication adherence. EXHIBIT 2.11. Patient–Provider Dialog: Talking About Drug Testing Frame drug testing in a clinical, nonpunitive way. For example, before obtaining a drug test, ask the patient, “What do you think we’ll fnd on this test?” The patient’s response is often quite informative and may make the patient less defensive than confrontation with a positive test result. SCENARIO: A provider discusses urine drug testing with a patient being assessed for OUD treatment with medication. Provider: When we assess patients for medication for opioid addiction, we always check urine samples for drugs. Patient: I’ll tell you if I used. You don’t need to test me. Provider: Thank you, I really appreciate that. The more we can talk about what’s going on with you, the more I can help. I’m not checking the urine to catch you or because I don’t trust you. I trust you. I can see how motivated you are. But I don’t trust the addiction because I know how powerful addiction can be, too. To monitor your safety on medication and help determine what other services you may need, it’s important for us to test you periodically and discuss the results. Does that sound okay? Patient: Yeah, that makes sense. 2-14 Medications for Opioid Use Disorder TIP 63 A national guideline on the use of drug testing is available from ASAM.60 Exhibit 2.11 provides guidance on talking with patients about drug testing. To assess and manage patients with OUD properly, providers must know which tests to order and how to interpret results. There are many drug testing panels; cutoffs for positive results vary by laboratory. One widely used panel, the NIDA-5, tests for cannabinoids, cocaine, amphetamines, opiates, and phencycli- dine. Additional testing for benzodiazepines, the broader category of opioids, and specifc drugs commonly used in the patient’s locality may be warranted. The typical opioid immunoassay will only detect morphine, which is a metabolite of heroin, codeine, and some other opioids. The typical screen will not detect methadone, buprenorphine, or fentanyl and may not detect hydrocodone, hydromorphone, or oxycodone. Specifc testing is needed to identify these substances. Co-occurring SUDs require separate, specifc treatment plans. Testing for substances that can complicate OUD medication is essential. Testing for cocaine, benzodiazepines, and methamphet- amine is clinically important because these and other substances (and related SUDs, which may require treatment in their own right), especially benzodiazepines, can complicate medication treatment for OUD. Benzodiazepine and other sedative misuse can increase the risk of overdose among patients treated with opioid agonists. When assessing benzodiazepine use, note that typical benzodiazepine urine immunoassays will detect diazepam but perhaps not lorazepam or clonazepam. Providers must specifcally request testing for these two benzodiazepines. Exhibit 2.12 shows urine drug testing windows of detection. EXHIBIT 2.12. Urine Drug Testing Window of Detection61,62 DRUG POSITIVE TEST WINDOW OF DETECTION* COMMENTS Amphetamine; methamphetamine; 3,4-methylenedioxy- methamphetamine Amphetamine 1–2 days False positives with bupropion, chlorpromazine, desipramine, fuoxetine, labetalol, promethazine, ranitidine, pseudoephedrine, trazadone, and other common medications. Confrm unexpected positive results with the laboratory. Barbiturates Barbiturates Up to 6 weeks N/A Benzodiazepines Benzodiazepines 1–3 days; up to 6 weeks with heavy use of long-acting benzodiazepines Immunoassays may not be sensitive to therapeutic doses, and most immunoassays have low sensitivity to clonazepam and lorazepam. Check with your laboratory regarding sensitivity and cutoffs. False positives with sertraline or oxaprozin. *Detection time may vary depending on the cutoff. Continued on next page 2-15 TIP 63Part 2 of 5—Addressing Opioid Use Disorder in General Medical Settings EXHIBIT 2.12. Urine Drug Testing Window of Detection (continued) DRUG POSITIVE TEST WINDOW OF DETECTION* COMMENTS Buprenorphine Buprenorphine 3–4 days Will screen negative on opiate screen. Tramadol can cause false positives. Can be tested for specifcally. Cocaine Cocaine, benzoylecgonine 2–4 days; 10–22 days with heavy use N/A Codeine Morphine, codeine, high-dose hydrocodone 1–2 days Will screen positive on opiate immunoassay. Fentanyl Fentanyl 1–2 days Will screen negative on opiate screen. Can be tested for specifcally. May not detect all fentanyl-like substances.63 Heroin Morphine, codeine 1–2 days Will screen positive on opiate immunoassay. 6-monoacetylmorphine, a unique metabolite of heroin, is present in urine for about 6 hours. Can be tested for specifcally to distinguish morphine from heroin, but this is rarely clinically useful. Hydrocodone Hydrocodone, hydromorphone 2 days May screen negative on opiate immunoassay. Can be tested for specifcally. Hydromorphone May not be detected 1–2 days May screen negative on opiate immunoassay. Can be tested for specifcally. Marijuana Tetrahydrocan- nabinol Infrequent use of 1–3 days; chronic use of up to 30 days False positives possible with efavirenz, ibuprofen, and pantoprazole. Methadone Methadone 2–11 days Will screen negative on opiate screen. Can be tested for specifcally. Morphine Morphine, hydromorphone 1–2 days Will screen positive on opiate immunoassay. Ingestion of poppy plant/ seed may screen positive. Oxycodone Oxymorphone 1–1.5 days Typically screens negative on opiate immunoassay. Can be tested for specifcally. *Detection time may vary depending on the cutoff. 2-16 Medications for Opioid Use Disorder TIP 63 Positive opioid tests can confrm recent use. Document recent use before starting patients on buprenorphine or methadone. Positive methadone or buprenorphine tests are expected for patients receiving these treatments. Positive opioid tests contraindicate starting naltrexone. Negative opioid test results require careful interpretation. A patient may test negative for opioids despite presenting with opioid withdrawal symptoms if he or she hasn’t used opioids for several days. A negative opioid test in the absence of symptoms of opioid withdrawal likely indicates that the patient has little or no opioid tolerance, which is important information for assessment and treatment planning. Consider that the opioid the patient reports using may not be detected on the particular immunoassay. Screening tests are not defnitive; false positive and false negative test results are possible. Confrmatory testing should follow all unexpected positive screens. Urine drug testing will detect metabolites from many prescription opioids but miss others, so it is easy to misinterpret results in patients taking these medications.64 False positives are also common in amphetamine testing.65 Point-of-service testing provides the opportu- nity to discuss results with patients immedi- ately. However, cutoffs for positive screens are not standardized across point-of-service tests. Know the specifcations of the screens used.66 Other laboratory tests Patients with OUD, particularly those who inject drugs, are at risk for liver disease and blood-borne viral infections. Pregnancy is another important consideration in determining treatment course. Recommended laboratory tests for patients with OUD include: Pregnancy testing, which is important because: • It is not advisable for patients to start naltrex- one during pregnancy. • Pregnant women treated for active OUD typically receive buprenorphine or methadone. • The American College of Obstetricians and Gynecologists and a recent SAMHSA- convened expert panel on the treatment of OUD in pregnancy67 recommend that pregnant women with OUD receive opioid receptor agonist medication.68 • Providers should refer pregnant women to prenatal care or, if qualifed, provide it themselves. Liver function tests (e.g., aspartate aminotransfer- ase, alanine aminotransferase, bilirubin), which can: • Guide medication selection and dosing. • Rule out severe liver disease, which may contraindicate OUD medication (see Part 3 of this TIP). Hepatitis B and C serology, which can indicate: • Patients with positive tests (evaluate for hepatitis treatment). • The need to administer hepatitis A and B and tetanus vaccines, if appropriate. HIV serology, which can help identify: • Patients who are HIV positive (evaluate for antiretroviral treatment). • Patients who are HIV negative (evaluate for preexposure prophylaxis and targeted education). Review the PDMP Before initiating OUD medication, providers should check their states’ PDMPs to determine whether their patients receive prescriptions for controlled substances from other healthcare professionals. Using the PDMP improves the ability to manage the risks of controlled substances and to identify potentially harmful drug interactions.69 Although OTPs are not permitted to report methadone treatment to PDMPs, pharmacies that dispense buprenorphine and other controlled substances do report to PDMPs. Medications that need monitoring and required frequency of updates vary by state (for more information about state PDMPs, visit www.pdmpassist.org/content /state-profles). 2-17 TIP 63Part 2 of 5—Addressing Opioid Use Disorder in General Medical Settings Determine Diagnosis and Severity of OUD Use DSM-5 criteria to make an OUD diagnosis (Exhibit 2.13).70 Patients who meet two or three criteria have mild OUD. Those meeting four or fve criteria have moderate OUD, and those meeting six or more criteria have severe OUD.71 A printable checklist of DSM-572 criteria is available in the Part 2 Appendix. Treatment Planning or Referral Making Decisions About Treatment Start by sharing the diagnosis with patients and hearing their feedback. Patients with OUD need to make several important treatment decisions: • Whether to begin medication to treat OUD. • What type of OUD medication to take. RESOURCE ALERT EXHIBIT 2.13. DSM-5 Criteria for OUD73 A problematic pattern of opioid use leading to clinically signifcant impairment or distress, as manifested by at least two of the following, occurring within a 12-month period: 1. Opioids are often taken in larger amounts or over a longer period of time than was intended. 2. There is a persistent desire or unsuccessful efforts to cut down or control opioid use. 3. A great deal of time is spent in activities to obtain the opioid, use the opioid, or recover from its effects. 4. Craving, or a strong desire or urge to use opioids. 5. Recurrent opioid use resulting in a failure to fulfll major role obligations at work, school, or home. 6. Continued opioid use despite having persistent or recurrent social or interpersonal problems caused by or exacerbated by the effects of opioids. 7. Important social, occupational, or recreational activities are given up or reduced because of opioid use. 8. Recurrent opioid use in situations in which it is physically hazardous. 9. Continued opioid use despite knowledge of having a persistent or recurrent physical or psychological problem that’s likely to have been caused or exacerbated by the substance. 10. Tolerance,* as defned by either of the following: a. A need for markedly increased amounts of opioids to achieve intoxication or desired effect b. A markedly diminished effect with continued use of the same amount of an opioid 11. Withdrawal,* as manifested by either of the following: a. The characteristic opioid withdrawal syndrome b. The same—or a closely related—substance is taken to relieve or avoid withdrawal symptoms *This criterion is not met for individuals taking opioids solely under appropriate medical supervision. Severity: mild = 2–3 symptoms; moderate = 4–5 symptoms; severe = 6 or more symptoms Shared Decision-Making Resources for Patients and Family Members SAMHSA’s shared decision-making resource page is a good information source for patients to review before their visit or in the office (www.samhsa.gov/brss-tacs/recovery-support- tools/shared-decision-making). In addition, providers can suggest that family, friends, and other potential recovery supports (e.g., 12-Step program sponsors, employers, clergy) read educational material tailored for them. See Medication-Assisted Treatment for Opioid Addiction: Facts for Families and Friends (https://portal.ct.gov/-/media/DMHAS/Opioid- Resources/MATInfoFamilyFriendspdf.pdf). 2-18 Medications for Opioid Use Disorder TIP 63 • Where and how to access desired treatment. • Whether to access potentially benefcial mental health, recovery support, and other ancillary services, whether or not they choose medication for OUD. Offer information to patients about the various treatments for OUD and collaborate with them to make decisions about treatment plans or referrals (Exhibit 2.14). Consider discussing: • Indications, risks, and benefts of medications and alternatives to medication for OUD. • Types of settings that deliver medications (including healthcare professionals’ own practice locations, if applicable). • Availability of and accessibility to treatment (i.e., transportation). • Alternative treatments without medication (e.g., residential treatment, which often offers medically supervised opioid withdrawal). • Costs of treatment with OUD medication, including insurance coverage and affordability. Give patients’ expressed preferences signif- icant weight when making decisions. Patient characteristics can’t reliably predict greater likeli- hood of success with one approved medication or another. For detailed information on medications to treat OUD, refer to Part 3 of this TIP. Strategies to engage patients in shared decision making include: • Indicating to patients a desire to collaborate with them to fnd the best medication and treatment setting for them. • Including family members in the treatment planning process, if possible (and only with patients’ consent). • Exploring what patients already know about treatment options and dispelling misconceptions. • Offering information on medications and their side effects, benefts, and risks (Exhibit 2.14; Part 3). Part 1 of this TIP gives an overview of the three FDA-approved medications used to treat OUD. Part 3 covers the details of their use. • Informing patients of the requirements of the various treatment options (e.g., admission criteria to an OTP; frequency of visits to an OBOT or OTP). • Offering options, giving recommendations after deliberation, and supporting patients’ informed decisions. Understanding Treatment Settings and Services Support patient preferences for treatment settings and services. Some patients prefer to receive OUD medication via physicians’ offces. Others choose outpatient treatment programs that provide opioid receptor agonist treatment for medically supervised withdrawal (with or without naltrexone) or for ongoing opioid receptor agonist maintenance treatment. Still others may want OUD treatment in a residential program with or without medication (Exhibit 2.15). Many patients initially form a preference for a certain treatment without knowing all the risks, benefts, and alternatives. Providers should ensure that patients understand the risks and benefts of all options. Without this understand- ing, patients can’t give truly informed consent. Outpatient OUD Treatment Settings Refer patients who prefer treatment with methadone or buprenorphine via an OTP and explain that: • They will have to visit the program from 6 to 7 times per week at frst. • Additional methadone take-home doses are possible at every 90 days of demonstrated progress in treatment. • Buprenorphine take-home doses are not bound by the same limits as methadone. 2-19 TIP 63Part 2 of 5—Addressing Opioid Use Disorder in General Medical Settings EXHIBIT 2.14. Comparison of OUD Medications To Guide Shared Decision Making CATEGORY BUPRENORPHINE METHADONE NALTREXONE Appropriate Typically for patients with Typically for patients Typically for patients with patients OUD who are physiologically dependent on opioids with OUD who are physiologically dependent on opioids and who meet federal criteria for OTP admission OUD who are abstinent from short-acting opioids for 7 days and long-acting opioids for 10–14 days Outcome: Higher than treatment Higher than treatment Treatment retention with Retention in without medication and without OUD medication oral naltrexone is no better treatment treatment with placebo74 and treatment with placebo75 than with placebo or no medication;76 for XR-NTX, treatment retention is higher than for treatment without OUD medication and treatment with placebo77,78 Outcome: Suppression of illicit opioid use Effective Effective Effective Outcome: Overdose mortality Lower for people in treatment than for those not in it Lower for people in treatment than for those not in it Unknown Location/ Offce/clinic: Begins daily OTP only: 6–7 days/week Offce/clinic: Varies from frequency of to weekly, then tailored to initially; take-homes are weekly to monthly offce visits patient’s needs OTP: Can treat with buprenorphine 6–7 days/ week initially; take-homes are allowed without the time-in- treatment requirements of methadone allowed based on time in treatment and patient progress Who can Physicians, NPs,* PAs, and, OTP physicians order the Physicians, NPs,* PAs, prescribe/ until October 1, 2023, clinical medication; nurses and and, until October 1, 2023, order? nurse specialists, certifed registered nurse anesthetists, and certifed nurse midwives possessing a federal waiver can prescribe and dispense; also can be dispensed by a community pharmacy or an OTP pharmacists administer and dispense it clinical nurse specialists, certifed registered nurse anesthetists, and certifed nurse midwives *NPs, PAs, clinical nurse specialists, certifed registered nurse anesthetists, and certifed nurse midwives should check with their state to determine whether prescribing buprenorphine, naltrexone, or both is within their allowable scope of practice. Continued on next page 2-20 Medications for Opioid Use Disorder TIP 63 EXHIBIT 2.14. Comparison of OUD Medications To Guide Shared Decision Making (continued) CATEGORY BUPRENORPHINE METHADONE NALTREXONE Administration Sublingual/buccal; injection; implant by specially trained provider, and only for stabilized patients Oral Oral or intramuscular (Note: Oral naltrexone is less effective than the other OUD medications.) Misuse/diver- Low in OTPs or other Low in OTPs with directly None sion potential settings with observed dose administration; moderate for take-home doses; risk can be mitigated by providing take- homes to stable patients only and having a diversion control plan for the practice or program. Appropriate patients may be transitioned to a depot formulation of buprenorphine if and when it is appropriate. observed therapy; moderate for take- home doses; risk can be mitigated by a diversion control plan Sedation Low unless concurrent substances are present (e.g., alcohol, benzodiazepines) Low unless dose titration is too quick or dose is not adjusted for the presence of concurrent substances (e.g., alcohol, benzodiazepines) None Risk of medication- induced respira- tory depression Very rare; lower than methadone Rare, although higher than buprenorphine; may be elevated during the frst 2 weeks of treatment or in combination with other sedating substances None Risk of Can occur if started too None Severe withdrawal is precipitated prematurely after recent use possible if period of withdrawal of other opioids abstinence is inadequate when starting before starting medication medication Withdrawal symptoms on discontinuation Present; lower than methadone if abruptly discontinued Present; higher than buprenorphine if abruptly discontinued None Most common Constipation, vomiting, Constipation, vomiting, Diffculty sleeping, anxiety, side effects headache, sweating, insomnia, blurred vision sweating, dizziness, sedation nausea, vomiting, low energy, joint and muscle pain, headache, liver enzyme elevation XR-NTX: Injection site pain, nasopharyngitis, insomnia, toothache D. Coffa, December 2017 (personal communication). Adapted with permission. 2-21 TIP 63Part 2 of 5—Addressing Opioid Use Disorder in General Medical Settings EXHIBIT 2.15. Treatment Setting Based on Patient’s Choice of OUD Medication MEDICATION POSSIBLE TREATMENT SETTING Buprenorphine Offce-based treatment, outpatient or residential SUD treatment programs (prescriber must have a federal waiver), OTP. REMS program participation is required for use of depot formulations. Methadone OTP Naltrexone Offce-based treatment, outpatient or residential SUD treatment programs, OTP • Counseling and drug testing are required parts of OTP treatment. • Some programs also offer case management, peer support, medical services, mental disorder treatment, and other services. Try to arrange OTP intake appointments for patients before they leave the offce. If no immediate openings are available, consider starting buprenorphine as a bridge or alternative to the OTP. Gauge the appropriate intensity level for patients seeking non-OTP outpatient treatment for OUD. These programs range from low intensity (individual or group counseling once to a few times a week) to high intensity (2 or more hours a day of individual and group counseling several days a week). Appropriate treatment intensity depends on each patient’s:79 • Social circumstances. • Severity of addiction. • Personal preferences. • Psychiatric/psychological needs. • Ability to afford treatment at a given intensity. Outpatient medical settings Healthcare professionals cannot provide methadone in their clinics. Only those with a buprenorphine waiver can provide buprenor- phine. Any healthcare professional with a pre- scribing authority can provide naltrexone. Once providers obtain the necessary waiver, they should offer buprenorphine treatment to all patients who present with OUD if such treatment is available and appropriate. Referring them to treatment elsewhere will likely result in delay or lack of patient access to care. Develop a treatment plan to determine where patients will receive continuing care (see the “Treatment Planning” section). Continue to provide nal- trexone for patients who were already receiving it from some other setting (e.g., a prison, a specialty addiction treatment program) or for patients who meet opioid abstinence require- ments and wish to take a medication for relapse prevention. Residential drug treatment settings Patients who have OUD, concurrent other substance use problems, unstable living situations, or a combination of the three may be appropriate candidates for residential treatment, which can last from a week to several weeks or more. Inform patients about the services and requirements typical of this treatment setting. Some patients taking buprenorphine (or methadone) who have other SUDs, such as AUD or cocaine use disorder, can beneft from residential treatment. If such treatment is indicated, determine whether the residential program allows patients to continue their opioid receptor agonist medication while in treatment. Some residential programs require patients to discontinue these medications to receive residential treatment, which could destabilize patients and result in opioid overdose. 2-22 Medications for Opioid Use Disorder TIP 63 • • • Residential treatment programs typically provide: • Room and board. • Recovery support. • Counseling. • Case management. • Medically supervised withdrawal (in some programs). • Starting buprenorphine or naltrexone (in some programs). • Onsite mental health services (in some cases). • Buprenorphine or methadone continuation for patients already enrolled in treatment prior to admission if their healthcare professionals have waivers or their OTP permits. Transitioning out of residential settings requires careful planning. During a patient’s stay in residential treatment, plan for his or her transition out of the program. A good transition plan maximizes the likelihood of continuity of care after discharge. Plans should also address overdose risk. Patients who are no longer RESOURCE ALERT Treatment and Provider Locator SAMHSA’s Behavioral Health Treatment Services Locator (https://fndtreatment.samhsa .gov) provides information on drug and alcohol treatment programs across states. Another SAMHSA tool identifes the locations of buprenorphine providers (www.samhsa.gov /medication-assisted-treatment/physician -program-data/treatment-physician-locator). opioid tolerant are at heightened risk of opioid overdose if they don’t get OUD medication at discharge. Providing XR-NTX, buprenorphine, or methadone during treatment and continuing the medication after discharge can help prevent return to opioid use after discharge. Providing a naloxone prescription and overdose prevention information is appropriate. RESOURCE ALERT Maintaining Confdentiality Providers who treat patients with addiction must know substance use-related disclosure rules and confdentiality requirements. SAMHSA’s webpage lists frequently asked questions on substance use confdentiality and summarizes federal regulations about disclosure and patient records that federal programs maintain on addiction treatment (www.samhsa.gov/about-us/ who-we-are/laws-regulations/confdentiality- regulations-faqs). Key points include: Confdentiality regulations prohibit specialty SUD treatment programs from sharing information with healthcare professionals about patients’ SUD treatment without specifc consent from patients. Referrals to other behavioral health services require consent for sharing information on treatment progress. Healthcare professionals should discuss confdentiality and consent with patients during the referral process. • OUD medication prescribers may consider requiring patient consent for communicating with treatment programs as a condition of receiving OUD treatment. Treatment program staff members can help identify returns to substance use, or risk of such, before the prescriber and can work with the prescriber to stabilize patients. 2-23 TIP 63Part 2 of 5—Addressing Opioid Use Disorder in General Medical Settings Determining OUD Service Intensity and Ensuring Follow-Through Use ASAM placement criteria for guidance on selecting the right level of OUD treatment. ASAM criteria defne the level of care and key features that may make a given level (e.g., residential, intensive outpatient, standard outpatient) appropriate for a patient80 (see the “Treatment Planning” section). To help patients select programs, note that some focus on specifc populations (e.g., gender-specifc programs; parents with children; lesbian, gay, bisexual, transgender, and questioning populations). Make an appointment with the referral program during the patient’s visit rather than giving the patient a phone number to call. Follow up with the patient later to determine whether he or she kept the appointment. Doing so increases the chances of a successful referral. Referring patients to behavioral health and support services Discuss patients’ potential need for behavioral health, peer support, and other ancillary services, like: • Drug and alcohol counseling. • Mental health services. • Case management. • Mutual-help groups. • Peer recovery support services. Offer referrals to counseling and tailored psychosocial support to patients receiving OUD medication (Exhibit 2.16). Drug Addiction Treatment Act of 2000 legislation requires that buprenorphine pre- scribers be able to refer patients to counseling, but making referrals is not mandatory.81 Many patients beneft from referral to mental health services or specialized addiction counseling and recovery support services. However, four ran- domized trials found no extra beneft to adding adjunctive counseling to well-conducted medical RESOURCE ALERT Mutual-Support Groups For an introduction to mutual-support groups, see SAMHSA’s Substance Abuse in Brief, “An Introduction to Mutual Support Groups for Alcohol and Drug Abuse” (http://www. williamwhitepapers.com/pr/CSAT%20 Mutual%20Support%20Groups%202008.pdf). management visits delivered by the buprenor- phine prescriber. There is evidence of benefts to adding contingency management to medication for OUD.82,83,84,85,86 Make referrals to mutual-help groups. Patients may wish to participate in mutual- help groups (e.g., Alcoholics Anonymous, Narcotics Anonymous, Methadone Anonymous, Medication-Assisted Recovery Services, SMART Recovery) in addition to or instead of specialized treatment. These programs can be highly supportive, but they may pressure patients to stop taking OUD medication. If possible, refer patients to groups that welcome patients who take OUD medication. Make referrals to medical and mental health services. Respectful, consistent medical care can support patients’ efforts to recover from OUD and all other SUDs. As for any patient, providers should make appropriate referrals for patients with OUD to receive medical or mental health services beyond the providers’ own scope of practice. Patients with depression, anxiety disorders, and other mental disorders may be more likely to succeed in addiction treatment if those condi- tions are managed.87 If the severity or type of a patient’s psychiatric comorbidity is beyond a provider’s scope of practice, the provider should refer the patient to mental health services as appropriate. 2-24 Medications for Opioid Use Disorder TIP 63 EXHIBIT 2.16. Referring Patients Who Receive OUD Medications to Behavioral Health Therapies Case management Vocational training Yes No Yes No Is the patient willing to engage in additional behavioral health therapies? Is the patient entering an OTP for methadone or intensive treatment? Offer best advice and ongoing motivational interviewing; revisit offer for behavioral health therapies. Counseling, peer support, and case management will likely be provided through the OTP. Identify specifc needs, and refer appropriately to one or more of the following: Counseling: Individual, family, and/or group Peer support groups: Alcoholics Anonymous, Narcotics Anonymous, SMART Recovery, buprenorphine groups Housing, transportation, food, legal, and other support programs RESOURCE ALERT Guidance on Providing Integrated Care Fragmented healthcare services are less likely to meet all patient needs. Integrated medical and behavioral healthcare delivery can effectively provide patient-focused, comprehensive treat- ments that address the full range of symptoms and service needs patients with OUD often have.88 The key components of integration should be in place to make sure that SUD treatment in a primary care setting works. For more information about how to provide integrated services for individuals taking medication for OUD, see: • The Agency for Healthcare Research and Quality’s report Medication-Assisted Treatment Models of Care for Opioid Use Disorder in Primary Care Settings (www.ncbi.nlm.nih.gov/ books/NBK402352). • The Agency for Healthcare Research and Quality’s Academy for Integrating Behavioral Health and Primary Care (https:// integrationacademy.ahrq.gov). 2-25 TIP 63Part 2 of 5—Addressing Opioid Use Disorder in General Medical Settings OPPORTUNITY ALERT Becoming an OUD Medication Treatment Provider SAMHSA strongly urges physicians, NPs, PAs, and, until October 1, 2023, clinical nurse specialists, certifed registered nurse anesthetists, and certifed nurse midwives to obtain waivers that will qualify them to offer buprenorphine treatment. They can become qualifed to use buprenorphine to taper appropriate patients with OUD off illicit or prescription opioids or to provide long-term OUD treatment. Only healthcare professionals with a federal waiver may prescribe buprenorphine for the treatment of OUD. There are two pathways by which providers can obtain waivers. In the traditional pathway, providers must meet set criteria, complete buprenorphine training (online or in person), and apply for a waiver from SAMHSA by submitting a notice of intent (NOI). An alternate pathway was established in April 2021 under which healthcare professionals who are state licensed and possess a valid DEA registration may be exempted from the training requirement, as well as the required attestation about providing patients with access to or referrals for psychosocial services if they wish to treat up to 30 patients only. This exemption applies not just to physicians but to NPs, PAs, clinical nurse specialists, certifed registered nurse anesthetists, and certifed nurse midwives as well. Providers applying under this exemption must still submit an NOI, and time spent practicing under this exemption does not qualify the provider for subsequent increases in their patient cap.89 If after 1 year providers wish to treat more than 30 patients, they must submit an NOI using the traditional pathway. Regardless of which method is used to submit an NOI, waivered prescribers are assigned an additional DEA registration number (usually their existing number with an added “X”).90 NPs, PAs, clinical nurse specialists, certifed registered nurse anesthetists, and certifed nurse midwives need to meet additional criteria for waivers.91 These providers who are state licensed and possess a valid DEA registration may be exempted from training and psychosocial services attestation requirements and may instead apply for a waiver by submitting an NOI.92 Providers can still apply for the traditional NOI if they wish to apply for increases in their patient cap after 1 year. Check with the state licensing board about restrictions and requirements at the state level before applying for a waiver. Wavier training: ASAM, the American Academy of Addiction Psychiatry, the American Psychiatric Association, and the American Osteopathic Academy of Addiction Medicine all provide the waiver training courses for physicians. Providers’ Clinical Support System for Medication Assisted Treatment (PCSS- MAT) provides the required 8-hour OUD medication waiver course for physicians and 24- hour waiver course for NPs, PAs, clinical nurse specialists, certifed registered nurse anesthetists, and certifed nurse midwives for free (https:// pcssnow.org/medication- assisted-treatment/). Other providers also provide NP, PA, clinical nurse specialist, certifed registered nurse anesthetist, and certifed nurse midwife courses. Providers who are state licensed and DEA registered may submit an NOI in lieu of these training requirements as well as the required attestation about providing patients access to or referrals for psychosocial services. Providers practicing under this exemption are limited to treating no more than 30 patients at a time, however. Learn more by reading SAMHSA’s “FAQs About the New Buprenorphine Practice Guidelines” at www.samhsa.gov/ medication-assisted-treatment/ practitioner-resources/faqs. New prescribers can beneft from mentorship from experienced providers in their practice or community. Mentorship is available for free from PCSS-MAT (http://pcssmat .org/mentoring). For detailed information on prescribing OUD medications, review Part 3 of this TIP. 2-26 Medications for Opioid Use Disorder TIP 63 Make referrals to ancillary services. Besides medical care and mental health services, OUD patients, like patients with other illnesses, may need more support in some areas, including ancillary services such as: • Case management. • Food access. • Vocational training. • Housing. • Transportation. • Legal assistance. Helping patients who are not ready to engage in OUD treatment Help reluctant patients be safer and approach readiness. Patients may seem unwilling to discuss their drug use if they’re ashamed or fear being judged. Accepting, nonjudgmental attitudes help patients overcome shame and discuss concerns honestly while also instilling hope. Every visit is a chance to help patients begin healthy changes and move toward treatment and recovery. Patients may not be ready to change right away. Successfully quitting drug use can take many attempts. Returns to substance use, even after periods of remission, are expected parts of the recovery process. Patients with OUD are much more likely to die than their peers,93,94 and HIV, hepatitis C, and skin and soft tissue infections are common among this population. Help reduce these OUD- related risks by testing patients for HIV and hepatitis and by educating patients about: • Using new syringes. • Avoiding syringe sharing. • Avoiding sharing other supplies during the injection process. • Preventing opioid overdose (see the “Preventing Opioid-Related Overdose” section). • Obtaining overdose prevention infor- mation and resources (e.g., SAMHSA Opioid Overdose Prevention Toolkit [https://store.samhsa.gov/product/ Opioid-Overdose-Prevention-Toolkit/ SMA18-4742]). • Obtaining naloxone and instructions for its use. Refer patients to syringe exchange sites. The North American Syringe Exchange Network provides options (see the “Syringe Exchange” section). Preventing Opioid-Related Overdose Every patient who misuses opioids or has OUD should receive opioid overdose preven- tion education and a naloxone prescription.95 Healthcare professionals should educate patients and their families about overdose risk, prevention, identifcation, and response (Exhibit 2.17). FDA has approved an autoinjectable naloxone device (Evzio) and a naloxone nasal spray (Narcan) for use by patients and others. For information about all forms of naloxone, prescribing, and patient and community education, see the SAMHSA Opioid Overdose Prevention Toolkit (https://store.samhsa.gov/ product/Opioid-Overdose-Prevention-Toolkit/ SMA18-4742). 2-27 TIP 63Part 2 of 5—Addressing Opioid Use Disorder in General Medical Settings EXHIBIT 2.17. Opioid Overdose: Risk, Prevention, Identifcation, and Response Overdose risk • Using heroin (possibly mixed with illicitly manufactured fentanyl or fentanyl analogs) • Using prescription opioids that were not prescribed • Using prescription opioids more frequently or at higher doses than prescribed • Using opioids after a period of abstinence or reduced use (e.g., after medically supervised withdrawal or incarceration) • Using opioids with alcohol, benzodiazepines, or both Overdose prevention • Don’t use opioids that were not prescribed. • Take medications only as prescribed. • Don’t use drugs when you are alone. • Don’t use multiple substances at once. • Have naloxone available and make sure others know where it is and how to use it. • Use a small “test dose” if returning to opioid use after a period of abstinence, if the substance appears altered, or if it has been acquired from an unfamiliar source. Beware: This doesn’t guarantee safety; illicitly manufactured fentanyl or other substances may be present in the drug, and any use may be fatal. The United States is experiencing an epidemic of opioid overdose deaths. Opioids (including prescription opioids and heroin) killed 49,860 people in 2019, more than in any prior year. Less than one-third of overdose deaths involved prescription opioids.97 From 2010 to 2018, heroin-related overdose deaths rose about fvefold.98,99 Overdose deaths from illicit fentanyl have also risen sharply.100 Overdose identifcation • Fingernails or lips are blue or purple. • Breathing or heartbeat is slow or stopped. • The person is vomiting or making gurgling noises. • The person can’t be awakened or is unable to speak. Overdose response • Call 9-1-1. • Administer naloxone (more than one dose may be needed to restore adequate spontaneous breathing). • Perform rescue breathing. If certifed to provide cardiopulmonary resuscitation, perform chest compressions if there is no pulse. • Put the person in the “recovery position,” on his or her side and with the mouth facing to the side to prevent aspiration of vomit, if he or she is breathing independently. • Stay with the person until emergency services arrive. Naloxone’s duration of action is 30–90 minutes. The person should be observed after this time for a return of opioid overdose symptoms. Adapted from material in the public domain.96 Municipalities with community-based naloxone distribution programs have seen substantial decreases in opioid overdose death rates.101,102 Many syringe exchange programs also dispense naloxone. For information and resources on prescribing naloxone for overdose prevention, including educational patient handouts and videos, see the “Opioid-Related Overdose Prevention” section. 2-28 Medications for Opioid Use Disorder TIP 63 Resources The following selected resources address key content presented in Part 2. Part 5 of this TIP includes comprehensive resources on topics pertaining to substance misuse and medications to treat OUD. Alcohol and Drug Use Screening • American Academy of Addiction Psychiatry: Provides Performance in Practice Clinical Modules for screening of tobacco use and AUD. www.cvent.com/events/ aaap-pips/event-summary-9f3d326cf2a94a- f49153a1834832534e.aspx • NIAAA, Professional Education Materials: Provides links to screening, treatment planning, and general information for clinicians in outpatient programs. www.niaaa.nih.gov /publications/clinical-guides-and-manuals • NIDA, Medical and Health Professionals: Provides resources for providers to increase awareness of the impact of substance use on patients’ health and help identify drug use early and prevent it from escalating to misuse or addiction. www.drugabuse.gov /nidamed-medical-health-professionals Tobacco Screening • American Psychiatric Nursing Association, Tobacco & Nicotine Use Screening Tools and Assessments: Provides the Fagerström screening tools for nicotine dependence and smokeless tobacco and a screening checklist for tobacco use. www.apna.org/i4a/pages /index.cfm?pageID=6150 • U.S. Department of Health and Human Services’ Be Tobacco Free: Provides infor- mation for individuals struggling with nicotine addiction and links for clinicians that provide guidance on caring for patients with nicotine addiction. https://betobaccofree.hhs.gov/ • U.S. Department of Health and Human Services’ Million Hearts Initiative: Provides templates for developing and guidance on implementing tobacco cessation programs and guidance on implementing them as part of clinical care. https://millionhearts.hhs.gov /tools-protocols/protocols.html • Centers for Disease Control and Prevention (CDC): Offers resources and information for patients and clinicians; includes a webpage with resource links for clinicians on treating tobacco dependence. www.cdc.gov/tobacco /index.htm and www.cdc.gov/tobacco/basic _information/related_links/index.htm Buprenorphine Treatment Locator • SAMHSA, Buprenorphine Treatment Practitioner Locator: Provides a state-by- state list of providers who offer buprenor- phine. www.samhsa.gov/medication-assisted -treatment/physician-program-data /treatment-physician-locator Buprenorphine Training, Mentorship, and Waivers • SAMHSA, Buprenorphine Waiver Management: Provides information on buprenorphine waivers with links to waiver applications; explains waiver processes, training and psychosocial service attestation exemptions, requirements, and recordkeep- ing. www.samhsa.gov/medication-assist- ed-treatment/training-materials-resources/ apply-for-practitioner-waiver • SAMHSA, Buprenorphine Practice Guidelines: Provides information about how and why providers might be exempt from training and psychosocial service attestation requirements for obtaining a SAMHSA X waiver. www.federalregister.gov/ documents/2021/04/28/2021-08961/prac- tice-guidelines-for-the-administration-of-bu- prenorphine-for-treating-opioid-use-disorder • SAMHSA, Buprenorphine Training for Physicians: Provides links to organizations that train physicians on buprenorphine treatment. www.samhsa.gov/medication-as- sisted-treatment/training-materials-resources/ apply-for-practitioner-waiver 2-29 TIP 63Part 2 of 5—Addressing Opioid Use Disorder in General Medical Settings • SAMHSA, Qualify for a Practitioner Waiver: Provides information for NPs, PAs, clinical nurse specialists, certifed registered nurse anesthetists, and certifed nurse midwives about the buprenorphine waiver training, with links to trainings and the application process. www.samhsa.gov/medication-assist- ed-treatment/training-materials-resources/ apply-for-practitioner-waiver • PCSS-MAT: Provides buprenorphine waiver training and mentorship for healthcare pro- fessionals (physicians, NPs, PAs, clinical nurse specialists, certifed registered nurse anesthe- tists, and certifed nurse midwives); includes updates and other resources about medication for OUD. https://pcssnow.org/ Medication Treatment for OUD • SAMHSA, Advisory, Sublingual and Transmucosal Buprenorphine for Opioid Use Disorder: Review and Update: Summarizes information on the use of buprenorphine to treat OUD. https://store.samhsa.gov/product/ Advisory-Sublingual-and-Transmucosal- Buprenorphine-for-Opioid-Use-Disorder-/ SMA16-4938 • SAMHSA, Clinical Use of Extended-Release Injectable Naltrexone in the Treatment of Opioid Use Disorder: A Brief Guide: Provides a brief review of the use of XR-NTX. https://store.samhsa.gov/product/Clinical -Use-of-Extended-Release-Injectable -Naltrexone-in-the-Treatment-of-Opioid -Use-Disorder-A-Brief-Guide/SMA14-4892R • ASAM, The ASAM National Practice Guideline for the Treatment of Opioid Use Disorder. 2020 Focused Update: Provides national practice guidelines for the use of medications to treat OUD. www.asam.org/docs/default-source/ quality-science/npg-jam-supplement. pdf?sfvrsn=a00a52c2_2 • Department of Veterans Affairs/ Department of Defense, VA/DoD Clinical Practice Guideline for the Management of Substance Use Disorders: Provides substance use disorder practice guidelines. www.healthquality.va.gov/guidelines/MH/sud /VADoDSUDCPGRevised22216.pdf • PCSS-MAT: Provides training and mentorship for healthcare professionals (physicians, NPs, PAs, clinical nurse specialists, certifed regis- tered nurse anesthetists, and certifed nurse midwives) on medications for OUD treatment including buprenorphine, naltrexone, and methadone. https://pcssnow.org/ Syringe Exchange • North American Syringe Exchange Network: Provides a national directory of syringe exchange programs in the United States. https://nasen.org/directory Opioid-Related Overdose Prevention • Prescribe To Prevent: Provides information about naloxone prescribing for overdose prevention, including educational patient handouts and videos. http://prescribeto prevent.org • SAMHSA Opioid Overdose Prevention Toolkit: Provides healthcare professionals, communities, and local governments with material to develop practices and policies to help prevent opioid-related overdoses and deaths. It addresses issues for healthcare professionals, frst responders, treatment providers, and those recovering from opioid overdose as well as their families. https://store.samhsa.gov/product/ Opioid-Overdose-Prevention-Toolkit/ SMA18-4742 • CDC—Overdose Prevention: Provides links and tools for clinicians to help prevent opioid overdose deaths. www.cdc.gov/drugover- dose/prevention/index.html 2-30 Medications for Opioid Use Disorder TIP 63 • NIDA, Opioid Overdose Reversal with Naloxone (Narcan, Evzio): Provides naloxone information for providers. www.drugabuse .gov/related-topics/opioid-overdose -reversal-naloxone-narcan-evzio Opioid Withdrawal Scales • WHO Guidelines for the Psychosocially Assisted Pharmacological Treatment of Opioid Dependence: Annex 10: Provides COWS and other opioid withdrawal scales. www.ncbi.nlm.nih.gov/books/NBK143183 • The Clinical Institute Narcotic Assessment Scale for Withdrawal Symptoms: Provides a scale that measures signs and symptoms observed in patients during withdrawal. www .ncpoep.org/wp-content/uploads/2015/02 /Appendix_7_Clinical_Institute_Narcotic _Assessment_CINA_Scale_for_Withdrawal _Symptoms.pdf Patient and Family Education on Medications To Treat OUD • SAMHSA Store: Provides patient and family educational resources about OUD and medication treatment for OUD; some resources are available in multiple languages, including Spanish. https://store.samhsa.gov − Buprenorphine. https://store.samhsa.gov /product/The-Facts-about-Buprenorphine -for-Treatment-of-Opioid-Addiction /SMA15-4442 − Methadone. https://roar.nevadaprc. org/system/documents/3100/original/ NPRC.168.WhatEveryIndividualNeeds ToKnow.pdf?1435165554 • ASAM Resources: Provides patient and family education tools about addiction in general and OUD specifcally. − Patient Resources. www.asam.org /resources/patientresources − Opioid Addiction Treatment: A Guide for Patients, Families, and Friends. www.asam. org/docs/default-source/publications/asam- opioid-patient-piece_-5bopt2-5d_3d.pdf Referral and Treatment Locators • SAMHSA, OTP Directory: Provides a state- by-state directory of methadone OTPs. https:// dpt2.samhsa.gov/treatment/directory.aspx • SAMHSA, Behavioral Health Treatment Services Locator: Provides a directory of treatment facilities. https://fndtreatment .samhsa.gov • SAMHSA, Behavioral Health Treatment Services Locator—Self-Help, Peer Support, and Consumer Groups: Provides a directory for mutual-help groups. https://fndtreatment. samhsa.gov/ Screening, Assessment, and Drug Testing Resources • NIDA, Screening Tools and Prevention: Provides an evidence-based screening tool chart for adolescents and adults, drug use screening tool support materials, and a clinician resource and quick reference guide for drug screening in general medical settings, including the NIDA- Modifed ASSIST (NM ASSIST). www. drugabuse.gov/nidamed-medical-health- professionals/tool-resources-your-practice/ additional-screening-resources • ASAM, The ASAM Appropriate Use of Drug Testing in Clinical Addiction Medicine: Discusses appropriate use of drug testing in identifying, diagnosing, and treating people with or at risk for SUDs. www.asam.org/ Quality-Science/quality/drug-testing • USPSTF, Final Recommendation Statement—Unhealthy Drug Use: Screening Discusses updated recommendations about screening for illicit drug use and prescription medication misuse in adults in primary care settings. https://uspreventiveser- vicestaskforce.org/uspstf/recommendation/ drug-use-illicit-screening 2-31 TIP 63Part 2 of 5—Addressing Opioid Use Disorder in General Medical Settings Treatment Planning • SAMHSA, Shared Decision-Making Tools: Provides resources to help people with OUD make informed decisions about their care. www.samhsa. gov/brss-tacs/recovery- support-tools/shared-decision-making An accompanying handbook is also available. https://store.samhsa.gov/product/Decisions- in-Recovery-Treatment-for-Opioid-Use -Disorders/SMA16-4993 • SAMHSA, TIP 42, Substance Use Disorder Treatment for People With Co-Occurring Disorders: Provides comprehensive treatment guidance for individuals with co-occurring mental and substance use disorders. https://store.samhsa.gov/product/ TIP-42-Substance-Abuse-Treatment-for- Persons-With-Co-Occurring-Disorders/ SMA13-3992 2-32 Medications for Opioid Use Disorder TIP 63 Part 2 Appendix Stable Resource Toolkit Audit-C – Overview The AUDIT-C is a 3-item alcohol screen that can help identify persons who are hazardous drinkers or have active alcohol use disorders (including alcohol abuse or dependence). The AUDIT-C is a modifed version of the 10 question AUDIT instrument. Clinical Utility The AUDIT-C is a brief alcohol screen that reliably identifes patients who are hazardous drinkers or have active alcohol use disorders. Scoring The AUDIT-C is scored on a scale of 0-12. Each AUDIT-C question has 5 answer choices. Points allotted are: a = 0 points, b = 1 point, c = 2 points, d = 3 points, e = 4 points • In men, a score of 4 or more is considered positive, optimal for identifying hazardous drinking or active alcohol use disorders. • In women, a score of 3 or more is considered positive (same as above). • However, when the points are all from Question #1 alone (#2 & #3 are zero), it can be assumed that the patient is drinking below recommended limits and it is suggested that the provider review the patient’s alcohol intake over the past few months to confrm accuracy. • Generally, the higher the score, the more likely it is that the patient’s drinking is affecting his or her safety. Psychometric Properties For identifying patients with heavy/hazardous drinking and/or Active-DSM alcohol abuse or dependence MEN1 WOMEN2 ≥3 Sens: 0.95 / Spec. 0.60 Sens: 0.66 / Spec. 0.94 ≥4 Sens: 0.86 / Spec. 0.72 Sens: 0.48 / Spec. 0.99 For identifying patients with active alcohol abuse or dependence MEN1 WOMEN2 ≥3 Sens: 0.90 / Spec. 0.45 Sens: 0.80 / Spec. 0.87 ≥4 Sens: 0.79 / Spec. 0.56 Sens: 0.67 / Spec. 0.94 1. Bush K, Kivlahan DR, McDonell MB, et al. The AUDIT Alcohol Consumption Questions (AUDIT-C): An effective brief screening test for problem drinking. Arch Internal Med. 1998 (3): 1789-1795. 2. Bradley KA, Bush KR, Epler AJ, et al. Two brief alcohol-screening tests from the Alcohol Use Disorders Identifcation Test (AUDIT): Validation in a female veterans affairs patient population. Arch Internal Med Vol 165, April 2003: 821-829. Continued on next page 2-33 TIP 63Part 2 of 5—Addressing Opioid Use Disorder in General Medical Settings AUDIT-C Questionnaire Patient Name: _____________________________________________________ Dates of Visit: ______________________ 1. How often do you have a drink containing alcohol? □ a. Never □ b. Monthly or less □ c. 2-4 times a month □ d. 2-3 times a week □ e. 4 or more times a week 2. How many standard drinks containing alcohol do you have on a typical day? □ a. 1 or 2 □ b. 3 or 4 □ c. 5 or 6 □ d. 7 to 9 □ e. 10 or more 3. How often do you have six or more drinks on one occasion? □ a. Never □ b. Less than monthly □ c. Monthly □ d. Weekly □ e. Daily or almost daily AUDIT-C is available for use in the public domain. Reprinted from material in the public domain.103 2-34 Medications for Opioid Use Disorder TIP 63 Drug Abuse Screening Test (DAST-10) General Instructions “Drug use” refers to (1) the use of prescribed or over-the-counter drugs in excess of the directions, and (2) any nonmedical use of drugs. The various classes of drugs may include cannabis (i.e., marijuana, hashish), solvents (e.g., paint thinner), tran- quilizers (e.g., Valium), barbiturates, cocaine, stimulants (e.g., speed), hallucinogens (e.g., LSD), or narcotics (e.g., heroin). The questions do not include alcoholic beverages. Please answer every question. If you have trouble with a question, then choose the response that is mostly right. Segment: ____________ Visit Number: ___________ Date of Assessment: ______/______/________ These questions refer to drug use in the past 12 months. Please answer No or Yes. 1. Have you used drugs other than those required for medical reasons? □ No □ Yes 2. Do you use more than one drug at a time? □ No □ Yes 3. Are you always able to stop using drugs when you want to? □ No □ Yes 4. Have you had “blackouts” or “fashbacks” as a result of drug use? □ No □ Yes 5. Do you ever feel bad or guilty about your drug use? □ No □ Yes 6. Does your spouse (or parents) ever complain about your involvement with drugs? □ No □ Yes 7. Have you neglected your family because of your use of drugs? □ No □ Yes 8. Have you engaged in illegal activities to obtain drugs? □ No □ Yes 9. Have you ever experienced withdrawal symptoms (i.e., felt sick) when you stopped □ No □ Yes taking drugs? 10. Have you had medical problems as a result of your drug use (e.g., memory loss, □ No □ Yes hepatitis, convulsions, bleeding)? Comments: Scoring Score 1 point for each “Yes,” except for question 3, for which a “No” receives 1 point. DAST Score: __________ Interpretation of Score: Score Degree of Problems Related to Drug Abuse Suggested Action 0 No problems reported None at this time 1–2 Low level Monitor, reassess at a later date 3–5 Moderate level Further investigation 6–8 Substantial level Intensive assessment 9–10 Severe level Intensive assessment Adapted with permission.104,105 2-35 TIP 63Part 2 of 5—Addressing Opioid Use Disorder in General Medical Settings DSM-5 Opioid Use Disorder Checklist106 Patient’s Name: ____________________________________________________________ Date of Birth: _______________________ Worksheet for DSM-5 Criteria for Diagnosis of Opioid Use Disorder DIAGNOSTIC CRITERIA (Opioid use disorder requires that at least 2 criteria be met within a 12-month period.) MEETS CRITERIA? Yes OR No NOTES/SUPPORTING INFORMATION 1. Opioids are often taken in larger amounts or over a longer period of time than intended. 2. There is a persistent desire or unsuccessful efforts to cut down or control opioid use. 3. A lot of time is spent in activities necessary to obtain the opioid, use the opioid, or recover from its effects. 4. Craving, or a strong desire to use opioids. 5. Recurrent opioid use resulting in failure to fulfll major role obligations at work, school, or home. 6. Continued opioid use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of opioids. 7. Important social, occupational, or recreational activities are given up or reduced because of opioid use. 8. Recurrent opioid use in situations in which it is physically hazardous. 9. Continued use despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by opioids. 10. Tolerance,* as defned by either of the following: (a) a need for markedly increased amounts of opioids to achieve intoxication or desired effect (b) markedly diminished effect with continued use of the same amount of an opioid 11. Withdrawal,* as manifested by either of the following: (a) the characteristic opioid withdrawal syndrome (b) the same (or a closely related) substance is taken to relieve or avoid withdrawal symptoms *This criterion is not met for individuals taking opioids solely under appropriate medical supervision. Severity: mild = 2–3 symptoms; moderate = 4–5 symptoms; severe = 6 or more symptoms Signed: _____________________________________________________ Date: _______________________ 2-36 Medications for Opioid Use Disorder TIP 63 TAPS Tool Part I Directions: The TAPS Tool Part 1 is a 4-item screening for tobacco use, alcohol use, prescription medication misuse, and illicit substance use in the PAST YEAR. Question 2 should be answered by males, and Question 3 should be answered by females. Each of the four multiple-choice items has fve possible responses to choose from. Check the box to select your answer. In the PAST 12 MONTHS: 1. How often have you used any tobacco product (for example, cigarettes, ecigarettes, cigars, pipes, or smokeless tobacco)? □ Never □ Less than monthly □ Monthly □ Weekly □ Daily or almost daily 2. How often have you had 5 or more drinks containing alcohol in 1 day? One standard drink is about 1 small glass of wine (5 oz), 1 beer (12 oz), or 1 single shot of liquor. (Note: This question should only be answered by males.) □ Never □ Less than monthly □ Monthly □ Weekly □ Daily or almost daily 3. How often have you had 4 or more drinks containing alcohol in 1 day? One standard drink is about 1 small glass of wine (5 oz), 1 beer (12 oz), or 1 single shot of liquor. (Note: This question should only be answered by females.) □ Never □ Less than monthly □ Monthly □ Weekly □ Daily or almost daily 4. How often have you used any drugs including marijuana, cocaine or crack, heroin, methamphetamine (crystal meth), hallucinogens, or ecstasy/MDMA? □ Never □ Less than monthly □ Monthly □ Weekly □ Daily or almost daily 5. How often have you used any prescription medications just for the feeling, more than prescribed, or that were not prescribed for you? Prescription medications that may be used this way include opiate pain relievers (for example, OxyContin, Vicodin, Percocet, or methadone), medications for anxiety or sleeping (for example, Xanax, Ativan, or Klonopin), or medications for ADHD (for example, Adderall or Ritalin). □ Never □ Less than monthly □ Monthly □ Weekly □ Daily or almost daily 2-37 TIP 63Part 2 of 5—Addressing Opioid Use Disorder in General Medical Settings TAPS Tool Part 2 Directions: The TAPS Tool Part 2 is a brief assessment for tobacco use, alcohol use, illicit substance use, and prescription medication misuse in the PAST 3 MONTHS ONLY. Each of the following questions and subquestions has two possible answers, yes or no. Check the box to select your answer. In the PAST 3 MONTHS: 1. Did you smoke a cigarette containing tobacco? □ Yes □ No If “Yes,” answer the following questions: • Did you usually smoke more than 10 cigarettes each day? • Did you usually smoke within 30 minutes after waking? □ Yes □ Yes □ No □ No 2. Did you have a drink containing alcohol? □ Yes □ No If “Yes,” answer the following questions: • Did you have 4 or more drinks containing alcohol in a day?* □ Yes □ No (Note: This question should only be answered by females.) • Did you have 5 or more drinks containing alcohol in a day?* □ Yes □ No (Note: This question should only be answered by males.) • Have you tried and failed to control, cut down, or stop drinking? • Has anyone expressed concern about your drinking? □ Yes □ Yes □ No □ No 3. Did you use marijuana (hash, weed)? □ Yes □ No If “Yes,” answer the following questions: • Have you had a strong desire or urge to use marijuana at least once a week or more often? □ Yes □ No • Has anyone expressed concern about your use of marijuana? □ Yes □ No 4. Did you use cocaine, crack, or methamphetamine (crystal meth)? □ Yes □ No If “Yes,” answer the following questions: • Did you use cocaine, crack, or methamphetamine (crystal meth) at least once a week or more often? □ Yes □ No • Has anyone expressed concern about your use of cocaine, crack, or methamphetamine (crystal meth)? □ Yes □ No 5. Did you use heroin? □ Yes □ No If “Yes,” answer the following questions: • Have you tried and failed to control, cut down, or stop using heroin? □ Yes □ No • Has anyone expressed concern about your use of heroin? □ Yes □ No 6. Did you use a prescription opiate pain reliever (for example, Percocet or Vicodin) not as □ Yes □ No prescribed or that was not prescribed for you? If “Yes,” answer the following questions: • Have you tried and failed to control, cut down, or stop using an opiate pain reliever? □ Yes □ No • Has anyone expressed concern about your use of an opiate pain reliever? □ Yes □ No *One standard drink is about 1 small glass of wine (5 oz), 1 beer (12 oz), or 1 single shot of liquor. Continued on next page 2-38 Medications for Opioid Use Disorder TIP 63 TAPS Tool Part 2 (continued) 7. Did you use medication for anxiety or sleep (for example, Xanax, Ativan, or Klonopin) not as prescribed or that was not prescribed for you? If “Yes,” answer the following questions: • Have you had a strong desire or urge to use medications for anxiety or sleep at least once a week or more often? • Has anyone expressed concern about your use of medication for anxiety or sleep? □ Yes □ Yes □ Yes □ No □ No □ No 8. Did you use medication for ADHD (for example, Adderall or Ritalin) not as prescribed or that was not prescribed for you? If “Yes,” answer the following questions: • Did you use a medication for ADHD (for example, Adderall or Ritalin) at least once a week or more often? • Has anyone expressed concern about your use of medication for ADHD (for example, Adderall or Ritalin)? □ Yes □ Yes □ Yes □ No □ No □ No 9. Did you use any other illegal or recreational drugs (for example, ecstasy, molly, GHB, □ Yes □ No poppers, LSD, mushrooms, special K, bath salts, synthetic marijuana ["spice"], or whip-its)? If “Yes,” answer the following question: • What were the other drug(s) you used? (write in response) The complete tool is available online (https://cde.drugabuse.gov/instrument/29b23e2e-e266-f095-e050-bb89ad43472f). Adapted from material in the public domain.107 2-39 TIP 63Part 2 of 5—Addressing Opioid Use Disorder in General Medical Settings Notes 1 Shapiro, B., Coffa, D., & McCance-Katz, E. F. (2013). A primary care approach to substance misuse. American Family Physician, 88(2), 113–121. 2 Center for Behavioral Health Statistics and Quality. (2020). Results from the 2019 National Survey on Drug Use and Health: Detailed tables. Rockville, MD: Substance Abuse and Mental Health Services Administration. Retrieved May 21, 2021, from www.samhsa.gov/data/ 3 American Society of Addiction Medicine. (2011). Defnition of addiction. Retrieved October 30, 2017, from www.asam.org/resources/defnition-of-addiction 4 American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Arlington, VA: American Psychiatric Publishing. 5 Department of Health and Human Services, Offce of the Surgeon General. (2016). Facing addiction in America: The Surgeon General’s report on alcohol, drugs, and health. Washington, DC: Department of Health and Human Services. 6 Substance Abuse and Mental Health Services Administration. (2015). Federal guidelines for opioid treatment programs. 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Drug and Alcohol Dependence, 132(1–2), 352–361. 39 Smith, P. C., Schmidt, S. M., Allensworth-Davies, D., & Saitz, R. (2010). A single-question screening test for drug use in primary care. Archives of Internal Medicine, 170(13), 1155–1160. 40 Tiet, Q. Q., Leyva, Y. E., Moos, R. H., Frayne, S. M., Osterberg, L., & Smith, B. (2015). Screen of drug use: Diagnostic accuracy of a new brief tool for primary care. JAMA Internal Medicine, 175(8), 1371–1377. 41 Tiet, Q. Q., Leyva, Y. E., Moos, R. H., Frayne, S. M., Osterberg, L., & Smith, B. (2015). Screen of drug use: Diagnostic accuracy of a new brief tool for primary care. JAMA Internal Medicine, 175(8), 1371–1377. 42 National Institute on Drug Abuse. (2012). Resource guide: Screening for drug use in general medical settings. Rockville, MD: Author. 43 National Institute on Drug Abuse. (2012). Resource guide: Screening for drug use in general medical settings. Rockville, MD: Author. 44 Ali, R., Meena, S., Eastwood, B., Richards, I., & Marsden, J. (2013). Ultra-rapid screening for substance-use disorders: The Alcohol, Smoking and Substance Involvement Screening Test (ASSIST-Lite). Drug and Alcohol Dependence, 132(1–2), 352–361. 45 Schwartz, R. P., McNeely, J., Wu, L. T., Sharma, G., Wahle, A., Cushing, C., … Subramaniam, G. (2017). Identifying substance misuse in primary care: TAPS Tool compared to the WHO ASSIST. Journal of Substance Abuse Treatment, 76, 69–76. 46 Wang, X., Zhang, T., & Ho, W. Z. (2011). Opioids and HIV/ HCV infection. Journal of Neuroimmune Pharmacology, 6(4), 477–489. 47 U.S. Preventive Services Task Force. (2019). Final Recommendation Statement on Human Immunodefciency Virus (HIV) Infection: Screening. Retrieved June 11, 2019, from www. uspreventiveservicestaskforce.org/Page/Document/ RecommendationStatementFinal/human- immunodefciency-virus-hiv-infection-screening#consider 48 Centers for Disease Control and Prevention. Testing Recommendations for Hepatitis C Virus Infection. Retrieved October 15, 2015, from www.cdc.gov/ hepatitis/hcv/guidelinesc.htm 2-41 TIP 63Part 2 of 5—Addressing Opioid Use Disorder in General Medical Settings 49 Merrill, J. O., Rhodes, L. A., Deyo, R. A., Marlatt, G. A., & Bradley, K. A. (2002). Mutual mistrust in the medical care of drug users: The keys to the “narc” cabinet. Journal of General Internal Medicine, 17(5), 327–333. 50 Shapiro, B., Coffa, D., & McCance-Katz, E. F. (2013). A primary care approach to substance misuse. American Family Physician, 88(2), 113–121. 51 Miller, W. R., & Rollnick, S. (2013). Motivational interviewing: Helping people change (3rd ed.). New York, NY: Guilford Press. 52 Center for Substance Abuse Treatment. (1999). Brief interventions and brief therapies for substance abuse. Treatment Improvement Protocol (TIP) Series. 34. HHS Publication No. (SMA) 12-3952. Rockville, MD: Substance Abuse and Mental Health Services Administration. 53 Miller, W. R., & Rollnick, S. (2013). Motivational interviewing: Helping people change (3rd ed.). New York, NY: Guilford Press. 54 Savant, J. D., Barry, D. T., Cutter, C. J., Joy, M. T., Dinh, A., Schottenfeld, R. S., & Fiellin, D. A. (2013). Prevalence of mood and substance use disorders among patients seeking primary care offce-based buprenorphine/ naloxone treatment. Drug and Alcohol Dependence, 127(1–3), 243–247. 55 Hassan, A. N., Howe, A. S., Samokhvalov, A. V., Le Foll, B., & George, T. P. (2017). Management of mood and anxiety disorders in patients receiving opioid agonist therapy: Review and meta-analysis. American Journal on Addictions, 26(6), 551–563. 56 Hall, W. D., & Strang, J. (2017). Alcohol problems need more attention in patients receiving long-term opioid substitution therapy. Lancet Psychiatry, 4(4), 265–266. 57 Saitz, R. (2014). Medical and surgical complications of addiction. In R. K. Ries, D. A. Fiellin, S. C. Miller, & R. Saitz (Eds.), The ASAM principles of addiction medicine (5th ed.). Philadelphia, PA: Wolters Kluwer. 58 Soper, R. G. (2014, October 6). Intimate partner violence and co-occurring substance abuse/addiction. ASAM Magazine. Retrieved October 16, 2017, from www.asam. org/magazine/read/article/2014/10/06 /intimate-partner-violence-and-co-occurring-substance -abuse-addiction 59 Stone, A. L., Becker, L. G., Huber, A. M., & Catalano, R. F. (2012). Review of risk and protective factors of substance use and problem use in emerging adulthood. Addictive Behaviors, 37(7), 747–775. 60 American Society of Addiction Medicine. (2017). The ASAM appropriate use of drug testing in clinical addiction medicine. Rockville, MD: ASAM. Retrieved October 30, 2017, from www.asam.org/resources /guidelines-and-consensus-documents/drug-testing 61 Lynch, K. (2014). San Francisco General Hospital laboratory protocol. San Francisco, CA: San Francisco General Hospital. 62 Warner, E., & Lorch, E. (2014). Laboratory diagnosis. In R. K. Ries, D. A. Fiellin, S. C. Miller, & R. Saitz (Eds.), Principles of addiction medicine (5th ed., pp. 332–343). Philadelphia, PA: Wolters Kluwer. 63 Milone, M. C. (2012). Laboratory testing for prescription opioids. Journal of Medical Toxicology, 8(4), 408–416. 64 Reisfeld, G. M., Bertholf, R., Barkin, R. L., Webb, F., & Wilson, G. (2007). Urine drug test interpretation: What do physicians know? Journal of Opioid Management, 3(2), 80–86. 65 Standridge, J. B., Adams, S. M., & Zotos, A. P. (2010). Urine drug screening: A valuable offce procedure. American Family Physician, 81(5), 635–640. 66 Standridge, J. B., Adams, S. M., & Zotos, A. P. (2010). Urine drug screening: A valuable offce procedure. American Family Physician, 81(5), 635–640. 67 Substance Abuse and Mental Health Services Administration. (2018). Clinical guidance for treating pregnant and parenting women with opioid use disorder and their infants. HHS Publication No. (SMA) 18-5054. Rockville, MD: Substance Abuse and Mental Health Services Administration. 68 American College of Obstetricians and Gynecologists. (2017, August). Opioid use and opioid use disorder in pregnancy. 69 Ali, M. M., Dowd, N., Classen, T., Mutter, R., & Scott, P. (2017). Prescription drugs monitoring program, nonmedical use of prescription drug and heroin use: Evidence from the National Survey of Drug Use and Health. Addictive Behaviors, 69, 65–77. 70 American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Arlington, VA: American Psychiatric Publishing. 71 American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Arlington, VA: American Psychiatric Publishing. 72 Clinical Tools. (n.d.). DSM 5 opioid use disorder checklist. Retrieved October 16, 2017, from www.asam.org/docs/ default-source/education-docs/dsm-5-dx-oud-8-28-2017. pdf?sfvrsn=70540c2_2 73 American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Arlington, VA: American Psychiatric Publishing. 74 Mattick, R. P., Breen, C., Kimber, J., & Davoli, M. (2014). Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. Cochrane Database of Systematic Reviews, 2014(2), 1–84. 75 Mattick, R. P., Breen, C., Kimber, J., & Davoli, M. (2009). Methadone maintenance therapy versus no opioid replacement therapy for opioid dependence. Cochrane Database of Systematic Reviews, 2009(3), 1–19. 2-42 Medications for Opioid Use Disorder TIP 63 76 Minozzi, S., Amato, L., Vecchi, S., Davoli, M., Kirchmayer, U., & Verster, A. (2011). Oral naltrexone maintenance treatment for opioid dependence. Cochrane Database of Systematic Reviews, 4, CD001333. 77 Krupitsky, E., Zvartau, E., Blokhina, E., Verbitskaya, E., Wahlgren, V., Tsoy-Podosenin, M., … Woody, G. E. (2012). Randomized trial of long-acting sustained-release naltrexone implant vs oral naltrexone or placebo for preventing relapse to opioid dependence. Archives of General Psychiatry, 69(9), 973–981. 78 Lee, J. D., Friedmann, P. D., Kinlock, T. W., Nunes, E. V., Boney, T. Y., Hoskinson, R. A., Jr., … O’Brien, C. P. (2016). Extended-release naltrexone to prevent opioid relapse in criminal justice offenders. New England Journal of Medicine, 374(13), 1232–1242. 79 McCarty, D., Braude, L., Lyman, D. R., Dougherty, R. H., Daniels, A. S., Ghose, S. S., & Delphin-Rittmon, M. E. (2014). Substance abuse intensive outpatient programs: Assessing the evidence. Psychiatric Services, 65(6), 718–726. 80 Mee-Lee, D., Shulman, G. D., Fishman, M. J., Gastfriend, D. R., & Miller, M. M. (Eds.). (2013). The ASAM criteria: Treatment criteria for addictive, substance-related, and co-occurring conditions (3rd ed.). Carson City, NV: The Change Companies. 81 Drug Enforcement Administration. (n.d.). Informational documents. Retrieved November 21, 2017, from www.deadiversion.usdoj.gov/pubs/docs/index.html 82 Carroll, K. M., & Weiss, R. D. (2016). The role of behavioral interventions in buprenorphine maintenance treatment: A review. American Journal of Psychiatry, 174(8), 738–774. 83 Fiellin, D. A., Barry, D. T., Sullivan, L. E., Cutter, C. J., Moore, B. A., O’Connor, P. G., & Schottenfeld, R. S. (2013). A randomized trial of cognitive behavioral therapy in primary care-based buprenorphine. American Journal of Medicine, 126(1), 74.e11–74.e77. 84 Fiellin, D. A., Barry, D. T., Sullivan, L. E., Cutter, C. J., Moore, B. A., O’Connor, P. G., & Schottenfeld, R. S. (2013). A randomized trial of cognitive behavioral therapy in primary care-based buprenorphine. American Journal of Medicine, 126(1), 74.e11–74.e77. 85 Ling, W., Hillhouse, M., Ang, A., Jenkins, J., & Fahey, J. (2013). Comparison of behavioral treatment conditions in buprenorphine maintenance. Addiction, 108(10), 1788–1798. 86 Weiss, R. D., Potter, J. S., Fiellin, D. A., Byrne, M., Connery, H. S., Dickinson, W., … Ling, W. (2011). Adjunctive counseling during brief and extended buprenorphine-naloxone treatment for prescription opioid dependence: A 2-phase randomized controlled trial. Archives of General Psychiatry, 68(12), 1238–1246. 87 Pettinati, H. M., O’Brien, C. P., & Dundon, W. D. (2013). Current status of co-occurring mood and substance use disorders: A new therapeutic target. American Journal of Psychiatry, 170(1), 23–30. 88 Chou, R., Korthuis, P. T., Weimer, M., Bougatsos, C., Blazina, I., Zakher, B., … McCarty, D. (2016). Medication-assisted treatment models of care for opioid use disorder in primary care settings. Technical Brief No. 28. Rockville, MD: Agency for Healthcare Research and Quality. 89 Department of Health and Human Services. (2021, April 28). Practice guidelines for the administration of buprenorphine for treating opioid use disorder. HHS Notice, 86 Fed. Reg. 22439. Retrieved May 21, 2021, from www.federalregister.gov/ documents/2021/04/28/2021-08961/practice-guidelines- for-the-administration-of-buprenorphine-for-treating- opioid-use-disorder#:~:text=The%20Practice%20 Guidelines%20for%20the%20Administration%20of%20 Buprenorphine,training%2C%20counseling%20and%20 other%20ancillary%20services%20%28i.e%20 90 Department of Health and Human Services. (2021, April 28). Practice guidelines for the administration of buprenorphine for treating opioid use disorder. HHS Notice, 86 Fed. Reg. 22439. Retrieved May 21, 2021, from www.federalregister.gov/ documents/2021/04/28/2021-08961/practice-guidelines- for-the-administration-of-buprenorphine-for-treating- opioid-use-disorder#:~:text=The%20Practice%20 Guidelines%20for%20the%20Administration%20 of%20Buprenorphine,counseling%20and%20other%20 ancillary%20services%20%28i.e.%2C%20psychosocial%20 services%29 91 Substance Abuse and Mental Health Services Administration. (n.d.). Apply for a Practitioner Waiver [Webpage]. Retrieved February 14, 2020, from www.samhsa.gov/medication-assisted-treatment/ training-materials-resources/apply-for-practitioner-waiver 92 Department of Health and Human Services. (2021, April 28). Practice guidelines for the administration of buprenorphine for treating opioid use disorder. HHS Notice, 86 Fed. Reg. 22439. Retrieved May 21, 2021, from www.federalregister.gov/ documents/2021/04/28/2021-08961/practice-guidelines- for-the-administration-of-buprenorphine-for-treating- opioid-use-disorder#:~:text=The%20Practice%20 Guidelines%20for%20the%20Administration%20 of%20Buprenorphine,counseling%20and%20other%20 ancillary%20services%20%28i.e.%2C%20psychosocial%20 services%29 93 Bogdanowicz, K. M., Stewart, R., Broadbent, M., Hatch, S. L., Hotopf, M., Strang, J., & Hayes, R. D. (2015). Double trouble: Psychiatric comorbidity and opioid addiction— All-cause and cause-specifc mortality. Drug and Alcohol Dependence, 148, 85–92. 2-43 TIP 63Part 2 of 5—Addressing Opioid Use Disorder in General Medical Settings 94 Bogdanowicz, K. M., Stewart, R., Chang, C. K., Downs, J., Khondoker, M., Shetty, H., … Hayes, R. D. (2016). Identifying mortality risks in patients with opioid use disorder using brief screening assessment: Secondary mental health clinical records analysis. Drug and Alcohol Dependence, 164, 82–88. 95 Department of Health and Human Services. (2016). The opioid epidemic: By the numbers. Washington, DC: Department of Health and Human Services. 96 Substance Abuse and Mental Health Services Administration. (2016). SAMHSA opioid overdose prevention toolkit. HHS Publication No. (SMA) 16-4742. Rockville, MD: Author. 97 Centers for Disease Control and Prevention, National Center for Health Statistics. (2020). Multiple Cause of Death 2018-2019 on CDC WONDER Online Database, released in 2020. Retrieved April 29, 2021, from https:// wonder.cdc.gov/mcd.html 98 Scholl, L., Seth, P., Kariisa, M., Wilson, N., & Baldwin, G. (2019). Drug and opioid-involved overdose deaths— United States, 2013–2017. Morbidity and Mortality Weekly Report, 67(5152), 1419. 99 Centers for Disease Control and Prevention, National Center for Health Statistics. (2020). Multiple Cause of Death 2018–2019 on CDC WONDER Online Database, released in 2020. Retrieved April 29, 2021, from https:// wonder.cdc.gov/mcd.html 100Centers for Disease Control and Prevention. (2016). Increases in drug and opioid-involved overdose deaths— United States, 2010–2015. Morbidity and Mortality Weekly Report, 65(50–51), 1445–1452. 101Albert, S., Brason, F. W., II, Sanford, C. K., Dasgupta, N., Graham, J., & Lovette, B. (2011). Project Lazarus: Community-based overdose prevention in rural North Carolina. Pain Medicine, 12(Suppl. 2), S77–S85. 102Walley, A. Y., Xuan, Z., Hackman, H. H., Quinn, E., Doe-Simkins, M., Sorensen-Alawad, A., … Ozonoff, A. (2013). Opioid overdose rates and implementation of overdose education and nasal naloxone distribution in Massachusetts: Interrupted time series analysis. British Medical Journal, 346, f174. 103Bush, K., Kivlahan, D. R., McDonell, M. B., Fihn, S. D., & Bradley, K. A. (1998). The AUDIT alcohol consumption questions (AUDIT-C): An effective brief screening test for problem drinking. Ambulatory Care Quality Improvement Project (ACQUIP). Alcohol Use Disorders Identifcation Test. Archives of Internal Medicine, 158(16), 1789–1795. 104Skinner, H. A. (1982). The Drug Abuse Screening Test. Addictive Behavior, 7(4), 363–371. 105Yudko, E., Lozhkina, O., & Fouts, A. (2007). A comprehensive review of the psychometric properties of the Drug Abuse Screening Test. Journal of Substance Abuse Treatment, 32, 189–198. 106American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed., p. 541). Arlington, VA: American Psychiatric Publishing. 107McNeely, J., Wu, L. T., Subramaniam, G., Sharma, G., Cathers, L. A., Svikis, D., … Schwartz, R. P. (2016). Performance of the Tobacco, Alcohol, Prescription Medication, and Other Substance Use (TAPS) Tool for substance use screening in primary care patients. Annals of Internal Medicine, 165(10), 690–699. This page intentionally left blank. MEDICATIONS FOR OPIOID USE DISORDERTIP 63 Substance Abuse and Mental Health Services Administration Part 3: Medications for Opioid Use Disorder For Healthcare Professionals Part 3 of this Treatment Improvement Protocol (TIP) describes general principles of opioid use disorder (OUD) medication and discusses medication formulations, indications, and dosing for the three medications used to treat OUD—methadone, naltrexone, and buprenorphine. TIP Navigation Executive Summary For healthcare and addiction professionals, policymakers, patients, and families Part 1: Introduction to Medications for Opioid Use Disorder Treatment For healthcare and addiction professionals, policymakers, patients, and families Part 2: Addressing Opioid Use Disorder in General Medical Settings For healthcare professionals Part 3: Medications for Opioid Use Disorder For healthcare professionals Part 4: Bringing Together Addiction Treatment Counselors, Clients, and Healthcare Professionals For healthcare and addiction professionals Part 5: Resources Related to Medications for Opioid Use Disorder For healthcare and addiction professionals, policymakers, patients, and families KEY MESSAGES • OUD medications are safe and effective when used appropriately. • OUD medications can help patients reduce or stop illicit opioid use and improve their health and functioning. • Medication should be considered for all patients with OUD. Reserve opioid pharmacotherapies for those with moderate-to-severe OUD with physical dependence. • Patients with OUD should be informed of the risks and benefts of medication, treatment without medication, and no treatment. • Patients should be advised on where and how to get treatment with OUD medication. • Doses and schedules of medication for OUD must be individualized. 3-ii TIP 63 MEDICATIONS FOR OPIOID USE DISORDER—Part 3 of 5 Contents MEDICATIONS FOR OPIOID USE DISORDER 3-1 Scope of the Problem 3-1 CHAPTER 3A: OVERVIEW OF MEDICATIONS FOR OPIOID USE DISORDER 3-5 Introduction to Medications That Address OUD 3-8 Methadone 3-8 Naltrexone 3-8 Buprenorphine 3-9 Choosing an OUD Medication 3-10 Comparative Efectiveness 3-11 Duration of Medication 3-11 Principles of OUD Medications 3-11 Basic Function 3-11 Intrinsic Activity 3-13 Overview of Medication Indications and Dosing 3-13 CHAPTER 3B: METHADONE 3-17 Formulations 3-17 Pharmacology 3-17 Bioavailability 3-18 Dosing Considerations 3-18 Contraindications 3-18 Precautions and Warnings 3-18 Drug Interactions 3-22 Side Efects 3-25 Assessment 3-25 Patient Selection 3-27 Informed Consent 3-27 Initiating Methadone Treatment 3-29 Day 1 3-29 Dose Titration (Weeks 1 to 2) 3-30 Dose Titration (Weeks 3 to 4) 3-31 Serum Levels 3-31 Dose Stabilization (Week 5 and Beyond) 3-32 Take-Home Medication 3-32 3-iii TIP 63MEDICATIONS FOR OPIOID USE DISORDER—Part 3 of 5 Duration of Methadone Treatment 3-33 Dose Tapering and Methadone Discontinuation 3-34 Methadone Dosing Summary 3-35 Enhancing Access to OUD Medication in OTPs 3-35 Chapter 3B Appendix 3-36 Sample Standard Consent to Opioid Maintenance Treatment Form for OTPs 3-36 CHAPTER 3C: NALTREXONE 3-37 Formulations 3-37 Pharmacology 3-38 Bioavailability 3-38 Dosing Considerations 3-38 XR-NTX 3-38 Patient Selection 3-46 Oral Naltrexone 3-46 Naltrexone Dosing Summary 3-47 XR-NTX 3-47 Oral Naltrexone 3-47 Chapter 3C Appendix 3-48 Sample XR-NTX Treatment Agreement 3-48 Patient Counseling Tool for XR-NTX 3-49 Key Techniques for Reducing Injection Site Reactions 3-50 CHAPTER 3D: BUPRENORPHINE 3-51 Formulations 3-51 History of Approvals 3-51 Implants 3-52 Injectables 3-53 Pharmacology 3-53 Bioavailability 3-53 Metabolism and Excretion 3-54 Dosing Considerations 3-54 Contraindications 3-54 Precautions and Warnings 3-54 Drug Interactions 3-57 Side Efects 3-60 Assessment 3-60 Patient Selection 3-62 Informed Consent 3-62 3-iv TIP 63 MEDICATIONS FOR OPIOID USE DISORDER—Part 3 of 5 Initiating Buprenorphine Treatment 3-63 Ofce-Based Induction 3-63 Home Induction 3-63 Induction 3-64 Dose Stabilization 3-65 Risk Evaluation and Mitigation Strategy 3-67 Transmucosal Buprenorphine Dosing Summary 3-67 Initiation of Buprenorphine Implants 3-68 Initiation of Buprenorphine Extended-Release Injection 3-69 Duration of Buprenorphine Treatment 3-70 Successful Buprenorphine Treatment 3-70 Dose Tapering and Buprenorphine Discontinuation 3-71 Chapter 3D Appendix 3-73 Buprenorphine Induction and Maintenance Appropriate Use Checklists 3-73 Sample Goal Sheet and Coping Strategies Form 3-75 Sample Goal-Setting Form 3-76 Buprenorphine/Naloxone Home Dosage Schedule: Films or Tablets 3-77 Buprenorphine Treatment Agreement 3-78 Patient Urine Drug Screen and Medication Count Monitoring Form 3-80 Pharmacy Tablet/Film Count Form 3-81 CHAPTER 3E: MEDICAL MANAGEMENT STRATEGIES FOR PATIENTS TAKING OUD MEDICATIONS IN OFFICE-BASED SETTINGS 3-83 Patient Selection 3-83 Patient Management and Treatment Monitoring 3-84 Course of Treatment 3-85 Role of the Treatment Plan and Treatment Agreement in Medical Management 3-86 Medical Management Strategies 3-86 Administrative Considerations 3-93 Patient Limits 3-93 Diversion Control Policies for OBOT With Buprenorphine 3-94 Storage of Buprenorphine 3-95 Records for Dispensers 3-96 DEA Inspections 3-96 Emergency Protocols and Patient Safety Measures 3-96 Recommendations for Staf Member Training 3-97 Chapter 3E Appendix 3-98 Sample Goal-Setting Form 3-98 Sample Medical Management Visit Form 3-99 Sample Buprenorphine Diversion Control Policy 3-100 3-v TIP 63MEDICATIONS FOR OPIOID USE DISORDER—Part 3 of 5 CHAPTER 3F: MEDICAL MANAGEMENT OF PATIENTS TAKING OUD MEDICATIONS IN HOSPITAL SETTINGS 3-103 Hospitalized or ED Patients Taking Medication for OUD 3-103 Pain Management 3-103 Buprenorphine 3-104 Methadone 3-105 Naltrexone 3-106 Hospitalized or ED Patients Not Taking Medication for OUD 3-106 Buprenorphine Induction in the Hospital Setting 3-106 Methadone Induction in the Hospital Setting 3-107 Naltrexone Induction in the Hospital Setting 3-108 Medical Management Plan 3-108 Notes 3-109 This page intentionally left blank. 3-1 MEDICATIONS FOR OPIOID USE DISORDERTIP 63 PART 3 of 5 Medications for Opioid Use Disorder Part 3 of this TIP describes general principles of OUD medication and discusses medication for- mulations, indications, and dosing for the three Food and Drug Administration (FDA)-approved medications used to treat OUD—methadone, naltrexone, and buprenorphine. Part 3 also discusses patient management and monitoring in outpatient settings other than opioid treatment programs (OTPs) as well as medical management of patients with OUD in hospital settings. Scope of the Problem The United States is experiencing an opioid addiction epidemic.1 In 2019, an estimated 1.6 million people aged 12 or older had OUD in the United States.2 Illicit opioid use contributes to the development of OUD, the spread of HIV and hepatitis infections, and increasing numbers of overdose deaths. OUD is a set of cognitive, behavioral, and physiological symptoms marked by an inability to stop opioid use despite negative consequences.3 When severe, it can present as a chronic, recurring condition with compulsive opioid use that is often termed “addiction.” It can cause serious physical and mental health, employment, legal, and family problems. Each FDA-approved medication used to treat OUD can help patients achieve remission and begin or maintain recovery. Medication O P I O I D - R E L AT E D EMERGENCY DEPARTMENT visits more than tripled from 2005 to 2017.4,5 for OUD should be accompanied by individually tailored medical management and psychosocial and recovery support services as needed and wanted by patients to support their remission and recovery. Medication supports the efforts of the individual to achieve lasting recovery. Exhibit 3.1 defnes key terms in Part 3. For more defnitions, see the glossary in Part 5 of this TIP. NOTE TO HEALTHCARE PROFESSIONALS This TIP cannot replace sound clinical judgment and shared decision making based on careful patient assessment. Providers should familiarize themselves with FDA labeling of all OUD medications and current practices standards described here and in other resources such as the Providers’ Clinical Support System (https://pcssnow.org/resources/ resource-category/clinical-resources/). 3-2 Medications for Opioid Use Disorder TIP 63 EXHIBIT 3.1. Key Terms Addiction: As defned by the American Society of Addiction Medicine,6 “a primary, chronic disease of brain reward, motivation, memory, and related circuitry.” It is characterized by inability to consistently abstain, impairment in behavioral control, craving, diminished recognition of signifcant problems with one’s behaviors and interpersonal relationships, and a dysfunctional emotional response. Like other chronic diseases, addiction often involves cycles of relapse and remission. The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition,7 does not use the term for diagnostic purposes, but it commonly describes the more severe forms of OUD. Induction: Process of initial dosing with medication for OUD treatment until the patient reaches a state of stability; also called initiation. Maintenance treatment: Providing medications to achieve and sustain clinical remission of signs and symptoms of OUD and support the individual process of recovery without a specifc endpoint (as is the typical standard of care in medical and psychiatric treatment of other chronic illnesses). Medically supervised withdrawal (formerly called detoxifcation): Using an opioid agonist (or an alpha-2 adrenergic agonist if opioid agonist is not available) in tapering doses or other medications to help a patient discontinue illicit or prescription opioids. Medical management: Process whereby healthcare professionals provide medication, basic brief supportive counseling, monitoring of drug use and medication adherence, and referrals, when necessary, to addiction counseling and other services to address the patient’s medical, mental health, comorbid addiction, and psychosocial needs. Offce-based opioid treatment: Providing medication for OUD in outpatient settings other than certifed OTPs. Opioid treatment program (OTP): An accredited treatment program with Substance Abuse and Mental Health Services Administration certifcation and Drug Enforcement Administration registration to administer and dispense opioid agonist medications that are approved by FDA to treat opioid addiction. Currently, these include methadone and buprenorphine products. Other pharmacotherapies, such as naltrexone, may be provided but are not subject to these regulations. OTPs must provide adequate medical, counseling, vocational, educational, and other assessment and treatment services either onsite or by referral to an outside agency or practitioner through a formal agreement.8 Key Terms Related to OUD Medication Pharmacology Abuse liability: The likelihood that a medication with central nervous system activity will cause desirable psychological effects, such as euphoria or mood changes, that promote the medication’s misuse. Bioavailability: Proportion of medication administered that reaches the bloodstream. Cross-tolerance: Potential for people tolerant to one opioid (e.g., heroin) to be tolerant to another (e.g., methadone). Dissociation: Rate at which a drug uncouples from the receptor. A drug with a longer dissociation rate will have a longer duration of action than a drug with a shorter dissociation rate. Half-life: Rate of removal of a drug from the body. One half-life removes 50 percent from the plasma. After a drug is stopped, it takes fve half-lives to remove about 95 percent from the plasma. If a drug is continued at the same dose, its plasma level will continue to rise until it reaches steady-state concentrations after about fve half-lives. Continued on next page 3-3 TIP 63Part 3 of 5—Medications for Opioid Use Disorder EXHIBIT 3.1. Key Terms (continued) Intrinsic activity: The degree of receptor activation attributable to drug binding. Full agonist, partial agonist, and antagonist are terms that describe the intrinsic activity of a drug. Opiates: A subclass of opioids derived from opium (e.g., morphine, codeine, thebaine). Opioid blockade: Blunting or blocking of the euphoric effects of an opioid through opioid receptor occupancy by an opioid agonist (e.g., methadone, buprenorphine) or antagonist (e.g., naltrexone). Opioid receptor agonist: A substance that has an affnity for and stimulates physiological activity at cell receptors in the nervous system that are normally stimulated by opioids. Mu-opioid receptor full agonists (e.g., methadone) bind to the mu-opioid receptor and produce actions similar to those produced by the endogenous opioid beta-endorphin. Increasing the dose increases the effect. Mu-opioid receptor partial agonists (e.g., buprenorphine) bind to the mu-opioid receptor. Unlike with full agonists, increasing their dose in an opioid-tolerant individual may not produce additional effects once they have reached their maximal effect. At low doses, partial agonists may produce effects similar to those of full agonists. Methadone and buprenorphine can blunt or block the effects of exogenously administered opioids. Opioid receptor antagonist: A substance that has an affnity for opioid receptors in the central nervous system without producing the physiological effects of opioid agonists. Mu-opioid receptor antagonists (e.g., naltrexone) can block the effects of exogenously administered opioids. Opioids: All natural, synthetic, and semisynthetic substances that have effects similar to morphine. They can be used as medications having such effects (e.g., methadone, buprenorphine, oxycodone). Receptor affnity: Strength of the bond between a medication and its receptor. A medication with high mu-opioid receptor affnity requires lower concentrations to occupy the same number of mu-opioid receptors as a drug with lower mu-opioid receptor affnity. Drugs with high mu-opioid receptor affnity may displace drugs with lower affnity. This page intentionally left blank. 3-5 TIP 63Part 3 of 5—Medications for Opioid Use Disorder Chapter 3A: Overview of Medications for Opioid Use Disorder Chapter 3A describes general principles of OUD medication and summarizes formulations, indications, and dosing for the three FDA-approved OUD medications. There are three FDA-approved medications used to treat OUD: the mu-opioid receptor partial agonist buprenorphine, the mu-opioid receptor full agonist methadone, and the mu-opioid receptor antagonist naltrexone. Discussing medications that can treat OUD with patients who have this disorder is the clinical standard of care and should cover at least: • The proven effectiveness of methadone, naltrexone, and buprenorphine compared with placebo and with outpatient counseling without medication. • Risks and benefts of treatment with all three types of medication, treatment without medi- cation, and no treatment. • Safety and effectiveness of the medications when used appropriately. • Pharmacologic properties, routes of ad- ministration, and where and how to access treatment with each medication (Exhibit 3A.1). 3-6 Medications for Opioid Use Disorder TIP 63 EXHIBIT 3A.1. OUD Medications: An Overview9,10 CATEGORY BUPRENORPHINE* METHADONE XR-NTX** TRANSMUCOSAL DEPOT Appropriate Typically for Typically for patients Typically for Typically for patients patients with for whom diversion or patients with patients with OUD who are safe medication storage OUD who are OUD who have physiologically are concerns or for physiologically abstained from dependent on patients who must travel dependent on short-acting opioids. large distances to the opioids and who opioids for at least prescriber. meet federal 7–10 days and long- criteria for OTP acting opioids for at admission. least 10–14 days. Pharmacology Opioid receptor partial agonist Reduces opioid withdrawal and craving; blunts or blocks euphoric effects of self- administered illicit opioids through cross- tolerance and opioid receptor occupancy. Opioid receptor partial agonist Reduces opioid withdrawal and craving; blunts or blocks euphoric effects of self-administered illicit opioids through cross- tolerance and opioid receptor occupancy. Note: Patients receiving a depot formulation of buprenorphine must be inducted onto buprenorphine using a transmucosal product. Opioid receptor agonist Reduces opioid withdrawal and craving; blunts or blocks euphoric effects of self- administered illicit opioids through cross- tolerance and opioid receptor occupancy. Opioid receptor antagonist Blocks euphoric effects of self- administered illicit opioids through opioid receptor occupancy. Causes no opioid effects. Reduces opioid craving. Patient Tell patients: Tell patients: Tell patients: Tell patients: education • That they • For implantable rods • That their dose • That they will will need to (Probuphine®), they will start low need to be opioid be in opioid will need to be stable and build up free for at least withdrawal to on no more than slowly to avoid 7–10 days for receive their frst 8 mg of transmucosal oversedation; short-acting dose to avoid Suboxone or generic it takes several opioids and at buprenorphine- equivalents. days for a given least 10–14 days precipitated opioid withdrawal. • About the risk of overdose with concurrent benzodiazepine or alcohol use, with injecting buprenorphine, • For subcutaneous injection (Sublocade®), they must frst be on a transmucosal form of buprenorphine for at least 7 days at a dose equivalent to 8 to 24 mg of buprenorphine. dose to have its full effect. • About overdose risk in the frst 2 weeks of treatment, especially with concurrent benzodiazepine or alcohol for long-acting opioids before their frst dose of extended-release naltrexone (XR- NTX) to avoid precipitated withdrawal (which may require hospitalization). and after use, and after • About the risk of stopping the stopping the overdose after medication. medication. stopping the medication. Continued on next page 3-7 TIP 63Part 3 of 5—Medications for Opioid Use Disorder EXHIBIT 3A.1. OUD Medications: An Overview (continued) CATEGORY BUPRENORPHINE* METHADONE XR-NTX** TRANSMUCOSAL DEPOT Administration Daily (or off-label less-than-daily dosing regimens) administration of sublingual or buccal tablet or flm. Subdermal implants every 6 months, for up to 1 year, for stable patients. Monthly subcutaneous injection of Subdermal implants every 6 months, for up to 1 year, for stable patients. Monthly subcutaneous injection of extended- release formulation in abdominal region for patients treated with transmucosal buprenorphine for at least 1 week. Daily oral administration as liquid concentrate, tablet, or oral solution from dispersible tablet or powder (unless patients can take some home). Every 4 weeks or once-per-month intramuscular injection. extended-release formulation in abdominal region for patients treated with transmucosal buprenorphine for at least 1 week. Prescribing Physicians, nurse practitioners (NPs), and physician assistants (PAs) need a waiver to prescribe. Until October 1, 2023, qualifed clinical nurse specialists, certifed registered nurse anesthetists, and certifed nurse Prescribers must have a waiver (as for transmucosal buprenorphine) and complete the product’s REMS program. Providers of the implantable rods must complete additional training in their insertion and removal. SAMHSA-certifed OTPs can provide methadone for daily onsite administration or at-home self- administration for stable patients. Physicians, NPs, PAs, and, until October 1, 2023, clinical nurse specialists, certifed registered nurse anesthetists, and certifed nurse midwives can prescribe or order administration by qualifed midwives also can obtain a waiver to prescribe. Any pharmacy can fll a prescription for sublingual or buccal formulations. OTPs can administer/ dispense by OTP physician order without a waiver. Both the implantable rods and subdermal injections are available via restricted distribution programs and are not available in retail pharmacies. OTPs can be providers of depot formulations of buprenorphine, provided the above criteria are satisfed. healthcare professionals. *Long-acting buprenorphine implants (every 6 months) for patients on a stable dose of buprenorphine are also available through implanters and prescribers with additional training and certifcation through the Probuphine Risk Evaluation and Mitigation Strategy (REMS) Program. Extended-release buprenorphine monthly subcutaneous injections are available only through prescribers and pharmacies registered with the Sublocade REMS Program. **Naltrexone hydrochloride tablets (50 mg each) are also available for daily oral dosing but have not been shown to be more effective than treatment without medication or placebo because of poor patient adherence. 3-8 Medications for Opioid Use Disorder TIP 63 Introduction to Medications That Address OUD Methadone Methadone is the most used and most studied OUD medication in the world.11,12 The World Health Organization (WHO) considers it an essential medication.13 Many clinical trials and me- ta-analyses have shown that it effectively reduces illicit opioid use, treats OUD, and retains patients in treatment better than placebo or no medica- tion.14,15,16 (Part 1 of this Treatment Improvement Protocol [TIP] further covers methadone’s effcacy.) In the United States, roughly 1,500 federally certifed opioid treatment programs (OTPs) offer methadone for OUD. Increasingly, they also offer buprenorphine, and some provide XR-NTX. Core OTP services include medical oversight of treatment, direct observation of dose administra- tion, take-home dose dispensing under certain conditions, counseling, and drug testing. Some OTPs provide other services, including mental health and primary care, HIV and hepatitis C virus care, and recovery support. Even so, signifcant demand remains for better integration and coordination of care among OTPs, primary care services, and mental health services to treat the range of needs common in people with OUD.17 Coordination is especially important for people with co-occurring medical, mental, and substance use disorders, who need multiple services and face challenges in treatment access and adherence. Naltrexone XR-NTX has demonstrated effcacy in reducing return to illicit opioid use, increasing treatment retention, and reducing opioid craving compared with placebo or no medication Although only OTPs can administer or dispense methadone for OUD, all healthcare professionals and addiction and mental health counselors should be familiar with methadone. Their patients may be enrolled in or need referral to OTPs. RESOURCE ALERT Substance Abuse and Mental Health Services Administration (SAMHSA) Federal Guidelines for OTPs Federal Guidelines for Opioid Treatment Programs offers guidance on how to satisfy federal OTP regulations (https://store.samhsa. gov/product/Federal-Guidelines-for-Opioid- Treatment-Programs/PEP15-FEDGUIDEOTP). in randomized controlled trials.18,19,20 (See Part 1 for more information on XR-NTX’s effcacy in OUD treatment.) Because the injectable form was approved more recently by FDA than methadone and buprenorphine, XR-NTX has been less studied than those medications. Physicians, NPs, and, PAs, and, until October 1, 2023, clinical nurse specialists, certifed registered nurse anesthetists, and certifed nurse midwives may prescribe or order XR-NTX for administration by qualifed staff members without additional waiver requirements. XR-NTX initiated prior to release from controlled environments (e.g., jails, prisons, residential rehabilitation programs) may be useful in preventing return to opioid use after release.21 These settings are typically associated with extended periods of opioid abstinence, so maintaining abstinence for suffcient time to start naltrexone is less challenging than initiating it among outpatients in the community. Short-term pilot studies show that offering XR-NTX under these circumstances can increase treatment engagement after release.22,23 The oral formulation of naltrexone is not widely used to treat OUD because of low rates of patient acceptance and high rates of non- adherence leading to a lack of effcacy.24 However, consideration should be given to its use in situations where adherence can be ensured, such as with observed daily dosing. Naltrexone is also FDA approved for the treatment of alcohol use disorder and therefore may be useful for patients with both OUD and alcohol use disorder. 3-9 TIP 63Part 3 of 5—Medications for Opioid Use Disorder RESOURCE ALERT SAMHSA Brief Guide on the Use of XR-NTX SAMHSA’s Clinical Use of Extended-Release Injectable Naltrexone in the Treatment of Opioid Use Disorder: A Brief Guide offers guidance on the use of XR-NTX and is available online (https://store.samhsa.gov/product /Clinical-Use-of-Extended-Release-Injectable -Naltrexone-in-the-Treatment-of-Opioid-Use -Disorder-A-Brief-Guide/SMA14-4892R). Buprenorphine Buprenorphine is effective in retaining patients in treatment and reducing illicit opioid use, as demonstrated by many clinical trials comparing buprenorphine with placebo or no medication.25 Buprenorphine treatment is available throughout the world. WHO includes it in its list of essential medicines.26 (See Part 1 for more information on buprenorphine’s effcacy in OUD treatment.) Buprenorphine is a partial agonist with a ceiling effect on opioid activity. Hence, it is less likely than methadone and other full agonists to cause respiratory depression in an accidental overdose. This property contributed to the decision permitting buprenorphine to be prescribed to treat opioid dependence outside OTPs.27 That being said, lethal overdose with buprenorphine is possible in opioid-naïve individuals or when it is taken in combination with central nervous system depressants such as benzodiazepines or alcohol. Transmucosal buprenorphine is available by pre- scription through pharmacies, because the Drug Addiction Treatment Act of 2000 (DATA 2000) created an exception to the Controlled Substances Act to permit FDA schedule III, IV, and V med- ications approved to treat opioid dependence to be prescribed for that purpose outside OTPs. Buprenorphine, in various formulations, is the only medication to which DATA 2000 currently applies. Qualifying physicians, NPs, and PAs can prescribe buprenorphine if they receive special training, obtain a SAMHSA waiver under DATA 2000, and get a unique Drug Enforcement Administration registration number. Until October 1, 2023, clinical nurse specialists, certifed registered nurse anesthetists, and certifed nurse midwives also are waiver- eligible to prescribe buprenorphine. Additionally, providers who are state licensed and possess a valid Drug Enforcement Agency registration may be exempted from training requirements and the required attestation (about providing patients access to or referrals for psy- chosocial services) that are normally needed to obtain the X waiver.28 These providers are limited to treating no more than 30 patients. This has greatly increased the number and type of settings where medication for OUD is available and the number of patients in treatment. New settings include non-OTP outpatient addiction treatment programs, as well as general medical and mental health practices or clinics (offce-based opioid treatment). OTPs can also provide buprenorphine. In 2016, FDA approved buprenorphine implants (Probuphine) that last about 6 months for patients stabilized on sublingual or buccal formulations. Implants have been found to be more effective than placebo in reducing illicit opioid use among opioid-dependent patients receiving counseling.29 Implants are available in the same settings as other buprenorphine formulations but require waivered providers to receive specifc training from the manufacturer on insertion and removal per the FDA-approved REMS (www.accessdata. fda.gov/scripts/cder/rems/index.cfm?event= IndvRemsDetails.page&REMS=356). In 2017, FDA approved a monthly extended- release buprenorphine injectable formulation (Sublocade) for patients with moderate-to- severe OUD who had been initiated and treated with transmucosal buprenorphine for at least 7 days. The medication is for subcutaneous abdominal injection by a healthcare provider DATA 2000 restrictions currently apply only to buprenorphine used to treat OUD. They do not apply to pain treatment using buprenorphine formulations approved to treat pain. 3-10 Medications for Opioid Use Disorder TIP 63 RESOURCE ALERT How To Obtain a Waiver To Prescribe Buprenorphine • Learn how to qualify for a DATA 2000 physician waiver: www.samhsa.gov/medication-assisted- treatment/training-materials-resources/apply- for-practitioner-waiver • Learn how to qualify for an NP, PA, clinical nurse specialist, certifed registered nurse anesthetist, or certifed nurse midwife waiver: www.samhsa.gov/medication-assisted- treatment/training-materials-resources/apply- for-practitioner-waiver • Learn how providers may be exempted from training and psychosocial service attestation requirements usually needed for obtaining the X waiver: www.federalregister. gov/documents/2021/04/28/2021-08961/ practice-guidelines-for-the-administration- of-buprenorphine-for-treating-opioid-use- disorder. Also review SAMHSA’s “FAQs About the New Buprenorphine Practice Guidelines” at www.samhsa.gov/medication-assisted- treatment/practitioner-resources/faqs • Learn how waivered practitioners can increase their patient limit from 30 to 100, and then to 275 patients: www.samhsa.gov/ medication-assisted-treatment/training- materials-resources/apply-for-practitioner- waiver Choosing an OUD Medication Currently, no empirical data indicate which patients will respond better to which OUD medications. All patients considering treatment should be educated about the effectiveness, risks, and benefts of each of the three OUD medi- cations, treatment without medication, and no treatment. Emphasize that OUD medications are safe and effective when used appropriately, and point out that these medications can help patients reduce or stop illicit opioid use and improve their health and functioning. Tailor decisions to patients’ medical, psychiatric, and substance use histories; to their preferences; and to treatment availability when deciding which medication and treatment to provide. Consider: • Patients’ prior response to a medication. • The medication’s side effect profle. • The strength of the published data on safety and effectiveness. • Patients’ use of other substances (e.g., naltrexone is also approved for the treatment of alcohol dependence). • Patients’ occupation. For patients in safety- sensitive occupations, consider XR-NTX. • Patients’ pregnancy status.* • Patients’ physical dependence on opioids. Patients not currently physically dependent on opioids who are returning to the community from a residential treatment program or incar- ceration should have the option of XR-NTX,30 and is intended to be available for ordering and dispensing (not by prescription to patients) in healthcare settings that receive special certifca- tion, pursuant to the FDA-approved REMS (www. accessdata.fda.gov/scripts/cder/rems/index. cfm?event=IndvRemsDetails.page&REMS=376). methadone, or buprenorphine based on which best suits their needs and circumstances (see below for special safety dosing considerations for methadone and buprenorphine in nontoler- ant patients).31,32,33,34 *Methadone or buprenorphine maintenance is recommended for OUD treatment during pregnancy,35 as these medications have better maternal and infant outcomes than no treatment or medically supervised withdrawal.36,37,38 Methadone and buprenorphine are not associated with birth defects and have minimal long-term neurodevelopmental impact on infants.39 However, neonatal abstinence syndrome can occur, which requires hospitalization.40 The American College of Obstetricians and Gynecologists notes that limited data exist on the safety and effectiveness of naltrexone in pregnancy.41 Starting naltrexone rather than opioid agonist treatment in pregnancy is not recommended, given the risk of precipitated withdrawal. An expert panel did not agree on whether women already receiving treatment with naltrexone at the onset of pregnancy should remain on that medication during pregnancy.42 Patients who were taking naltrexone before their pregnancy should weigh with their providers the risks regarding unknown potential harm to the developing fetus versus the potential benefts of continuing this medication during pregnancy.43 Pregnant patients who discontinue naltrexone and return to opioid use should be considered for methadone or buprenorphine treatment.44 3-11 TIP 63Part 3 of 5—Medications for Opioid Use Disorder • Patients’ preferences. Respect patients’ preferences for agonist versus antagonist medication. (See Part 2 of this TIP for an indepth discussion of treatment planning.) Comparative Efectiveness A Cochrane review of 5 randomized clinical trials with 788 participants found that, when provided at fexible doses on an outpatient basis, methadone retained patients in treatment longer than buprenorphine.45 That same review found that methadone and buprenorphine equally reduced illicit opioid use based on 8 studies with urine drug testing data from 1,027 participants and 4 studies with self-reported drug use from 501 participants. There is not yet a Cochrane review on the comparative effectiveness of XR-NTX and bu- prenorphine. However, in 2017, two randomized trials comparing buprenorphine to XR-NTX were published. A multisite study with 570 partici- pants in the United States compared initiating buprenorphine versus XR-NTX at 8 inpatient treatment programs.46 That study found that patients randomly assigned to start buprenor- phine had signifcantly lower return-to-use rates during 24 weeks of outpatient treatment compared with those patients assigned to start XR-NTX. This fnding was because of the known diffculty in successfully completing induction in the XR-NTX group. However, comparing only the subgroups of those participants who did start their assigned medication, there were no signifcant between-group differences in return- to-use rates. In a 12-week trial in Norway with 159 participants who were opioid abstinent at the time of random assignment, XR-NTX was found to be noninferior to buprenorphine in terms of treatment retention and illicit opioid use.47 There is no extant literature evaluating the comparative effectiveness of methadone, XR-NTX, buprenor- phine implant, or extended-release buprenor- phine injection to one another. Duration of Medication Continued treatment with buprenorphine or methadone is associated with better outcomes than medically supervised The TIP expert panel recommends offering maintenance therapy with medication, not short-term medically supervised withdrawal. The TIP expert panel also supports maintaining patients on OUD medication for years, decades, and even a lifetime if patients are benefting. withdrawal.48,49,50 Continued treatment with XR-NTX is associated with better outcomes than discontinuing XR-NTX.51 Patients should be informed of the risks and benefts of discontin- uing medication. Buprenorphine or methadone can be used for medically supervised withdrawal over a period of days to weeks (Exhibit 3A.2) for patients who prefer it to ongoing opioid agonist treatment. When opioid agonist med- ications are unavailable, the alpha2-adrenergic agonist clonidine can relieve some withdrawal symptoms, although clinical trials found it less effective.52 Pair medically supervised withdrawal with the chance to begin XR-NTX. Discontinuing medication increases risk of return to substance use and overdose death.53 Stable patients can continue on their selected OUD medication indefnitely as long as it is benefcial.54,55,56,57 During medically supervised withdrawal, ancillary medications can treat some of the withdrawal symptoms (Exhibit 3A.3). Principles of OUD Medications Basic Function Several factors underlie the development of addiction involving opioids and the diffculty people have in achieving and maintaining absti- nence from them. These factors include:58,59 • Short-term direct and indirect mu-opioid receptor agonist effects. • Neuroplastic changes in the brain. • Genetic, developmental, and environmental factors (e.g., exposure to high-risk environ- ments, effect of stress on the hypothalamic– pituitary–adrenal axis). 3-12 Medications for Opioid Use Disorder TIP 63 EXHIBIT 3A.2. Medically Supervised Withdrawal Using Buprenorphine or Methadone Medically supervised withdrawal using buprenorphine or methadone is appropriate when patients: • Prefer it to treatment without medications, after they have been told the risks and benefts of this approach compared with treatment with medications. • Wish to start XR-NTX, which is also FDA approved for the treatment of alcohol dependence. • Are entering a controlled environment or workplace that disallows opioid agonists. Data confict on the ideal duration of medically supervised withdrawal.60,61,62Even so, shorter term dose reductions alone (formerly, “detoxifcation”) are rarely effective.63,64,65 The TIP expert panel does not recommend short-term medically supervised withdrawal alone because of its high rates of return to illicit opioid use.66,67,68 If patients prefer this approach, it should be provided with psychosocial treatment.69 XR-NTX treatment should always be considered to reduce the likelihood of return to use after medically supervised withdrawal is completed and an adequate period of abstinence achieved,70 as well as to reduce the likelihood of overdose death upon a return to opioid use. If withdrawal is appropriate for the patient, the TIP expert panel recommends the following strategies: • Individualize supervised withdrawal duration per patient preference and response to lower medication doses. • Note that patients may beneft from nonopioid medication (e.g., clonidine, ondansetron, loperamide) or nonsteroidal anti-infammatory medications to manage withdrawal symptoms near the end of the taper. • Consider discontinuing dose reduction and increasing the dose if the patient begins to use illicit opioids. • Encourage patients to continue receiving counseling, monitoring, and other psychosocial support after medication discontinuation. • Urge patients to reenter treatment promptly if they return or think they may return to illicit opioid use. EXHIBIT 3A.3. Medications for Management of Opioid Withdrawal Symptoms SYMPTOM MEDICATION Nausea Ondansetron, metoclopramide (avoid promethazine; it potentiates opioids) Diarrhea Loperamide Anxiety, irritability, sweating Clonidine Insomnia Diphenhydramine, trazodone Pain Nonsteroidal anti-infammatory drugs 3-13 TIP 63Part 3 of 5—Medications for Opioid Use Disorder Methadone, buprenorphine, and naltrexone bind to the mu-opioid receptors in the central and peripheral nervous systems, gastrointestinal tract, and vascular system. In the brain, these receptors mediate opioids’ analgesic and other effects (e.g., euphoria, respiratory depression, meiosis).71,72,73 Through modulation of mu-opioid receptor activity in the brain, these medications exert therapeutic effcacy in treating OUD. Intrinsic Activity Intrinsic activity at the mu-opioid receptor varies based on whether the medication is a full agonist, partial agonist, or antagonist (Exhibit 3A.4). The amount of intrinsic activity corre- sponds to the amount of opioid receptor agonist effects. A full agonist exerts maximal effects at increasing doses. A partial agonist has a ceiling effect. Its opioid effects increase as the dose increases, but only up to a certain point. An antagonist binds to the opioid receptor but does not stimulate the receptor at all. Thus, it has no intrinsic activity regardless of its dose. Overview of Medication Indications and Dosing Healthcare professionals should consider med- ication for all patients with OUD. Prescribers must read FDA labels (i.e., package inserts) for the medications they prescribe. They must also evaluate patients clinically to determine the safety and effectiveness of the medication and dose. Exhibit 3A.4. Intrinsic Activity of OUD Medications74 100 90 80 70 60 50 40 30 20 10 0 -10 -9 -8 -7 -6 -5 -4 Full Agonist (Methadone) Partial Agonist (Buprenorphine) Antagonist (Naltrexone) In tr in si c A ct iv it y Log Dose of Opioid 3-14 Medications for Opioid Use Disorder TIP 63 Exhibit 3A.5 summarizes OUD medication formu- lations, indications, and dosing. • A review of the literature. • A review of national and international organizations’ guidelines. The dosing guidance in subsequent chapters for methadone (Chapter 3B), naltrexone (Chapter 3C), and buprenorphine (Chapter 3D) is for healthcare professionals in general medical and addiction treatment settings. This guidance is based on: • FDA-approved medication labels. • The TIP expert panel’s recommendations. EXHIBIT 3A.5. OUD Medications: Formulations75,76 GENERIC/ TRADE NAME FORMULATIONS ACTION AT THE RECEPTOR FDA INDICATIONS DOSING REGIMEN Methadone Orally as liquid Mu-opioid receptor Medically supervised Once daily (also (Methadose, concentrate, full agonist withdrawal and off-label dosing Dolophine) tablet, or oral solution of powder or dispersible tablet maintenance treatment of opioid dependence; additional formulations FDA approved for pain are not a focus of this TIP regimens if appropriate, such as split dose twice daily) Generic Sublingual tablet Mu-opioid receptor Treatment of opioid Once daily (also buprenorphine partial agonist dependence; additional alternative off-label monoproduct formulations FDA approved for pain are not a focus of this TIP regimens) Generic buprenorphine/ naloxone combination product Sublingual tablet, flm Mu-opioid receptor partial agonist combined with mu-opioid receptor antagonist; the latter is not absorbed sublingually Treatment of opioid dependence Once daily (also alternative off-label regimens) Buprenorphine/ Sublingual tablet Mu-opioid receptor Treatment of opioid Once daily (also naloxone partial agonist dependence alternative off-label (Zubsolv) combined with mu-opioid receptor antagonist; the latter is not absorbed sublingually regimens) Buprenorphine/ Buccal flm Mu-opioid receptor Treatment of opioid Once daily (also naloxone partial agonist dependence alternative off-label (Bunavail) combined with mu-opioid receptor antagonist; the latter is not absorbed sublingually regimens) Continued on next page 3-15 TIP 63Part 3 of 5—Medications for Opioid Use Disorder EXHIBIT 3A.5. OUD Medications: Formulations (continued) GENERIC/ TRADE NAME FORMULATIONS ACTION AT THE RECEPTOR FDA INDICATIONS DOSING REGIMEN Buprenorphine/ Sublingual flm; Mu-opioid receptor Treatment of opioid Once daily (also naloxone may also be partial agonist dependence alternative off-label (Suboxone) administered buccally combined with mu-opioid receptor antagonist; the latter is not absorbed sublingually regimens) Buprenorphine Implants Mu-opioid receptor Maintenance Implants last for (Probuphine) partial agonist treatment of opioid dependence in clinically stable patients taking 8 mg/day or less of Suboxone equivalents 6 months and are then removed, after which a second set can be inserted Extended- release injection buprenorphine (Sublocade) Subcutaneous injection in the abdominal region Mu-opioid receptor partial agonist Treatment of moderate-to-severe OUD among patients initiated and taking transmucosal buprenorphine for at least 7 days Monthly Oral naltrexone (Naltrexone hydrochloride) Oral tablet Mu-opioid receptor antagonist Block the effects of administered opioid agonists Once daily (also alternative off-label regimens) XR-NTX (Vivitrol) Intramuscular injection Mu-opioid receptor antagonist Prevent return to opioid dependence after medically supervised opioid withdrawal Once monthly by injection This page intentionally left blank. 3-17 TIP 63Part 3 of 5—Medications for Opioid Use Disorder Chapter 3B: Methadone Chapter 3B provides an overview of methadone pharmacology and discussion of key methadone dosing considerations for healthcare professionals working in opioid treatment programs (OTPs). Methadone is the most studied medication for opioid use disorder (OUD). Of all OUD pharma- cotherapies, it is used to treat the most people throughout the world and has by far the longest track record (nearly 50 years).77,78 Numerous clinical trials and meta-analyses have shown that methadone treatment is associated with signif- cantly higher rates of treatment retention and lower rates of illicit opioid use compared with placebo and with no treatment.79 Other research associates methadone treatment with reduced mortality, criminal behavior, and HIV serocon- version.80,81,82 A Cochrane meta-analysis found that, at fexible doses, methadone compared with buprenorphine retains patients in treatment signifcantly longer and equally reduces illicit opioid use.83 In the United States, OTPs can offer methadone to treat OUD, but all providers who may care for patients with OUD should be familiar with this treatment. Formulations There are several formulations of methadone: • Liquid concentrate, which is the formulation most commonly used in treatment programs. • Powder, which is dissolved in water and administered as a liquid. • Dispersible tablets, which are scored tablets that are dissolved in water. • Tablets, which are most commonly used outside of OTPs for analgesia. Pharmacology Methadone, a long-acting mu-opioid receptor full agonist, is a schedule II controlled medica- tion. It is highly plasma–protein bound and binds to proteins within tissues throughout the body.84 Through mu-opioid receptor binding and opioid cross-tolerance to other mu-opioid agonists, at adequate doses, methadone reduces opioid craving and withdrawal and blunts or blocks the effects of illicit opioids. There is wide individual variability in methadone pharmacokinetics. The half-life of methadone can vary from 8 to 59 hours85 depending on the patient. The average is 24 hours.86 Methadone has no ceiling effect. As a full agonist, increasing doses of methadone produce maximal physiological effects at the opioid receptors. Plasma levels reach steady state in about 5 days (i.e., fve half-lives). Before achievement of steady state, release from tissue reservoirs can lead to increasing serum plasma levels and toxicity, even if the daily methadone dose is not changed. Methadone induction, thus, should begin at a low dose and increase gradually with daily monitoring over days or weeks. At stable daily doses, serum levels peak 2 to 4 hours after dosing, then slowly decrease, providing 24 hours without overmedication or withdrawal.87 3-18 Medications for Opioid Use Disorder TIP 63 Bioavailability Methadone is approximately 70 to 80 percent bioavailable when patients take it orally for OUD. There is notable individual variability in bioavailability, ranging from 36 to 100 percent.88,89 The liver’s CYP450 3A4 enzyme is primarily responsible for metabolizing methadone,90 although CYP2B6 and CYP2D6 enzymes are also involved.91 At the start of methadone treatment, methadone can increase CYP3A4 activity and accelerate its own metabolism in some individuals.92 Dosing must be individualized because methadone’s bioavailability, clearance, and half-life can vary considerably among patients. Providers should check for potential drug–drug interactions and monitor patients receiving con- comitant medications. Some medications (e.g., benzodiazepines, anticonvulsants, antibiotics, antiretroviral agents, some antidepressants) can induce or inhibit CYP450 enzymes, resulting in potential changes in methadone serum concentration, effectiveness, and side effect profle. Dosing Considerations Methadone is indicated for people meeting OTP admission criteria, which for people 18 and older are: • Being currently “opioid-addicted”—the term the Substance Abuse and Mental Health Services Administration (SAMHSA) OTP regulations use (e.g., meeting Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition,93 criteria for OUD). Not all patients meeting OUD criteria, particularly those with mild OUD, are appropriate candidates for methadone. This is discussed in detail in Part 2 of this Treatment Improvement Protocol (TIP). • Having a history of at least 1 year of opioid addiction before admission. • Providing voluntary, written informed consent. OTP physicians can waive the history require- ment per Code of Federal Regulations (42 CFR 8.12)94 for: • Women who are pregnant. • Former patients (up to 2 years after discharge). • Patients within 6 months of release from incarceration. For patients younger than 18, admission criteria are different. They include two documented, unsuccessful, medically supervised withdrawals or treatments without OUD medica- tion (e.g., methadone) in a 12-month period. The parent or legal guardian must provide written informed consent. Contraindications Contraindications to treatment with methadone include an allergy to methadone and other instances in which opioids are contraindicated, such as acute asthma, in patients with abnormal- ly high carbon dioxide blood levels (e.g., from pulmonary disease or sleep apnea), or paralytic ileus. Precautions and Warnings Respiratory depression Methadone can cause respiratory depression, particularly during initial dosing and dose titration. The goal of methadone dosing in the frst weeks of treatment (i.e., induction) is to relieve withdrawal but avoid oversedation and respiratory depression. Patients who are older or cachectic or who have chronic obstructive pulmonary disease are more susceptible to respiratory depression and should be treated cautiously with lower doses. A standard formula for dose induction for all patients, without careful monitoring of response to treatment, and individualized dose adjustment is inadvisable. This can lead to methadone intoxication and overdose death. 3-19 TIP 63Part 3 of 5—Medications for Opioid Use Disorder Individualize dosing decisions through daily monitoring of patients’ responses to treatment. Opioid tolerance cannot be accurately gauged based on patient self-reports of the type, amount, or purity of the opioids they’ve used or of the severity of their opioid withdrawal symptoms. The best approach to dosing is to start low and go slow. Methadone has a relatively long half-life (24–36 hours or longer). Steady-state serum levels are generally not reached until about fve half-lives. This means that patients will not feel the full effect of the initial dose for 4 or more days even if the daily dose is the same. Slow release of methadone from tissues causes serum levels to continue to increase until reaching steady state. Initially a dose may seem appropriate, but the third or fourth day of the same dose can lead to oversedation and even respiratory depression and death.95 Use a lower-than-usual starting dose in individuals with no or low opioid tolerance (5 mg to 10 mg). Increase doses slowly and with careful monitoring for patients who: • Have not used opioids for 5 or more days (e.g., after leaving a controlled environment). • Do not use opioids daily. • Use weaker opioids (e.g., codeine). Do not determine doses by analgesic equivalence dose conversion tables for patients using high doses of prescription opioids, whether by prescription or illicitly. This can lead to death owing to incomplete cross-tolerance96 and the unique pharmacology of methadone. Concurrent substance use disorders (SUDs) involving benzodiazepines or alcohol Concurrent misuse of alcohol or benzodiaz- epines with methadone (or buprenorphine) increases respiratory depression risk. Use of alcohol and benzodiazepines (illicit and prescription) is common in patients with OUD. Managing OUD with methadone for patients with alcohol or benzodiazepine use disorders is challenging and should be undertaken with care. A 2017 Food and Drug Administration (FDA) Drug Safety Communication noted that although concomitant use of buprenorphine or methadone with benzodiazepines increases the risk of an adverse reaction, including overdose death, opioid agonist treatment should not be denied to patients solely on the basis of their taking benzodiazepines, because untreated OUD can pose a greater risk of morbidity and mortality.97 FDA advises that careful medication management by healthcare professionals can reduce risk (see www.fda.gov/downloads /Drugs/DrugSafety/UCM576377.pdf for more information). Strategies to manage patients with concurrent alcohol or benzodiazepine use disorders include the following (see also Exhibit 3B.1): • Obtain permission to communicate with the benzodiazepine prescriber to confrm the reason for use, adherence to treatment, and prescriber awareness of the patient’s OUD. It can also help to speak (with permission) with close family members or friends to assess the extent and impact of any alcohol or benzodi- azepine misuse. • Ensure that patients understand the risk of potential respiratory depression and un- intentional overdose death when combining methadone with alcohol, benzodiazepines, or other central nervous system (CNS) depressants. • Determine whether patients require medically supervised withdrawal or tapering from alcohol or benzodiazepines. Patients at risk for serious alcohol or benzo- diazepine withdrawal syndrome (including seizures and delirium tremens) may need inpatient medically supervised withdrawal. • Attempt gradual outpatient medically supervised withdrawal for benzodiazepines when indicated. Some OTPs have the staffng and capacity to provide a supervised 3-20 Medications for Opioid Use Disorder TIP 63 EXHIBIT 3B.1. Strategies for Managing Benzodiazepine Use by Patients in OUD Treatment • Carefully assess the patient’s benzodiazepine use, including: - Intent of use. - Source (check the state’s prescription drug monitoring program [PDMP]). - Amount and route of use. - Binge use. - Prior overdoses. - Harms (e.g., car crashes, criminal acts, sleep trouble). - Co-use with other substances that further increase risk for respiratory depression and overdose. - Withdrawal history (e.g., seizures, delirium). • Also assess for: - Psychiatric and medical comorbidity. - Motivation for change. - Psychosocial support system (obtain history from a signifcant other if the patient permits). • Gauge level of care and setting needed (e.g., residential, outpatient). Inpatient treatment may be best for patients with poor motivation, limited psychosocial support, serious or complicated comorbidity, or injection or binge use. outpatient taper from benzodiazepines. This usually requires use of a long-acting benzodiazepine, management of anxiety and sleeplessness, and careful monitoring with observed dosing and toxicology screening. It may also require lower-than-usual methadone doses. Engage in outpatient medically super- vised withdrawal only with patients who are physically dependent on benzodiazepines but do not inject or binge. This may only be successful in a minority of patients. Attempt the taper while continuing treatment with methadone, subject to certain conditions that promote safety and reduce risk. • Consider increasing counseling frequency as appropriate. • Coordinate with other prescribers. Some patients may have taken appropriately prescribed benzodiazepines for years with limited or no evidence of misuse. For such patients, tapering benzodiazepines may be contraindicated and unrealistic. • Address comorbid mental disorders (e.g., anxiety, depression) with other medications or psychosocial treatments, when feasible. • Provide medically supervised withdrawal from benzodiazepines or refer to specialty care for same. • Create a treatment plan with built-in conditions (e.g., urine testing, more frequent visits, short medication supply). • Frequently review patient progress and objective outcomes, such as: - Urine drug testing. - PDMP reports. - Psychosocial functioning. - Reports from signifcant others. • Revise treatment plans as needed, and document the rationale for treatment decisions. Adapted with permission.98 For more information on managing benzodiaze- pine use, see Management of Benzodiazepines in Medication-Assisted Treatment (https://ireta. org/wp-content/uploads/2018/03/BP_Guidelines_ for_Benzodiazepines.pdf). QTc prolongation and cardiac arrhythmia Methadone treatment has been associated with QTc prolongation, which often occurs without clinical consequences.99,100 Since 2006, methadone has had an FDA black box warning on QTc prolongation and Torsades de Pointes. QTc intervals above 500 milliseconds can increase risk for this rare ventricular arrhythmia, which can be lethal.101,102 The prevalence of QTc prolongation among methadone patients is 3-21 TIP 63Part 3 of 5—Medications for Opioid Use Disorder QTc prolongation is an abnormally long time in electrocardiogram (ECG) tracing between the start of a Q wave and the end of a T wave. Various cutoffs defne prolonged QTc interval, including greater than 450 milliseconds for men, greater than 460 to 470 milliseconds for women, or greater than 450 milliseconds for either gender.103 However, the faster the heart rate, the shorter the QTc interval. Hence, correct the QTc interval for heart rate; divide the QTc interval in milliseconds by the square root of the R-R interval in seconds.104 not known with certainty. It has been estimated that about 2 percent of patients in methadone treatment have QTc intervals greater than 500 milliseconds.105 According to methadone’s FDA label, most Torsades de Pointes cases occur in patients receiving methadone for pain treatment, although some cases have occurred among those in methadone maintenance.106 High methadone doses may be associated with prolonged QTc intervals.107 Other risk factors include:108 • Some medications (e.g., antidepressants, antibiotics, antifungals). • Congenital prolonged QTc interval. • Hypokalemia. • Bradycardia. There is considerable controversy about how best to screen for QTc prolongation without creating barriers to methadone treatment entry.109 Indeed, a Cochrane review of the liter- ature was unable to draw any conclusions about the effectiveness of QTc screening strategies in preventing cardiac morbidity or mortality among methadone patients.110 Notwithstanding the uncertainty about the best approach, OTPs can take steps to identify patients who may be at risk for cardiac arrhythmia. The TIP expert panel concurs with the recommendations of other expert panels (which included cardiologists) that OTPs develop a cardiac risk management plan,111,112 to the extent possible. OTPs should consider the following elements in crafting a cardiac risk management plan: • An intake assessment of risk factors, which can include: − Family history of sudden cardiac death, arrhythmia, myocardial infarction, heart failure, prolonged QTc interval, or unex- plained syncope. − Patient history of arrhythmia, myocardial infarction, heart failure, prolonged QTc interval, unexplained syncope, palpitations, or seizures. − Current use of medications that may increase QTc interval (for a complete list, see https://crediblemeds.org/index.php/ login/dlcheck; register for free for the most current list). − Patient history of use of cocaine and methamphetamines (which can prolong the QTc interval). − Electrolyte assessment (for hypokalemia or hypomagnesemia). • A risk stratifcation plan, which can include the following: − Conduct an ECG for patients with sig- nifcant risk factors at admission; repeat within 30 days. Repeat once a year and if the patient is treated with more than 120 mg of methadone per day. − Discuss risks and benefts of methadone with patients with QTc intervals between 450 and 500 milliseconds. Adjust modif- able risk factors to reduce their risk. − Do not start methadone treatment for patients with known QTc intervals above 500 milliseconds. If such an interval is discovered during treatment, have a risk/ beneft discussion. Strongly consider lowering the methadone dose, changing concurrent medications that prolong the 3-22 Medications for Opioid Use Disorder TIP 63 QTc interval, eliminating other risk factors, and, if necessary, switching to buprenor- phine. Include follow-up ECG monitoring. − Consider providing routine universal ECG screening if feasible, although there is in- suffcient evidence to formally recommend doing so.113 Accidental ingestion Inform patients that accidental ingestion can be fatal for opioid-naïve individuals, particularly children. Patients should safeguard take-home methadone in a lockbox out of the reach of children. Neonatal abstinence syndrome (NAS) Ensure awareness among pregnant patients or patients who may become pregnant that NAS can occur in newborns of mothers treated with methadone. Women receiving methadone treatment while pregnant should talk with their healthcare provider about NAS and how to reduce it. Research has shown that the dose of opioid agonist medication is not reliably related to the severity of NAS.114,115,116 Thus, each woman should receive the dose of medication that best manages her illness. Misuse and diversion Alert patients to the potential for misuse and diversion of methadone. Physical dependence Inform patients that they will develop physical dependence on methadone and will experience opioid withdrawal if they stop taking it. Sedation Caution patients that methadone may affect cognition and psychomotor performance and can have sedating effects. Urge patients to be cautious in using heavy machinery and driving until they are sure that their abilities are not compromised. Adrenal insufciency Adrenal insuffciency has been reported in patients treated with opioids. Ask patients to alert healthcare providers of nausea, vomiting, loss of appetite, fatigue, weakness, dizziness, or low blood pressure.117 Drug Interactions Methadone has more clinically signifcant drug–drug interaction than buprenorphine.118 Carefully monitor each patient’s response to treatment if they are prescribed or stop taking a CYP450 34A inducer or inhibitor. Methadone dosages may need to be adjusted up or down depending on the medication and whether treatment is starting or stopping. Exhibit 3B.2 lists common interactions between methadone and other medications. Medications that induce CYP450 activity can increase methadone metabolism. Patients may experience craving or opioid withdrawal symptoms between doses if they begin these medications or become sedated if they discon- tinue them: • Some antibiotics (e.g., rifampin). • Antiretrovirals (e.g., efavirenz, nevirapine, ritonavir). • Anticonvulsants (carbamazepine, phenobarbi- tal, phenytoin). Other medications can inhibit CYP450 activity and decrease methadone metabolism, causing symptoms of overmedication (e.g., sedation) when the medication is started and possibly withdrawal or cravings when it is stopped. Among such medications are:119 • Some antibiotics (ciprofoxacin, erythromycin). • Antacids (cimetidine). • Antifungals (fuconazole). • Antidepressants (e.g., fuvoxamine, paroxe- tine, sertraline). 3-23 TIP 63Part 3 of 5—Medications for Opioid Use Disorder EXHIBIT 3B.2. Common Potential Methadone Drug–Drug Interactions Antiretrovirals CLASS OR SPECIFIC DRUG INTERACTION PUTATIVE MECHANISM NOTES Efavirenz, lopinavir, nevirapine Reduction in serum methadone levels Induction of CYP450 enzymes Clinically signifcant opioid withdrawal symptoms likely Abacavir, etravirine, nelfnavir, ritonavir, saquinavir, tipranavir May reduce serum methadone levels Induction of CYP450 enzymes Clinically pertinent opioid withdrawal symptoms unlikely Didanosine Reduction in didanosine plasma concentrations Decreased bioavailability Possible decreased effcacy of didanosine Zidovudine Increase in zidovudine plasma concentration Unknown Risk of zidovudine toxicity Antidepressants CLASS OR SPECIFIC DRUG INTERACTION PUTATIVE MECHANISM NOTES Tricyclic: Amitriptyline, Increased risk for Anticholinergic Clinical experience with clomipramine, desipra- constipation, sedation, effects; blockade combination indicates it is mine, doxepin, imipra- QTc prolongation, and of human ether-a- generally safe with careful mine, nortriptyline, pro- arrhythmia go-go-related gene clinical monitoring triptyline, trimipramine (hERG) channel Serotonin reuptake May increase serum Inhibition of CYP Clinical experience with inhibitors: citalopram, es- methadone levels; enzymes; blockade combination indicates it is citalopram, fuvoxamine, increased risk for of serotonin generally safe with careful fuoxetine, paroxetine, serotonin syndrome transporter clinical monitoring sertraline Monoamine oxidase Increased risk for Inhibition Avoid or use with extreme inhibitors: Isocarboxazid, serotonin syndrome of serotonin caution and careful clinical phenelzine, selegiline, metabolism monitoring tranylcypromine Serotonin/norepineph- Increased risk for Blockade of Clinical experience with rine reuptake inhibitors: serotonin syndrome; serotonin combination indicates it is Duloxetine, desvenlafax- increased risk for QTc transporter; generally safe with careful ine, venlafaxine prolongation and blockade of clinical monitoring arrhythmia (venlafaxine) hERG channel (venlafaxine) Continued on next page 3-24 Medications for Opioid Use Disorder TIP 63 EXHIBIT 3B.2. Common Potential Methadone Drug–Drug Interactions (continued) Antibiotics CLASS OR SPECIFIC DRUG INTERACTION PUTATIVE MECHANISM NOTES Ciprofoxacin, clarithro- mycin, erythromycin, azithromycin May increase methadone serum levels; increased risk for QTc prolongation and arrhythmia Inhibition of CYP enzymes; blockade of hERG channel One case report of sedation (ciprofoxacin); clinical monitoring required Rifampin Reduction in serum methadone levels Induction of CYP enzymes Severe opioid withdrawal can occur; need increased methadone dose Antifungals CLASS OR SPECIFIC DRUG INTERACTION PUTATIVE MECHANISM NOTES Ketoconazole, fuconazole May increase methadone serum levels Inhibition of CYP enzymes Little evidence for important clinical effects Anticonvulsants CLASS OR SPECIFIC DRUG INTERACTION PUTATIVE MECHANISM NOTES Carbamazepine, phenyto- in, phenobarbital Reduction in serum methadone levels Induction of CYP enzymes Severe opioid withdrawal can occur; will need increased methadone dose Antiarrhythmics CLASS OR SPECIFIC DRUG INTERACTION PUTATIVE MECHANISM NOTES Procainamide, quinidine Increases risk for QTc Blockade of hERG Careful clinical monitoring prolongation and channel required arrhythmia Amiodarone May increase methadone serum levels; increased risk for QTc prolongation and arrhythmia Inhibition of CYP enzymes; blockade of hERG channel Careful clinical monitoring required Continued on next page 3-25 TIP 63Part 3 of 5—Medications for Opioid Use Disorder EXHIBIT 3B.2. Common Potential Methadone Drug–Drug Interactions (continued) Other Drugs and Specifc Classes CLASS OR SPECIFIC DRUG INTERACTION PUTATIVE MECHANISM NOTES Benzodiazepines Additive CNS and respiratory depressant effects Increased GABA activity Careful clinical monitoring required Barbiturates Additive CNS and respiratory depressant effects Increased GABA activity Careful clinical monitoring required Cimetidine May increase serum methadone levels Inhibition of CYP enzymes No evidence of major clinical effect Naltrexone Precipitated opioid withdrawal Displaces methadone from mu-opioid receptors Contraindicated Adapted with permission.120 Methadone can affect the metabolism of other medications. For example, zidovudine levels are reported to increase signifcantly during methadone treatment. Monitoring for zidovudine side effects during treatment is warranted.121 Check drug–drug interactions online (www .drugs.com/drug_interactions.php). Side Efects Possible side effects of methadone include the following (methadone FDA labels list all potential side effects and are available at https://dailymed.nlm.nih.gov/dailymed/search .cfm?labeltype=all&query=METHADONE): • Constipation • Nausea • Sweating • Sexual dysfunction or decreased libido • Drowsiness • Amenorrhea • Weight gain • Edema Assessment A thorough assessment will help decide whether a patient is appropriate for admission and meets federal and any state regulatory requirements for methadone treatment. (See Part 2 of this TIP for detailed discussion of screening and assess- ment.) Before ordering methadone: • Check the state PDMP for opioid or benzo- diazepine prescriptions from other providers (see www.nascsa.org/stateprofles.htm for links to state PDMPs). Note that methadone for OUD treatment will not appear in the PDMP because of confdentiality regulations regarding substance use treatment records. Obtain the patient’s consent to release infor- mation and speak with treating providers to coordinate care for patient safety. • Take the patient’s history. − Conduct a medical, psychiatric, substance use, and substance use treatment history. 3-26 Medications for Opioid Use Disorder TIP 63 − Assess recent opioid use, including frequency, quantity, type, route, and recency (last day of use and use in the past 30 days). − Establish OUD diagnosis. − Assess for other SUDs, including those that involve alcohol, benzodiazepines, or stimulants. • Conduct a physical exam. − Assess for signs and symptoms of intoxication. Do not give patients who are sedated or intoxicated their frst dose. Instead, assess and treat them appropriately: • Identify causes of sedation or intoxication. • Ensure the patient’s immediate safety. • Reassess methadone induction appropriateness. • Develop a plan to reattempt induction or follow a different course of treatment as appropriate. • Obtain laboratory tests. − Conduct drug and alcohol tests. Use reliable urine tests for drugs, including opioids (e.g., morphine, methadone, buprenorphine, oxycodone), benzodiaze- pines, cocaine, and other drugs that may be commonly used in the area (e.g., meth- amphetamine). Obtain an opioid urine or oral fuid test before initiating treatment. A negative opioid test in the absence of clear opioid withdrawal symptoms indicates that the patient is likely no longer opioid tolerant; diagnosis should be reconfrmed. If such patients are to start taking methadone (rather than naltrexone for relapse prevention), use caution in initiating treatment (see the subsection “First dose for patients without current opioid tolerance” in the section “Initiating Methadone Treatment”). Use an alcohol breathalyzer to estimate the patient’s blood alcohol content. Do not provide methadone until the alcohol reading is considerably below the legal level of alcohol intoxication. − Assess for signs and symptoms of opioid withdrawal and physiological depen- dence. One approach to documenting withdrawal symptoms is to use a scale such as the Clinical Opioid Withdrawal Scale (COWS) or the Clinical Institute Narcotic Assessment (CINA) Scale for Withdrawal Symptoms (see “Resource Alert: Opioid Withdrawal Scales”). Before the frst dose of methadone, confrm signs of opioid withdrawal to provide some confdence that the patient is opioid tolerant and can begin dose induction. The Naloxone Challenge should not be routinely used to determine physiologic withdrawal because withdrawal symptoms will be visible, if present, on physical exam if enough time has passed since last opioid use.122 RESOURCE ALERT Opioid Withdrawal Scales The COWS and other opioid withdrawal scales from Annex 10 of the World Health Organization’s Guidelines for the Psychosocially Assisted Pharmacological Treatment of Opioid Dependence can be downloaded from the National Center for Biotechnology Information website (www.ncbi.nlm.nih.gov/books /NBK143183). The CINA Scale for Withdrawal Symptoms also is available online (https://ncpoep.org/wp- content/uploads/2015/02/Appendix_7_Clinical_ Institute_Narcotic_Assessment_CINA_Scale_ for_Withdrawal_Symptoms.pdf). 3-27 TIP 63Part 3 of 5—Medications for Opioid Use Disorder − Conduct a pregnancy test. Pregnant patients with OUD should be treated with methadone or transmucosal buprenor- phine.123,124 Discuss risks and benefts of treatment with methadone and alternative approaches for each patient and fetus versus the risks of continued illicit opioid use. Refer pregnant patients to prenatal care. Women should be advised that their menstrual cycle may return to normal once they are stabilized on medication, and hence they should use birth control if they wish to avoid pregnancy. − Conduct liver function tests. If possible, assess liver function tests. It is not necessary to wait for the results of these tests to begin treatment, because the risk of not starting methadone outweighs the benefts of having the test results. Patients with suspected cirrhosis based on history and clinical exam should be started at a lower methadone dose than typical patients, with more cautious titration. Patients who have chronic hepatitis can be treated with methadone. Have a risk/ beneft discussion with patients whose liver enzymes are at or greater than fve times the normal level and monitor their liver function during treatment. − Conduct hepatitis and HIV testing. Hepatitis B and C are common among patients who enter methadone treatment. HIV infection is also prevalent. Everyone ages 15 to 65 should be tested at least once for HIV. Persons at higher risk, such as people who use drugs by injection, should be tested annually.125 Anyone who is injecting or has ever injected drugs, even once, no matter how long ago, should be tested for hepatitis C, regardless of their intention to seek treatment for SUD.126 The Centers for Disease Control and Prevention recommends hepatitis B vaccination for people seeking treatment for SUDs.127 Patient Selection No evidence clearly predicts which patients will respond best to methadone treatment versus alternative pharmacotherapies. Inform patients of all options and the settings in which they’re available, as appropriate. (See “Treatment Planning or Referral” in Part 2 of this TIP for more on shared decision making.) Patients who responded well to methadone in the past should be considered for this treatment. Unsuccessful treatment experiences with methadone in the past do not necessarily indicate that methadone will be ineffective again. Motivation and circumstances change over time. Also, treatment varies by OTP, as it does for other medical illnesses. Records from previous providers can contextualize the extent of past treatment. Pregnant women should be considered for methadone treatment. Methadone (or buprenorphine) treatment through OTPs may be best for patients who need a higher level of outpatient structure or supervision of medication adherence. Tailor medication decisions to patients’ medical and substance use histories, patient preferences, and treatment availability. Informed Consent Inform all patients of: • Their OUD diagnosis and the nature of the disorder. • Risks and benefts of methadone and other OUD medications. • Risks and benefts of nonmedication treatments. Use language and written materials appropriate to each patient’s comprehension level to ensure that he or she understands the options and can make informed decisions. 3-28 Medications for Opioid Use Disorder TIP 63 • • • • • • • Inform OTP nursing/medical staff about prescribed and over-the-counter medications and herbs (e.g., St. John’s wort) they are taking, stopping, or changing doses of to allow assessment of potential drug–drug interactions. Inform other treating healthcare professionals that they are receiving methadone treatment. Plan to avoid driving or operating heavy machinery until their dose is stabilized. Learn about other possible side effects of methadone, including dizziness, nausea, vomiting, sweating, constipation, edema, and sexual dysfunction. Agree to keep take-home doses locked up and out of the reach of others. Understand that giving methadone, even small amounts, to others may be fatal. Inform providers if they become pregnant. Understand that stopping methadone increases their risk of overdose death if they return to illicit opioid use. EXHIBIT 3B.3. Key Points of Patient Education for Methadone Before starting OUD treatment with methadone, patients should: • • • • • Be told that the methadone dose is started low and increased slowly over days and weeks with monitoring, because it takes 4 or more days for the body to adjust to a dose change. This is necessary to avoid the risk of overdose. Understand that the goal of the frst weeks of treatment is to improve withdrawal symptoms without oversedation. Patients should inform providers if they feel sedated or “high” within the frst 4 hours after their dose. Learn the symptoms of methadone intoxication and how to seek emergency care. The frst 2 weeks of treatment have the highest risk of overdose. Be aware that rescue naloxone does not last very long, so they should remain in emergency care for observation if they are treated for opioid overdose. Know that concurrent alcohol, benzodiazepine, or other sedative use with methadone increases the risk of overdose and death. Patients should sign consent forms before starting treatment. The Chapter 3B Appendix provides a sample consent form for treatment in an OTP. Educate patients about what to expect when receiving methadone treatment (Exhibit 3B.3). Caution them against using alcohol and drugs during methadone treatment. Warn them of the increased risk of overdose during the frst 2 weeks of treatment. Also warn them that discon- tinuing treatment and returning to opioid use will increase their risk of overdose. Document patient education in the medical record. Educate patients about the importance of safe storage of take-home methadone doses. Discuss with patients where they will store their take-home medication. Advise them against storing medication in common areas of the home RESOURCE ALERT Patient and Family Member Educational Resources Decisions in Recovery: Treatment for Opioid Use Disorder offers information for patients on the use of medications for OUD (https://store .samhsa.gov/product/SMA16-4993). Medication-Assisted Treatment for Opioid Addiction: Facts for Families and Friends offers information for family members and friends (https://portal.ct.gov/-/media/DMHAS/ Opioid-Resources/MATInfoFamilyFriendspdf. pdf). 3-29 TIP 63Part 3 of 5—Medications for Opioid Use Disorder where visitors or children would have access, such as kitchens and bathrooms. Take-home doses should be kept in their original childproof packaging in a lockbox. The key should not be left in the box. Inform patients that any portion of a dose taken by another person, a child, or pet can be deadly. If this occurs, call 9-1-1 immediately. Initiating Methadone Treatment Observing patients directly when they take doses early in treatment is not just required; it’s benefcial. It maximizes adherence, provides a daily opportunity to assess response to the medication, and minimizes the likelihood of med- ication diversion. Federal OTP regulations permit patients to receive one take-home dose per week, given routine clinic closure on weekends. Patients who demonstrate progress can earn one additional take-home dose per week for the frst 90 days of treatment at the OTP medical director’s discretion. All other doses are directly observed at the clinic in the frst 90 days. The goal of initiating methadone treatment is to increase the patient’s methadone dose gradually and safely, stabilizing the patient and reducing his or her opioid use while recognizing that the risk of dropout or overdose from illicit opioid use may increase if induction is too slow. Day 1 The frst dose should reduce opioid withdrawal symptoms. Perform induction cautiously; it’s impossible to judge a patient’s level of tolerance with certainty. For patients addicted to prescrip- tion opioids, opioid conversion tables should not be relied on to determine methadone dosage. First dose for patients with opioid tolerance The frst dose for patients tolerant to opioids is generally between 10 mg and 30 mg (30 mg is the maximum frst dose per federal OTP regulations). After the frst dose, patients should remain for observation for 2 to 4 hours if possible to see whether the dose is sedating or relieves withdrawal signs. • If withdrawal symptoms lessen, the patient should return the next day to be reassessed and to continue the dose induction process. • If sedation or intoxication occurs after the frst dose, the patient should stay under observa- tion at the clinic until symptoms resolve. In this case, the patient should be reassessed the following day, and the subsequent day’s dose should be substantially reduced. Extremely rarely, the patient will need to be treated for overdose with naloxone. If necessary, begin rescue breathing and call 9-1-1. • If the patient shows neither sedation nor reduction of objective signs of opioid with- drawal during the 2- to 4-hour waiting period, administer another 5 mg dose. A fnal 5 mg dose after another waiting period of 2 to 4 hours can be administered if necessary. The maximum total methadone dose on the frst day of treatment should not exceed 40 mg.128 However, caution dictates against exceeding a total frst day’s dose of 30 mg except in rare cases. In such cases, the patient should be carefully monitored on subsequent days to rule out oversedation. • Patients transferring from another OTP whose methadone dose and last date of medication administration can be confrmed by the medical staff and documented in the medical record can be continued on the same methadone dose administered in the original OTP, even if the dose exceeds the maximum permitted 40 mg. For some patients, the lower range of initial doses is best. Dose with 10 mg to 20 mg in patients who: • Are ages 60 and older. • May have lower levels of opioid tolerance based on their recent history. • Use sedating medications, such as benzodiaz- epines, antipsychotics, or antidepressants. • Engage in problem drinking or have alcohol use disorder. • Take medications that can increase methadone serum levels or are stopping medications that decrease methadone serum levels.129 3-30 Medications for Opioid Use Disorder TIP 63 • Have medical disorders that may cause hypoxia, hypercapnia, or cardiac arrhythmias. These include: − Asthma, chronic obstructive pulmonary disease, and kyphoscoliosis. − Obesity. − Sleep apnea. − QTc prolongation. − A family history of cardiac arrhythmias, fainting or dizziness, or sudden death. − Cor pulmonale. − Electrolyte abnormalities, such as hypoka- lemia or hypomagnesemia. First dose for patients without current opioid dependence In some circumstances, patients who are not currently dependent on opioids may be admitted to an OTP (e.g., individuals with a history of OUD who are returning from controlled environments).130 In these instances, consider treatment with extended-release naltrexone (XR-NTX) to avoid establishing new physiological opioid dependence. Instead of starting methadone, consider starting with a low dose of buprenorphine because of buprenor- phine’s superior safety threshold.131 In one such study, 1 mg of buprenorphine was the starting dose, which was increased slowly132 (see Chapter 3D of this TIP). If XR-NTX and buprenorphine are not available, or the patient prefers methadone treatment, consider starting methadone at a 5 mg daily dose (as was done in one study133) after discussing risks and benefts with the patient. Titrate the dose much more slowly than for patients who are opioid tolerant. Increase initially by 5 mg about every week, based on patient response. Doses can be increased somewhat more rapidly after careful assessment of response if the patient begins to use illicit opioids. As with other methadone dosing, induction in these cases should not be based on a standing order. Dose Titration (Weeks 1 to 2) The goals of early dose titration for patients with current opioid dependence starting on Day 2 of the frst week of treatment through stabilization are to avoid sedation at peak serum levels and to gradually extend time without opioid withdrawal symptoms and craving. When patients attend the program, before dose administration, nursing and/or medical staff members should ask patients whether they felt sedation, opioid intoxication effects, or opioid withdrawal symptoms 2 to 4 hours after their methadone administration the prior day (Exhibit 3B.4). Doses should be decreased for reports of symptoms of opioid intoxication or oversedation. Dosing must be individualized based on careful patient assess- ment and generally should not be increased every day, because plasma methadone levels do not reach steady state until about fve methadone half-lives (Exhibit 3B.5). Even when holding the methadone dose constant over several days, the patient’s methadone serum level will rise each day until it reaches steady state (Exhibit 3B.5). For example, if the patient remains on 20 mg per day for the frst few days of induction, the serum level on Day 2 would refect the 20 mg second day’s dose plus 10 mg that remained in the body from the frst day’s dose (for the equivalent single dose total of 30 mg). The third day would refect the 20 mg third day’s dose, plus 10 mg remaining in the body from the second day’s dose, and 5 mg remaining from the frst day’s dose (for the equivalent single dose total of 35 mg), and so on. Patients who report relief from withdrawal 4 to 12 hours after their last dose may beneft from staying at that same dose for a few days so that their serum level can stabilize.134 An American Society of Addiction Medicine expert panel recommended increasing the methadone dose in this phase by 5 mg or less every 5 or more days.135 Other expert recom- mendations suggest somewhat faster dose increases,136 including increases of 5 mg to 10 mg no sooner than every 3 to 4 days.137,138 3-31 TIP 63Part 3 of 5—Medications for Opioid Use Disorder Se ru m M et h ad on e Le ve l 1 2 3 4 5 6 7 8 9 10 Time (Days) EXHIBIT 3B.4. Using Signs and Symptoms To Determine Optimal Methadone Level Methadone Comfort Zone Serum Level 0 2 4 6 8 10 12 14 16 18 20 22 24 Opioid Overmedication Signs: Pinpoint pupils, drowsy or nodding off, listless mental status, itching/scratching, fushing, decreased body temperature, slowed heartbeat and/or respirations Opioid Withdrawal—Subjective Symptoms: Drug craving, anxious feelings or depression, irritability, fatigue, insomnia, hot/cold fashes, aching muscles/joints, nausea, disorientation, restlessness Severe Opioid Withdrawal—Objective Signs: Dilated pupils, illicit opioid use, “goose fesh,” perspiring, shaking, diarrhea, vomiting, runny nose, sneezing, yawning, fever, hypertension, increased heartbeat and/or respirations Peak Trough No Illicit Opioid Use No Withdrawal or Overmedication Hours Adapted with permission.139 EXHIBIT 3B.5. Steady-State Methadone Concentration Reached in About 5 Days Adapted with permission.140,141 The most important principle is to individualize dose induction based on careful assessment of the patient’s response to the medication. Dose Titration (Weeks 3 to 4) Methadone doses can be increased further in 5 mg increments about every 3 to 5 days based on the patient’s symptoms of opioid withdrawal or sedation.142 Patients who miss more than four doses must be reassessed. Their next methadone dose should be decreased substantially and built back up gradually. It may be necessary to restart the dose induction process from Day 1. Be aware of any specifc state requirements regarding missed doses. Serum Levels Dosing must be individualized because meth- adone’s bioavailability, clearance, and half-life vary among patients, affecting their clinical 3-32 Medications for Opioid Use Disorder TIP 63 responses and requiring doses to be changed. Many factors can affect serum levels and clinical responses to treatment. Along with age and diet, these factors include: • Other medications and herbs (e.g., St. John’s wort). • Genetic differences in metabolizing enzymes. • Pregnancy. • Changes in urinary pH.143 Consider measuring serum methadone levels in patients who, after being on a stable methadone dose, report feeling drowsy 2 to 4 hours after dose administration but develop craving or withdrawal symptoms before the next dose is due to be administered. This may occur in the third trimester of pregnancy, when concomitant medications interact with methadone, or when patients rapidly metabolize opioids. In such cases, consider dividing the daily methadone dose into twice-daily dosing.144 To assess serum methadone levels, draw peak and trough blood specimens at about 3 hours and 24 hours, respectively, after dose administra- tion. Serum methadone levels generally correlate with methadone dose,145 but there is no defned therapeutic window based on serum methadone level because response varies widely among patients. Minimum trough methadone levels of 300 ng/mL to 400 ng/mL may be associated with reduced likelihood of heroin use,146 but deter- mining the therapeutic dose should depend on the overall patient response, not the serum plasma levels. Peak:trough ratios above 2:1 may indicate rapid metabolism.147 Dose Stabilization (Week 5 and Beyond) Once the patient achieves an adequate dose, extended continuation is possible without dose adjustment. Continuing treatment goals are to avoid sedation, eliminate withdrawal and craving, and blunt or block euphoric effects of illicit opioids. The TIP expert panel advises against arbitrary methadone dosage caps. There may be reasons to further adjust the dose, including: • Changes in health that can affect medica- tions (e.g., acute hepatitis, exacerbation of pulmonary disease, sleep apnea). • Changes in patient medications. • Pregnancy. Increased metabolism in the last trimester may warrant dose increase or split dosing.148,149 This may require a SAMHSA exception for daily take-home half-doses via an SMA-168 Exception Request (www.samhsa.gov/medication-assisted -treatment/opioid-treatment-programs /submit-exception-request). • Concurrent illicit opioid or other drug or alcohol use. As illicit opioid use stops and stabilization is achieved, the patient may wish to lower the dose to reduce any unpleasant side effects. Typical stabilization doses of at least 60 mg are associated with greater treatment retention; 80 mg to 120 mg150 is the typical daily range.151 However, there is wide variation, and some patients beneft from higher daily doses. Take-Home Medication OTPs can provide gradually increasing numbers of take-home doses to patients who discontinue illicit drug use and begin achieving treatment goals, commensurate with their tenure in the program. This provides a powerful incentive for patients to achieve treatment goals.152 It also furthers patients’ recovery goals by allowing them to attend work, school, or other activities without daily OTP visits. Federal OTP regulations describe the conditions under which take-home doses are permitted. Some states have additional regulations. OTPs should be familiar with these regulations and have written procedures to address take-home dosing. 3-33 TIP 63Part 3 of 5—Medications for Opioid Use Disorder The benefts of take-home doses must outweigh the risks and further patients’ rehabilitation goals. When deciding whether patients can handle the responsibility of take-home doses of methadone or buprenor- phine, OTP medical directors should consider whether patients demonstrate: • No recent misuse of substances. • Regular clinic attendance. • No serious behavioral problems at the clinic. • No recent criminal activity (e.g., selling drugs). • Stability at home and in social relationships. • Suffcient time in treatment. • Ability and intent to store take-home medication safely. • Rehabilitative benefts from decreasing the frequency of clinic attendance that outweigh the potential risks of diversion. Federal regulations based on patients’ time in treatment determine eligibility to be considered for receiving take-home doses of methadone (but buprenorphine is not bound by these limits): • One earned dose/week (beyond a weekly clinic closure day or federal holiday, when clinics typically close) in the frst 90 days of treatment • Two doses during the second 90 days • Three doses during the third 90 days • Up to 6 doses during the last 90 days • Up to 2 weeks of doses after 1 year • Up to 1 month of doses after 2 years Assessing responsible handling of take-home doses Methadone diversion is a risk. People with OUD who are not in treatment more frequently use illicit methadone to self-medicate withdrawal symptoms than to achieve euphoria.153,154 Still, diversion is a public health risk; people who self-medicate may not know what dose they are taking. Moreover, opioid-naïve people (including children) who ingest methadone can die of methadone intoxication. OTPs must assess patients’ adherence to responsible take-home-dose handling and have a diversion control plan. The plan may require that the OTP: • Remain open 7 days per week or arrange dosing at another clinic on days the clinic is closed for certain patients to avoid providing take-home doses to new or unstable patients. • Contact patients randomly and request that they return their take-home containers within a day or two to see whether they still have the medication in their possession or have altered the medication in any way. • Establish an appropriate drug testing program with policies to prevent falsifcation of specimens and to respond to tests that are negative for methadone. • Require patients to store their take-home medication in a lockbox to prevent theft or accidental use by children or others. Duration of Methadone Treatment Longer lengths of stay in methadone treatment are associated with superior treatment outcomes.155 Leaving methadone treatment is associated with increased risk of death from overdose and other causes.156,157 Patients should continue as long as they beneft, want to, and develop no contraindications. RESOURCE ALERT Guidance on Federal Take-Home Methadone Dose Regulations For more information on federal take-home dose regulations for OTPs, see SAMHSA’s Federal Guidelines for Opioid Treatment Programs (https://store.samhsa.gov/product/ Federal-Guidelines-for-Opioid-Treatment- Programs/PEP15-FEDGUIDEOTP). 3-34 Medications for Opioid Use Disorder TIP 63 • • • • • The TIP expert panel considers arbitrary time limits on OUD treatment with methadone to be medically unwarranted and inappropriate. They pose a risk to patients and the public. Dose Tapering and Methadone Discontinuation Discuss risks and benefts with patients who wish to discontinue treatment. Explore their reasons for wanting to discontinue and solutions for potential barriers to treatment, which may include: Logistics (e.g., travel, scheduling). Transportation services, including publicly funded ride services, ride sharing, or peer support workers, may be available. If not, transferring patients to a closer OTP or to one with more suitable hours of operation may resolve the problem. Costs. Providers can help patients explore publicly supported treatment options or apply for insurance. Side effects. Changing the dose or treating side effects may resolve the problem. Opinions of friends or family. When external pressure from family or friends drives the decision, a discussion with the patient and those individuals may help. A desire to switch to buprenorphine or XR-NTX treatment. These options should be discussed. Caution patients who are not yet stable against discontinuing treatment, because of high rates of return to illicit opioid use and increased chance of overdose death.158 Discuss the alternative of switching to a different OUD medication. Give patients who stop treatment information about overdose prevention and encourage them to return to treatment. Prescribe naloxone to use in case of overdose. Create a plan collaboratively with stable patients who wish to discontinue treatment that addresses: • Gradually tapering their dose. • Increasing psychosocial and recovery supports. • Discontinuing dose reduction if necessary. • Returning to medication treatment after discontinuation if they return to illicit opioid use. • Increasing dosage if destabilization occurs. Individualize the pace of methadone dose reduction to the patient’s response. One approach is to decrease the methadone dose gradually by 5 to 10 percent every 1 to 2 weeks. Once patients reach a relatively low dose, often between 20 mg and 40 mg, they may begin to feel more craving. Some patients may choose to switch to buprenorphine for a period to complete the dose reduction. They may also wish to begin XR-NTX after an appropriate period of opioid abstinence. Encourage patients to use techniques for preventing return to use, such as participating in recovery support groups and gaining support from counseling and family. Doing so can help patients succeed in tapering off their medication. RESOURCE ALERT Guidance on Opioid Overdose Prevention For more information on preventing opioid overdose, see the SAMHSA Opioid Overdose Prevention Toolkit (https://store.samhsa.gov/ product/Opioid-Overdose-Prevention-Toolkit/ SMA18-4742). 3-35 TIP 63Part 3 of 5—Medications for Opioid Use Disorder Methadone Dosing Summary The initial goal is to reduce opioid withdrawal and craving safely. • Use the “start low and go slow” approach but increase dose at a rate that minimizes chances of continued illicit drug use, while monitoring for side effects. • Increase doses gradually over several weeks. • Assess for sedation at peak serum concentra- tion (2–4 hours after the dose). The eventual target is an adequate dose that: • Stops withdrawal symptoms for 24 hours. • Reduces or eliminates craving. • Blunts or blocks euphoria from self- administered illicit opioids. In general, after induction is complete, higher doses are more effective than lower doses. Enhancing Access to OUD Medication in OTPs Individuals on waiting lists for OTPs should receive interim methadone maintenance treatment. People on waiting lists typically continue to use illicit opioids. Many never gain admission through the waiting list process. Federal OTP regulations permit use of interim methadone maintenance to address this problem by providing methadone treatment for up to 120 days to someone on an OTP waiting list. Routine counseling and treatment planning are not required during this period. Interim methadone maintenance has been shown to be more effective than a waiting list to facilitate entry into com- prehensive methadone treatment and to reduce illicit opioid use, according to two randomized trials.159,160 Interim methadone requires approval by SAMHSA and the state opioid treatment authority. For more detailed information on interim methadone maintenance, see SAMHSA’s Federal Guidelines for Opioid Treatment Programs (https://store.samhsa.gov/product/Federal- Guidelines-for-Opioid-Treatment-Programs/ PEP15-FEDGUIDEOTP). OTPs can overcome geographic barriers by opening a medication unit of the parent OTP site. Under the aegis of a certifed OTP, a medication unit may provide methadone or buprenorphine administration, dispensing capacity, and urine drug testing, but not coun- seling. The parent clinic must provide counseling and other required services. Such arrangements can lessen the amount of time required to drive to a parent OTP location in large states with rural populations. SAMHSA’s Federal Guidelines for Opioid Treatment Programs offers more information on medication units and other OTP regulations (https://store.samhsa.gov/product/Federal- Guidelines-for-Opioid-Treatment-Programs/ PEP15-FEDGUIDEOTP). 3-36 Medications for Opioid Use Disorder TIP 63 Chapter 3B Appendix Sample Standard Consent to Opioid Maintenance Treatment Form for OTPs CONSENT TO PARTICIPATE IN METHADONE OR BUPRENORPHINE TREATMENT Patient’s Name: _____________________________________________________ Date: _______________ I authorize and give voluntary consent to _________________________________ [insert name of program] to dispense and administer medications—including methadone or buprenorphine—to treat my opioid use disorder. Treatment procedures have been explained to me, and I understand that I should take my medication at the schedule determined by the program physician, or his/her designee, in accordance with federal and state regulations. I understand that, like all other medications, methadone or buprenorphine can be harmful if not taken as prescribed. It has been explained to me that I must safeguard these medications and not share them with anyone because they can be fatal to children and adults if taken without medical supervision. I also understand that methadone and buprenorphine produce physical opioid dependence. Like all medications, they may have side effects. Possible side effects, as well as alternative treatments and their risks and benefts, have been explained to me. I understand that it is important for me to inform any medical and psychiatric provider who may treat me that I am enrolled in an opioid treatment program. In this way, the provider will be aware of all the medications I am taking, can provide the best possible care, and can avoid prescribing medications that might affect my treatment with methadone or buprenorphine or my recovery. I understand that I may withdraw voluntarily from this treatment program and discontinue the use of these medications at any time. If I choose this option, I understand I will be offered medically supervised withdrawal. For women of childbearing age: Pregnant women treated with methadone or sublingual or buccal buprenorphine have better outcomes than pregnant women not in treatment who continue to use opioid drugs. Newborns of mothers who are receiving methadone or buprenorphine treatment may have opioid withdrawal symptoms (i.e., neonatal abstinence syndrome). The delivery hospital may require babies who are exposed to opioids before birth to spend a number of days in the hospital for monitoring of withdrawal symptoms. Some babies may also need medication to stop withdrawal. If I am or become pregnant, I understand that I should tell the medical staff of the OTP right away so I can receive or be referred to prenatal care. I understand that there are ways to maximize the healthy course of my pregnancy while I am taking methadone or buprenorphine. Signature of Patient: ___________________________________________________ Date of Birth: ________________ Date: ________________ Witness: ______________________________________________________________________ Adapted from material in the public domain.161 3-37 TIP 63Part 3 of 5—Medications for Opioid Use Disorder Chapter 3C: Naltrexone Chapter 3C gives an overview of naltrexone pharmacology and specifc guidance on dosing for oral and injectable naltrexone. The opioid receptor antagonist naltrexone was synthesized in the 1960s to block the euphoric effects of morphine.162 Oral naltrexone was approved by the Food and Drug Administration (FDA) in 1984 for the blockade of the effects of exogenously administered opioids. Long-acting, sustained-release opioid agonist preparations have been investigated since the 1970s to improve adherence over oral medications. In 2010, FDA approved injectable extended-release naltrexone (XR-NTX) for preventing return to opioid dependence after medically supervised withdrawal. Despite its potential advantages (e.g., no abuse liability, no special regulatory requirements), oral naltrexone is not widely used to treat opioid use disorder (OUD) because of low rates of patient acceptance, diffculty in achieving abstinence for the necessary time before initiation of treatment, and high rates of medication nonadherence.163 Before initiating either formulation of naltrexone, patients must be opioid abstinent for an adequate period of time after completing opioid with- drawal. Medically supervised opioid withdrawal can be conducted on an outpatient or inpatient basis. The latter is often reserved for patients with co-occurring substance use disorders (SUDs) or medical or psychiatric illness. There are several pharmacological approaches to medically supervised withdrawal. Methadone can be used for this purpose in opioid treatment programs (OTPs) and hospital settings. Patients in opioid withdrawal typically receive an indi- vidualized dose between 20 mg and 30 mg per day, gradually reduced over 6 days or more. Buprenorphine can be used in an adequate dose to lessen withdrawal symptoms and then reduced gradually over several days or more. If an opioid agonist is used for medically supervised withdraw- al, an adequate interval of time following the last dose must occur before naltrexone induction. When it is not possible to use opioid agonists, alpha-2 adrenergic agonists such as clonidine can be used off label at doses from 0.1 mg to 0.3 mg every 6 to 8 hours to treat symptoms.164 Formulations Oral: Oral naltrexone is a 50 mg tablet of naltrexone hydrochloride. It was approved by FDA in 1984 for blockade of the effects of exogenously administered opioids and in 1994 for alcohol dependence treatment. A Cochrane review examined 13 randomized trials among 1,158 patients who were opioid dependent and provided counseling. They were treated with or without oral naltrexone. The review concluded that oral naltrexone was not superior to placebo or to no medication in treatment retention or illicit opioid use reduction.165 XR-NTX: In 2006, FDA approved XR-NTX as an intramuscular (IM) injection every 4 weeks or once a month for the treatment of alcohol dependence. In 2010, FDA approved XR-NTX for the prevention of return to opioid dependence following medically supervised withdrawal. XR-NTX is a suspension of 380 mg naltrexone embedded in microspheres made from a biode- gradable copolymer that undergoes hydrolysis as it absorbs water. XR-NTX requires refrigeration and is supplied as a vial of dry powder along with a separate vial of an aqueous diluent, which providers combine just before use.166 XR-NTX is more effective than placebo167 or no medication168 in reducing risk of return to opioid use.169 A multisite randomized trial in the United States started in residential treatment 3-38 Medications for Opioid Use Disorder TIP 63 programs found that buprenorphine treatment was associated with lower rates of return to use during 24 weeks of postdischarge outpatient treatment compared with XR-NTX,170 given the signifcant proportion of patients who did not actually receive XR-NTX because of challenges related to XR-NTX induction. The same study found no signifcant between-group differences in rates of return to use when data were analyzed based solely on patients who did begin assigned medications. Study fndings may not generalize to outpatient settings, where XR-NTX induction may be more diffcult than in residential treatment settings. One additional study merits mention. A 12-week trial was conducted in Norway with 159 partic- ipants who, at the time of random assignment to XR-NTX or buprenorphine, had completed medically supervised withdrawal or were already opioid abstinent. XR-NTX was found to be non- inferior to buprenorphine in terms of treatment retention or reduction in illicit opioid use.171 Pharmacology Naltrexone is a competitive mu-opioid receptor antagonist with strong receptor affnity. Naltrexone does not activate the mu-opioid receptor and exerts no opioid effects. Unlike opioid agonists, naltrexone will not alleviate withdrawal symptoms, will not cause withdrawal when stopped, and cannot be diverted. If patients maintained on naltrexone use opioid agonists, naltrexone can block their effects—a key feature of its therapeutic effcacy. However, because the interaction at the receptor is competitive, the blockade can potentially be overridden with high doses of opioids. Taking naltrexone after recent use of opioids can precipitate opioid withdrawal. Given its strong affnity, naltrexone can displace other opioids from the receptor. Patients must typically wait 7 to 10 days after their last use of short- acting opioids and 10 to 14 days after their last use of long-acting opioids before taking their frst dose of naltrexone. Bioavailability Oral: The gastrointestinal tract readily absorbs oral naltrexone. Peak concentrations occur in 1 to 2 hours.172 XR-NTX: IM injection causes a transient peak blood concentration 2 hours after injection and another at 2 to 3 days after injection.173 About 14 days after injection, concentrations gradually diminish, with measurable blood levels for more than 1 month. Both formulations are extensively metabolized by the kidneys and liver, but without CYP450 enzyme system involvement. Unlike methadone and buprenorphine, naltrexone has limited potential drug–drug interactions. Its major metabolite, 6-beta naltrexol, is also a mu-opioid receptor antagonist. It is eliminated primarily by the kidneys in the urine.174 Orally administered naltrexone has a half-life of approximately 4 hours. Its primary me- tabolite, 6-beta-naltrexol, is a weak mu-opioid receptor antagonist with a half-life of approxi- mately 12 hours.175 XR-NTX, or “depot naltrexone,” is encapsu- lated in biodegradable polymer microspheres. It provides opioid blockade by delivering steady naltrexone concentrations for about 1 month.176 Elimination half-life is 5 to 10 days. Repeated administration causes no accumulation of naltrexone or its metabolites. Dosing Considerations XR-NTX XR-NTX is indicated for the prevention of return to opioid dependence following medically super- vised opioid withdrawal. Appropriate patients should have an adequate period of abstinence with no signs of opioid withdrawal before XR-NTX administration. Patients must be willing to receive monthly IM injections. Become acquainted with the FDA label for XR-NTX, which is available online (https://dailymed.nlm.nih.gov/dailymed/ drugInfo.cfm?setid=cd11c435-b0f0-4bb9-ae78- 60f101f3703f). 3-39 TIP 63Part 3 of 5—Medications for Opioid Use Disorder • • • • • Contraindications Contraindications to receiving XR-NTX (as well as to receiving oral naltrexone, with the exception of hypersensitivity to the XR-NTX suspension and diluent) include:177 • Current pain treatment with opioid analgesics. • Current physiological opioid dependence. • Current acute opioid withdrawal. • Severe hepatic impairment. • Naloxone challenge (Exhibit 3C.1) or oral naltrexone dose causing opioid withdrawal symptoms. • History of hypersensitivity to naltrexone, polylactide-co-glycolide, carboxymethylcellu- lose, or any other components of the diluent. Research suggests that patients who test positive for current opioid use are not contraindicated for XR-NTX induction as long as they pass the naloxone challenge, indicating they are not opioid dependent.178 In one study, patients being tran- sitioned to XR-NTX using a 7-day detoxifcation protocol could safely begin receiving XR-NTX as long as they passed a naloxone challenge on Day 8 of the protocol, even if they were unable to completely refrain from using opioids during the transition period.179,180 Patients who tested positive for either methadone or buprenorphine were excluded from enrollment in the study, however. Precautions and warnings Discuss the risks and benefts of continuing naltrexone with patients who become pregnant while receiving naltrexone treatment and whose OUD is in remission. Unlike methadone and buprenorphine, nal- trexone has been little researched in pregnant populations.181,182 Patients are vulnerable to opioid overdose death after completing the every-4-weeks or once-monthly dosing period, missing a dose, or stopping treatment. Trying to override opioid blockade with high opioid doses may cause overdose. Patients may experience injection site reactions including pain, tenderness, indura- tion, swelling, erythema, bruising, or pruritus. Severe injection site reactions may occur (e.g., cellulitis, hematoma, abscess, sterile abscess, necrosis). Some cases may require surgical in- tervention and may result in signifcant scarring. (See the Chapter 3C Appendix for techniques to reduce injection site reactions.) As with any IM injection, use caution in patients with thrombo- cytopenia or a coagulation disorder. Precipitated opioid withdrawal can occur in patients who used illicit opioids recently or switched from an opioid agonist med- ication. Symptoms may be severe enough for hospitalization. To avoid precipitated withdrawal from either formulation, patients should typically stop use of short-acting opioid agonists for 7 to 10 days and long- acting agonists for 10 to 14 days.183 There is also research on approaches to initiate XR-NTX more quickly for patients physically dependent on opioid agonists.184,185,186 Hepatitis has been associated with XR-NTX, often in the presence of other potential causes of hepatic toxicity (e.g., alcohol liver disease, viral hepatitis). Monitor liver function tests during treatment. Discontinue treatment in the presence of acute hepatitis and severe liver disease.187 Initiate or refer patients to treatment for hepatitis. • Use cautiously in patients with moderate- to-severe renal impairment, because the medication is eliminated primarily through the kidneys. • Hypersensitivity reactions can occur, including rash, urticaria, angioedema, and anaphylaxis. • Monitor patients with OUD for depression and suicidal ideation. Oral naltrexone use has been occasionally associated with dysphoria,188 although it’s unclear whether this is a side effect of the medication or a manifestation of underlying depression or depressed mood related to OUD.189 Monitor patients for depres- sion, which is common with OUD. • If a patient needs emergency pain treatment, regional anesthesia or nonopioid analgesics are alternatives to opioid analge- sics. A patient who must have opioids for pain treatment or anesthesia requires continuous monitoring in an anesthesia care setting. 3-40 Medications for Opioid Use Disorder TIP 63 EXHIBIT 3C.1. Naloxone Challenge Use the naloxone challenge to assess lack of physical opioid dependence. Naloxone can be administered via intravenous, subcutaneous, or IM routes to patients who report an adequate period of opioid abstinence and have a negative opioid urine test (including morphine, methadone, buprenorphine, and oxycodone). A negative naloxone challenge does not guarantee that the patient will not experience precipitated opioid withdrawal upon naltrexone administration.190 Intravenous Administration 1. Draw 0.8 mg naloxone into a sterile syringe. 2. Inject 0.2 mg naloxone intravenously. 3. Wait 30 seconds for signs and symptoms of withdrawal. If withdrawal signs/symptoms are present, stop the naloxone challenge and treat symptomatically. 4. If no withdrawal signs and symptoms are present and vital signs are stable, inject remaining naloxone (0.6 mg) and observe for 20 minutes. Check the patient’s vital signs and monitor for withdrawal. 5. If withdrawal signs and symptoms are present, stop the naloxone challenge and treat symptomatically. The test can be repeated in 24 hours or the patient can be considered for opioid agonist treatment. 6. If no withdrawal signs and symptoms are present* and oral naltrexone is the desired treatment course, give the patient two tablets of 25 mg naltrexone (take one tablet on each of the next 2 days) and a suffcient number of 50 mg naltrexone tablets (take one 50 mg tablet daily starting on the third day) until they are able to fll their prescription for oral naltrexone. Skip to Step 8. 7. If no withdrawal signs and symptoms are present** and XR-NTX is the desired treatment course, administer XR-NTX in the upper outer quadrant of the buttock, following package insert directions (summarized below). 8. Instruct the patient about the risk of overdose and death if they use opioids to override the blockade. Subcutaneous Administration 1. Inject 0.8 mg naloxone subcutaneously. 2. Wait 20 minutes while checking vital signs and observing for signs and symptoms of opioid withdrawal. 3. If withdrawal signs and symptom are present, stop the naloxone challenge and treat symptomatically. The test can be repeated in 24 hours or the patient can be considered for opioid agonist treatment. 4. If no withdrawal signs and symptoms are present, follow Step 6 (for oral naltrexone treatment) or Step 7 (for XR-NTX treatment) above. * Optional: If withdrawal signs and symptoms are absent, administer 25 mg oral naltrexone and observe for 2 hours. If the patient develops opioid withdrawal, treat symptomatically. If no withdrawal signs or symptoms are present following the 25 mg naltrexone dose and oral naltrexone is the desired treatment course, give the patient one tablet of 25 mg naltrexone to take the next day and 50 mg naltrexone tablets to take daily starting the day after. ** Optional: If withdrawal signs and symptoms are absent, administer 25 mg oral naltrexone and observe for 2 hours. If the patient develops opioid withdrawal, treat symptomatically and do not administer XR-NTX. This step is recommended to minimize the likelihood of longer lasting precipitated withdrawal in patients given XR-NTX who took buprenorphine recently (naloxone may not displace it from opioid receptors). This step can help identify a naltrexone allergy before providing XR-NTX. If no withdrawal symptoms are present following the 25 mg naltrexone dose and XR-NTX is the desired course, administer XR-NTX as described above. Adapted from material in the public domain.191 3-41 TIP 63Part 3 of 5—Medications for Opioid Use Disorder • Side efects Possible side effects of XR-NTX include (see the FDA label for a complete list https://dailymed .nlm.nih.gov/dailymed/drugInfo.cfm?setid=cd 11c435-b0f0-4bb9-ae78-60f101f3703f):192 • Insomnia. • Injection site pain. • Hepatic enzyme abnormalities. • Nasopharyngitis. Assessment Thorough assessment helps determine whether naltrexone treatment is appropriate for a patient. (Part 2 of this Treatment Improvement Protocol [TIP] covers screening and assessment in more detail.) Patients who have been abstinent from short-acting opioids (including tramadol) for 7 to 10 days or long-acting opioids (e.g., methadone, buprenorphine) for 10 to 14 days can initiate naltrexone following assessment that includes: • Checking the state prescription drug moni- toring program database. • Taking the patient’s history. − Conduct a medical, psychiatric, substance use, and substance use treatment history. can be used to assess withdrawal signs (see “Resource Alert: Opioid Withdrawal Scales”). The patient should not exhibit any signs of opioid withdrawal before taking the frst dose of naltrexone, to avoid precipitat- ed withdrawal. • Obtaining laboratory tests. − Conduct drug and alcohol tests. Use reliable urine tests for opioids (including morphine, methadone, buprenorphine, and oxycodone), benzodiazepines, cocaine, and other drugs commonly used in the area. Use a breathalyzer to estimate the patient’s blood alcohol content. − Conduct a pregnancy test. Naltrexone is not recommended for OUD treatment in pregnancy. Refer pregnant patients to prenatal care.193 − Assess liver function. Obtain liver function tests followed by periodic monitoring at 6- or 12-month intervals during treatment.194 − Obtain kidney function tests (e.g., creati- nine) for people who inject drugs. − Conduct hepatitis and HIV tests. Hepatitis B and C are common among patients entering naltrexone treatment. HIV infection is also prevalent. Everyone ages 15 to 65 should be tested at least once for HIV. − Assess recent opioid use, including frequency, quantity, type, route, and last day of use. Confrm an adequate opioid abstinence period. − Establish OUD diagnosis. − Assess for other SUDs, including those that involve alcohol, benzodiazepines, or stimulants. Conducting a physical exam. − Assess for signs and symptoms of intoxi- cation. Do not give a frst dose to a patient who is sedated or intoxicated. Assess and treat him or her appropriately. − Assess for evidence of opioid withdrawal and physiological dependence. The Clinical Opioid Withdrawal Scale (COWS) or the Clinical Institute Narcotic Assessment (CINA) Scale for Withdrawal Symptoms RESOURCE ALERT Opioid Withdrawal Scales The COWS and other opioid withdrawal scales from Annex 10 of the World Health Organization’s Guidelines for the Psychosocially Assisted Pharmacological Treatment of Opioid Dependence can be downloaded from the National Center for Biotechnology Information website (www.ncbi.nlm.nih.gov/books /NBK143183). The CINA Scale for Withdrawal Symptoms is also available online (www.ncpoep.org/wp -content/uploads/2015/02/Appendix_7_Clinical _Institute_Narcotic_Assessment_CINA_Scale _for_Withdrawal_Symptoms.pdf). 3-42 Medications for Opioid Use Disorder TIP 63 Persons at higher risk, such as people who use drugs by injection, should be tested annually.195 Anyone who is injecting or has ever injected drugs, even once, no matter how long ago, should be tested for hepatitis C, regardless of their intention to seek treatment for SUD.196 The Centers for Disease Control and Prevention recom- mends hepatitis B vaccine for individuals seeking treatment for SUDs.197 During assessment, discuss with patients the risks and benefts of naltrexone and alternative treatment approaches. Explore patients’ moti- vation to initiate medication treatment and to adhere to the dosing regimen. Start naltrexone if the patient: • Meets Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria for OUD. • Understands risks and benefts. • Reports opioid abstinence for 7 to 10 days (short acting) or 10 to 14 days (long acting). • Reports no allergies to naltrexone or the components of the XR-NTX preparation. • Does not have a coagulation disorder. • Will not soon require opioid analgesia. • Has a negative pregnancy test. • Has a negative urine opioid screen for morphine, methadone, buprenorphine, oxycodone, and other opioids. • Is free of current opioid withdrawal signs Inform patients of all their treatment options and the settings in which they are available. OTPs may be best for patients needing more structure. Tailor decisions about which medica- tion to use to patients’ medical and substance use histories, patient preferences, and treatment availability. Pregnant women are not appropriate candidates for XR-NTX treatment. Potentially suitable candidates for XR-NTX treatment include patients who:199 • Do not wish to take opioid agonists. • Have been opioid abstinent for at least 1 week, have recently been or will soon be released from controlled environments (e.g., incarceration, residential addiction treatment), and do not wish to initiate (or are not able to access) opioid agonist treatment. For patients requesting opioid agonist treatment, methadone or buprenorphine must be started at much lower doses and increased much more slowly than for opioid-tolerant patients (see sections on methadone and buprenor- phine dosing). • Have not responded well to prior adequate treatment with opioid agonist therapy.200 • Are part of an overall program with external monitoring and signifcant, immediate external consequences for lack of adherence (because these patients [e.g., healthcare professionals, and symptoms (Exhibit 3C.2). • Has liver function test results that do not indicate acute hepatitis or liver failure. • Has a negative naloxone challenge result (Exhibit 3C.1). Patient selection No evidence clearly predicts which patients are best treated with XR-NTX versus other OUD medications. A secondary analysis of the data from a randomized trial of XR-NTX versus placebo conducted in Russia found no signifcant baseline predictors of successes among the 25 variables examined, including demographics, clinical severity, level of functioning, craving, and HIV serostatus.198 EXHIBIT 3C.2. Signs and Symptoms of Opioid Withdrawal Signs Runny nose Tearing Yawning Sweating Tremor Vomiting Piloerection Pupillary dilation Symptoms Skin crawling Abdominal cramps Temperature changes Nausea Vomiting Diarrhea Bone or muscle pain Dysphoria Craving for opioids 3-43 TIP 63Part 3 of 5—Medications for Opioid Use Disorder pilots, probationers, parolees] may show higher rates of retention with XR-NTX because of required external monitoring).201 • Have home locations or work schedules making daily or almost-daily OTP visits impossible or risky (e.g., job loss). One study demonstrated that stable patients who were able to taper to 8 mg or less of buprenor- phine may be successfully started on XR-NTX using a regimen consisting of a buprenorphine taper and ancillary medications to palliate withdrawal symptoms.202 The study employed a hybrid outpatient and residential care model and excluded patients who consistently tested positive for illicit or nonprescribed opioids. Informed consent Inform all patients of the following basic information: • Their OUD diagnosis and the nature of the disorder • Risks and benefts of XR-NTX and other OUD medications • Risks and benefts of nonmedication treatments Consider asking patients to sign a treatment agreement form before starting treatment. (See Appendix 3C for a sample treatment agreement.) Document informed consent discus- sions in the medical record. Educate patients and their families about what to expect from XR-NTX treatment (Exhibit 3C.3). A naltrexone medication guide should be dispensed to patients with each injection. Caution them about increased risk of overdose if they stop treatment and return to illicit opioid use or attempt to override the receptor blockade of XR-NTX. Document education in the medical record. Chapter 3C Appendix has a patient education counseling tool for XR-NTX. Use language and written materials appropriate to each patient’s comprehension level to ensure that he or she understands the options and can make informed decisions. Initiating XR-NTX treatment Storage and preparation A pharmacy will send XR-NTX and its diluent in a refrigerated package with two sets of administra- tion needles (1.5 and 2 inches), a 1-inch prepara- tion needle, and a needle protection device. The XR-NTX microspheres are temperature sensitive. When the carton arrives from the pharmacy, store it in a refrigerator at 36 to 46 degrees Fahrenheit (2 to 8 degrees Celsius). The refrigerator should have a working thermometer; check the temperature regularly. Do not freeze the carton or expose it to tem- peratures above 77 degrees Fahrenheit (25 degrees Celsius). XR-NTX can be stored unrefrig- erated for up to 7 days before administration. Before preparing XR-NTX for administration, keep it at room temperature for about 45 minutes. Examine the microspheres and diluent to ensure that no particulate matter or discolor- ation are present. Mix following FDA-approved package insert directions, using the 1-inch preparation needle. Resulting suspension should be milky white, without clumps, and able to move freely down the wall of the vial. Two sets of needles of two different lengths are shipped with the medication in case the frst needle clogs before injection. Use the 1.5-inch needle for lean patients and the 2-inch needle for patients with more subcutaneous tissue overlying the gluteal muscle. The longer needle helps ensure that the injection reaches the muscle. Inject patients with average body habitus with either needle. Administration Administer XR-NTX every 4 weeks or once a month as a 380 mg IM gluteal injection. Alternate buttocks for each 4-week injection. Given the risk of severe injection site reactions, FDA requires a risk evaluation and mitigation strategy (www.vivitrolrems.com) for XR-NTX including a patient counseling tool, a patient medication guide, and a visual aid to reinforce proper XR-NTX injection technique. 3-44 Medications for Opioid Use Disorder TIP 63 • • • • • • • • • • EXHIBIT 3C.3. Key Points of Patient Education for XR-NTX • • • • Do not use any opioids in the 7 to 10 days (for short acting) or 10 to 14 days (for long acting) before starting XR-NTX, to avoid potentially serious opioid withdrawal symptoms. Opioids include: - Heroin. - Prescription opioid analgesics (including tramadol). - Cough, diarrhea, or other medications that contain codeine or other opioids. - Methadone. - Buprenorphine. Seek immediate medical help if symptoms of allergic reaction or anaphylaxis occur, such as: - Itching. - Swelling. - Hives. - Shortness of breath. - Throat tightness. Do not try to override the opioid blockade with large amounts of opioids, which could result in overdose. Understand the risk of overdose from using opioids near the time of the next injection, after missing a dose, or after stopping medications. Report injection site reactions including: - Pain. - Hardening. - Lumps. Follow-up care afer frst dose Examine patients within a week of administer- ing their frst XR-NTX dose. It can be clinically benefcial to maintain weekly contact in the frst month to: • Provide supportive counseling. • Assess ongoing drug or alcohol use. • Monitor side effects. • Obtain drug testing. • Follow up on status of referrals to counseling or other services. - Blisters. - Blackening. - Scabs. - An open wound. Some of these reactions could require surgery to repair (rarely). Report signs and symptoms of hepatitis (e.g., fatigue, abdominal pain, yellowing skin or eyes, dark urine). Report depression or suicidal thoughts. Seek immediate medical attention if these symptoms appear. Seek medical help if symptoms of pneumonia appear (e.g., shortness of breath, fever). Inform providers of naltrexone treatment, as treatment differs for various types of pneumonia. Inform all healthcare professionals of XR-NTX treatment. Report pregnancy. Inform providers of any upcoming medical procedures that may require pain medication. Understand that taking XR-NTX may result in diffculty achieving adequate pain control if acute medical illness or trauma causes severe acute pain. Wear medical alert jewelry and carry a medical alert card indicating you are taking XR-NTX. A patient wallet card or medical alert bracelet can be ordered at 1-800-848-4876. Patients who test the opioid blockade of XR-NTX may discontinue use because of the blocking of the euphoric effects of illicit opioids.203 Patients who miss a dose can restart medication (use procedures outlined earlier in this section) after an adequate period of opioid abstinence (7 to 14 days). The TIP expert panel cautions that, based on current data, arbitrary time limits on XR-NTX are inappropriate. 3-45 TIP 63Part 3 of 5—Medications for Opioid Use Disorder See Chapter 3E for information on the manage- ment of patients taking naltrexone in offce- based treatment settings. Duration of treatment Barring contraindications, patients should continue taking XR-NTX as long as they beneft from it and want to continue. Data are limited on the long-term effectiveness of XR-NTX compared with methadone or buprenorphine. Treatment discontinuation When patients wish to discontinue naltrexone, engage in shared decision making and explore: • Their reasons for wanting to discontinue. • The risks and benefts of discontinuing. • Problem-solving strategies that can help them make an informed choice. • Their appropriateness for buprenorphine or methadone treatment. Discourage patients who are not yet stable from discontinuing treatment, because of the high rate of return to illicit opioid use and the increased chance of overdose death. Signs that a patient may be ready to discontinue medication include:204 • Sustaining illicit drug abstinence over time. • Having stable housing and income. RESOURCE ALERT • Having no legal problems. • Having substantially reduced craving. • Attending counseling or mutual-help groups. Patients who discontinue should have a recovery plan that may include monitoring as well as adjunctive counseling and recovery support. If they return to opioid use, encourage them to return for assessment and reentry into treatment. Given the high risk of return to illicit opioid use, offer patients information about opioid overdose prevention and a naloxone pre- scription they can use in case of overdose. When patients stop using naltrexone, they will have no tolerance for opioids. Their risk of overdose is very high if they use again. For more information, see the SAMHSA Opioid Overdose Prevention Toolkit (https://store.samhsa.gov/ product/Opioid-Overdose-Prevention-Toolkit/ SMA18-4742). Rapid naltrexone induction Patients with OUD need to discontinue opioids and wait 7 to 14 days after last opioid use (including any given for with- drawal treatment) before receiving XR-NTX. As described above, they can do so through medically supervised withdrawal in a controlled environment, such as an inpatient unit, residen- tial addiction treatment program, correctional facility, or hospital, or on an outpatient basis. Financial issues and managed care constraints may infuence patients’ access to controlled treatment environments. The alternative— abstaining long enough after outpatient medically supervised withdrawal—is challeng- ing. Thus, various approaches to rapid naltrexone induction have been developed205 and more recently refned in research settings.206,207,208 Consider rapid induction in specialty addiction treatment programs, not general medical settings. It may be hard for providers in general medical settings to start XR-NTX successfully with patients who need medically supervised opioid withdrawal. Rapid induction approaches are likely beyond the scope of general outpatient Patient and Family Educational Resources Decisions in Recovery: Treatment for Opioid Use Disorder offers information for patients on the use of medications for OUD (https://store .samhsa.gov/product/SMA16-4993). Medication-Assisted Treatment for Opioid Addiction: Facts for Families and Friends offers information for family and friends (https://portal. ct.gov/-/media/DMHAS/Opioid-Resources/ MATInfoFamilyFriendspdf.pdf). 3-46 Medications for Opioid Use Disorder TIP 63 settings. However, patients can successfully initiate XR-NTX in a general outpatient medical setting if they: • Have been abstinent for suffcient time and pass the naloxone challenge. • Started taking XR-NTX elsewhere and are due for the next injection. One randomized trial compared two approaches to starting XR-NTX on an outpatient basis. This study assigned adults dependent on opioids to either a standard 14-day buprenorphine- assisted opioid withdrawal or more rapid 7-day oral naltrexone-assisted opioid withdrawal.209 Naltrexone-assisted withdrawal was conducted over 7 days. It included 1 day of buprenorphine administration; 1 day with ancillary medications including clonidine and clonazepam but no buprenorphine; followed by 4 days of ancillary medications and increasing daily doses of oral naltrexone (starting with 1 mg, 3 mg, 12 mg, and 25 mg); and concluding on day 7 with XR-NTX administration. Buprenorphine-assisted withdrawal consisted of a 7-day buprenorphine taper followed by the recommended 7 days without opioids. The naltrexone-assisted withdrawal group was signifcantly more likely to begin XR-NTX compared with the buprenorphine-assisted withdrawal group (56.1 percent versus 32.7 percent, respectively). This type of approach, which must be conducted with careful daily monitoring, is used in some residential programs and may prove to be a useful approach to outpatient XR-NTX induction in specialty programs. More discussion on rapid induction approaches is available in Implementing Antagonist-Based Relapse Prevention Treatment for Buprenorphine-Treated Individuals,210 available online (http://pcssmat.org/wp-content /uploads/2015/02/PCSSMAT-Implementing -Antagonist-with-Case.Bisaga.CME_.pdf). Oral Naltrexone The effectiveness of oral naltrexone is limited, given poor adherence and the requirement of 7 to 14 days of opioid abstinence before initiation. During this waiting period, patients may drop out of care. One study found signifcantly lower patient retention in treatment after incarcera- tion for patients treated with oral naltrexone compared with methadone.211 Oral naltrexone blocks opioid-induced euphoria for only a day or two. When patients stop taking it, risks of return to opioid use and overdose increase. The TIP expert panel doesn’t recommend using oral naltrexone except in the limited circumstances described in the following sections. This view is in keeping with expert reviews for the United Kingdom’s National Health Service,212 a clinical practice guideline published by the Department of Veterans Affairs and Department of Defense,213 and a Cochrane review.214 Indications and contraindications, precautions and warnings, side efects, and assessment. All are similar to those for XR-NTX, save issues specifc to suspension/diluent contents and the injection itself. Patient Selection In limited circumstances, oral naltrexone may be considered after the risks and benefts, as well as alternative treatments, are discussed with the patient. Examples include: • Patients who cannot afford XR-NTX but wish to take an opioid receptor antagonist. • Patients with high levels of monitoring and negative consequences for nonadherence, such as healthcare professionals who may not be permitted to have opioid agonist treatment.215,216 The TIP expert panel does not recommend that payers require patients to fail oral naltrexone before providing access to XR-NTX, given the risk of unintentional overdose death if the patient returns to illicit opioid use. 3-47 TIP 63Part 3 of 5—Medications for Opioid Use Disorder • • • • • • • Patients leaving controlled environments (e.g., prisons, hospitals, inpatient addiction re- habilitation) who may beneft from medication to prevent return to illicit drug use but cannot or will not take XR-NTX and do not wish to be treated with (or do not have access to) opioid agonists. Patients who have taken methadone or ex- tensively used heroin are especially poor oral naltrexone candidates.217 Dosing Following a negative naloxone challenge, the frst oral dose of naltrexone can be 25 mg (half of the usual daily naltrexone maintenance dose). This reduces risk of a more severe precipitated opioid withdrawal than could occur with a full 50 mg dose. This lower dose may also reduce nausea associated with the frst oral naltrexone dose. The dose can be increased to 50 mg daily on the second day. To increase adherence, arrange for directly observed administration of oral naltrexone. This is more feasible if patients who tolerate a daily dose of 50 mg are switched to a 3-days- per-week regimen for a total weekly dose of 350 mg (e.g., administer 100 mg on Monday and Wednesday and 150 mg on Friday). A member of the patient’s social network (e.g., spouse) may also directly observe therapy. Duration of treatment The optimal length of treatment with oral naltrexone is not known. In general, the longer patients take an effective medication, the better their outcomes. Use of illicit opioids during treatment with oral naltrexone is a cause of concern and may be a precursor to treatment discontinuation.218 Some patients will initially test the opioid blockade with illicit opioids and then discontinue opioid use. However, others will continue using illicit opioids.219 If patients continue to test the blockade, immediately discuss alternative treatment plans that include: • Increased counseling. • Switching to XR-NTX. • Closer monitoring. • Directly observed oral naltrexone therapy. • Residential treatment. • Assessment for the appropriateness of buprenorphine or methadone. Naltrexone Dosing Summary XR-NTX Before administering XR-NTX, keep it at room temperature for about 45 minutes. Use the correct needle length to ensure the injection is in the gluteal muscle. − Use the 2-inch needle for patients with more subcutaneous tissue and the 1.5-inch needle for patients with less adipose tissue. − Use either length in patients with normal body habitus. Use proper aseptic technique. Use proper gluteal IM injection technique. Never inject intravenously or subcutaneously. Repeat the injection every 4 weeks or once per month. Oral Naltrexone • Use in limited circumstances after discussing risks and benefts, as well as alternative treatment options, with the patient. • Do the naloxone challenge. • The frst oral naltrexone dose should be 25 mg. • The dose can be increased on the second day to 50 mg daily if necessary. • If desired, switch patients who tolerate a daily dose of 50 mg to a 3-days-per-week regimen for a total weekly dose of 350 mg. 3-48 Medications for Opioid Use Disorder TIP 63 Chapter 3C Appendix Sample XR-NTX Treatment Agreement This form is for educational/informational purposes only. It doesn’t establish a legal or medical standard of care. Healthcare professionals should use their judgment in interpreting this form and applying it in the circumstances of their individual patients and practice arrangements. The information provided in this form is provided “as is” with no guarantee as to its accuracy or completeness. TREATMENT AGREEMENT I agree to accept the following treatment agreement for extended-release injectable naltrexone (XR-NTX) offce-based opioid use disorder treatment: 1. The risks and benefts of XR-NTX treatment have been explained to me, and I understand the information provided. 2. The risks and benefts of other treatment for opioid use disorder (including methadone, buprenorphine, and nonmedication treatments) have been explained to me. 3. I will be on time to my appointments and respectful to the offce staff and other patients. 4. I will keep my healthcare provider informed of all my medications (including herbs and vitamins) and medical problems. 5. I agree not to obtain or take prescription opioid medications prescribed by any other healthcare provider. 6. If I am going to have a medical procedure that will cause pain, I will let my healthcare provider know in advance so that my pain will be adequately treated. 7. If I miss a scheduled appointment for my XR-NTX injection, I understand that I should reschedule the appointment as soon as possible because it is important to receive the medication on time to reduce the risk of opioid overdose should I return to use. 8. If I come to the offce intoxicated, I understand that my healthcare provider will not see me. 9. Violence, threatening language or behavior, or participation in any illegal activity at the offce will result in treatment termination from the clinic. 10. I understand that random urine drug testing is a treatment requirement. If I do not provide a urine sample, it will count as a positive drug test. 11. I understand that initially I will have weekly offce visits until my condition is stable. 12. I can be seen every 2 weeks in the offce starting the second month of treatment if I have two negative urine drug tests in a row. 13. I may be seen less than every 2 weeks based on goals made by my healthcare provider and me. 14. I understand that people have died trying to overcome the opioid blockade by taking large amounts of opioids. 15. I understand that treatment of opioid use disorder involves more than just taking medication. I agree to follow my healthcare provider’s recommendations for additional counseling and/or for help with other problems. 16. I understand that there is no fxed time for being on XR-NTX and that the goal of treatment is for me to stop using all illicit drugs and become successful in all aspects of my life. 17. I understand that my risk of overdose increases if I go back to using opioids after stopping XR-NTX. 18. I have been educated about the other two FDA-approved medications used to treat opioid use disorder, methadone and buprenorphine, and I prefer to receive treatment with XR-NTX. 19. I have been educated about the increased chance of pregnancy when stopping illicit opioid use and starting XR-NTX treatment and have been informed about methods for preventing pregnancy. 20. I have been informed that if I become pregnant during naltrexone treatment, I should inform my provider and have a discussion about the risks and benefts of continuing to take XR-NTX. Other specifc items unique to my treatment include: Patient’s Name (print): _____________________________________________________ Patient’s Signature: ________________________________________________________ Date: ____________________ This form is adapted from the American Society of Addiction Medicine’s Sample Treatment Agreement, which is updated periodically; the most current version of the agreement is available online (www.asam.org/docs/default-source/advocacy/sample -treatment-agreement30fa159472bc604ca5b7ff000030b21a.pdf?sfvrsn=0). Adapted with permission.220 3-49 TIP 63Part 3 of 5—Medications for Opioid Use Disorder • • • • Intense pain The area feels hard Large areas of swelling Lumps • • • Blisters Open wound Dark scab • • Stomach area pain lasting more than a few days Dark urine • • Yellowing of the whites of eyes Tiredness Patient Counseling Tool for XR-NTX Patient Counseling Tool VIVITROL® (naltrexone for extended-release injectable suspension) Risk of sudden opioid withdrawal during initiation and re-initiation of VIVITROL Using any type of opioid including street drugs, prescription pain medicines, cough, cold or diarrhea medicines that contain opioids, or opioid dependence treatments buprenorphine or methadone, in the 7 to 14 days before starting VIVITROL may cause severe and potentially dangerous sudden opioid withdrawal. Risk of opioid overdose Patients may be more sensitive to the effects of lower amounts of opioids: • After stopping opioids (detoxifcation) • If a dose of VIVITROL is missed • When the next VIVITROL dose is due • After VIVITROL treatment stops Patients should tell their family and people close to them about the increased sensitivity to opioids and the risk of overdose even when using lower doses of opioids or amounts that they used before treatment. Using large amounts of opioids, such as prescription pain pills or heroin, to overcome effects of VIVITROL can lead to serious injury, coma, and death. Risk of severe reactions at the injection site Remind patients of these possible symptoms at the injection site: Some of these injection site reactions have required surgery. Tell your patients to contact a healthcare provider if they have any reactions at the injection site. Risk of liver injury, including liver damage or hepatitis Remind patients of the possible symptoms of liver damage or hepatitis. Patients may not feel the therapeutic effects of opioid-containing medicines for pain, cough or cold, or diarrhea while taking VIVITROL. Patients should carry written information with them at all times to alert healthcare providers that they are taking VIVITROL, so they can be treated properly in an emergency. A Patient Wallet Card or Medical Alert Bracelet can be ordered from: 1-800-848-4876, Option #1. PLEASE SEE PRESCRIBING INFORMATION AND MEDICATION GUIDE. Alkermes® and VIVITROL® are registered trademarks of Alkermes, Inc. ©2013 Alkermes, Inc. All rights reserved VIV-001317 Printed in U.S.A w w w.vivitrol.com Available online (www.vivitrolrems.com/content/pdf/patinfo-counseling-tool.pdf). Reprinted with permission.221 3-50 Medications for Opioid Use Disorder TIP 63 Key Techniques for Reducing Injection Site Reactions222 To reduce severe injection site reactions when administering XR-NTX via intramuscular injection, use the following techniques: • Use one of the administration needles provided with the XR-NTX kit to ensure that the injection reaches the gluteal muscle. Use the 2-inch needle for patients who have more subcuta- neous adipose tissue. Use the 1.5-inch needle for patients with less subcutaneous adipose tissue. Either needle is appropriate for use with patients who have average amounts of subcutaneous adipose tissue. • Use aseptic technique when administering intramuscularly. Using a circular motion, clean the injection site with an alcohol swab. Let the area dry before administering the injection. Do not touch this area again before administration. • Use proper deep intramuscular injection technique into the gluteal muscle. XR-NTX must not be injected intravenously, subcutaneously, or into adipose tissue. Accidental subcutaneous injection may increase the risk of severe injection site reactions. − Administer the suspension by deep intramuscular injection into the upper outer quadrant of gluteal muscle, alternating buttocks per monthly injection. − Remember to aspirate for blood before injection. If blood aspirates or the needle clogs, do not inject. Change to the spare needle provided in the package and administer into an adjacent site in the same gluteal region, again aspirating for blood before injection. − Inject the suspension in a smooth, continuous motion. A patient counseling tool is available to help you counsel your patients before administration about the serious risks associated with XR-NTX. The above information is a selection of key safety information about the XR-NTX injection. For complete safety information, refer to the directions for use and the prescribing information provided in the medication kit. You can also obtain this information online (www.vivitrolrems.com) or by calling 1-800-VIVITROL. Available online (www.vivitrolrems.com/content/pdf/patinfo-injection-poster.pdf). 3-51 TIP 63Part 3 of 5—Medications for Opioid Use Disorder • • • • • • • Chapter 3D: Buprenorphine Chapter 3D is an overview of buprenorphine pharmacology and specifc dosing guidance for sublingual and buccal formulations and buprenorphine implants and injections. Buprenorphine and buprenorphine/naloxone formulations are effective treatments for opioid use disorder (OUD). Numerous clinical studies and randomized clinical trials have demonstrated buprenorphine’s effcacy in retaining patients in treatment and reducing illicit opioid use compared with treatment without medication and medically supervised withdrawal.223,224,225 Other research has associated it with reduction in HIV risk behavior and risk of overdose death, and its effectiveness has been shown in primary care settings.226,227,228,229,230 Buprenorphine is on the World Health Organization (WHO) list of essential medications.231 The Treatment Improvement Protocol (TIP) expert panel recommends offering the option of Food and Drug Administration (FDA)- approved buprenorphine formulations to appropriate patients with OUD, considering patient preferences for and experience with other medications or no medication. These recommendations align with Department of Veterans Affairs guidelines.232 Formulations History of Approvals FDA originally approved buprenorphine for analgesia. Formulations for OUD treatment were approved in: 2002: Sublingual buprenorphine/naloxone sublingual tablets (Suboxone); sublingual buprenorphine tablets (Subutex). The manu- facturer discontinued the tablet formulations of both from the U.S. market after the flm’s approval, but generic tablet formulations are still available (Exhibit 3A.5, Chapter 3A). 2010: Buprenorphine/naloxone sublingual flms. 2013: Buprenorphine/naloxone sublingual tablets (Zubsolv).233 2014: Buprenorphine/naloxone buccal flms (Bunavail).234 2016: Buprenorphine implants (Probuphine). 2017: Buprenorphine extended-release injection (Sublocade). 2018-2019: Additional dosage strengths of buprenorphine/naloxone sublingual flms. FDA approved generic buprenorphine and buprenorphine/naloxone formulations based on evidence that they produce similar (within 90 percent confdence intervals) bioequivalence on pharmacokinetic measures, such as peak serum concentration, compared with the original sublingual buprenorphine/naloxone product. The 2013 and 2014 branded formulations have greater bioavailability than Suboxone, meaning they deliver more buprenorphine to the bloodstream, thus achieving the same effect as the original product with lower doses. For example, 5.7 mg/1.4 mg of Zubsolv and 4.2 mg/0.7 mg of Bunavail provide the same buprenorphine exposure as 8 mg/2 mg of Suboxone. Opioid treatment programs (OTPs) may administer or dispense buprenorphine, but only providers with Substance Abuse and Mental Health Services Administration (SAMHSA) waivers can prescribe buprenorphine for OUD. See “Resource Alert: How To Obtain a Waiver To Prescribe Buprenorphine” in Chapter 3A of this TIP. 3-52 Medications for Opioid Use Disorder TIP 63 Exhibit 3D.1 lists product strengths and recom- mended once-daily maintenance doses. For simplicity, dosing information here refers to sublingual Suboxone or generic equivalents. An 8 mg/2 mg dosage of sublingual Suboxone is equivalent to 5.7 mg/1.4 mg of sublingual Zubsolv and 4.2 mg/0.7 mg of buccal Bunavail. Patients who switch formulations may experience clinically signifcant plasma concentration changes that may require dose adjustments; bioavail- ability is similar, but not identical, between formulations. Implants In 2016, FDA approved buprenorphine implants for OUD maintenance treatment in patients who have achieved sustained clinical stability (e.g., periods of abstinence, minimal or no desire to use illicit opioids, stable housing, social support) while taking no more than 8 mg of Suboxone or generic equivalents. The implants are a set of four rods, each 2.5 mm in diameter and 26 mm in length. Each rod contains the equivalent of 80 mg of buprenorphine hydrochloride. The implants are for EXHIBIT 3D.1. Buprenorphine Transmucosal Products for OUD Treatment PRODUCT NAME/ ACTIVE INGREDIENT ROUTE OF ADMINISTRATION/ FORM AVAILABLE STRENGTHS RECOMMENDED ONCE- DAILY MAINTENANCE DOSE Bunavail235 • Buprenorphine hydrochloride • Naloxone hydrochloride Buccal flm 2.1 mg/0.3 mg 4.2 mg/0.7 mg 6.3 mg/1 mg Target: 8.4 mg/1.4 mg Range: 2.1 mg/0.3 mg to 12.6 mg/2.1 mg Generic combination product236,237 • Buprenorphine hydrochloride • Naloxone hydrochloride Sublingual tablet, flm 2 mg/0.5 mg 4 mg/1 mg 8 mg/2 mg 12 mg/3 mg Target: 16 mg/4 mg Range: 4 mg/1 mg to 24 mg/6 mg* Generic monoproduct238,239 • Buprenorphine hydrochloride Sublingual tablet 2 mg 8 mg Target: 16 mg Range: 4 mg to 24 mg* Suboxone240,241 • Buprenorphine hydrochloride • Naloxone hydrochloride Sublingual flm 2 mg/0.5 mg 4 mg/1 mg 8 mg/2 mg 12 mg/3 mg Target: 16 mg/4 mg Range: 4 mg/1 mg to 24 mg/6 mg* Zubsolv242,243 • Buprenorphine hydrochloride • Naloxone hydrochloride Sublingual tablet 0.7 mg/0.18 mg 1.4 mg/0.36 mg 2.9 mg/0.71 mg 5.7 mg/1.4 mg 8.6 mg/2.1 mg 11.4 mg/2.9 mg Target: 11.4 mg/2.9 mg Range: 2.9 mg/0.71 mg to 17.2 mg/4.2 mg *Dosages above 24 mg buprenorphine or 24 mg/6 mg buprenorphine/naloxone per day have shown no clinical advantage.244,245 Adapted from material in the public domain.246 3-53 TIP 63Part 3 of 5—Medications for Opioid Use Disorder subdermal insertion on the inside of the upper arm and provide 6 months of buprenorphine. The implants must be removed after 6 months. Peak buprenorphine plasma concentrations occur 12 hours after implant insertion, slowly decrease, and reach steady-state concentrations in about 4 weeks. Steady-state concentrations are comparable to trough buprenorphine plasma levels produced by daily sublingual buprenor- phine doses of 8 mg or less. Implant effective- ness lasts up to 6 months. Injectables In November 2017, FDA approved extended- release (monthly) subcutaneous injectable buprenorphine for moderate-to-severe OUD treatment among patients who initiated treatment with transmucosal buprenorphine, followed by at least 7 days of dose adjustment. It is available in two doses, 300 mg/1.5 mL and 100 mg/0.5 mL. Both are stored refrigerated in preflled syringes with safety needles and administered by subcutaneous injection in the abdomen. The frst two monthly doses recom- mended are 300 mg each followed by a 100 mg monthly maintenance dose. Peak buprenorphine concentrations occur about 24 hours after the injection. Steady state is achieved after 4 to 6 months. After discontinuation, patients may have detectable plasma levels of buprenorphine for 12 months or longer. Duration of detection in urine is not known.247 Pharmacology Buprenorphine, an opioid receptor partial agonist, is a schedule III controlled medication derived from the opium alkaloid thebaine. Through cross-tolerance and mu-opioid receptor occupancy, at adequate doses, buprenorphine reduces opioid withdrawal and craving and blunts the effects of illicit opioids. Buprenorphine binds tightly to the mu-opioid receptor because of its particularly high receptor affnity. This prevents other opioids with lower affnity (e.g., heroin) from binding. The net result is a blunting or blocking of the euphoria, respiratory depression, and other effects of these opioids. Buprenorphine has less potential to cause respiratory depression, given its ceiling effect. As a partial agonist, buprenorphine’s maximum effect on respiratory depression is more limited than full agonists. Once reaching a moderate dose, its effects no longer increase if the dose is increased.248,249,250 There is wide individual variability in bu- prenorphine pharmacokinetics. For example, the mean time to maximum plasma buprenor- phine concentration after a single sublingual dose ranges from 40 minutes to 3.5 hours.251 Thus, after providing the frst dose of buprenor- phine, wait at least 2 hours to decide whether a second dose is necessary. Buprenorphine has a long elimination half-life, which varies from 24 to 69 hours252 with a mean half-life of 24 to 42 hours.253 It dissociates slowly from the receptor. Buprenorphine can be safely dosed (even at double the stabilized dose) less than daily.254 For example, a patient stabilized on 12 mg of buprenorphine/naloxone daily can be treated with 24 mg every other day or 24 mg on Monday/Wednesday and 36 mg on Friday. Such schedules reduce travel burden for patients who need or want supervised dosing at an OTP or a clinic. Such schedules may also be useful for patients who must spend weekends in jails that disallow buprenorphine dosing. Bioavailability Buprenorphine has poor oral bioavailabil- ity compared with sublingual and buccal bioavailability. Naloxone, a short-acting mu-opioid receptor antagonist, has very poor oral, sublingual, and buccal bioavailability but is absorbed when injected or snorted. The addition of naloxone decreases buprenorphine’s potential for misuse. In the Suboxone formu- lation of buprenorphine/naloxone, the ratio of 3-54 Medications for Opioid Use Disorder TIP 63 • buprenorphine to naloxone is 4:1. The ratio of buprenorphine to naloxone varies across products, as the absorption of both active ingre- dients is different for buccal versus sublingual flms versus tablets. Buprenorphine/naloxone transmucosal products are abuse-deterrent formulations, although they can still be misused. When a patient takes these formulations as prescribed, he or she absorbs buprenorphine but only a biologically negligible amount of naloxone. But if crushed or dissolved for intranasal or intravenous (IV) misuse, both medications are bioavailable. Naloxone then blunts the immediate opioid agonist effects of buprenorphine. It also induces opioid withdrawal in people who are physically dependent on opioids. This reduces misuse liability compared with transmucosal formulations with buprenorphine alone.255,256 Subdermal buprenorphine implants release bu- prenorphine in steady concentrations over 6 months. These concentrations are approximately equivalent to 8 mg or less of the buprenorphine sublingual formulations. Once implanted, these rods are unlikely to be diverted. Extended-release buprenorphine for subcuta- neous injection releases buprenorphine over at least a 1-month period. After injection, an initial buprenorphine plasma level peaks around 24 hours and then slowly declines to a plateau. With monthly injections, steady state is reached at 4 to 6 months.257 Metabolism and Excretion Buprenorphine:258,259 • Is highly plasma bound. • Crosses the blood–brain barrier readily because of its high lipid solubility. • Is excreted in urine and feces. • Has only one known pharmacologically active metabolite: norbuprenorphine. Be aware of potential CYP450 3A4 inducers,260 substrates, and inhibitors while monitoring for potential drug–drug interactions (see the “Drug Interactions” section below). Buprenorphine undergoes metabolism in the liver primarily by cytochrome P450 (CYP450) 3A4 enzymes. Coadministration of other medications metabolized along this pathway can affect the rate of buprenorphine metabolism. Buprenorphine has fewer clinically relevant drug interactions than methadone in general. For detailed explanations of metabolism and excretion, see the package inserts for each buprenorphine product. Dosing Considerations Buprenorphine is used for the treatment of OUD. Formulations are available as sublingual tablets and flm, buccal flm, implants, and extended- release injection (Exhibit 3A.5 in Chapter 3A of this TIP). Contraindications Buprenorphine is contraindicated in patients who are allergic to it. Patients with true allergic reactions to naloxone should not be treated with the combination buprenorphine/naloxone product. Allergy to naloxone is infrequent. Some patients may falsely or mistakenly claim an allergy to naloxone and request buprenorphine monoproduct. Carefully assess such claims and explain the differences between an allergic reaction and symptoms of opioid withdrawal precipitated by buprenorphine or naloxone; the monoproduct has more abuse liability than buprenorphine/naloxone.261 Precautions and Warnings Respiratory depression and overdoses are uncommon in adults, but they do happen.262 Most fatal overdoses involve IV buprenorphine misuse or concurrent central nervous system depressant use, including high doses of benzodiazepines, alcohol, or other 3-55 TIP 63Part 3 of 5—Medications for Opioid Use Disorder • • sedatives.263,264 However, fatal overdoses have been reported in opioid-naïve patients treated with 2 mg buprenorphine for pain.265 Exhibit 3D.2 summarizes the management of patients with preexisting respiratory impairment. Unintentional pediatric exposure can be life threatening or fatal.266 Thus, emphasize safe storage of medication, and teach patients to remove any buprenorphine found in a child’s mouth immediately (even if it was only a partial tablet or flm). Call 9-1-1 so the child can go to the nearest emergency department for immediate medical attention. Cases of hepatitis and liver failure exist but often involve predisposing hepatic risk factors, such as preexisting liver enzyme abnormalities, hepatitis B or C infections, and use of other potentially hepatotoxic drugs or IV drugs. A multisite randomized trial of hepatic effects in patients taking methadone or buprenorphine found no evidence of liver damage in the frst 6 months of treatment. The authors concluded that prescribing these medications should not cause major concern for liver injury.267 Exhibit 3D.2 summarizes man- agement of patients with hepatic impairment. EXHIBIT 3D.2. Medication Management for Patients With Respiratory or Hepatic Impairment CONTRAINDICATION/CAUTION MANAGEMENT Compromised respiratory function For example, chronic obstructive pulmonary disease, decreased respiratory reserve, hypoxia, hypercapnia (abnormally elevated blood levels of carbon dioxide), preexisting respiratory depression. • • • • • • Prescribe with caution; monitor closely. Warn patients about the risk of using benzodiazepines or other depressants while taking buprenorphine.270 Support patients in their attempts to discontinue tobacco use. Hepatic impairment Mild impairment (Child-Pugh score of 5–6)271 No dose adjustment needed. Moderate impairment (Child-Pugh score of 7–9):272 Combination products are not recommended; they may precipitate withdrawal. *Use combination products cautiously for maintenance treatment in patients who’ve been inducted with a monoproduct;273,274 monitor for signs and symptoms of buprenorphine toxicity or overdose.275 Naloxone may interfere with buprenorphine’s effcacy.276,277 Severe impairment (Child-Pugh score of 10–15):278 Do not use the combination product.279 For monoproduct, consider halving the starting and titration doses used in patients with normal liver function; monitor for signs and symptoms of toxicity or overdose caused by increased buprenorphine levels.280 Buprenorphine and naloxone are extensively metabolized by the liver. Moderate-to-severe impairment results in decreased clearance, increased overall exposure to both medications, and higher risk of buprenorphine toxicity and precipitated withdrawal from naloxone. These effects have not been observed in patients with mild hepatic impairment.268,269 *Moderate-to-severe impairment results in much more reduced clearance of naloxone than of buprenorphine. Nasser et al.281 found that moderate impairment doubled or tripled exposure (compared with subjects with no or mild impairment) for both medications. In subjects with severe impairment, buprenorphine exposure was also two to three times higher; naloxone exposure increased more than tenfold. Adapted from material in the public domain.282 3-56 Medications for Opioid Use Disorder TIP 63 • • Potential for misuse and diversion exists. People can misuse buprenorphine via intra- nasal or IV routes or divert it for others to misuse. Do not give early or multiple reflls without careful assessment and monitoring suited to the patient’s level of stability.283,284 Discourage misuse and diversion by: − Requiring frequent offce visits until patients are stable. − Testing urine for buprenorphine and norbu- prenorphine or buprenorphine glucuronide (both metabolites of buprenorphine). − Using other methods to ensure adequate adherence to the medication as pre- scribed, such as developing and adopting a diversion control plan (see Chapter 3E: Medical Management Strategies). • Adrenal insuffciency has been reported with opioid use, most often after more than 1 month of buprenorphine maintenance.285 • Patients will develop physical dependence on buprenorphine. Alert patients that they’ll experience opioid withdrawal if they stop buprenorphine. • Buprenorphine may affect cognition and psychomotor performance and can have sedating effects in some people (particularly those who’ve lost tolerance after a period of abstinence from opioids). Concurrent use of illicit drugs, other prescribed medications, or medical or psychiatric comorbidity can affect cognition and psychomotor performance. Urge patients to exercise caution in using heavy machinery and driving until they’re sure that their abilities are not compromised.286 • Allergic reactions have occurred in patients treated with buprenorphine, including rash, urticaria, angioedema, and anaphylaxis. • Buprenorphine can cause precipitated opioid withdrawal. It has weaker opioid agonist effects and stronger receptor affnity than full agonists (e.g., heroin, methadone). It can displace full agonists from receptors, precipitating opioid withdrawal.287 Factors affecting this possibility include: − Current level of opioid physical depen- dence. The higher the level of physical dependence, the higher the likelihood of precipitating withdrawal.288 Ensuring that patients are in opioid withdrawal when initiating buprenorphine decreases this risk. − Time since the last mu-opioid receptor full agonist dose. The longer the time since the last dose, the lower the likelihood of precipitated withdrawal.289 − Dose of buprenorphine administered. The smaller the dose of buprenorphine, the less likely it is to precipitate withdrawal.290,291 • Neonatal abstinence syndrome (NAS) may occur in newborns of pregnant women who take buprenorphine. Women receiving opioid agonist therapy while pregnant should talk with their healthcare provider about NAS and how to reduce it. Not all babies born to women treated with opioid agonists require treatment for NAS. Research has shown that the dose of opioid agonist medication is not reliably related to the severity of NAS.292,293,294 Thus, each woman should receive the dose of medication that best manages her illness. REDUCING NAS SEVERITY Offer the following advice to pregnant women receiving treatment with an opioid agonist: • Avoid smoking during pregnancy. • Avoid benzodiazepines. • Meet with the neonatologist and/or pediatrician to learn how the hospital assesses and treats NAS and what they suggest you can do as a parent to help soothe a baby with NAS. • Request rooming-in with the child. • Talk with the healthcare professional providing obstetric care about breastfeeding, as this may help make NAS less severe. • In the frst week after birth, keeping lights low, speaking softly, avoiding too much stimulation, and providing frequent skin-to-skin contact can help prevent or limit symptoms of NAS. 3-57 TIP 63Part 3 of 5—Medications for Opioid Use Disorder Drug Interactions Buprenorphine has fewer documented clinically signifcant drug interactions than methadone.295 Monitoring is still needed for patients who are starting or stopping medi- cations that are CYP450 3A4 enzyme inhibitors or inducers or that compete with buprenorphine for this enzyme. A previously therapeutic and stable dose of either buprenorphine or the coadministered medication may be altered when one of these medications is started or stopped. In the case of buprenorphine, oversedation or withdrawal symptoms may result. In the case of altered levels of other pharmacotherapies, the patient may experience a lack of therapeutic beneft or toxic side effects of that drug. Special attention should be paid to patients using or starting depot formulations of buprenorphine. Prior to initiating a depot formulation, talk with the patient about waiting until any time-limited therapy with a potential inhibitor, inducer, or substrate of CYP450 3A4 is complete, and ensure that adherence to any such medications needed chronically is good. Make sure the patient fully understands the possible risk of fuctuations in buprenorphine serum levels resulting in sedation or withdrawal symptoms and if compliance with an inhibitor, inducer, or substrate of CYP450 3A4 is erratic. If an inhibitor, inducer, or substrate of CYP450 3A4 is to be started or stopped for a patient stable on a depot formulation of buprenorphine, the patient should be monitored closely for oversedation or signs of withdrawal. Remember, signs and symptoms may not appear until the new med- ication approaches a therapeutic blood level. Signs of withdrawal may be relieved, if necessary, with the short-term use of additional low doses of transmucosal buprenorphine. Patients who experience sedation may need to take safety precautions with some activities. In severe cases, removal of the depot formulation, if possible, may need to be considered. Exhibit 3D.3 EXHIBIT 3D.3. Partial List of Medications Metabolized by Cytochrome P450 3A4 Drugs that may DECREASE buprenorphine serum levels Drug Mechanism Anticonvulsants Phenobarbital, phenytoin, primidone, carbamazepine Induces cytochrome P450 3A4 Antibiotics Rifampin Induces cytochrome P450 3A4 Immune Suppressants Dexamethasone Induces cytochrome P450 3A4 Drugs that may INCREASE buprenorphine serum levels Drug Mechanism Antibiotics Clarithromycin Inhibits cytochrome P450 3A4 Clindamycin, dapsone, erythromycin Competes with buprenorphine for cytochrome P450 3A4 enzyme Antidepressants Fluoxetine, fuvoxamine, nefazodone Inhibits cytochrome P450 3A4 Continued on next page 3-58 Medications for Opioid Use Disorder TIP 63 EXHIBIT 3D.3. Partial List of Medications Metabolized by Cytochrome P450 3A4 (continued) DRUGS THAT MAY INCREASE BUPRENORPHINE SERUM LEVELS DRUG MECHANISM Antifungals Fluconazole, itraconazole, miconazole Inhibits cytochrome P450 3A4 Ketoconazole Inhibits and competes with buprenorphine for cytochrome P450 3A4 Antihypertensives Nicardipine, verapamil Inhibits cytochrome P450 3A4 Amlodipine, diltiazem, felodipine, nifedipine, nimodipine Competes with buprenorphine for cytochrome P450 3A4 enzyme Antiarrhythmics Amiodarone Inhibits cytochrome P450 3A4 Disopyramide, quinidine Competes with buprenorphine for cytochrome P450 3A4 enzyme Hormones Estrogen, oral contraceptives, progestins Competes with buprenorphine for cytochrome P450 3A4 enzyme Sedative/Hypnotics Alprazolam, clonazepam, diazepam, midazolam Competes with buprenorphine for cytochrome P450 3A4 enzyme Immune Suppressants Cyclosporine, zafrlukast Inhibits cytochrome P450 3A4 Statins Atorvastatin, lovastatin, simvastatin Competes with buprenorphine for cytochrome P450 3A4 enzyme Gastric Agents Aprepitant, cimetidine Inhibits cytochrome P450 3A4 Analgesics Fentanyl Competes with buprenorphine for cytochrome P450 3A4 enzyme Antihistamines Loratadine Competes with buprenorphine for cytochrome P450 3A4 enzyme Chemotherapeutics Doxorubicin, etoposide, ifosfamide, paclitaxel, vinblastine Competes with buprenorphine for cytochrome P450 3A4 enzyme Blood Thinners Warfarin Competes with buprenorphine for cytochrome P450 3A4 enzyme Note: Consult a point-of-service medical reference application for the most up-to-date drug–drug interactions before making medication management decisions. Adapted from material in the public domain.296 3-59 TIP 63Part 3 of 5—Medications for Opioid Use Disorder partially lists these medications, including some anticonvulsants, and antibiotics, and Exhibit 3D.4 lists HIV medications. More informa- tion on drug–drug interactions is available online (www.drugs.com /drug-interactions/buprenorphine-index.html ?flter=3&generic_only=). Monitor responses to buprenorphine in patients taking nonnucleoside reverse tran- scriptase inhibitors. Changes in buprenorphine concentrations can be clinically signifcant.297 Combination antiretroviral therapy (atazana- vir/ritonavir) increases buprenorphine and norbuprenorphine serum concentrations.298 Case reports have demonstrated signs of buprenorphine excess (sedation). Decreasing buprenorphine can improve this symptom.299 Other research has demonstrated no need to adjust the buprenorphine dose among patients taking atazanavir.300 For tuberculosis treatment, rifampin but not rifabutin may decrease buprenorphine concen- trations. Rifampin produced opioid withdrawal in 50 percent of research volunteers with opioid dependence.301 FDA warns of increased serotonin syndrome risk with prescription opioids, including bu- prenorphine. Serotonin syndrome can include: • Changes in mental status. • Fever. • Tremor. • Sweating. • Dilated pupils. EXHIBIT 3D.4. Potential Interactions Between Buprenorphine and HIV Medications MEDICATION TYPE POTENTIAL INTERACTION Atazanavir Protease inhibitor Increased buprenorphine concentrations. May cause cognitive impairment302,303 or oversedation.304,305 Slower titration or dose reduction of buprenorphine may be warranted.306,307 Darunavir-ritonavir Protease inhibitor Some pharmacokinetic (PK) effect; dose adjustments unlikely to be needed, but clinical monitoring is recommended.308 Delavirdine Nonnucleoside reverse transcriptase inhibitor Increased buprenorphine concentrations, but no clinically signifcant effect. Dose adjustments unlikely to be needed. However, use with caution, as long- term effects (more than 7 days) are unknown.309,310 Efavirenz Nonnucleoside reverse transcriptase inhibitor Some PK effect; dose adjustments unlikely to be needed.311 Elvitegravir (with cobicistat) Integrase inhibitor Some PK effect; no dose adjustments needed.312 Nevirapine Nonnucleoside reverse transcriptase inhibitor Some PK effect; no dose adjustments needed.313 Ritonavir Protease inhibitor Some PK effect; no dose adjustments needed.314 Tipranavir Protease inhibitor Some PK effect; no dose adjustments needed.315 Adapted from material in the public domain.316 3-60 Medications for Opioid Use Disorder TIP 63 − − Serotonin syndrome can occur with simultaneous opioid and antidepressant treatment. There are only a few case reports of serotonin syndrome with buprenorphine,317 but be aware of this possibility given the frequent treatment of mood disorders in patients with OUD. Side Efects Buprenorphine’s side effects may be less intense than those of full agonists. Otherwise, they resemble those of other mu-opioid agonists. Possible side effects include the following (buprenorphine FDA labels list all potential side effects https://dailymed.nlm.nih .gov/dailymed/drugInfo.cfm?setid=8a5edcf9 -828c-4f97-b671-268ab13a8ecd): • Oral hypoesthesia (oral numbness) • Constipation • Glossodynia (tongue pain) • Oral mucosal erythema • Vomiting • Intoxication • Disturbance in attention • Palpitations • Insomnia • Opioid withdrawal syndrome • Excessive sweating • Blurred vision Serious implant-related adverse events are uncommon but possible according to the FDA label (www.accessdata.fda.gov/drugsatfda_docs /label/2016/204442Orig1s000lbl.pdf). Still, more than 10 percent of patients experience implant site pain, itching, or swelling. Migration beyond the local insertion site is rare but possible, as is nerve damage. Buprenorphine may be extruded from implants for potential misuse. Insert implants only in stable patients, for whom FDA has approved this formulation. Implants may extrude and potentially come out (e.g., from incomplete insertion or infection). Tell patients to call the implanting physician if an implant looks like it is extruding or comes out. If the implant comes out, patients should safely store and dispose of it (following local and federal regulations) to protect others from unintended exposure. Serious injection site adverse events for the extended-release formulation are uncommon but possible. The most common injection site adverse reactions were pain (7.2 percent), pruritus (6.6 percent), and erythema (4.7 percent) in phase three trials. Two cases of surgical removal of the monthly depot were reported in premarketing clinical studies. Surgical excision under local anesthesia within 14 days of injection is possible. It is recommended that, before treatment, baseline liver function tests be assessed with monthly monitoring during treatment, particularly with the 300 mg dose. There are limited data regarding use of the extended-release injection formulation in pregnant women with OUD. In animal repro- ductive studies with Sublocade’s excipient, N-Methyl-2-pyrrolidone, there were reported fetal adverse reactions. Women should be advised that the use of Sublocade during pregnancy should be considered only if the benefts outweigh the risks (see FDA package insert for full details www.accessdata.fda.gov /drugsatfda_docs/label/2017/209819s000lbl.pdf). Assessment No evidence clearly predicts which patients are best matched to buprenorphine versus other OUD medications. Thorough assess- ment helps determine whether buprenorphine treatment is appropriate for a patient. (Part 2 of this TIP covers screening and assessment in more detail.) Before prescribing buprenorphine: • Check the state prescription drug monitoring program database. • Assess the patient’s history. Conduct a medical, psychiatric, substance use, and substance use treatment history. Assess recent opioid use, including frequency, quantity, type, route, and last day of use. 3-61 TIP 63Part 3 of 5—Medications for Opioid Use Disorder − Establish OUD diagnosis. − Assess for other substance use disorders (SUDs), including those involving alcohol, benzodiazepines, or stimulants. • Conduct a focused physical examination, refer for a physical exam, or get a record of a recent one. − Assess for signs and symptoms of intoxi- cation. Do not give a frst dose to a patient who is sedated or intoxicated. Assess and treat him or her appropriately. − Assess for evidence of opioid with- drawal and physiological dependence. The Clinical Opioid Withdrawal Scale (COWS) or the Clinical Institute Narcotic Assessment (CINA) Scale for Withdrawal Symptoms can be used to assess withdrawal signs (see “Resource Alert: Opioid Withdrawal Scales”). The patient should exhibit signs of opioid withdrawal before taking the frst dose of buprenor- phine to avoid precipitated withdrawal. For example, the Risk Evaluation and Mitigation Strategy (REMS) for buprenor- phine indicates that a COWS score of 12 or higher is typically adequate for a frst dose. Confrming opioid withdrawal suggests that the patient is physically dependent on opioids and can begin induction with a typical 2 mg/0.5 mg or 4 mg/1 mg bu- prenorphine/naloxone dose. • Obtain laboratory tests. − Conduct drug and alcohol tests. Use reliable urine tests for opioids (including morphine, methadone, buprenorphine, and oxycodone), benzodiazepines, cocaine, and other drugs commonly used in the area. Use a breathalyzer to estimate the patient’s blood alcohol content. Do not provide buprenorphine until the alcohol reading is considerably below the legal level of alcohol intoxication. − Conduct a pregnancy test. Transmucosal buprenorphine or methadone maintenance treatment is recommended for OUD in pregnancy.318 There are limited data regarding use in pregnant women with OUD with the buprenorphine implants and with the extended-release injection for- mulation. If buprenorphine is used during pregnancy, it should generally be trans- mucosal monoproduct.319 Refer pregnant patients to prenatal care. − Assess liver function. If possible, obtain liver function tests, but do not wait for results before starting transmucosal buprenorphine treatment. A patient with chronic hepatitis can receive OUD treatment with buprenorphine. Discuss risks and benefts if the patient’s liver enzymes are at or above fve times the normal level and monitor liver function during treatment. Patients with transam- inase levels less than fve times normal levels, including patients with hepatitis C virus, appear to tolerate buprenor- phine well.320,321 Exhibit 3D.2 gives more information about hepatic impairment and buprenorphine. Liver function tests should be obtained and reviewed before initiating buprenorphine implants or extended-release buprenorphine because these formulations are long acting. RESOURCE ALERT Opioid Withdrawal Scales The COWS and other opioid withdrawal scales can be downloaded from Annex 10 of WHO’s Guidelines for the Psychosocially Assisted Pharmacological Treatment of Opioid Dependence from the National Center for Biotechnology Information website (www.ncbi .nlm.nih.gov/books/NBK143183). The CINA Scale for Withdrawal Symptoms is also available online (www.ncpoep.org/wp -content/uploads/2015/02/Appendix_7_Clinical _Institute_Narcotic_Assessment_CINA_Scale _for_Withdrawal_Symptoms.pdf). 3-62 Medications for Opioid Use Disorder TIP 63 − Conduct hepatitis and HIV tests. Hepatitis B and C are common among patients entering buprenorphine treatment. HIV infection is also prevalent. Everyone ages 15 to 65 should be tested at least once for HIV. Persons at higher risk, such as people who use drugs by injection, should be tested annually.322 Anyone who is injecting or has ever injected drugs, even once, no matter how long ago, should be tested for hepatitis C, regardless of their intention to seek treatment for SUD.323 The Centers for Disease Control and Prevention recommends hepatitis B vaccination for individuals seeking treatment for SUDs.324 Patient Selection No evidence clearly predicts which patients are best treated with buprenorphine versus other OUD medications. Inform all patients with OUD about treatment with transmucosal buprenorphine and where it’s available. (See “Treatment Planning or Referral” in Part 2 of this TIP for more on shared decision making.) Patients who responded well to buprenorphine in the past should be considered for this treatment. Prior use of diverted buprenorphine doesn’t rule out OUD treatment with buprenorphine. Diverted buprenorphine is often associated with an inability to access treatment,325 and it’s often used to self-treat opioid withdrawal rather than to “get high.”326,327 Unsuccessful treatment experiences with buprenorphine in the past do not necessarily indicate that buprenorphine will be ineffective again. Motivation and circumstances change over time. Also, treatment varies by provider, clinic, and setting, as it does for other medical illnesses. Records from previous providers can contextualize the extent of past treatment. Pregnant women should be considered for transmucosal buprenorphine treatment. Do not taper patients to 8 mg daily solely to switch them to implants. Stable patients are the best candidates for buprenorphine implants. Implants are indicated for patients who have already achieved illicit opioid abstinence and clinical stability while taking transmucosal buprenorphine for at least 90 days. Their current dose should be 8 mg/ day or less.328 There is no absolute defnition of clinical stability, but per the implant package insert, patients may be stable if they are:329 • Abstaining currently from illicit opioids. • Having little or no craving for illicit opioids. • Living in a stable environment. • Participating in a structured job or activity. • Engaging in a positive social support system. • Lacking recent hospitalizations, emergency department visits, or crisis interventions for substance use or mental illness. • Adhering to clinic appointments and other aspects of treatment and recovery plans. Informed Consent Inform all patients of: • Their OUD diagnosis and the nature of the disorder. • Risks and benefts of all available medications for OUD. • Risks and benefts of nonmedication treatments. Educate patients about basic buprenorphine pharmacology and induction expectations (Exhibit 3D.5). They should understand the need to be in opioid withdrawal that’s visible to the Use language and written materials appropriate to each patient’s comprehension level to ensure that he or she understands the options and can make informed decisions. 3-63 TIP 63Part 3 of 5—Medications for Opioid Use Disorder EXHIBIT 3D.5. Key Points of Patient Education for Buprenorphine Before starting OUD treatment with buprenorphine, patients should: prescriber (or, for home induction, that meets predefned self-assessment criteria) to avoid precipitated withdrawal. Initiating Buprenorphine Treatment It can be helpful to use a buprenorphine treatment agreement for patients treated in offce-based settings (see Chapter 3D Appendix for a sample treatment agreement). Induction can occur in the offce or at home. Most clinical trials were conducted with offce- based induction, and extant guidance recom- mends this approach.330 However, offce-based induction can be a barrier to treatment initia- tion. Home induction is increasingly common.331 Ofce-Based Induction Providers can perform offce-based induction by ordering and storing induction doses in the offce or by prescribing medication and instruct- ing patients to bring it to the offce on the day of induction. Offce-based induction allows providers to: • Ensure that patients know how to take medication without swallowing or spitting it out if they have too much saliva or experience unpleasant tastes. Tell them to wait to eat or drink until the medication is totally dissolved. • Enhance the therapeutic relationship. • Verify the presence of opioid withdrawal and absence of precipitated opioid withdrawal. • Ensure the lack of sedation 1 to 2 hours after the frst dose in patients taking sedatives. • Use time between doses for patient self- assessment. See the Chapter 3D Appendix for sample goal-setting forms that help patients identify treatment goals and triggers for use. Home Induction Home induction can be safe and effective.332 Retention rates are similar to offce inductions,333 but no comparison data from large randomized • Tell providers the prescribed and over-the- counter medications they take to allow drug interaction assessment. • Understand the goal of the first week of treatment: To improve withdrawal symptoms without oversedation. • Tell providers if they feel sedated or euphoric within 1 to 4 hours after their dose. • Be given the appropriate buprenorphine medication guide. • Know possible side effects, including: - Headache. - Dizziness. - Nausea. - Vomiting. - Sweating. - Constipation. - Sexual dysfunction. • Agree to store medication securely and out of the reach of others. • Alert providers if they discontinue medications, start new ones, or change their medication dose. • Understand that discontinuing buprenorphine increases risk of overdose death upon return to illicit opioid use. • Know that use of alcohol or benzodiazepines with buprenorphine increases the risk of overdose and death. • Understand the importance of informing providers if they become pregnant. • Tell providers if they are having a procedure that may require pain medication. • Be aware of resources through which to obtain further education for: - Themselves: Decisions in Recovery: Treatment for Opioid Use Disorder (https:// store.samhsa.gov/product/SMA16-4993) - Their families and friends: Medication- Assisted Treatment for Opioid Addiction: Facts for Families and Friends (https://portal. ct.gov/-/media/DMHAS/Opioid-Resources/ MATInfoFamilyFriendspdf.pdf) 3-64 Medications for Opioid Use Disorder TIP 63 controlled studies exist. The American Society of Addiction Medicine National Practice Guideline recommends home induction only if the patient or prescriber has experience with using buprenor- phine.334,335 Clinical experience indicates that patients suitable for home induction: • Can describe, understand, and rate withdrawal. • Can understand induction dosing instructions. • Can and will contact their provider about problems. Educate patients about how to assess their withdrawal, when to start the frst dose, how to take the medication properly, and how to manage withdrawal on induction day. Instruct patients to take their frst dose when they expe- rience opioid withdrawal at least 12 hours after last use of heroin or a short-acting prescription opioid. Effectively switching from methadone to buprenorphine can be challenging. This should generally be started with offce-based induction. Consult with a medical expert knowledgeable about methadone in these situations until experi- ence is gained. Withdrawal can include: • Goose bumps. • Nausea. • Abdominal cramps. • Running nose. • Tearing. • Yawning. Be available for phone consultation during the induction period and for an in-offce evalua- tion should the need arise. See patients in the Advise patients to abstain from tobacco before dosing. Many patients with OUD use tobacco products. Nicotine causes vasoconstriction, decreasing the surface area of blood vessels that absorb buprenorphine. offce within approximately 7 days of the start of home induction. (See the Chapter 3D Appendix for a sample buprenorphine/naloxone home dosage schedule.) Induction Patients who are currently physically dependent on opioids Patients should begin buprenorphine when they are exhibiting clear signs of opioid withdrawal. Induction typically starts with a 2 mg to 4 mg dose of buprenorphine or a 2 mg/0.5 mg to 4 mg/1 mg dose of buprenor- phine/naloxone.336 Depending on the formula- tion used and whether a given patient has a dry mouth, the dose can take between 3 and 10 minutes to dissolve fully. After approximately 2 hours, an additional 2 mg to 4 mg dose of buprenorphine/naloxone can be given if there is continued withdrawal and lack of sedation. Always individualize dosing. The FDA label recommends a maximum buprenorphine/ naloxone dose of 8 mg on Day 1 and 16 mg on Day 2.337 When dosing outside of FDA recom- mendations, document the clinical rationale, including risks and benefts. Remember that some patients stabilize on lower doses. If patients experience sedation upon frst dose, stop and reevaluate the following: • Did they recently take other sedating medications (e.g., benzodiazepines)? • Have they recently been in a controlled envi- ronment, such as a hospital, jail, or residential drug treatment facility? • Was the history of recency and amount of opioid use inaccurate? • Was the heroin used of poor quality? • Was their use mostly of low-potency opioids (e.g., codeine)? Consider whether a dose decrease, change in treatment plan, or both are necessary. If induction is still indicated, adjust the dose 3-65 TIP 63Part 3 of 5—Medications for Opioid Use Disorder more slowly as needed to minimize sedation. The dose can be adjusted on subsequent days to address continued withdrawal or uncontrollable craving if the patient is not sedated. Patients with a history of OUD who are not currently physically dependent on opioids Buprenorphine induction can be appropriate for certain patients with a history of opioid addiction at high risk for return to use of opioids but not currently dependent on them. This includes patients who’ve been incarcerated or in other controlled environments.338 Before starting treatment, discuss risks and benefts of buprenorphine and other medications (including extended-release naltrexone [XR-NXT]). Buprenorphine doses should begin at lower- than-usual levels (e.g., 1 mg). They should be increased more slowly than in tolerant patients to avoid oversedation and possible overdose. Take particular care with patients who are being treated with other central nervous system depressant medications.339 At the beginning of treatment, directly administer doses in an OTP or in the offce. This will allow patients to be observed for sedation after dosing and will reduce the risk that patients take more medication than prescribed. In one study, research participants not currently physically dependent on opioids but with a history of OUD were started on 1 mg buprenor- phine with weekly 1 mg dose increases to 4 mg, followed by 2 mg weekly increases to 8 mg. Most patients tolerated this dose induction, and the mean daily dose exceeded 8 mg per day by the ffth week, when the planned dose was 6 mg.340 As with all opioid agonist treatment, dosing should be individualized and based on careful patient assessment during treatment. Patients who are currently taking methadone Some patients who take methadone may wish to switch to buprenorphine treatment for a variety of reasons. This often requires methadone dose reduction before switching medications, which may increase the risk of return to opioid use. Exercise caution with this approach and thoroughly discuss the risks and benefts with the patients before embarking on the change in medication. Experienced prescribers should conduct this procedure in the offce, not via home induction. The lower the methadone dose and the longer it’s been since the last dose, the easier the transition. Before initiating buprenorphine, carefully taper methadone to lower the risk of return to illicit opioid use during transition. Patients who take methadone for OUD should taper to 30 mg to 40 mg methadone per day and remain on that dose for at least 1 week before starting buprenorphine.341 With patients’ permission, OTPs can confrm the time and amount of patients’ last methadone dose. Do not start buprenorphine until the patient manifests signs of opioid withdrawal. At least 24 hours should pass between the last dose of methadone and the frst dose of buprenorphine. Waiting 36 hours or more reduces risk of pre- cipitated withdrawal. Lower doses of buprenor- phine/naloxone are less likely to precipitate methadone withdrawal.342 For example, once opioid withdrawal is verifed, an initial dose of 2 mg/0.5 mg can be given. If patients continue to have unrelieved opioid withdrawal after the frst 2 mg dose, administer another 2 mg/0.5 mg dose approximately every 2 hours as needed (holding for sedation). Induction should be conducted slowly; consider palliating unrelieved withdrawal with nonopioid therapies for the frst few days of transition to buprenorphine. Be alert to any increase in withdrawal symptoms, as this may suggest precipitated withdrawal. Dose Stabilization Stabilization occurs when there is evidence of: • Markedly reduced or eliminated illicit opioid use. • Reduced craving. 3-66 Medications for Opioid Use Disorder TIP 63 • Suppression of opioid withdrawal. Buprenorphine treatment should substantially • Minimal side effects. • Patient-reported blunted or blocked euphoria during illicit opioid use. Remind patients to take their dose once daily rather than splitting it. Document reduced illicit drug use via patient self-report and urine drug testing. Consecutive negative urine test results suggest a positive prognosis. Continue monitoring dose effectiveness during early stabilization. Dose adjust- ments may still be necessary (Exhibit 3D.6). reduce opioid cravings. See Chapter 3E: Medical Management Strategies for detailed information on the management of patients taking buprenor- phine in offce-based treatment settings. Once patients have stabilized, continue to screen and evaluate for mental disorders and psychosocial problems that may need to be addressed (e.g., having a spouse or cohabitant who is using illicit opioids). Support patients’ engagement in prosocial activities and progress toward treatment goals and recovery as they decrease use of illicit substances. EXHIBIT 3D.6. Adjusting the Buprenorphine Dose When to increase the dose: • Are patients taking medication correctly and as scheduled? - If they take at least 16 mg per day, mu-opioid receptors are approximately 80 to 95 percent occupied.343 - If there are adherence problems, assess causes and intervene to promote adherence and proper administration (e.g., offer supervised dosing at the clinic, by a network support, at a pharmacy). - If patients are taking doses correctly, a dose increase may be indicated, if certain conditions exist. • Are patients taking other medications that may interfere with buprenorphine metabolism? • If patients are taking doses properly, increase the dose if they still have opioid withdrawal (document with a clinical tool like COWS), opioid craving, or “good” effects (e.g., feeling “high”) from using illicit opioids. - Craving can be a conditioned response. It may not decrease with dose increases if patients spend time with people who use opioids in their presence. - Dose increases typically occur in 2 mg to 4 mg increments. - It will take about 5 to 7 days to reach steady-state plasma concentrations after a dose increase. - Offer psychosocial referrals to help decrease and manage cravings. • Determine whether nonpharmacological problems are contributing to the need for increase. - For example, do patients show signs and symptoms of untreated major depressive or generalized anxiety disorders? Are they living in a chaotic household? Do they have childcare problems or fnancial diffculties? Are they experiencing trauma or trauma-related mental disorders? - Address or refer to counseling to address these problems. When to decrease the dose: • Decrease the dose when there is evidence of dose toxicity (i.e., sedation or, rarely, clearly linked clinically relevant increases in liver function tests). • Hold the dose when there is acute alcohol or benzodiazepine intoxication. 3-67 TIP 63Part 3 of 5—Medications for Opioid Use Disorder Offer referrals for adjunctive counseling and recovery support services as needed. It may not be possible to eliminate opioid craving completely, regardless of the dose. Counseling can help patients reduce and manage craving. A more important measure of dose adequacy than craving is whether patients report that the feeling of euphoria associated with self- administered illicit opioids is blunted or blocked. Patients who were not interested in adjunc- tive addiction or mental health counseling during induction may become receptive to it when they are feeling more stable. Be cautious when increasing doses above 24 mg/6 mg per day. Nearly all patients stabilize on daily doses of 4 mg/1 mg to 24 mg/6 mg. Very limited data show additional benefts of doses higher than the FDA label’s recommended maximum of 24 mg/6 mg.344 Carefully document clinical justifcation for higher doses and always have a diversion control plan in place. Doses above 24 mg/6 mg a day may unintentionally heighten diversion risk. Patients not responding to high doses of buprenorphine at the upper limit approved by FDA should be considered for methadone treatment. Risk Evaluation and Mitigation Strategy Practitioners should become familiar with the FDA-approved REMS for buprenorphine. It provides useful information and checklists for providers. REMS can be found online for: • Buprenorphine monoproduct and buprenorphine/naloxone (www.accessdata.fda.gov/scripts/cder /rems/index.cfm?event=IndvRemsDetails .page&REMS=352) • Transmucosal buprenorphine (www.accessdata.fda.gov/scripts/cder /rems/index.cfm?event=RemsDetails .page&REMS=9) • Buprenorphine implants (www.accessdata.fda.gov/scripts/cder /rems/index.cfm?event=IndvRemsDetails .page&REMS=356) • Buprenorphine extended-release injection (www.accessdata.fda.gov/scripts/cder /rems/index.cfm?event=indvremsdetails .page&rems=376) See also “Buprenorphine Induction and Maintenance Appropriate Use Checklists” in Chapter 3D Appendix. Transmucosal Buprenorphine Dosing Summary Induction and stabilization The goal is to reduce or eliminate opioid with- drawal and craving without causing sedation: • Induction and stabilization strategies can vary based on patient variables and use of short- versus long-acting opioids. For more discussion on induction models, see the Providers’ Clinical Support System’s Models of Buprenorphine Induction (http://pcssmat .org/wp-content/uploads/2015/01/Models -of-Buprenorphine-Induction.pdf). • The combination buprenorphine/naloxone product is safe to use for induction for most patients. • The buprenorphine monoproduct (without naloxone) has been recommended for the treatment of pregnant women345 because of the danger to the fetus of precipitated opioid withdrawal if the combination product were to be injected. Although there are some publica- tions with small sample sizes that indicate that the combination product appears to be safe in pregnancy,346,347 the safety data are insuffcient at this time to recommend its use.348 This is an area of some uncertainty. An expert panel on the treatment of OUD in pregnancy was unable to agree whether pregnant women should be treated with the monoproduct or combination product.349 • Prescribers should observe the patient taking the medication to ensure proper use, espe- cially if the patient is new to buprenorphine treatment. It can be helpful to do this peri- odically after induction, especially when the prescribed dose is not providing the expected beneft. 3-68 Medications for Opioid Use Disorder TIP 63 • Before the frst dose, the patient should be in opioid withdrawal (to avoid precipitated withdrawal). • The frst dose is typically 4 mg/1 mg (2 mg if withdrawal is from methadone). • Repeat dose as needed for continuing with- drawal every 2 hours up to typically 8 mg on the frst day. At the start of the next day, patients typically take the frst day’s total dose all at once: • If necessary, an additional 2 mg to 4 mg can be given every 2 hours up to approximately a 16 mg total daily dose to treat continuing opioid withdrawal and craving on Day 2 or 3, barring sedation. • The initial stabilization dose can often be achieved within the frst several days of treatment. Maintenance Typical maintenance doses range from 4 mg/1 mg to 24 mg/6 mg per day. An effective main- tenance dose is the lowest dose that can: • Eliminate withdrawal. • Reduce or eliminate opioid craving. • Reduce or stop illicit opioid use’s desirable effects. • Be well tolerated (e.g., not produce sedation). Duration of treatment • Treatment should last for as long as patients beneft from treatment. • Longer treatment length is associated with positive treatment outcomes. Initiation of Buprenorphine Implants Prescribers and implanters of buprenorphine implants require special certifcation to make this formulation available to their patients. In addition, implanters must get special training in the Probuphine REMS program to obtain certi- fcation to implant and remove this formulation. After completing training, providers can order implants through a central pharmacy for delivery, along with an implant insertion kit that contains all necessary implant procedure materials except a local anesthetic. If the prescriber is not performing the procedure, the prescriber should ensure that the implanter has completed the required training. For more information, see the Probuphine REMS program webpage (https:// probuphinerems.com/). The prescriber and implanter/remover must record the number of implanted/removed rods and their serial numbers and location, the date of the implant, and who performed the procedure. The implanter should document implant and inspection procedures, as with any other standard procedure. Instruct patients to take the last transmu- cosal dose of buprenorphine 12 to 24 hours before insertion. Remind them to shower and thoroughly wash the nondominant arm, which is preferred for insertion. Implant procedure Subdermal insertion of the four rods takes less than 30 minutes. Local anesthetic (lidocaine) is typically used. The implant procedure includes the following steps: • Provide education about what to expect during the procedure. • Obtain appropriate consent form(s). • Provide a local anesthetic (e.g., lidocaine). • Using sterile procedures, make a single incision in the inner upper arm between the biceps and triceps muscles, about 8 cm to 10 cm from the medial epicondyle. • Using a cannula and an obturator, insert rods serially, pivoting the cannula slightly after each rod insertion in the subdermal space so that the rods lie next to one another, nearly parallel in a fanlike pattern. • After implantation, apply butterfy strips and a pressure bandage. • Review wound care with the patient, and provide a copy of the instructions. • Advise the patient not to drive or engage in heavy physical activity for approximately 24 hours. 3-69 TIP 63Part 3 of 5—Medications for Opioid Use Disorder • Do not give the patient a prescription for transmucosal buprenorphine at this time. Wound care The patient should return within 1 week of the implant procedure for a wound care check. Check for signs of infection, trouble healing, or implant extrusion. The rods are subdermal, so they should remain palpable. Document that all four rods were palpated. Stabilization Maintain contact with patients after implant placement. Even among highly stable patients, return to illicit opioid use can occur. Explain the risk of unintentional overdose if patients return to illicit opioid or alcohol or benzodiazepine use while implants are in place. It is important to monitor the patient between implant placements. Schedule offce visits no less than once a month for continued assessment of main- tenance of stability, manual palpation of the four implanted rods, and ongoing psychosocial support and counseling per the FDA label (www .accessdata.fda.gov/drugsatfda_docs/label/2016 /204442Orig1s000lbl.pdf). If the patient returns to illicit opioid use, consider whether adequate psychosocial treatment has been given. Consider transmucosal medication supplemen- tation if a patient with implants destabilizes and reports inadequate opioid blockade. In one study,350 17.9 percent of participants with buprenorphine implants needed supplemental sublingual buprenorphine/naloxone. Most required small doses, such as 2 mg/0.5 mg per day. Consider more frequent assessment and higher intensity of treatment for patients who continue using illicit opioids or other substances. Removal After 6 months, have a certifed implanter remove them. Implantation of a second set of rods in the opposite arm can then occur. There is no experience with inserting additional implants into other sites or second insertion into a previously used arm. After one insertion in each arm, most patients should transition to a transmucosal buprenorphine-containing product for continued treatment. Patients should follow the same directions to prepare for implant removal as they did for insertion. The removal procedure may require stitches. Patients should visit the clinic for removal of stitches and wound assessment within 1 week of removal. Store and dispose of rods safely in accordance with local and federal regulations. Initiation of Buprenorphine Extended- Release Injection Healthcare settings and pharmacies need special certifcation to order and dispense extended-release injectable buprenorphine to ensure long-acting preparations are dispensed directly to healthcare providers for administra- tion and by healthcare providers to patients (see www.accessdata.fda.gov/scripts/cder/rems/index .cfm?event=indvremsdetails.page&rems=376 for more details). Before initiating extended-release buprenor- phine treatment, patients with moderate- to-severe OUD should be stabilized on trans- mucosal buprenorphine (8 mg to 24 mg daily) for at least 7 days. Do not use in opioid-naïve patients. Obtain liver function and pregnancy tests. Extended-release buprenorphine is not recommended for patients with severe hepatic impairment and may not be appropriate for patients with moderate hepatic impairment because of the long-acting nature of this formu- lation. There are insuffcient data on its use in pregnancy to recommend initiating this formula- tion during pregnancy. Inform patients that: • The medication is only available in a restricted program (the Sublocade REMS Program) via specifc pharmacies and healthcare providers, as intravenous self-injection by patients can cause death. • After abdominal injection, a lump may be present at the injection site for a few weeks. It 3-70 Medications for Opioid Use Disorder TIP 63 will get gradually smaller. Patients should not rub or massage it or let belts or waistbands rub against it. • Patients should tell their healthcare providers that they are being treated with this medication. • Using alcohol, benzodiazepines, sleeping pills, antidepressants, or some other medications with extended-release buprenorphine can lead to drowsiness or overdose. • The most common side effects are constipa- tion, headache, nausea, vomiting, increased liver enzymes, tiredness, and injection site itching or pain. • Patients should inform their provider if they become pregnant during treatment with this formulation. They should have a risk/beneft discussion about continuing with this for- mulation given the limited safety data on its impact on the developing fetus. They should be informed that their newborn can have symptoms of opioid withdrawal at birth. Storage Follow package insert directions for medication storage under refrigeration. Keep at room temperature for at least 15 minutes before injection (discard if left at room temperature for more than 7 days). Administration Rotate the abdominal subcutaneous injection site with each injection, following the instructions in the package insert. Record the location of each injection in the medical record. Each of the frst two monthly doses (with at least 26 days between doses) should be 300 mg. Subsequent monthly doses should be 100 mg. Some patients may beneft from increasing the maintenance dose to 300 mg monthly if they have tolerated the 100 mg dose but continue to use illicit opioids. Medical management Monitor patient progress and response to treatment during regular offce visits and with periodic urine drug testing. Examine the injection site for reactions, infections, or evidence of attempts to remove the depot medication. If the medication is discontinued, the patient should continue to be seen and evaluated for several months for sustained progress in treatment and for signs and symptoms of opioid withdrawal, which should be treated as clinically appropriate. Duration of Buprenorphine Treatment There is no known duration of therapy with buprenorphine (or methadone or XR-NTX) after which patients can stop medication and be certain not to return to illicit opioid use. Those who stay in treatment often abstain longer from illicit opioid use and show increasing clinical stability. Long-term treatment outcomes up to 8 years after buprenorphine treatment entry show lower illicit opioid use among those with more time on medication.351 Patients should take buprenorphine as long as they beneft from it and wish to continue. Successful Buprenorphine Treatment The goal of buprenorphine treatment is full remission from OUD. Maintaining illicit opioid abstinence is ideal, but imperfect abstinence does not preclude treatment benefts. Patients should do better in treatment than before treatment. If not, seek alternatives. Do not judge treatment progress and success on the amount of medication a patient needs or how long treatment is required. Rather, gauge treatment progress and success based Given the often-chronic nature of OUD and the potentially fatal consequences of unintended opioid overdose, it is critical that you base patients’ length of time in treatment on their individual needs. 3-71 TIP 63Part 3 of 5—Medications for Opioid Use Disorder on patients’ achievement of specifc goals that were agreed on in a shared decision-making and treatment planning process. Consider this analogy: A patient with poorly controlled diabetes was previously unable to work and was admitted to the hospital several times for diabetic ketoacidosis. When taking insulin regularly, the patient worked part time, had fewer hospitalizations for diabetic ketoaci- dosis despite a nondiabetic diet, and had lower (but still high) hemoglobin A1C. This patient’s treatment with insulin is not a “failure” because perfect control and function were not restored, and the patient would not be discharged from care against his or her will. Dose Tapering and Buprenorphine Discontinuation Following short-term medically supervised withdrawal, patients frequently restart illicit opioid use.352 In contrast to short-term medically supervised withdrawal, dose tapering refers to gradually reducing the buprenorphine dose in patients who have been stabilized on the medi- cation for some time. Base decisions to decrease dose or stop buprenorphine on patients’ circumstances and preferences. Successful dose reductions may be more likely when patients have sustained abstinence from opioids and other drugs, psychosocial support, housing, effective coping strategies, stable mental health, employment, and involvement in mutual-help programs or other meaningful activities.353 However, there is no guarantee that even patients with years of ab- stinence, full-time employment, stable housing, and psychosocial supports can remain abstinent after discontinuing buprenorphine. It is up to patients to decide whether to taper or eventually discontinue medication. Help them make informed choices by educating them about the process and fully including them in decision making. Invite them to reenter treatment if they believe they may return or have already returned to opioid use. Before beginning to taper the dose of med- ication, explore these considerations with patients: • How have they responded to treatment so far? Are they in full remission from OUD? Do they have adequate mental and social supports to remain in remission and maintain recovery? • Why do they want to taper? They may be motivated by inconvenience, expense, loss of insurance coverage, side effects, feelings of shame, pressure from family, and lack of recovery supports. Many of these reasons are not predictive of a successful outcome. • What do they expect to be different after tapering or discontinuing buprenorphine? • Do they understand the risks and benefts of dose decrease and discontinuation of buprenorphine? • What strategies do they have for engaging family members and recovery supports to reduce the risk of return to illicit substance use? • Do they grasp the risk of overdose associ- ated with a return to illicit opioid use? • Do they have a safety plan? To reduce overdose risk after a return to use, plans should include: − A prescription for naloxone or a naloxone kit. − Instructions on recognizing and responding to an overdose. − Information on naloxone use for family members and others in the patient’s recovery support network. − See the SAMHSA Opioid Overdose Prevention Toolkit (https://store.samhsa. gov/product/Opioid-Overdose-Prevention- Toolkit/SMA18-4742) for more guidance. 3-72 Medications for Opioid Use Disorder TIP 63 − If patients return to opioid use, it may be appropriate for them to restart buprenor- phine or switch to methadone or XR-NTX treatment. These options should be discussed with them. • Have they thought about how they will feel if they attempt to taper off of medication but cannot do so? Convey to patients that the inability to taper is not a failure and that they should not be afraid or embarrassed to discuss stopping the taper. Document the discussion, patient education, and decision in the medical record. There is no ideal tapering protocol. Providers and patients should understand this before beginning a taper. Whether buprenorphine is ultimately discontinued, patients need additional psychosocial and recovery support during this time. Generally, taper occurs over several months to permit patients to acclimate to the lower dose and to reduce potential discomfort from opioid withdrawal and craving. For patients who wish to discontinue buprenorphine, national and international guidelines recommend gradual dose reductions and advice to patients that they can stop the taper at any time.354,355,356 Consider increased monitoring and proactive discussions about how to address and manage cravings and withdrawal symptoms. Taper protocols vary in duration and may include use of ancillary medication, such as clonidine, if needed (Exhibit 3A.2).357 Continue to monitor patients who successfully taper off buprenorphine completely. Establish a post-taper monitoring and support plan (see Chapter 3E for more information on medical management strategies). Continue to assess and monitor patients’ progress and how they cope with stress and triggers to use. Discuss the role of XR-NTX in preventing return to opioid use after completing treatment with an opioid agonist (see Chapter 3C for more information on naltrexone). 3-73 TIP 63Part 3 of 5—Medications for Opioid Use Disorder Chapter 3D Appendix Buprenorphine Induction and Maintenance Appropriate Use Checklists Continued on next page 3-74 Medications for Opioid Use Disorder TIP 63 Available online (www.accessdata.fda.gov/drugsatfda_docs/rems/BTOD_2017-01-23_Appropriate_Use_Checklist.pdf). Reprinted from material in the public domain.358 3-75 TIP 63Part 3 of 5—Medications for Opioid Use Disorder Sample Goal Sheet and Coping Strategies Form Patient’s Name: _______________________________________________________________ Date: _________________________ 3-MONTH 1 GOALS 2 3 6-MONTH 1 GOALS 2 3 1-YEAR 1 GOALS 2 3 List of Triggers to Using Drugs People To Stay Away From Places To Stay Away From Ways To Cope or Manage Stress Without Using Drugs M. Lofwall, February 27, 2017 (personal communication). Adapted with permission. 3-76 Medications for Opioid Use Disorder TIP 63 Sample Goal-Setting Form Patient’s Name: ________________________________________________________________ Date: _________________________ GOAL CATEGORY CURRENT SITUATION SCORE 10 = major problems and 0 = no problems What would need to change to decrease this score? PRIORITY SCORE 10 = highest priority (“I really want to work on this”) and 1 = lowest priority (“I really do not want to work on this”) Opioid use Other illicit drug use: ______________ Alcohol use Tobacco use Physical health Mental health Legal/court issues Finances Job/employment Hobbies Family relations Partner relations Supportive drug-free network Education Keeping medication safe (e.g., not giving it away, selling it, having it stolen) Other Other M. Lofwall, February 27, 2017 (personal communication). Adapted with permission. 3-77 TIP 63Part 3 of 5—Medications for Opioid Use Disorder Buprenorphine/Naloxone Home Dosage Schedule: Films or Tablets Name: ________________________________________________________________ Date: ___________________________ Procedure for taking buprenorphine: • Let the medication dissolve under your tongue for at least 10 minutes. Do not suck on it.* • Do not eat, drink, or smoke cigarettes for 30 minutes after you take your medication. • Wait 2 hours between each dose. The maximum dose is 16 mg/4 mg. If you reach this dose, you cannot increase further without calling the offce frst. The offce phone number is ____________________________________ [insert phone number]. Day 1 Induction Day (In Offce): You have taken a total dose of _______ mg. Day 2 in the Morning: Take the total dose you took on Day 1 = _______ mg. • If you experience withdrawal 2 hours later, you may take one 2 mg/0.5 mg flm or tablet. • Record your withdrawal symptoms: __________________________________. • If you continue to experience withdrawal 2 hours later, you may take one more 2 mg/0.5 mg flm or tablet. • Record your withdrawal symptoms: __________________________________. Your total dose on Day 2 cannot exceed _______ mg. Record your total dose on Day 2: ______ mg. Day 3 in the Morning: Take the total dose you took on Day 2 = _______ mg. • If you experience withdrawal 2 hours later, you may take one more 2 mg/0.5 mg flm or tablet. • Record your withdrawal symptoms: ___________________________________. • If you continue to experience withdrawal 2 hours later, you may take one more 2 mg/0.5 mg flm or tablet. • Record your withdrawal symptoms: _____________________________________. Your total dose on Day 3 cannot exceed _______ mg. Record your total dose on Day 3: ______ mg. Day 4 in the Morning: Take the total dose you took on Day 3 = _______ mg. • If you experience withdrawal 2 hours later, you may take one more 2 mg/0.5 mg flm or tablet. • Record your withdrawal symptoms: ___________________________________. • If you continue to experience withdrawal 2 hours later, you may take one more 2 mg/0.5 mg flm or tablet. • Record your withdrawal symptoms: _____________________________________. Your total dose on Day 4 cannot exceed _______ mg. Record your total dose on Day 4: ______ mg. Day 5 to next visit: In the morning, take the total dose you took on Day 4 = _______ mg. General Rules • The maximum dose is 16 mg/4 mg. If you reach this dose, you cannot increase further without calling the offce frst. The offce phone number is _______________________________ [insert phone number]. • Please call if you have any questions. There are no “stupid” questions. • Call us if you feel sleepy after your dose. • Please bring this record to your next visit. • It’s okay to take Tylenol (acetaminophen) or Motrin (ibuprofen) for aches/pains. BRING THIS WITH YOU TO YOUR NEXT APPOINTMENT, scheduled for ______________________ [insert date and time]. Notes: *If prescribing the buccal flm, ensure the patient understands that the buccal flm is placed on the inner cheek (buccal mucosa) rather than sublingually (under the tongue). M. Lofwall, February 27, 2017 (personal communication). Adapted with permission. 3-78 Medications for Opioid Use Disorder TIP 63 Buprenorphine Treatment Agreement This form is for educational/informational purposes only. It doesn’t establish a legal or medical standard of care. Healthcare professionals should use their judgment in interpreting this form and applying it in the circumstances of their individual patients and practice arrangements. The information provided in this form is provided “as is” with no guarantee as to its accuracy or completeness. TREATMENT AGREEMENT I agree to accept the following treatment contract for buprenorphine offce-based opioid addiction treatment: 1. The risks and benefts of buprenorphine treatment have been explained to me. 2. The risks and benefts of other treatment for opioid use disorder (including methadone, naltrexone, and nonmedication treatments) have been explained to me. 3. I will keep my medication in a safe, secure place away from children (for example, in a lockbox). My plan is to store it [describe where and how _____________________________________________________________________]. 4. I will take the medication exactly as my healthcare provider prescribes. If I want to change my medication dose, I will speak with my healthcare provider frst. Taking more medication than my healthcare provider prescribes or taking it more than once daily as my healthcare provider prescribes is medication misuse and may result in supervised dosing at the clinic. Taking the medication by snorting or by injection is also medication misuse and may result in supervised dosing at the clinic, referral to a higher level of care, or change in medication based on my healthcare provider’s evaluation. 5. I will be on time to my appointments and respectful to the offce staff and other patients. 6. I will keep my healthcare provider informed of all my medications (including herbs and vitamins) and medical problems. 7. I agree not to obtain or take prescription opioid medications prescribed by any other healthcare provider without consulting my buprenorphine prescriber. 8. If I am going to have a medical procedure that will cause pain, I will let my healthcare provider know in advance so that my pain will be adequately treated. 9. If I miss an appointment or lose my medication, I understand that I will not get more medication until my next offce visit. I may also have to start having supervised buprenorphine dosing. 10. If I come to the offce intoxicated, I understand that my healthcare provider will not see me, and I will not receive more medication until the next offce visit. I may also have to start having supervised buprenorphine dosing. 11. I understand that it’s illegal to give away or sell my medication; this is diversion. If I do this, my treatment will no longer include unsupervised buprenorphine dosing and may require referral to a higher level of care, supervised dosing at the clinic, and/or a change in medication based on my healthcare provider’s evaluation. 12. Violence, threatening language or behavior, or participation in any illegal activity at the offce will result in treatment termination from the clinic. 13. I understand that random urine drug testing is a treatment requirement. If I do not provide a urine sample, it will count as a positive drug test. 14. I understand that I will be called at random times to bring my medication container into the offce for a pill or flm count. Missing medication doses could result in supervised dosing or referral to a higher level of care at this clinic or potentially at another treatment provider based on my individual needs. 15. I understand that initially I will have weekly offce visits until I am stable. I will get a prescription for 7 days of medication at each visit. 16. I can be seen every 2 weeks in the offce starting the second month of treatment if I have two negative urine drug tests in a row. I will then get a prescription for 14 days of medication at each visit. 17. I will go back to weekly visits if I have a positive drug test. I can go back to visits every 2 weeks when I have two negative drug tests in a row again. 18. I may be seen less than every 2 weeks based on goals made by my healthcare provider and me. 19. I understand that people have died by mixing buprenorphine with alcohol and other drugs like benzodiazepines (drugs like Valium, Klonopin, and Xanax). Continued on next page 3-79 TIP 63Part 3 of 5—Medications for Opioid Use Disorder 20. I understand that treatment of opioid use disorder involves more than just taking medication. I agree to comply with my healthcare provider’s recommendations for additional counseling and/or for help with other problems. 21. I understand that there is no fxed time for being on buprenorphine and that the goal of treatment is for me to stop using all illicit drugs and become successful in all aspects of my life. 22. I understand that I may experience opioid withdrawal symptoms when I stop taking buprenorphine. 23. I have been educated about the other two FDA-approved medications used for opioid dependence treatment, methadone and naltrexone. 24. I have been educated about the increased chance of pregnancy when stopping illicit opioid use and starting buprenorphine treatment and been informed about methods for preventing pregnancy. Other specifc items unique to my treatment include: Patient’s Name (print): _____________________________________________________ Patient’s Signature: ________________________________________________________ Date: ____________________ This form is adapted from the American Society of Addiction Medicine’s Sample Treatment Agreement, which is updated periodically; the most current version of the agreement is available online (www.asam.org/docs /default-source/advocacy/sample-treatment-agreement30fa159472bc604ca5b7ff000030b21a.pdf?sfvrsn =bd4675c2_0). Adapted with permission.359 3-80 Medications for Opioid Use Disorder TIP 63 Patient Urine Drug Screen and Medication Count Monitoring Form Patient’s Name: ______________________________________________________ Date To Be Called:______________________ Called for: □ Urine Drug Screen □ Medication Count at □Offce or □Pharmacy FOR: _____________________________________________________________ □ Buprenorphine/Naloxone □ Other (list drug: ___________________________, ___________________________, ___________________________) Documentation of Phone Call to Patient Patient was called at _____________________________ (insert phone #) on ____________________ (date) at _____:_____ (time) and informed of monitoring required (described above) within the next _______ hours. Check One: □ I spoke with patient □ Message left on answering machine/voicemail □ Message left with ________________________________________________ □ Other __________________________________________________________ Signature of Staff Member Making Phone Call: _______________________________________________________ M. Lofwall, February 27, 2017 (personal communication). Adapted with permission. 3-81 TIP 63Part 3 of 5—Medications for Opioid Use Disorder ________________________________________________ Pharmacy Tablet/Film Count Form (Note: Before sending this form, discuss with the pharmacist frst to explain goals and procedures and to ensure agreement and understanding.) Date: ___________________ To: Pharmacists @ ________________________________________ Pharmacy From: Healthcare Provider: ____________________________________________ Clinic Address: _________________________________________________ Phone Number: ________________________________________________ My patient, __________________________________, is starting offce-based buprenorphine treatment for opioid dependence. As part of monitoring this treatment, we ask the patient to do buprenorphine tablet/flm counts at random times (we call the patient when it’s time for a pill/flm count). The above-named patient lives much closer to your pharmacy than to our treatment clinic. It would be a big help to me and this patient if you would be able to perform periodic tablet/flm counts on his/her buprenorphine and then fax this form to us. On the days we call the patient for a random tablet/flm count, the patient would come to your pharmacy with his or her pill bottle. When we call the patient to go for a random tablet/flm count, we will fax this form to you. We would appreciate if you could record the tablet/flm count results on this form and fax it back to us the same day. This would be a real help to me in monitoring my patient’s treatment and also a great service to the patient. Thank you very much for your help with this! Sincerely, Signature Buprenorphine/Naloxone formulation: _________________________________________ Dose per tablet/flm: _______________ Total # of tablets/flms remaining in bottle: ______________ Fill date on bottle: ___________________ Total # of tablets/flms dispensed on fll date: ____________ Tablet/flm count correct? □Yes □No Please fax this back to: _____________________________________ Thank You! M. Lofwall, February 27, 2017 (personal communication). Adapted with permission. This page intentionally left blank. 3-83 TIP 63Part 3 of 5—Medications for Opioid Use Disorder Chapter 3E: Medical Management Strategies for Patients Taking OUD Medications in Ofce-Based Settings Chapter 3E examines key issues in medical management of patients who are prescribed buprenorphine or naltrexone in offce-based opioid treatment (OBOT) settings. It covers regulatory and administrative concerns specifc to buprenorphine and naltrexone that affect medical management of patients in offce settings. Management of patients taking medications for opioid use disorder (OUD) varies by setting. Whereas OBOT stabilizes patients on buprenorphine or naltrexone, providers focus on medication management and treatment of other substance use, medical comorbidities, and psychosocial needs. Treatment of comorbid conditions should be offered onsite or via referral and should be verifed as having been received. Exhibit 3E.1 addresses use of terminology in this chapter. EXHIBIT 3E.1. Key Terms In addition to the key terms defned in Exhibit 3.1 of this Treatment Improvement Protocol (TIP), these terms appear in Chapter 3E: Psychosocial support: Ancillary services to enhance a patient’s overall functioning and well-being, including recovery support services, case management, housing, employment, and educational services. Psychosocial treatment: Interventions that seek to enhance patient’s social and mental functioning, including addiction counseling, contingency management, and mental health services. Patient Selection To assess patients’ chances of success with standard offce-based treatment, consider: • Concurrent substance use disorder (SUD) involving alcohol or benzodiazepines. Benzodiazepine (illicit and prescription) and alcohol use are common in patients with OUD. This use presents clinical challenges, including increased risk of respiratory depression and unintentional overdose or death. Some patients may have taken appropriately pre- scribed benzodiazepines for years with limited or no evidence of misuse. For such patients, tapering benzodiazepines may be contrain- dicated and unrealistic. Others may require treatment for a benzodiazepine use disorder. (See Exhibit 3B.1 for strategies for assessing and managing patients in OUD treatment who have concurrent benzodiazepine use disorder.) • Although concomitant use of buprenorphine with benzodiazepines increases the risk of an adverse reaction, including overdose death, opioid agonist treatment should not be denied to patients solely because they take benzodiazepines,360 because untreated OUD can pose a greater risk of morbidity and mortality. The Food and Drug Administration (FDA) advises that careful medication man- agement by healthcare professionals can reduce risk (see www.fda.gov/Drugs/Drug Safety/ucm575307.htm for more information). 3-84 Medications for Opioid Use Disorder TIP 63 Approaches to addressing concurrent benzo- diazepine use include: − Get patients’ permission to contact their benzodiazepine prescribers to confrm their histories. Speaking with close family members or friends (with patients’ permis- sion) can also help in evaluating evidence of alcohol or benzodiazepine misuse (e.g., intoxication, accidents, withdrawal seizures). − Make sure patients understand that combining buprenorphine with alcohol, benzodiazepines, or other central nervous system depressants risks potential re- spiratory depression and unintentional overdose death.361 Overdose death with buprenorphine is most often associated with intravenous benzodiazepine and heavy alcohol use. − For patients misusing benzodiazepines (e.g., taking in high doses, bingeing, using intravenously), the TIP expert panel recom- mends referral to higher intensity addiction treatment with medically supervised ben- zodiazepine withdrawal if available (e.g., intensive outpatient programs, residential treatment). Do not rule out concurrent use of buprenorphine or extended-release in- jectable naltrexone (XR-NTX) for treatment of OUD in more structured settings for these patients. − For patients who are physically dependent on illicit benzodiazepines but do not inject or binge, a gradual outpatient medically supervised withdrawal can be attempted using long-acting benzodiazepines, under certain conditions that promote safety and reduce risk. These conditions may include: • Requiring frequent offce visits with ob- servation of patients taking medication. • Having signifcant others monitor patients and report back to the offce. • Offering a short-duration prescription supply. • Monitoring prescription drug monitoring program (PDMP) reports more frequently. • Conducting frequent urine tests. • Using written treatment agreements outlining conditions for dual buprenor- phine and benzodiazepine prescriptions. − Review patient progress regularly; adjust treatment plans as needed. Document treatment decisions, as research showing the effectiveness and safety of these approaches is lacking.362 • Signifcant comorbid mental illness or suicidal or homicidal ideation. Patients who are actively suicidal, homicidal, severely depressed, or psychotic or who are having other signifcant psychiatric problems may need assessment and treatment by a mental health professional who can treat both the psychiatric comorbidity and the OUD. Depending on the severity, they may need higher levels of mental health services in a crisis center, emergency department, or inpatient setting. An addiction psychiatrist can treat such patients upon discharge. • Signifcant medical comorbidity, including infections. Severe abscesses, endocarditis, or osteomyelitis from injecting drugs may require hospitalization. If hospitalization is necessary, buprenorphine can be initiated.363 Initiation of HIV and hepatitis C virus treatments do not contraindicate buprenorphine treatment.364 Patient Management and Treatment Monitoring Base management of OUD on a comprehen- sive assessment that is updated throughout treatment (see Part 2 of this TIP for more information on conducting assessments). Tailor the management approach to patients’ needs and goals. Components of the management approach include: • The length and frequency of offce visits. • The length of time between prescriptions or XR-NTX injections. • The frequency of drug testing. • Ancillary psychosocial and medical treatments and referrals. 3-85 TIP 63Part 3 of 5—Medications for Opioid Use Disorder Course of Treatment The typical course of OUD treatment is varied. There is often not a direct pathway from heavy illicit opioid use to no illicit opioid use.365 Some patients have only occasional returns to use and do not require reinduction on buprenorphine or naltrexone. Other patients may return to use in the context of medication nonadherence, requiring reinduction and restabilization on buprenorphine or medically supervised withdrawal from opioids and an ap- propriate period of abstinence before restarting naltrexone. Some patients may have sustained abstinence and choose to remain on their maintenance buprenorphine or naltrexone dose. However, others may try to taper their buprenor- phine dose, discontinue naltrexone, consider a change in medication (e.g., from buprenorphine to naltrexone or naltrexone to buprenorphine), or attempt maintenance of remission of OUD without any medication. Because OUD is often a chronic and relapsing illness, patients may have different types and durations of treatment over their lifetimes. Some may have periods of successful outpa- tient treatment at different times with all three available FDA-approved medications for OUD. Others may experience forced medication discontinuation (e.g., insurance lapse, time in controlled environments that disallow or discriminate against OUD medication, cases in family and drug courts, parole and probation). A relative few may remain in remission after successfully discontinuing medication voluntarily. Different treatment journeys occur in different treatment settings (e.g., intensive outpatient, residential programs) and with different phar- macotherapies and ancillary psychosocial and recovery support services. To the extent possible, coordinate primary care, behavioral health, and wraparound services needed and desired by the patients to address their medical, social, and recovery needs. Individuals with co-occurring physical, mental, and substance use disorders may beneft from collaborative care.366 RESOURCE ALERT Substance Abuse and Mental Health Services Administration (SAMHSA) Treatment Guidance for Individuals With Co-Occurring Disorders TIP 42, Substance Use Disorder Treatment for People With Co-Occurring Disorders, provides treatment strategies for SUD treatment for individuals with mental disorders (https://store.samhsa.gov/ product/TIP-42-Substance-Abuse-Treatment-for-Persons-With-Co-Occurring-Disorders/SMA13-3992). General Principles for the Use of Pharmacological Agents To Treat Individuals With Co-Occurring Mental and Substance Use Disorders offers assistance for the planning, delivery, and evaluation of medication for individuals with co-occurring mental and substance use disorders (https://store.samhsa. gov/product/general-principles-use-pharmacological-agents-treat-individuals-co-occurring-mental). Pharmacologic Guidelines for Treating Individuals With Post-Traumatic Stress Disorder and Co- Occurring Opioid Use Disorders is tailored to the provision of medication for OUD to individuals also diagnosed with posttraumatic stress disorder (https://store.samhsa.gov/product/pharmacologic- guidelines-treating-individuals-post-traumatic-stress-disorder-co-occurring). 3-86 Medications for Opioid Use Disorder TIP 63 Role of the Treatment Plan and Treatment Agreement in Medical Management The initial treatment plan should include: • Treatment goals. • Conditions for changing or stopping treatment (the Chapter 3E Appendix has a sample goal-setting form). • Therapeutic contingencies for nonadher- ence and failure to meet initial goals, such as: − Increase in the intensity or scope of services at the offce or through referral. − More intensive psychosocial treatment, including inpatient treatment or transfer to an opioid treatment program (OTP) for observed buprenorphine dosing if the offce-based practice is unable to provide such services. − Reassessment to ensure psychiatric and other comorbid addictions are adequately addressed via consultation with mental health, addiction treatment, or pain management providers as available and indicated. Some patients may need a more structured environment when there is continued opioid use or comorbid use of substances other than opioids or when mental disorders are impeding their progress toward remission and recovery. In these cases, medication for OUD should not be interrupted. Treatment agreements can help clarify expec- tations for patients and healthcare profession- als (see the Chapter 3C Appendix and Chapter 3D Appendix for sample treatment agreement forms for XR-NTX and buprenorphine, respec- tively). Review and amend treatment plans and treatment agreements periodically as patients progress (or destabilize) and new goals emerge. This will help healthcare professionals across settings deliver coordinated, effective care. Updating treatment plans and agreements helps If a patient does not discontinue all illicit drugs for extended periods, it doesn’t mean treatment has failed and should not result in automatic discharge. It means the treatment plan may require modifcation to meet the patient’s needs. patients recognize their progress and supports their motivation to remain engaged. Involving patients’ support networks makes patients accountable to a group of caring people rather than to a single healthcare professional. Engage patients’ family members and other recovery supports (with patients’ written consent) by sharing their treatment goals and agreements. Identify specifc ways they can support patients’ goals.367 Medical Management Strategies Medical management includes: • Providing brief supportive counseling. • Referring to ancillary psychosocial services. • Referring to psychiatric and medical care if not directly provided by the healthcare pro- fessional prescribing or administering OUD medication. • Adjusting the frequency of offce visits. • Conducting drug tests. • Monitoring patient adherence to medication with occasional observed dosing, random medication inventorying, or both. • Addressing patient concerns about side effects. The TIP expert panel recommends medication management and brief supportive counseling at each visit. Refer for adjunctive addiction counseling and other psychosocial supports as clinically indicated. 3-87 TIP 63Part 3 of 5—Medications for Opioid Use Disorder • Discussing any concerns with the patient or their support network. • Prescribing medication for co-occurring alcohol use disorder (e.g., disulfram, acamprosate). Strategies for optimizing medical management and brief supportive counseling involve: • Helping the patient manage stressors and identify triggers for a return to illicit opioid use. • Providing empathic listening and nonjudg- mental discussion of triggers that precede use or increased craving and how to manage them. • Providing ongoing assessment to mark progress. Revise treatment goals via shared decision making to incorporate new insights. (See “Treatment Planning or Referral” in Part 2 of this TIP for more on shared decision making.) • Providing medical care for comorbid health conditions. • Referring patients as needed to: − Adjunctive psychiatric treatment. − Addiction counseling. − Case management. − Community-based recovery support groups. • Inviting supportive family members and friends to medical visits to discuss strategies to support patients. • Engaging and educating family members and friends who are reluctant to accept medication’s role in treatment. • Advocating for patients as needed if their treatment becomes threatened by their employer, housing provider, insurance company, the courts, or criminal justice agencies. These threats, refusal of service, or frank coercion may constitute potential viola- tions of the Americans with Disabilities Act or other discrimination or parity violations. Referral to counseling and other psychosocial supports Prescribers of buprenorphine must be able to refer patients for appropriate adjunctive counseling and ancillary services as needed according to federal law.368 (However, patients can still receive buprenorphine treatment even if they do not use such services.) There’s no such referral requirement for naltrexone treatment, but patients should receive medical manage- ment and be referred as needed for adjunctive addiction, mental health, or recovery services. To achieve clinical stability and abstinence from illicit drug use, many patients need psychosocial counseling and support services beyond what their buprenorphine prescriber’s practice offers. For example, patients with mental disorders (e.g., depression, posttrau- matic stress disorder)369 should be assessed and treated with appropriate medications (as indicated) and adjunctive mental health services. Some patients are reluctant to engage in addiction counseling or recovery support groups until they stabilize on medication. Once stabilized, they may see benefts to participating in these supports. Recommend additional addiction, mental health, and social services as appropriate if patients: • Do not achieve full remission. • Continue to misuse nonopioid substances. • Do not reach their treatment goals with medication management alone. Behavioral treatment with contingency manage- ment (e.g., rewards for illicit drug abstinence) is highly effective and is offered in some specialty treatment programs. It can motivate the patient to reduce illicit drug use, including opioids and stimulants, and increase medication adherence.370 Alcoholics Anonymous, Narcotics Anonymous, Self-Management and Recovery Training, and other peer recovery support groups can be 3-88 Medications for Opioid Use Disorder TIP 63 helpful to patients, especially if they fnd groups with accepting attitudes toward OUD medication and people who take it. (See Part 5 of this TIP for resources on recovery support groups.) Some peer recovery support groups consider patients taking methadone and bu- prenorphine for OUD treatment as not being abstinent from opioids. Check with local groups before referring a patient. Groups not accepting of OUD medications are not appropriate for patients taking them. Patients are most likely to beneft from peer support programs if they actively participate in offered recovery activities.371 Monitor recovery activities to ensure that patients are accessing appropriate supports and are benefting from them (Exhibit 3E.2). Patients may need many other psychosocial services. Case managers can help patients obtain: • Housing support. • Medicaid or other health insurance. • Income support. • Food assistance services. • Vocational and educational services. • Mental health and family therapy. Refer to psychosocial services as appropriate. Get patient consent to share information and make provider introductions, just as referrals to other medical specialists would occur. Strategies include: • Referring per program availability, afford- ability, and patients’ needs, preferences, and treatment responses. Ensure referrals to programs that accept and support patients receiving OUD medication. • If possible, personally introducing patients to the new behavioral health service providers or peer recovery support specialists if changing settings, to encourage a successful transition. • Developing and maintaining a list of referral resources, including: − Drug and alcohol counselors. − Inpatient, residential, and outpatient addiction counseling programs. − OTPs. − Inpatient/outpatient behavioral health programs. − Primary care and mental health providers. − Community-based services. − Recovery support groups. EXHIBIT 3E.2. Monitoring Recovery Activities At medical management visits, do not simply ask about attendance at recovery support meetings— explore the level of participation and engagement in those activities. Some activities include: • Finding and working closely with a sponsor. • “Working” the 12 Steps at 12-Step meetings and with a sponsor. • Doing service at meetings (e.g., setting up chairs, making coffee, going on a “commitment” to speak at a meeting in a jail or an inpatient drug and alcohol program). • Having and frequently attending a regular “home” group.372 Remember this statement from recovery experts A. Thomas McLellan and William White: Recovery status is best defned by factors other than medication status. Neither medication-assisted treatment of opioid addiction nor the cessation of such treatment by itself constitutes recovery. Recovery status instead hinges on broader achievements in health and social functioning—with or without medication support.”373 3-89 TIP 63Part 3 of 5—Medications for Opioid Use Disorder • Using active referral procedures (e.g., linking patients directly via phone to a specifc program staff member) instead of passive ones (e.g., giving a patient a name and a phone number to call). • Avoiding leaving patients to fnd their own referrals. • Monitoring patients’ follow-through via phone contact or at the next offce visit. Frequency of medical management visits The TIP expert panel recommends that patients be seen approximately once a week until they demonstrate signifcant reduc- tions in or abstinence from illicit substance use.374 This is also a time to ensure medication adherence. Nonadherence to naltrexone or buprenorphine prevents optimal treatment outcomes. In scheduling patient visits, be sensitive to treatment barriers such as: • Work and childcare obligations. • Cost of care and lack of insurance coverage. • Driving time. • Lack of public transportation to visits, which may be particularly challenging for patients in rural areas. Goals of weekly visits include: • Assessing patients’ clinical needs and challenges. • Assessing medication effectiveness and side effects. • Assessing functional status (e.g., home, work, school). • Assessing and monitoring stress coping strategies and potential triggers for return to substance use. • Assessing adherence to the recommended frequency of attendance for XR-NTX injections or the prescribed buprenorphine dosing regimen and responsible handling of the medication (e.g., safely storing out of reach of children, taking as prescribed, not sharing or losing it). • Monitoring use of alcohol and illicit drugs and ensuring adequate therapeutic dosing (e.g., opioid blockade if there is ongoing illicit opioid use and adherence to medication). • Following up on any referrals made, such as adjunctive counseling, recovery support groups, or other psychosocial services (the Chapter 3E Appendix has a sample medical management visit form). Once patients adhere to therapeutic doses of OUD medication, decrease illicit drug and alcohol use, and increase negative opioid toxicological samples, consider less frequent visits. Monthly visits (or less for carefully selected patients who have been stable on buprenorphine for extended periods with adequate support) are reasonable for patients taking naltrexone or buprenorphine who show progress toward treatment objectives. Indications that a patient is ready to come less than weekly include: • Several weeks of illicit opioid abstinence based on self-report and negative drug tests. • Adherence to appointments and treatment plan. • No ongoing drug use that may risk patient safety (e.g., alcohol or benzodiazepine misuse). • Absence of signifcant medication side effects. • Stable mental health and medical conditions. • Responsible handling of medication (e.g., safe storage, no requests for early reflls). • Absence of unexpected controlled medication prescriptions from other providers in the PDMP. As visits become less frequent, consider random urine drug testing, medication counts (buprenorphine tablets or flms), and involve- ment of network supports if available. Buprenorphine implants are indicated only for stable patients already taking transmucosal buprenorphine with positive treatment response. Extended-release buprenorphine is indicated for patients treated with transmu- cosal buprenorphine for at least 1 week. It’s 3-90 Medications for Opioid Use Disorder TIP 63 Visit frequency should not depend only on dosing schedule for long- acting OUD medications. Also consider patients’ treatment needs, preferences, and responses. To ensure continued engagement, consider adding to the treatment agreement the expected visit frequency and frequency of other ancillary treatments tailored to patients’ needs, goals, and preferences. expected that patients with the implants or those treated with extended-release buprenorphine will receive medication management services with visits approximately weekly at the start and then less frequently as clinically indicated based on patient treatment response. Likewise, patients treated with XR-NTX should be seen more than once per month when initiating the medication to monitor progress and assess and address any side effects. Drug testing in ongoing medical management Ongoing clinical monitoring that includes drug testing of urine or oral fuid specimens is part of good practice. Objective evidence of any ongoing illicit substance use is important to consider along with patient reports. Patients may not wish to disclose recent drug use because of shame, fear of punishment, or even fear of discharge from treatment. Explain to patients that testing will help them meet treatment goals and is not performed to render punishments. Results help: • Detect medication nonadherence that could cause harm (e.g., unintentional overdose). • Monitor abstinence and response to medica- tion treatment. • Counsel and improve treatment plans. • Detect a return to illicit opioid use or other substance use. The TIP expert panel recommends periodic random testing. Drug testing frequency should be clinically determined. It should occur at least at the time of the initial evaluation and initiation of medication (naltrexone, buprenorphine) and at a frequency consistent with offce visits (e.g., weekly initially). Point-of-service tests give immediate results, allowing fndings and implications to be discussed with patients during visits. However, some circumstances require confrmatory labo- ratory testing, such as when the patient contests the results and when testing for employment or legal monitoring. In these cases, samples may need to be collected and sent to a Department of Health and Human Services-certifed labora- tory under strict chain-of-custody procedure. In addition, norbuprenorphine may not be available in point-of-service tests and therefore, periodi- cally, a specimen should be sent to a laboratory for testing. Important aspects of testing include: • Testing technology. • The cutoffs for positive tests. • Any administrative requirements. • Time windows to detect a positive result. • Cross-reactivity, sensitivity, and specifcity. • Test interpretation. (See Part 2 for more information about how to interpret drug testing results.) • Consideration of panels based on drugs most commonly used in the region. Conduct point-of-service drug tests following the manufacturer’s instructions. Use Clinical Laboratory Improvement Amendments-waived testing kits. A provider’s offce must enroll and pay a modest fee for certifcation. The applica- tion is available online (www.cms.gov/Medicare /CMS-Forms/CMS-Forms/downloads/cms116 .pdf). 3-91 TIP 63Part 3 of 5—Medications for Opioid Use Disorder Sample collection via oral swab is straightforward; follow the manufacturer’s directions. If collecting urine samples, take steps to reduce the likelihood of tampering. In settings that treat many patients or treat patients potentially facing criminal justice sanctions, consider taking these measures: • Have patients visit the bathroom alone, without bags or jackets, to deter use of another person’s urine specimen. • Set the sink to run only cold water and use a colored toilet bowl cleaner to prevent dilution of urine specimens. • Use specimen cups with specifc gravity testing, if possible, to identify diluted samples. • Use temperature-sensitive strips in collection cups to identify tampered specimens. Ongoing positive opioid tests during treatment indicate the need to reassess the patient and revise the treatment plan. Repeated positives may indicate that patients: • Are not taking some or all of their medication or may be taking the medication incorrectly. • Need a different medication. • Need directly observed medication adminis- tration in the offce or at an OTP. • Need a buprenorphine dose increase. • Need more counseling or a higher level of a specialty addiction treatment program. • Need to participate in recovery support services. For more information on drug testing in the primary care setting, see Technical Assistance Publication 32, Clinical Drug Testing in Primary Care375 (https://store.samhsa.gov/product/ tap-32-clinical-drug-testing-primary-care/sma12- 4668) and ASAM’s Consensus Statement on Appropriate Use of Drug Testing in Clinical Addiction Medicine.376 Opioids and opiates in point-of-service tests Point-of-service and laboratory screening tests for opiates only test for opioids metabolized to morphine (e.g., codeine, heroin). Semisynthetic and synthetic opioids, such as methadone, buprenorphine, and others (e.g., fentanyl, oxycodone), are not metabolized to morphine and do not test positive on most opiate tests. Specifc point-of-service tests exist for these opioids. Some point-of-service and laboratory tests can detect methadone, buprenorphine, and other opioids. Patients taking buprenorphine should have buprenorphine specifcally included in their urine test panel to assure the prescriber that the patient is indeed taking the medication. Some patients may put some of their buprenorphine in the urine to mask nonadherence. Periodically testing for a buprenorphine metabolite (e.g., norbuprenorphine, buprenorphine glucuronide) is advised. Assessing buprenorphine adherence Medication nonadherence and diversion can signal inadequately treated OUD (e.g., return to use with positive urine drug tests). Assess such behaviors clinically and develop therapeutic responses to them. Remember that nonadherence, misuse, and diversion occur with other medications as well—those with and without abuse potential. For instance, it’s clear that opioid analgesics have been overprescribed for pain, misused, and diverted; they have contributed to deaths among individuals prescribed as well as those not prescribed these medications. Antibiotics for bacterial infections are also overprescribed, and patient nonadherence (e.g., not completing the full course), misuse (e.g., saving leftover medi- cation for a later self-diagnosed and self-treated infection), and diversion (e.g., giving leftover medication to ill family members or friends) can cause signifcant public health harm, given the spread of drug-resistant bacteria. Medication nonadherence has largely fueled development of longer acting medications (e.g., depot anti- psychotics, long-acting contraceptives, XR-NTX, buprenorphine implants). 3-92 Medications for Opioid Use Disorder TIP 63 Strategies for addressing medication non- adherence and diversion include carefully assessing the patient to understand under- lying causes of the behavior. Address these causes and monitor adherence. For instance, if a patient gives his or her medication to a relative on a waiting list for treatment, getting the relative into treatment can help that patient become adherent. Monitor adherence by: • Asking patients to bring their unused medica- tion into the offce for counting. • Increasing the frequency of offce visits. • Increasing urine drug testing. • Talking with family members or signifcant others. • Writing prescriptions for shorter duration. • Observing medication administration at the offce, pharmacy, or OTP. • Checking urine for buprenorphine and its metabolites. • Checking the PDMP. • Avoiding doses over 24 mg (save in rare cases). Chapter 3D Appendix includes a sample patient urine drug screen and medication count form, as well as a pharmacy tablet/flm count form. If these steps have no positive effect, patients may need referral to higher levels of care at OTPs or residential addiction treatment programs. Different formulations of medications may need to be considered.377 If a change in setting is required, consider patients for return to OBOT once they stabilize. Discontinuing medication for OUD Patients should decide whether to taper off or discontinue medication with the support of their healthcare professional and, if applica- ble, their addiction or mental health counselor, family, and peer recovery supports (e.g., peer support specialist, recovery coach). If patients’ goals include stopping medication, discuss the risks and benefts of discontinuing. Work closely with patients to develop a buprenorphine dose taper plan, if needed, and a robust plan to sustain recovery and reengage in treatment before any return to substance use. Before patients begin a buprenorphine dose taper or discontinue XR-NTX, they should demonstrate: • Medication adherence. • Abstinence from illicit opioid use. • A stable living environment. • Social support. • Sustained improvements in functioning at home and at school or work. Consider treatment with XR-NTX following successful taper from an opioid agonist or partial agonist (after an appropriate period of absti- nence). Data are limited on the effectiveness of this approach. The TIP expert panel recommends that providers not discharge patients from treatment solely because of continued illicit opioid use if the benefts of treatment continue to outweigh the risks. If risks outweigh benefts or alternative treatments may offer more beneft, refer patients to alternative treatment (e.g., OTP). Discharging patients without attempting meaningful referral when illicit opioid use is ongoing can worsen the patient’s condition and may be considered patient abandonment. Forced tapers or abrupt discontinuation Forcing a patient to taper off of medication for nonmedical reasons or because of ongoing substance misuse is generally inappropriate. Many patients are abruptly discontinued or tapered from OUD medication against their will while detained or awaiting trial. A randomized Do not require discontinuation of medication for OUD because of incomplete treatment response. Doing so is not a rational therapeutic response to the predicted course of a chronic condition. 3-93 TIP 63Part 3 of 5—Medications for Opioid Use Disorder trial of continuing versus tapering off methadone for detainees found that those who kept taking medication in detention were signifcantly more likely to return to treatment on release.378 It is likely that the same holds true for forced discon- tinuation from buprenorphine during detention. As is sometimes the case in general medical practice, patients who are unable to pay their bills should not be discontinued from treatment without attempting meaningful referral. Attempt referrals to publicly funded addiction treatment services (e.g., specialty treatment programs, federally qualifed health centers). If patients cannot continue treatment because of inability to pay, providers can contact the pharmaceutical company about patient assistance programs to help defer the cost of medications. Forced dose tapers against the patient’s desire may be clinically indicated when risks of treatment outweigh benefts or, in unusual cases, where the patient has been violent toward staff or other patients. In these cases, attempt to place the patient in a higher level of care and document the attempt. In some circumstances, forced tapering or abrupt discontinuation may violate the Americans with Disabilities Act. The Legal Action Center (www.lac.org) and the National Alliance for Medication Assisted Recovery (www.methadone.org) offer informa- tion on how to legally manage forced tapers. Patient follow-up Medical management should not end when patients taper off of medication. The TIP expert panel recommends regular follow-up visits (or phone checkups by clinical staff or recovery support specialists) to help patients manage their condition, address potential concerns about returning to illicit opioid use, and discuss reinitiating OUD maintenance medication if warranted. Attendance at drug counseling or mutual-help groups can be helpful, as can periodic drug testing. Administrative Considerations Patient Limits Individual healthcare practitioners can prescribe buprenorphine in any medical setting, as long as they apply for and receive waivers of the special registration requirements defned in the Controlled Substances Act. Several laws and regulations contain information about which healthcare practitioners are eligible to apply for a waiver and how to qualify (www. samhsa.gov/medication-assisted-treatment/ training-materials-resources/apply-for-practi- tioner-waiver). This information is summarized below. Eligible physicians, nurse practitioners, physician assistants, and other qualifying practitioners (clinical nurse specialists, certifed registered nurse anesthetists, and certifed nurse midwives) can apply for a waiver. At present, clinical nurse specialists, certifed registered nurse anesthetists, and certifed nurse midwives are only eligible to apply for a waiver until October 1, 2023. For the frst year of waiver use, all providers can treat up to 30 patients at one time. However, providers who satisfy additional practice and reporting requirements, and physicians who are board certifed in addiction psychiatry or addiction medicine, may request to treat up to 100 patients at a time in the frst year of waiver use. Additionally, practitioners who provide MAT in “qualifed practice settings,” as defned in title 42, section 8.615 of the Code of Federal Regulations, may also request to treat up to 100 patients within the frst year. After the frst year of waiver use, all providers may request to increase their patient limit to 100. 3-94 Medications for Opioid Use Disorder TIP 63 Physicians who are board certifed in addiction psychiatry or addiction medicine or who satisfy additional practice and reporting requirements may apply to increase their patient limit to 275 after a year at the 100-patient limit. Diversion Control Policies for OBOT With Buprenorphine Controlled substance diversion refers to unau- thorized provision of medication to someone for whom it was not prescribed.379 Patients may divert buprenorphine for various reasons, such as: • To “help” someone who needs medically su- pervised withdrawal or awaits treatment.380,381 • To provide income for the seller. • To enable someone else to experience the euphoric effect of the medication.382 Address diversion of controlled substances with patients using the following strategies: • Clarify that continuing in offce-based treatment depends largely on taking med- ication as prescribed; nonadherence and diversion are thus problematic. • In a nonjudgmental way, discuss to whom within their network of family, friends, and acquaintances they might be tempted to divert their medication and why they might be tempted to do so. • Instruct patients to store medication securely (children may inadvertently ingest it and overdose, or other people may take the medication for their own use or to sell).383 − Discuss patients’ plans to safely store buprenorphine. Advise patients to keep the medication in the original packaging and out of the reach of children.384 − Tell patients not to store their medication in common areas (e.g., kitchen, bathroom) where others may access it. − Educate patients that any portion of a dose taken by a child or pet can be deadly and that they should call 9-1-1 immediately if this occurs. • Explain how diversion causes negative views of treatment, leading to discrimination against people with OUD. Therefore, healthcare pro- fessionals must proactively address diversion to help prevent it. Possible signs that a patient is diverting bu- prenorphine385 include: • Frequently missed appointments. • Requests for early reflls because medication was reportedly lost or stolen. • Negative buprenorphine urine screens. • Positive buprenorphine urine screens that are negative for buprenorphine metabolites. • Specifc requests for the buprenorphine monoproduct owing to naloxone allergy. • Specifc requests for doses of buprenorphine greater than 24 mg/6 mg. • PDMP shows prescription flls for opioids or other medications that are not positive on his or her drug tests. • Failed flm/pill callback counts. Establish a diversion control plan to minimize OUD medication diversion. The plan provides measures to reduce diversion and assigns specifc responsibility to medical and admin- istrative staff members for carrying out these measures.386 It should address medication storage, dispensing and administration (if applicable), and prescribing387 (see the Chapter 3E Appendix for a sample diversion control policy). For providers who store buprenorphine for administration and dispensing, plans should indicate how they will control diversion and which approaches they will use to ensure that patients take their medication. Exhibit 3E.3 summarizes key elements of a diversion control plan. Physicians who prescribe buprenorphine to more than 100 patients need a diversion control plan. Document diversion incidents and responses to incidents in the patient record. More information about Drug Enforcement Administration (DEA) requirements for Drug Addiction Treatment Act of 2000 (DATA 3-95 TIP 63Part 3 of 5—Medications for Opioid Use Disorder 2000)-waivered healthcare professionals is available online (www.deadiversion.usdoj.gov/ pubs/docs/index.html). Storage of Buprenorphine Practices that store buprenorphine onsite must have appropriate security, which includes storing the medication in a securely locked, substantially constructed cabinet.388 If a signif- cant amount of stored buprenorphine is lost or stolen, providers must notify the local DEA offce in writing within 1 business day and complete a Form DEA-106 (https://apps.deadiversion.usdoj .gov/webforms/dtlLogin.jsp). Employees convicted of a felony related to a controlled substance or who had a DEA registration denied, revoked, or surrendered “for cause” are not permitted to have access to buprenorphine. EXHIBIT 3E.3. Key Elements of an OBOT Clinic Diversion Control Plan389 New Patients Check the state’s PDMP before admission to determine whether patients are receiving opioids or benzodiazepine prescriptions from other providers. Ask patients to sign a release of information to speak with the other prescribers. Patients who are unwilling to sign a release of information are poor candidates for outpatient treatment. Review the clinic diversion control policy with new patients. This should include counseling patients to: • Keep buprenorphine locked up and out of children’s reach. • Never share medication with anyone. • Never sell medication to anyone. • Acknowledge giving or selling medication to others as illegal. • Take medication only as prescribed. • Review, understand, and agree to the practice’s buprenorphine treatment agreement before they start. Prescribe buprenorphine/naloxone when possible rather than monoproduct. Exceptions include prescribing the monoproduct for pregnant women with OUD. Prescribe an adequate but not excessive dose. Most patients respond to doses at or below 24 mg per day. Carefully evaluate requests for higher doses and confrm, document, and assess medication adherence continuously. Ongoing Patients Periodically check the state’s PDMP. Conduct random urine tests that include a wide spectrum of opioids—including morphine, oxycodone, and buprenorphine—and periodically include buprenorphine metabolites. This will help monitor response to treatment and determine whether patients are taking at least some of their prescribed buprenorphine. Use unobserved specimen collection to preserve patient privacy and dignity: • Do not let patients bring backpacks, jackets, or other items into the bathroom. • Do not let others enter bathrooms with patients. • Temperature test the urine sample. Use observed specimen collection (obtained by a staff member of the same gender) or oral fuid testing if there is reason to suspect tampering or falsifcation. Contact patients at random; ask them to bring in their medication within a reasonable period (24 to 48 hours) to count the tablets/flms to ensure that all medication is accounted for. Provide a limited number of days of medication per prescription without reflls (e.g., several days or 1 week per prescription) until the patient has demonstrated stability and lowered diversion risk. 3-96 Medications for Opioid Use Disorder TIP 63 Records for Dispensers Offce-based practices that dispense buprenor- phine must keep records of:390 • The number of units and doses dispensed with the names and addresses of the patients. • The dates the medication was dispensed. • The names (or initials) of the staff members who dispensed or administered the medication. The diversion control plan should include approaches to ensuring that patients take the medication and do not divert it to others. Recordkeeping for ordering, storing, and dispensing buprenorphine in the ofce All prescribers and staff members must follow federal and state laws for ordering, storing, administering, and dispensing buprenorphine in outpatient settings. Records of inventories of medication received, dispensed, destroyed, and lost or stolen must be maintained. For guidance on how to comply with federal requirements, see: • DEA Recordkeeping Requirements for Buprenorphine Treatment (https://docs. clinicaltools.com/pdf/Buppractice/V5-Bup- How-To-Comply.pdf). Recordkeeping for prescribing buprenorphine Consider writing an initial prescription for only a few days. An example of a 1-day in-offce induction prescription is: Buprenorphine/naloxone 2mg /0.5 mg: Dispense #4 for in-offce induction, no reflls, fll on __________________________ [insert date that is 1 day before the scheduled induction to make it less tempting for patients to use on their own before induction] Keep a log for possible DEA inspection that includes: • Patients’ names (or ID numbers). • Dates of prescriptions. • The names, strengths, and quantities of the medications. Although not required, such a log facilitates inspection and indicates that the provider is within the approved patient limits. Alternatively, electronic health records can be used for this purpose. DEA Inspections Under DATA 2000, DEA must ensure that providers administering, dispensing, or prescrib- ing buprenorphine are following recordkeeping, security, and other requirements. To fulfll this requirement, DEA conducts routine, unan- nounced onsite inspections. A description of the inspection process and how to comply with its requirements is available online (http:// pcssnow.org/wp-content/uploads/2014/02/ FINAL-How-to-Prepare-for-a-DEA-Inspection.pdf). Emergency Protocols and Patient Safety Measures Clinics that provide buprenorphine or naltrexone do not need special emergency protocols, crash carts, or other special equipment. However, for patient safety, the TIP expert panel recommends having injectable or intranasal naloxone onsite. Clinics that ad- minister XR-NTX or buprenorphine should have a written policy and procedure for responding to precipitated withdrawal and medication allergies. Providers who give more than 100 patients buprenorphine must have on- call services. Such services are valuable regardless of the number of patients in treatment. 3-97 TIP 63Part 3 of 5—Medications for Opioid Use Disorder On-call services and backup during absences should be available either directly or through contracts or cooperative agreements with other local providers with waivers. Qualifed medical staff can offer routine medical and psychiatric coverage even without a buprenorphine waiver. Recommendations for Staf Member Training All staff members who interact with patients are part of the treatment environment. They can affect patients’ treatment experiences and, ultimately, their outcomes. Staff members who interact with patients can include receptionists, billing clerks, urine specimen collection clerks, and all clinical staff members. Therefore, it is useful to educate and train all staff members in key areas, including: • Organizational mission. • The scientifc and empirical underpinnings for the use of FDA-approved medications for OUD, how these medications work, and the evidence for their effectiveness. • The similarity of medical management and support of patients with OUD to that of patients with other chronic illnesses. • The importance of maintaining a nonjudgmen- tal and welcoming attitude toward patients. • How to hold discussions about negative perceptions and prejudices associated with OUD. • Side effects of OUD medications and proce- dures to alert staff members when patients exhibit them. • The effect of OUD and other substance use and mental disorders (including posttraumatic stress disorder) on patients’ behavior and how staff members can respond appropriately. • Procedures for seeking help from other staff members to deescalate disagreements or solve problems. • Procedures for protecting patients’ confdenti- ality and safety. Treating OUD can be a challenging yet rewarding part of a clinical practice. Addressing key administrative issues keeps the focus on the rewarding aspects of developing long-term relationships with patients as they work to overcome negative effects of OUD on their lives and improve their health. RESOURCE ALERT Training and Mentorship for Prescribers The Providers’ Clinical Support System, with the American Academy of Addiction Psychiatry as the lead organization along with partners from ASAM and other professional organizations, delivers education, training, and mentorship to providers who wish to treat OUD with medications. More information about training and professional mentorship is available online (https://pcssnow.org/education-training/). 3-98 Medications for Opioid Use Disorder TIP 63 Chapter 3E Appendix Sample Goal-Setting Form Patient’s Name: ________________________________________________________________ Date: _________________________ GOAL CATEGORY CURRENT SITUATION SCORE 10 = major problems and 0 = no problems What would need to change to decrease this score? PRIORITY SCORE 10 = highest priority (“I really want to work on this”) and 1 = lowest priority (“I really do not want to work on this”) Opioid use Other illicit drug use: ______________ Alcohol use Tobacco use Physical health Mental health Legal/court issues Finances Job/employment Hobbies Family relations Partner relations Supportive drug-free network Education Keeping medication safe (e.g., not giving it away, selling it, having it stolen) Other Other M. Lofwall, February 27, 2017 (personal communication). Adapted with permission. 3-99 TIP 63Part 3 of 5—Medications for Opioid Use Disorder ________________________________________________________________________________________________________________ ________________________________________________________________________________________________________________ ________________________________________________________________________________________________________________ ________________________________________________________________________________________________________________ Sample Medical Management Visit Form Patient’s Name: ___________________________________________________________ ID#____________________________ Date: ____________________ Week#: _________ Dose: ________ mg □ No Show Heroin/cocaine or other illicit drug use since last visit? Symptoms or signs that might indicate return to use (e.g., changes in mood, physical appearance)? Since the last visit, are there any problems with the following: If yes, explain Drug Use □ Yes □ No Alcohol Use □ Yes □ No Psychiatric □ Yes □ No Medical □ Yes □ No Employment □ Yes □ No Social/Family □ Yes □ No Legal □ Yes □ No Any new problem to add to Treatment Plan Review? □ Yes □ No Plan to address any new problem _________________________________________________________________________________ Participation in Narcotics Anonymous or Alcoholics Anonymous since last visit? □ Yes □ No Length of Session: ________________ Healthcare Professional Signature: ___________________________________________ D. Fiellin, December 3, 2016 (personal communication). Adapted with permission. 3-100 Medications for Opioid Use Disorder TIP 63 Sample Buprenorphine Diversion Control Policy XYZ Medical Practice Offce-Based Opioid Use Disorder Policy and Procedure Manual Policy Title: Diversion Control for Patients Prescribed Transmucosal (Sublingual) Buprenorphine Effective Date: ______________________ (Month, Day, Year) This Diversion Control Policy is provided for educational and informational purposes only. It is intended to offer healthcare professionals guiding principles and policies regarding best practices in diversion control for patients who are prescribed buprenorphine. This policy is not intended to establish a legal or medical standard of care. Healthcare professionals should use their personal and professional judgment in interpreting these guidelines and applying them to the particular circum- stances of their individual patients and practice arrangements. The information provided in this Policy is provided “as is” with no guarantee as to its accuracy or completeness. Preamble: Healthcare professionals can now treat up to 275 patients with buprenorphine. This increased access may contrib- ute to increased diversion, misuse, and related harms. Signs that a patient is misusing or diverting buprenorphine include (1) missed appointments; (2) requests for early reflls because pills were lost, stolen, or other reasons; (3) urine screens negative for buprenorphine, positive for opioids; (4) claims of being allergic or intolerant to naloxone and requesting monotherapy; (5) nonhealing or fresh track marks; or (5) police reports of selling on the streets. Likewise, there are a range of reasons for diversion and misuse (e.g., diverting to family/friends with untreated opioid addiction with the intent of trying to “help” convince them to also get treatment; diverting to family/friends on a treatment waiting list; selling some or all of the medication to pay off old drug debts/purchase preferred opioid of misuse/pay for treatment in places where there are inadequate addiction treatment professionals taking private insurance or Medicaid for such reasons as inadequate reim- bursement/no reimbursement/burdensome prior authorization process). The safety and health of patients and others in the community could be at risk if misuse and diversion are not addressed proactively throughout treatment. The reputation of XYZ Medical Practice may also be put at risk. Defnitions: Diversion is defned as the unauthorized rerouting or misappropriation of prescription medication to someone other than for whom it was intended (including sharing or selling a prescribed medication); misuse includes taking medica- tion in a manner, by route or by dose, other than prescribed.391 Purpose: Misuse and diversion should be defned and discussed with patients at the time of treatment entry; periodically throughout treatment, particularly when there have been returns to illicit drug use; and when suspected (e.g., incorrect buprenorphine pill/flm count) or confrmed. These procedures will establish the steps to be taken to prevent, monitor, and respond to misuse and diversion of buprenorphine. The response should be therapeutic and matched to the patients’ needs, as untreated opioid use disorder and treatment dropout/administrative discharges may lead to increased patient morbidity and mortality and further use of diverted medications or illicit opioids associated with overdose death. Procedures for Prevention: • Use buprenorphine/naloxone combination products when medically indicated and cost is not an issue. Reserve the daily buprenorphine monoproducts for pregnant patients and patients who could not afford treatment if the combination product were required, who have a history of stability in treatment and low diversion risk, or who have arrangements for observed dosing. Buprenorphine monoproducts are recommended for pregnant women. • Counsel patients on safe storage of, and nonsharing of, medications. Patients must agree to safe storage of their medication. This is even more critical if there are children in the home where the patient lives. Counsel patients about acquiring locked devices and avoiding storage in parts of the home frequented by visitors (e.g., do not recommend storage in the kitchen or common bathrooms). Proactively discuss how medication should be stored and transported when traveling to minimize risk of unintended loss. • Counsel patients on taking medication as instructed and not sharing medication. Explicitly explain to patients the defnitions of diversion and misuse, with examples. Patients are required to take medication as instructed by the healthcare professional; for example, they may not crush or inject the medication. • Check the prescription drug monitoring program for new patients and check regularly thereafter. Prescription drug monitoring program reports can be a useful resource when there is little history available or when there is a concern based on observation. Check for prescriptions that interact with buprenorphine and for other buprenorphine prescribers. 3-101 TIP 63Part 3 of 5—Medications for Opioid Use Disorder • Prescribe a therapeutic dose that is tailored to the patient’s needs. Do not routinely provide an additional supply “just in case.” Question patients who say they need a signifcantly higher dose, particularly when they are already at 24 mg per day of buprenorphine equivalents. • Make sure the patient understands the practice’s treatment agreement and prescription policies. The XYZ Medical Practice’s treatment agreement and other documentation are clear about policies regarding number of doses in each prescription, reflls, and rules on “lost” prescriptions. Review the policies in person with the patient. Offer an opportunity for questions. Patient and provider must sign the agreement. Review the policies again with the patient at subsequent appointments. See Sample Buprenorphine Treatment Agreement or Sample XR-NTX Treatment Agreement as needed. Procedures for Monitoring: • Request random urine tests. The presence of buprenorphine in the urine indicates that the patient has taken some portion of the prescribed dose. Absence of buprenorphine in the urine supports nonadherence. Testing for bu- prenorphine metabolites (which are present only if buprenorphine is metabolized) should periodically be included to minimize the possibility that buprenorphine is added directly to the urine sample. Dipstick tests can be subverted or replaced. A range of strategies can be used to minimize falsifed urine collections, including (1) observed collection; (2) disallowing carry-in items (e.g., purses, backpacks) in the bathroom; (3) turning off running water and coloring toilet water to eliminate the possibility of dilution; (4) monitoring the bathroom door so that only one person can go in; and (5) testing the temperature of the urine immediately after voiding. • Schedule unannounced pill/flm counts. Periodically ask patients who are at high risk at initial or subsequent appoint- ments to bring in their medication containers for a pill/flm count. • With unannounced monitoring (both pill/flm counts and urine tests), the patient is contacted and must appear within a specifed time period (e.g., 24 hours) after the phone call. If the patient doesn’t show, then the provider should consider this as a positive indicator of misuse or diversion. • Directly observe ingestion. Patients take medication in front of the healthcare professional or another qualifed clinician and are observed until the medication dissolves in the mouth (transmucosal [sublingual or buccal] absorp- tion). Patients who are having diffculty adhering to their buprenorphine can have their medication provided under direct observation in the offce for a designated frequency (e.g., three times/week). • Limit medication supply. When directly observed doses in the offce are not practical, short prescription time spans can be used (e.g., weekly, 3 days at a time). Procedures To Respond to Misuse or Diversion: Misuse or diversion doesn’t mean automatic discharge from the practice. However, it will require consideration of one or more of the following procedures: • Evaluate the misuse and diversion. For instance, describe the incident of misuse (e.g., “the patient took the pre- scribed dose on three or more occasions by intravenous route immediately after starting treatment, stating that she believed the dose would not be adequate by sublingual route; she has just initiated treatment”) or diversion (“the patient gave half of dose to his wife, who is still using heroin and was withdrawing, because he did not want her to have to buy heroin off the street; she is on a waiting list for treatment”) and tailor the response to the behavior (e.g., reeducation of the patient on buprenorphine pharmacology in the frst example above; assistance with treatment entry for the spouse in the second example). Reassess the treatment plan and patient progress. Strongly consider smaller supplies of medication and supervised dosing for any patient who is taking medication intravenously or in- tranasally or diverting, regardless of reason. Treatment structure may need to be increased, including more frequent appointments, supervised administration, and increased psychosocial support. • Intensify treatment or level of care, if needed. Some patients may require an alternative treatment setting or pharma- cotherapy such as methadone. The clinician will discuss these alternatives with the patient to ensure optimal patient outcome. This should be discussed at treatment onset so the patient is aware of the consequences of misuse and diversion. • Document and describe the misuse and diversion incident. Also document the clinical thinking that supports the clinical response, which should be aimed at minimizing risk of diversion and misuse and treating the patient’s opioid use disorder at the level of care needed. Policy adapted from ASAM’s Offce-Based Opioid Use Disorder Policy and Procedure Manual, which is updated periodically; the most current version is available online (www.asam.org/docs/default-source/advocacy/sample-diversion-policy .pdf?sfvrsn=6). Adapted with permission.392 This page intentionally left blank. 3-103 TIP 63Part 3 of 5—Medications for Opioid Use Disorder Chapter 3F: Medical Management of Patients Taking OUD Medications in Hospital Settings Chapter 3F guides the management of patients taking OUD medications in hospital settings. The audience is healthcare professionals in emergency, general medical, surgical, psychiatric, and obstetric units. Patients with opioid use disorder (OUD) who present to emergency departments (EDs) or are admitted to hospitals for acute medical or psychiatric care can beneft from medication to treat OUD in the hospital setting. During acute medical illness, patients experiencing consequences of opioid use may be motivated to change.393 Hospital-based providers can take this opportunity to initiate long-term medication maintenance.394,395 Unfortunately, less than one-quarter of patients with an opioid-related hospitalization are offered Food and Drug Administration-approved med- ication for OUD within 30 days of discharge.396 Patients who already take OUD medication may also present to the hospital. Thus, a broad understanding of how to manage their OUD medication during hospitalization is necessary. The keys to effective patient management in general hospital settings are: • Balancing medication for OUD with other medical concerns (e.g., surgery, pain manage- ment) during hospitalization. • Careful management after discharge. • Seamless transfer to opioid treatment via an opioid treatment program (OTP) or offce- based opioid treatment (OBOT) provider after discharge. OPIOID-RELATED inpatient hospital stays INCREASED 119% nationally from 2005 to 2017.397,398 Hospitalized or ED Patients Taking Medication for OUD Buprenorphine, methadone, and naltrexone may be ordered in EDs or inpatient hospital units. It’s essential for the patient to continue receiving OUD medication while hospitalized. Pain Management Pain management for hospitalized patients who take OUD medication is a key element of medical management. Discuss pain manage- ment and engage in a shared decision-making process with patients being treated for OUD with buprenorphine, methadone, or naltrexone. 3-104 Medications for Opioid Use Disorder TIP 63 Patients may have strong preferences and opinions about pain and use of opioid analgesics for pain treatment. Some patients may want to avoid opioid analgesics. For others, inadequately treated pain may be a trigger for illicit drug use. Involve primary care pain specialists and addiction treatment providers in discussing options for managing OUD medication and pain during patient hospitalization. Buprenorphine The hospital team will need to manage bu- prenorphine for patients who present to the ED or are hospitalized on buprenorphine main- tenance. Physicians in inpatient settings can legally order buprenorphine without a waiver if a patient is admitted primarily for other medical reasons.399 Key medication manage- ment strategies include: • Obtaining written consent to contact the patient’s providers, including: − Primary care provider. − Buprenorphine prescriber. − Pharmacy. • Confrming the patient’s outpatient bu- prenorphine dose by: − Checking prescribing records. − Contacting the prescriber or pharmacy. − Examining recent prescription bottles. − Checking the prescription drug monitoring program database before administering buprenorphine. • Providing the usual daily dose to the patient, once that dose is confrmed. • Ensuring the patient’s outpatient prescriber understands the reason for any missed visits. • Informing the patient’s outpatient prescriber that the patient may test positive for opioids if treated with opioid analgesics while in the hospital. • Maintaining contact with the patient’s pre- scriber, especially when a buprenorphine dose change is considered and in discharge planning. Patients with pain may continue their buprenorphine while in the hospital. For mild-to-moderate pain, dividing the patient’s usual buprenorphine dose three times per day (TID) may provide suffcient pain relief.400 In some cases, increased buprenorphine dose may be appropriate. For moderate-to-severe pain, additional analgesia will be necessary. Two approaches to consider: 1. Continue buprenorphine treatment and use full agonist opioids for added pain relief. Because of the partial blockade caused by buprenorphine, higher-than-usual doses of opioids will probably be required for pain relief. Fentanyl, hydromorphone, and morphine have relatively high binding affnities for the mu-opioid receptor and are most likely to displace buprenorphine from receptors and provide improved analgesia. Once the painful condition has improved, if mild-to-moderate pain persists, bu- prenorphine can be divided TID to manage residual pain. This approach is usually successful and allows the patient to remain stable on buprenorphine. 2. Discontinue buprenorphine upon hospi- talization and use full agonist opioids to treat pain and prevent withdrawal. This approach avoids the blockade effect of buprenorphine on the mu-opioid receptors but leaves the patient vulnerable to a return to illicit opioid use. It may be useful if the frst approach does not achieve adequate pain control.401 Consider a consult by an addiction medicine, psychiatric, or pain management provider if appropriate and available. Pregnant women on buprenorphine can continue buprenorphine through their labor. Labor pain for pregnant patients on buprenor- phine can be managed effectively with epidural analgesia or intravenous opioids. Spinal anes- thesia is effective in patients on buprenorphine; patients can receive general anesthesia if needed.402 3-105 TIP 63Part 3 of 5—Medications for Opioid Use Disorder Perioperative pain management of patients on buprenorphine requires further study, but multiple approaches have been found effective. Most patients can continue buprenorphine through the operative period. Treat postoperative pain with regional anesthesia, nonopioid pain management, or full agonist opioids. Remember that higher doses are likely to be necessary. Some data suggest that buprenorphine divided TID may even be as effective as morphine for postopera- tive pain control.403 Alternatively, buprenorphine can be discontinued 72 hours before a planned surgery and restarted after resolution of acute postoperative pain. The risk of this approach is that it leaves the patient vulnerable to a return to use of illicit opioids.404 Methadone The hospital team will need to manage methadone for patients who present to the ED or are hospitalized on methadone maintenance treatment. This includes pregnant women. Generally, only physicians in OTPs can order methadone to treat OUD. However, physicians in an inpatient setting can legally order methadone administration to patients admitted primarily for other reasons.405 Contact the patient’s OTP directly to confrm the outpatient methadone dose, the last day of dose administration, and whether the patient was dispensed take-home doses (and how many doses) after the last dose administration at the OTP. This is to avoid double dosing and to avoid providing a full dose to a patient who hasn’t been to the OTP for several days. Notify the OTP of the patient’s admission and discharge so that OTP staff is aware of: • The patient’s upcoming missed visits. • Medications received during hospitalization. • Medications prescribed at discharge. Patients in pain should receive their full usual daily dose of methadone, barring contraindi- cations. This is their baseline dose and should not be considered a dose for pain management. The expert panel for this Treatment Improvement Protocol (TIP) recommends restarting buprenorphine before discharge when possible, with a proper handoff between inpatient and outpatient providers. They’ll need pain medication in addition to their usual methadone dose. If their condition is painful enough to require opioids, prescribe short-acting opioids as scheduled, not as- needed, treatment. Because these patients are already opioid tolerant, they’ll likely require higher doses of opioids than patients without tolerance.406 However, as with any patient, use nonopioid multimodal pain management when possible to minimize reliance on opioids and maximize pain control.407 CLINICAL CAUTION Do Not Rely Solely on Patient Self- Report of Methadone Dosage Do not administer the methadone dose based on patient self-report of OTP enrollment and methadone dose; get OTP confrmation. This is important because doses above 30 mg can be lethal if the patient is not currently receiving methadone treatment and has relatively low tolerance to opioids. If it’s not possible to confrm the patient’s methadone dose because the OTP is closed on nights or weekends and has no emergency contact, up to 20 mg per day can be administered to treat opioid withdrawal symptoms, but monitor for signs of opioid intoxication. If the patient shows no signs of sedation or opioid intoxication 3 to 4 hours after the initial dose and continues to display symptoms of withdrawal, an additional 5 mg to 10 mg may be safe to administer. 3-106 Medications for Opioid Use Disorder TIP 63 It is important to tell patients who receive take-home doses that they should not take their own medication while in the hospital. They will receive methadone from the treatment team. Patients can be asked to lock their take-home medications with their other valuables. It is also important to monitor these patients closely after the initial and subsequent methadone administration in the hospital. Some patients who receive take-home doses do not take their entire dose every day, so they may display signs of intoxication or frank overdose if the hospital staff gives them the full dose. Naltrexone Patients taking oral naltrexone for OUD treatment may continue naltrexone when admitted to the hospital if they do not have and are not at risk for developing a painful condition requiring opioid analgesia. Oral naltrexone provides full blockade of opioid receptors for up to 72 hours. Extended-release injectable naltrexone (XR-NTX) provides mea- surable naltrexone levels for 1 month or longer. Thus, managing acute pain in patients taking XR-NTX is complicated. In patients who have taken naltrexone, manage severe pain intensively via nonopioid approach- es, such as regional anesthesia or injected non- steroidal anti-infammatory drugs. Naltrexone blockade can be overcome with very high doses of opioids, but patients must be closely monitored for respiratory depression in a setting with anesthesia services. This is especially true upon discontinuation of oral naltrexone, which dissociates from opioid receptors. Hospitalized or ED Patients Not Taking Medication for OUD Patients with OUD who present to the ED or are admitted to the hospital for an acute medical problem may beneft from initiating medications for OUD during their hospital- ization. A thoughtful and respectful discussion of treatment options and patient-centered provision of medication can be a critical entry point into care. Research supports the effcacy of initiating either buprenorphine or methadone during acute hospital stays408,409 and starting patients on buprenorphine in the ED.410 Buprenorphine Induction in the Hospital Setting Patients admitted to the hospital for medical conditions incident to OUD can undergo medically supervised withdrawal or receive buprenorphine maintenance treatment during their inpatient stay.411 It is important to adequately address opioid withdrawal because hospital patients may otherwise sign out against medical advice or use illicit opioids in the hospital. Buprenorphine can also be initiated for maintenance treatment if there is a system in place that allows smooth and reliable discharge to an outpatient buprenorphine pre- scriber. Unlike methadone, a several-day delay between discharge and the frst visit to the out- patient provider is acceptable for stable patients, as long as suffcient medication is provided until the patient begins outpatient treatment. The prescription for medication to be taken outside the hospital must be written by a prescriber with a buprenorphine waiver. If there is no prescriber with a waiver, it is possible to have a patient return to the hospital ED or a clinic within the hospital to have the buprenorphine dose admin- istered by a physician (who does not need to be waivered) for up to 3 days. To provide continuity of care at discharge, use these strategies: • Develop and maintain a network of local buprenorphine prescribers and other drug treatment providers. • Discharge patients directly to a specifc outpatient prescriber for stabilization and maintenance after inpatient buprenorphine induction. • Send discharge information directly to the outpatient prescriber, including treatment course, medications administered, and medi- cations prescribed. 3-107 TIP 63Part 3 of 5—Medications for Opioid Use Disorder To initiate buprenorphine during hospitalization: • Confrm that there are no contraindications to buprenorphine before initiation. • Discontinue opioids for pain management only when no longer needed and the patient is stable enough to tolerate withdrawal. • Wait for patients to develop opioid withdraw- al symptoms. • Initiate buprenorphine treatment. • Individualize buprenorphine dosing. • Follow the dosing guidance found in Chapter 3D of this TIP. A clinical trial found that starting buprenorphine in the ED to treat OUD was more effective in linking patients to buprenorphine treatment in the community than were two other approaches without medication.412 When patients presented in opioid withdrawal, they received 8 mg of buprenorphine in the ED. Patients who were not in withdrawal received a detailed self-medication guide and were provided buprenorphine for an unobserved home induction. In both cases, patients were given suffcient buprenorphine to take 16 mg per day at home until they could see an outpatient prescriber within 72 hours. Close follow-up with an outpatient buprenorphine prescriber was critical for dose stabilization and ongoing medication management. Methadone Induction in the Hospital Setting Offer to treat hospitalized patients in opioid withdrawal with methadone (or buprenor- phine) maintenance if they can continue the medication in an OTP seamlessly after discharge. Do not start patients on methadone maintenance in the hospital without a clear follow-up plan. Form relationships with local OTPs that allow discharging of patients directly into methadone maintenance treatment. RESOURCE ALERT Telehealth Tools for the Treatment of OUD The Substance Abuse and Mental Health Services Administration and other federal agencies have developed numerous resources to guide healthcare professionals in their use of telehealth and telemedicine approaches for OUD. These resources include information on: • Guidance on the use of telemedicine in OTPs (https://store.samhsa.gov/product/Federal- Guidelines-for-Opioid-Treatment-Programs/ PEP15-FEDGUIDEOTP). • The policies that must be put in place (to comply with the Controlled Substances Act) by physicians who wish to use telehealth in treating patients with buprenorphine for OUD under the Drug Addiction Treatment Act of 2000. Federal (and sometimes state) restrictions apply, which can be reviewed by accessing 21 USC § 802 (www.gpo.gov/fdsys /pkg/USCODE-2011-title21/pdf/USCODE-2011 -title21-chap13-subchapI-partA-sec802.pdf). • Centers for Medicare and Medicaid guidance on telehealth (www.cms.gov/Medicare /Medicare-General-Information/Telehealth /index.html). • Challenges and opportunities in using telehealth for rural populations (https:// store.samhsa.gov/product/In-Brief-Rural- Behavioral-Health-Telehealth-Challenges- and-Opportunities/SMA16-4989). • How certifed community behavioral health clinics can use telehealth approaches to expand their services (www.samhsa.gov /section-223/care-coordination/telehealth -telemedicine). 3-108 Medications for Opioid Use Disorder TIP 63 The TIP expert panel urges providers not to force patients to withdraw from opioid agonist treatment in the hospital, especially if they have acute illness, pain, or a mental illness. Inpatient methadone inductions should follow the same “start low, go slow” principles that outpatient inductions do (see Chapter 3B of this TIP). The initial dose should be from 10 mg to 20 mg per day. Increase slowly by 5 mg every few days in response to symptoms of opioid withdrawal and level of sedation at the peak plasma level 2 to 4 hours after dosing. Naltrexone Induction in the Hospital Setting Consider XR-NTX initiation for patients who complete withdrawal in the hospital and are opioid free for 7 days (short acting) and up to 14 days (long acting). Only do so if: • There are no contraindications (such as the need for opioid analgesia). • The patient prefers it after a risk/beneft discussion that covers alternative treatments. • There are available follow-up opportunities for ongoing medication maintenance upon discharge. No published data indicate this approach’s effectiveness. If a patient desires and gives informed consent for medically supervised withdrawal and XR-NTX initiation while in the hospital, a frst dose of naltrexone can be given before discharge. As with other medications for OUD, discharge coordination is critical. Hospitals that develop XR-NTX induction protocols need to have a clear discharge plan in place for patients who will then need to continue treatment in the outpatient setting. Patients should be advised about the risk of overdose if return to opioid use occurs after discontinuing treatment. Medical Management Plan The key to effective treatment is to involve patients and all treating healthcare profes- sionals in developing a comprehensive plan for managing treatment with OUD medication during and after hospitalization. This plan should include: • Strategies for pain management (if required). • In-hospital dosing procedures. • Postdischarge coordination of care with out- patient programs and outpatient providers. 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London, England: National Treatment Agency for Substance Misuse. 374American Society of Addiction Medicine. (2015). The ASAM national practice guideline for the use of medications in the treatment of addiction involving opioid use. Chevy Chase, MD: Author. 375Substance Abuse and Mental Health Services Administration. (2012). Clinical drug testing in primary care. Technical Assistance Publication (TAP) Series 32. HHS Publication No. (SMA) 12-4668. Rockville, MD: Substance Abuse and Mental Health Services Administration. 376Jarvis, M., Williams, J., Hurford, M., Lindsay, D., Lincoln, P., Giles, L., … Safarian, T. (2017). Appropriate use of drug testing in clinical addiction medicine. Journal of Addiction Medicine, 11(3), 163–173. 377Stoller, K. B., Stephens, M. A. C., & Schorr, A. (2016). Integrated service delivery models for opioid treatment programs in an era of increasing opioid addiction, health reform, and parity. Retrieved May 21, 2017, from www. aatod.org/wp-content/uploads/2016/07/2nd -Whitepaper-.pdf 378Rich, J. D., McKenzie, M., Larney, S., Wong, J. B., Tran, L., Clarke, J., … Zaller, N. (2015, July 25). Methadone continuation versus forced withdrawal on incarceration in a combined US prison and jail: A randomised, open-label trial. Lancet, 386(9991), 350–359. 379Lofwall, M. R., & Walsh, S. L. (2014). A review of buprenorphine diversion and misuse: The current evidence base and experiences from around the world. Journal of Addiction Medicine, 8(5), 315–326. 380Genberg, B. L., Gillespie, M., Schuster, C. R., Johanson, C.-E., Astemborski, J., Kirk, G. D., … Mehta, S. H. (2013). Prevalence and correlates of street-obtained buprenorphine use among current and former injectors in Baltimore, Maryland. Addictive Behaviors, 38(12), 2868–2873. 381Genberg, B. L., Gillespie, M., Schuster, C. R., Johanson, C.-E., Astemborski, J., Kirk, G. D., … Mehta, S. H. (2013). Prevalence and correlates of street-obtained buprenorphine use among current and former injectors in Baltimore, Maryland. Addictive Behaviors, 38(12), 2868–2873. 3-126 Medications for Opioid Use Disorder TIP 63 382Cicero, T. J., Ellis, M. S., Surratt, H. L., & Kurtz, S. P. (2014). Factors contributing to the rise of buprenorphine misuse: 2008-2013. Drug and Alcohol Dependence, 142, 98–104. 383Lofwall, M. R., & Walsh, S. L. (2014). A review of buprenorphine diversion and misuse: The current evidence base and experiences from around the world. Journal of Addiction Medicine, 8(5), 315–326. 384United States National Library of Medicine. (2017, October). Buprenorphine sublingual and buccal (opioid dependence). Retrieved December 18, 2017, from https://medlineplus.gov/druginfo/meds/a605002.html 385American Society of Addiction Medicine. (2016). Sample offce-based opioid use disorder policy and procedure manual. Retrieved October 19, 2017, from www.asam. org/docs/default-source/advocacy/sample -diversion-policy.pdf?sfvrsn=0 386Substance Abuse and Mental Health Services Administration. (2015). Federal guidelines for opioid treatment programs. HHS Publication No. (SMA) PEP15- FEDGUIDEOTP. Rockville, MD: Substance Abuse and Mental Health Services Administration. 387Medication Assisted Treatment for Opioid Use Disorders. HHS Final Rule, Fed. Reg. 81 44711 (July 8, 2016) (to be codifed at 42 CFR pt. 8). 388Physical security controls for practitioners, 21 CFR § 1301.75 (2016). 389American Society of Addiction Medicine. (2016). Sample offce-based opioid use disorder policy and procedure manual. Retrieved October 19, 2017, from www.asam. org/docs/default-source/advocacy/sample -diversion-policy.pdf?sfvrsn=0 390Records for manufacturers, distributors, dispensers, researchers, importers, exporters, registrants that reverse distribute, and collectors, 21 CFR § 1304.22 (2014). 391Lofwall, M., & Walsh, S. (2014). A review of buprenorphine diversion and misuse: The current evidence base and experiences from around the world (p. 316). Journal of Addiction Medicine, 8(5), 315–326. 392American Society of Addiction Medicine. (2016). Sample offce-based opioid use disorder policy and procedure manual. Retrieved October 19, 2017, from www.asam. org/docs/default-source/advocacy/sample -diversion-policy.pdf?sfvrsn=0 393Velez, C. M., Nicolaidis, C., Korthuis, P. T., & Englander, H. (2016). “It’s been an experience, a life learning experience”: A qualitative study of hospitalized patients with substance use disorders. Journal of General Internal Medicine, 32(3), 296–303. 394Liebschutz, J. M., Crooks, D., Herman, D., Anderson, B., Tsui, J., Meshesha, L. Z., … Stein, M. (2014). Buprenorphine treatment for hospitalized, opioid- dependent patients: A randomized clinical trial. JAMA Internal Medicine, 174(8), 1369–1376. 395D’Onofrio, G., O’Connor, P. G., Pantalon, M. V., Chawarski, M. C., Busch, S. H., Owens, P. H., … Fiellin, D. A. (2015). Emergency department-initiated buprenorphine/naloxone treatment for opioid dependence: A randomized clinical trial. JAMA, 313(16), 1636–1644. 396Naeger, S., Ali, M. M., Mutter, R., Mark, T., & Hughey, L. (2016). Post-discharge prescription flls following an opioid hospitalization. Psychiatric Services, 67(11), 1264–1267. 397Weiss, A. J., Elixhauser, A., Barrett, M. L., Steiner, C. A., Bailey, M. K., & O’Malley, L. (2017, January). Opioid- related inpatient stays and emergency department visits by state, 2009–2014. HCUP Statistical Brief No. 219. Rockville, MD: Agency for Healthcare Research and Quality. 398Agency for Healthcare Research and Quality (2019). Rate of Opioid-Related Inpatient Stays per 100,000 Population. Retrieved January 11, 2020, from www. hcup-us.ahrq.gov/faststats/OpioidUseMap?setting=IP 399Administering or dispensing of narcotic drugs, 21 CFR § 1306.07 (2005). 400Alford, D., Compton, P., & Samet, H. (2006). Acute pain management for patients receiving maintenance methadone or buprenorphine therapy. Annals of Internal Medicine, 144(2), 127–134. 401Sen, S., Arulkumar, S., Cornett, E. M., Gayle, J. A., Flower, R. R., Fox, C. J., & Kaye, A. D. (2016). New pain management options for the surgical patient on methadone and buprenorphine. Current Pain and Headache Reports, 20(3), 16. 402Jones, H. E., Deppen, K., Hudak, M. L., Leffert, L., McClelland, C., Sahin, L., … Creanga, A. A. (2014). Clinical care for opioid-using pregnant and postpartum women: The role of obstetric providers. American Journal of Obstetrics and Gynecology, 210(4), 302–310. 403Alizadeh, S., Mahmoudi, G. A., Solhi, H., Sadeghi-Sedeh, B., Behzadi, R., & Kazemifar, A. M. (2015). Post-operative analgesia in opioid dependent patients: Comparison of intravenous morphine and sublingual buprenorphine. Addiction and Health, 7(1–2), 60–65. 404Sen, S., Arulkumar, S., Cornett, E. M., Gayle, J. A., Flower, R. R., Fox, C. J., & Kaye, A. D. (2016). New pain management options for the surgical patient on methadone and buprenorphine. Current Pain and Headache Reports, 20(3),16. 405Administering or dispensing of narcotic drugs, 21 CFR § 1306.07 (2005). 406Alford, D. P., Compton, P., & Samet, J. H. (2006). Acute pain management for patients receiving maintenance methadone or buprenorphine therapy. Annals of Internal Medicine, 144(2), 127–134. 3-127 TIP 63Part 3 of 5—Medications for Opioid Use Disorder 407Devin, C. J., & McGirt, M. J. (2015). Best evidence in multimodal pain management in spine surgery and means of assessing postoperative pain and functional outcomes. Journal of Clinical Neuroscience, 22(6), 930–938. 408Noska, A., Mohan, A., Wakeman, S., Rich, J., & Boutwell, A. (2015). Managing opioid use disorder during and after acute hospitalization: A case-based review clarifying methadone regulation for acute care settings. Journal of Addictive Behaviors, Therapy and Rehabilitation, 4(2), 1000138. 409Liebschutz, J. M., Crooks, D., Herman, D., Anderson, B., Tsui, J., Meshesha, L. Z., … Stein, M. (2014). Buprenorphine treatment for hospitalized, opioid- dependent patients: A randomized clinical trial. JAMA Internal Medicine, 174(8), 1369–1376. 410D’Onofrio, G., O’Connor, P. G., Pantalon, M. V., Chawarski, M. C., Busch, S. H., Owens, P. H., … Fiellin, D. A. (2015). Emergency department-initiated buprenorphine/naloxone treatment for opioid dependence: A randomized clinical trial. JAMA, 313(16), 1636–1644. 411Substance Abuse and Mental Health Services Administration. (2016, March). Special circumstances for providing buprenorphine. Retrieved December 18, 2017, from www.samhsa.gov/medication-assisted -treatment/legislation-regulations-guidelines/special -circumstances-providing-buprenorphine 412D’Onofrio, G., O’Connor, P. G., Pantalon, M. V., Chawarski, M. C., Busch, S. H., Owens, P. H., … Fiellin, D. A. (2015). Emergency department-initiated buprenorphine/naloxone treatment for opioid dependence: A randomized clinical trial. JAMA, 313(16), 1636–1644. 413Huxtable, C. A., Roberts, L. J., Somogyi, A. A., & Macintyre, P. E. (2011). Acute pain management in opioid-tolerant patients: A growing challenge. Anaesthesia and Intensive Care, 39(5), 804–823. This page intentionally left blank. MEDICATIONS FOR OPIOID USE DISORDERTIP 63 Substance Abuse and Mental Health Services Administration Part 4: Bringing Together Addiction Treatment Counselors, Clients, and Healthcare Professionals For Healthcare and Addiction Professionals Part 4 of this Treatment Improvement Protocol (TIP) is for addiction treatment professionals and peer recovery support specialists who work with individuals who take a Food and Drug Administration (FDA)-approved medication to treat opioid use disorder (OUD). TIP Navigation Executive Summary For healthcare and addiction professionals, policymakers, patients, and families Part 1: Introduction to Medications for Opioid Use Disorder Treatment For healthcare and addiction professionals, policymakers, patients, and families Part 2: Addressing Opioid Use Disorder in General Medical Settings For healthcare professionals Part 3: Medications for Opioid Use Disorder For healthcare professionals Part 4: Bringing Together Addiction Treatment Counselors, Clients, and Healthcare Professionals For healthcare and addiction professionals Part 5: Resources Related to Medications for Opioid Use Disorder For healthcare and addiction professionals, policymakers, patients, and families KEY MESSAGES • Many patients taking OUD medication beneft from counseling as part of their treatment. • Counselors play the same role for clients with OUD who take medication as for clients with any other SUD. • Counselors help clients recover by addressing the challenges and consequences of addiction. • OUD is often a chronic illness requiring ongoing communication among patients and providers to ensure that patients fully beneft from both medication and psychosocial treatment and support. • OUD medications are safe and effective when prescribed and taken appropriately. • Medication is integral to recovery for many people with OUD. Medication usually produces better treatment outcomes than outpatient treatment without medication. • Supportive counseling environments for clients who take OUD medication can promote treatment and help build recovery capital. 4-ii TIP 63 MEDICATIONS FOR OPIOID USE DISORDER—Part 4 of 5 Contents Overview and Context 4-1 Scope of the Problem 4-1 Setting the Stage 4-4 Distinguishing OUD From Physical Dependence on Opioid Medications 4-4 Understanding the Benefts of Medication for OUD 4-5 Reviewing the Evidence on Counseling in Support of Medication To Treat OUD 4-6 Using a Recovery-Oriented Approach to Treating Patients With OUD 4-8 Quick Guide to Medications 4-12 Understanding the Neurobiology of OUD 4-12 Learning How OUD Medications Work 4-12 Knowing What Prescribers Do 4-16 Counselor–Prescriber Communications 4-18 Obtaining Consent 4-18 Structuring Communications With Prescribers 4-19 Helping Clients Overcome Challenges in Accessing Resources 4-19 Creation of a Supportive Counseling Experience 4-20 Maintaining the Therapeutic Alliance 4-20 Educating Patients About OUD and a Chronic Care Approach to Its Treatment 4-21 Counseling Patients on Overdose Prevention and Treatment 4-21 Helping Patients Cope With Bias and Discrimination 4-22 Helping Patients Advocate for Themselves 4-26 Addressing Discrimination Against Clients Who Take OUD Medication 4-26 Helping Clients Find Accepting Mutual-Help Groups 4-30 Facilitating Groups That Include Patients Taking OUD Medication 4-33 Other Common Counseling Concerns 4-34 Notes 4-37 4-1 MEDICATIONS FOR OPIOID USE DISORDERTIP 63 PART 4 of 5 Bringing Together Addiction Treatment Counselors, Clients, and Healthcare Professionals Part 4 of this TIP is for addiction treatment professionals and peer recovery support specialists who work with individuals who take an FDA-approved medication for OUD—methadone, naltrexone, or buprenorphine. These providers have direct helping relationships with clients. They don’t prescribe or administer OUD medications, but they interact with healthcare profes- sionals who do. They also help people who take OUD medication access supportive services (e.g., transportation, child care, housing). Overview and Context Scope of the Problem Opioid misuse has caused a growing nationwide epidemic of OUD and unintentional overdose deaths.1 This epidemic affects people in all regions, of all ages, and from all walks of life. Opioid misuse devastates families, burdens emergency departments and frst responders, fuels increases in hospital admissions, and strains criminal justice and child welfare systems. Counselors can play an integral role in addressing this crisis. Counseling helps people with OUD and other substance use disorders (SUDs) change how they think, cope, react, and acquire the skills and confdence necessary for recovery. Counseling can provide support for people who take medication to treat their OUD. Patients may get counseling from prescribers or other staff members in the prescribers’ practices or by referral to counselors at specialty addiction treatment programs or in private practice. Counselors and peer recovery support specialists can work with patients who take OUD med- ication and refer patients with active OUD to healthcare professionals for an assessment for treatment with medication. 1.6MILLION , , , people in the U.S. ages 12 and older had OUD involving PRESCRIPTION OPIOIDS, HEROIN or both in 2019.2 Part 4 uses “counselor” to refer to the range of professionals—including recovery coaches and other peer recovery support services specialists —who may counsel, coach, or mentor people who take OUD medication, although their titles, credentials, and range of responsibilities vary. At times, Part 4 refers to individuals as “clients.” For other key terms, see Exhibit 4.1. Part 5 of this TIP provides a full glossary and other resources related to the treatment of OUD. Counseling clients who take OUD medication requires understanding: • Basic information about OUD. • The role and function of OUD medications. • Ways to create a supportive environment that helps clients work toward recovery. • Counseling’s role within a system of whole-person, recovery-oriented OUD care. 4-2 Medications for Opioid Use Disorder TIP 63 EXHIBIT 4.1. Key Terms Addiction: As defned by the American Society of Addiction Medicine,3 “a primary, chronic disease of brain reward, motivation, memory, and related circuitry” (p. 1). It is characterized by inability to consistently abstain, impairment in behavioral control, craving, diminished recognition of signifcant problems with one’s behaviors and interpersonal relationships, and a dysfunctional emotional response. Like other chronic diseases, addiction often involves cycles of relapse and remission. The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition4 (DSM-5), does not use the term for diagnostic purposes, but it commonly describes the more severe forms of OUD. Care provider: Encompasses both healthcare professionals and other professionals who do not provide medical services, such as counselors or providers of supportive services. Often shortened to “provider.” Healthcare professionals: Physicians, nurse practitioners, physician assistants, and other medical service professionals who are eligible to prescribe medications for and treat patients with OUD (i.e., until October 1, 2023, clinical nurse specialists, certifed registered nurse anesthetists, certifed nurse midwives). The term “prescribers” also refers to these healthcare professionals. Maintenance treatment: Providing medications to achieve and sustain clinical remission of signs and symptoms of OUD and support the individual process of recovery without a specifc endpoint (as is the typical standard of care in medical and psychiatric treatment of other chronic illnesses). Mutual-help groups: Groups of people who work together on obtaining and maintaining recovery. Unlike peer support (e.g., the use of recovery coaches), mutual-help groups consist entirely of people who volunteer their time and typically have no offcial connection to treatment programs. Most are self- supporting. Although 12-Step groups such as Alcoholics Anonymous (AA) and Narcotics Anonymous (NA) are the most widespread and well-researched type of mutual-help groups, other groups may be available in some areas. They range from groups affliated with a religion (e.g., Celebrate Recovery, Millati Islami) to purely secular groups (e.g., SMART Recovery, Women for Sobriety). Opioid misuse: The use of prescription opioids in any way other than as directed by a doctor; the use of any opioid in a manner, situation, amount, or frequency that can cause harm to self or others.5 Opioid receptor agonist: A substance that has an affnity for and stimulates physiological activity at cell receptors in the central nervous system (CNS) that are normally stimulated by opioids. Mu-opioid receptor full agonists (e.g., methadone) bind to the mu-opioid receptor and produce actions similar to those produced by the endogenous opioid beta-endorphin. Increasing the dose increases the effect. Mu- opioid receptor partial agonists (e.g., buprenorphine) bind to the mu-opioid receptor. Unlike with full agonists, increasing their dose may not produce additional effects once they have reached their maximal effect. At low doses, partial agonists may produce effects similar to those of full agonists. Opioid receptor antagonist: A substance that has an affnity for opioid receptors in the CNS without producing the physiological effects of opioid agonists. Mu-opioid receptor antagonists (e.g., naltrexone) can block the effects of exogenously administered opioids. Opioids: All natural, synthetic, and semisynthetic substances that have effects similar to morphine. They can be used as medications having such effects (e.g., methadone, buprenorphine, oxycodone). Opioid treatment program (OTP): An accredited treatment program with Substance Abuse and Mental Health Services Administration (SAMHSA) certifcation and Drug Enforcement Administration registration to administer and dispense opioid agonist medications that are approved by FDA to treat opioid addiction. Currently, these include methadone and buprenorphine. Other pharmacotherapies, such as naltrexone, may be provided but are not subject to these regulations. OTPs must provide adequate medical, counseling, vocational, educational, and other assessment and treatment services either onsite or by referral to an outside agency or practitioner through a formal agreement.6 Continued on next page 4-3 TIP 63 Part 4 of 5—Bringing Together Addiction Treatment Counselors, Clients, and Healthcare Professionals EXHIBIT 4.1. Key Terms (continued) Opioid use disorder (OUD): Per DSM-5,7 a disorder characterized by loss of control of opioid use, risky opioid use, impaired social functioning, tolerance, and withdrawal. Tolerance and withdrawal do not count toward the diagnosis in people experiencing these symptoms when using opioids under appropriate medical supervision. OUD covers a range of severity and replaces what the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, termed “opioid abuse” and “opioid dependence.” An OUD diagnosis is applicable to a person who uses opioids and experiences at least 2 of the 11 symptoms in a 12-month period. (See Exhibit 2.13 and the Appendix in Part 2 for full DSM-5 diagnostic criteria for OUD.) Peer support: The use of peer support specialists in recovery to provide nonclinical (i.e., not requiring training in diagnosis or treatment) recovery support services to individuals in recovery from addiction and to their families. Peer support specialist: Someone in recovery who has lived experience in addiction plus skills learned in formal training. Peer support specialists may be paid professionals or volunteers. They are distinguished from members of mutual-help groups because they maintain contact with treatment staff. They offer experiential knowledge that treatment staff often lack. Prescribers: Healthcare professionals who are eligible to prescribe medications for OUD. Psychosocial support: Ancillary services to enhance a patient’s overall functioning and well-being, including recovery support services, case management, housing, employment, and educational services. Psychosocial treatment: Interventions that seek to enhance a patient’s social and mental functioning, including addiction counseling, contingency management, and mental health services. Recovery: A process of change through which individuals improve their health and wellness, live a self-directed life, and strive to reach their full potential. Even individuals with severe and chronic SUDs can, with help, overcome their SUDs and regain health and social function. Although abstinence from all substance misuse is a cardinal feature of a recovery lifestyle, it is not the only healthy, prosocial feature. Patients taking FDA-approved medication to treat OUD can be considered in recovery. Recovery capital: The sum of the internal (e.g., motivation, self-effcacy, spirituality) and external (e.g., access to health care, employment, family support) resources that an individual can draw upon to begin and sustain recovery from SUDs. Recovery-oriented care: A service orientation that supports individuals with behavioral health conditions in a process of change through which they can improve their health and wellness, live self- directed lives, and strive to reach their full potential. Relapse: A process in which a person with OUD who has been in remission experiences a return of symptoms or loss of remission. A relapse is different from a return to opioid use in that it involves more than a single incident of use. Relapses occur over a period of time and can be interrupted. Relapse need not be long lasting. The TIP uses relapse to describe relapse prevention, a common treatment modality. Remission: A medical term meaning a disappearance of signs and symptoms of the disease.8 DSM-5 defnes remission as present in people who previously met OUD criteria but no longer meet any OUD criteria (with the possible exception of craving).9 Remission is an essential element of recovery. Return to opioid use: One or more instances of opioid misuse without a return of symptoms of OUD. A return to opioid use may lead to relapse. 4-4 Medications for Opioid Use Disorder TIP 63 Setting the Stage Since the 1990s, dramatic increases in controlled medication prescriptions—particularly opioid pain relievers—have coincided with increases in their misuse.10 Since the mid-2000s, heroin11,12 and fentanyl (mainly illicit formulations)13 consumption has also sharply increased. People who turn to illicit drugs after misusing opioid medications have driven greater use of heroin and fentanyl, which are cheaper and easier to obtain. Approximately 1,500 OTPs currently dispense methadone, buprenorphine, or both.14 They may also offer naltrexone. Historically, OTPs were the only source of OUD medication and offered only methadone. Buprenorphine is increasingly available in general medical settings. Physicians, nurse practitioners, and physician assistants (whether or not they’re addiction specialists) can get a federal waiver to prescribe buprenorphine. These healthcare professionals can also prescribe and administer naltrexone, which does not require a waiver or OTP program certifcation. Until October 1, 2023, qualifed clinical nurse specialists, certifed registered nurse anesthe- tists, and certifed nurse midwives also can obtain a waiver to prescribe and administer buprenorphine in offce-based settings. People with OUD should have access to the medication most appropriate for them. Medication helps establish and maintain OUD remission. By controlling withdrawal and cravings and blocking the euphoric effects of illicit opioids, OUD medication helps patients stop illicit opioid use and resolve OUD’s psychosocial problems. For some people, OUD medication may be lifesaving. Ideally, patients with OUD should have access to all three FDA-approved pharmacotherapies. (See the “Quick Guide to Medications” section for an overview of each medication.) Many patients taking OUD medication beneft from counseling as part of their treatment. Counseling helps people with OUD change how they think, cope, react, and acquire the skills and confdence needed for recovery. Patients may get The counselor’s role with clients who take OUD medication is the same as it is with all clients who have SUDs: Help them achieve recovery by addressing addiction’s challenges and consequences. counseling from medication prescribers or staff members in prescribers’ practices or by referral to counselors at specialty addiction treatment programs or in private practice. Exhibit 4.2 discusses recommending versus requiring counsel- ing as part of medication treatment for OUD. Distinguishing OUD From Physical Dependence on Opioid Medications According to DSM-5, 15 OUD falls under the general category of SUDs and is marked by: • Compulsion and craving. • Tolerance. • Loss of control. • Withdrawal when use stops. • Continued opioid use despite adverse consequences. Properly taken, some medications cause tolerance and physical dependence. Medications for some chronic illnesses (e.g., steroids for systemic lupus erythematosus) can make the body build tolerance to the medica- tions over time. If people abruptly stop taking medications on which they’ve become physically dependent, they can experience withdrawal symptoms. This can be serious, even fatal. Physical dependence on a prescribed, properly taken opioid medication is distinct from OUD and opioid addiction. OUD is a behavioral disorder associated with loss of control of opioid use, use despite adverse consequences, reduction in functioning, and compulsion to use. The professionals who revised DSM-5 diagnostic criteria for OUD made several signifcant changes. Among the most notable was differentiating physical dependence from OUD: 4-5 TIP 63 Part 4 of 5—Bringing Together Addiction Treatment Counselors, Clients, and Healthcare Professionals EXHIBIT 4.2. Recommending Versus Requiring Counseling The TIP expert panel affrms that counseling and ancillary services greatly beneft many patients. However, such counseling and ancillary services should target patients’ needs and shouldn’t be arbitrarily required as a condition for receiving OUD medication (although they are required by regulations in OTPs), especially when the benefts of medication outweigh the risks of not receiving counseling. The TIP expert panel recommends individualized treatment. Patients who choose to start medication and medication management with their prescriber without adjunctive counseling and don’t adequately respond to such treatment should be referred to adjunctive counseling and more intensive services as needed.16 The law requires buprenorphine prescribers to be able to refer patients taking OUD medication to counseling and ancillary services. Buprenorphine prescribers may meet this requirement by keeping a list of referrals or by providing counseling themselves. The law doesn’t require naltrexone prescribers to refer patients to additional services. However, FDA labels for both medications recommend counseling as part of treatment. Some treatment environments require counseling by regulation or contractual obligation. In other cases, a healthcare professional may believe that a patient taking OUD medication would beneft from counseling. Some healthcare professionals may require counseling, particularly if patients aren’t responding well to medication. OUD is often a chronic medical illness.17 Treatment isn’t a cure. • Tolerance or withdrawal symptoms related to FDA-approved medications appropriately prescribed and taken to treat OUD (buprenor- phine, methadone) don’t count toward diagnostic criteria for OUD. • If the individual is being treated with an OUD medication and meets no OUD criteria other than tolerance, withdrawal, or craving (but did meet OUD criteria in the past), he or she is considered in remission on medication. Accepting this distinction is essential to working with clients taking OUD medica- tion. One common question about patients taking medication for OUD is “Aren’t they still addicted?” The new DSM-5 distinction makes the answer to this question “No, they’re not still addicted.” A person can require OUD medica- tion and be physically dependent on it but still be in remission and recovery from OUD. Understanding the Benefts of Medication for OUD Medication is an effective treatment for OUD.18,19,20 People with OUD should be referred for an assessment for medication unless they decline.21 To be supportive and effective when counseling clients who could beneft from or who take medication for OUD, know that: • Treatment with methadone and buprenor- phine is associated with lower likelihood of overdose death compared with not taking these medications.22,23,24,25,26 • Medication helps people reduce or stop opioid misuse.27,28,29,30 As Jessica’s story in Exhibit 4.3 shows, even if people return to opioid use during treatment or don’t achieve abstinence in the short term, medication lessens misuse and its health risks (e.g., overdose, injection-related infections).31 • Patients taking FDA-approved medication used to treat OUD can join residential or outpatient treatment. Decades of clinical 4-6 Medications for Opioid Use Disorder TIP 63 EXHIBIT 4.3. Jessica’s Story About Medication Jessica is a 32-year-old who unsuccessfully quit heroin dozens of times. She had been in and out of treatment but says, “It just never stuck. I’d always start using again when I left the program.” Three years ago, her primary care doctor started prescribing her buprenorphine. Now Jessica says: Some days I pinch myself. I can’t believe I got my life back. I tried quitting so many times but always got pulled back into the scene. Ever since I’ve been on buprenorphine, I haven’t had any cravings. Even when I’m around triggers, they just don’t set me off the same way. I’ve been able to get a job and I’m starting to build a community of friends who don’t use. The hardest part about being on buprenorphine is that my emotions aren’t masked anymore. I have to feel all of the sadness and fear that I was avoiding all these years. But it’s good. I’m getting a chance to work through it.” experience in OTPs, which must provide counseling, suggest that patients taking OUD medication can fully participate in group and individual counseling, both cognitively and emotionally. Patients with concurrent SUDs (involving stimulants or alcohol) can beneft from residential treatment while continuing to take their OUD medication. • Randomized clinical trials indicate that OUD medication improves treatment retention and reduces illicit opioid use.32,33,34 Retention in treatment increases the oppor- tunity to provide counseling and supportive services that can help patients stabilize their lives and maintain recovery. • The longer patients take medication, the less likely they are to return to opioid use, whereas short-term medically supervised with- drawal rarely prevents return to use:35,36,37,38,39 − Conducting short-term medically super- vised withdrawal may increase the risk of unintentional fatal overdose because of decreased tolerance after withdrawal completion.40,41 − Providing short-term medical treatment for OUD is the same as treating a heart attack without managing the underlying coronary disease. − Providing longer courses of medication that extend beyond withdrawal can allow patients to stabilize. − Getting stabilized, which may take months or even years, allows patients to focus on building and maintaining a healthy lifestyle. • Patients taking OUD medication can achieve long-term recovery. People who continue to take medication can be in remission from OUD and live healthy, productive lives.42 Reviewing the Evidence on Counseling in Support of Medication To Treat OUD Dedicated counseling can help clients address the challenges of extended recovery. For clients who seek a self-directed, purposeful life, counseling can help them: • Improve problem-solving and interpersonal skills. • Find incentives for reduced use and abstinence. • Build a set of techniques to resist drug use. • Replace drug use with constructive, rewarding activities. Moreover, evidence shows that counseling can be a useful part of OUD treatment for people who take OUD medication. Impact studies of counseling for people with SUDs show that: 4-7 TIP 63 Part 4 of 5—Bringing Together Addiction Treatment Counselors, Clients, and Healthcare Professionals • Motivational enhancement/interviewing is generally benefcial.43 This approach helps get people into treatment. It also supports behavior change and, thus, recovery. • Cognitive–behavioral therapy (CBT) has demonstrated effcacy in the treatment of SUDs, whether used alone or in combination with other strategies.44 Clinical trials have not shown that CBT added to buprenorphine treatment with medical management is asso- ciated with signifcantly lower rates of illicit opioid use.45,46 However, a secondary analysis of one of those trials found that CBT added to buprenorphine and medical management was associated with signifcantly greater reduction in any drug use among participants whose OUD was primarily linked to misuse of prescription opioids than among those whose OUD involved only heroin.47 Thus, CBT may be helpful to those patients receiving buprenorphine treatment who have nonopioid drug use problems. • Case management helps establish the stability necessary for SUD remission.48,49,50 Case management helps some people in SUD treatment get or sustain access to services and necessities, such as: − Food. − Shelter. − Income support. − Legal aid. − Dental services. − Transportation. − Vocational services. • Family therapy can address SUDs and various other family problems (e.g., family confict, unemployment, conduct disorders). Several forms of family therapy are effective with adolescents51 and can potentially address family members’ biases about use of medica- tion for OUD.52 • There is more research on combined methadone treatment and various psycho- social treatments (e.g., different levels of counseling, contingency management) than on buprenorphine or naltrexone treatment in offce-based settings. More research is needed to identify the best interventions to use with specifc medications, populations, and treatment phases in outpatient settings.53 • Motivational intervention, case manage- ment, or both can improve likelihood of entry into medication treatment for OUD among people who inject opioids, according to a systematic review of 13 studies plus data from a prior systematic review.54 • Clinical trials have shown no differences in outcomes for buprenorphine with medical management between participants who get adjunctive counseling and those who don’t (i.e., prescriber-provided guidance focused specifcally on use of the medication).55,56,57,58 RESOURCE ALERT Principles of Effective Treatment In its Principles of Drug Addiction Treatment, the National Institute on Drug Abuse lists 13 principles of effective treatment (p. 2).59 Two principles that pertain to counseling are: in returning to productive functioning in the family, workplace, and society.” • “Effective treatment attends to multiple needs of the individual, not just his or her drug abuse. To be effective, treatment must address the individual’s drug abuse and any associated medical, psychological, social, vocational, and legal problems. It is also important that treatment be appropriate to the individual’s age, gender, ethnicity, and culture.” • “No single treatment is effective for everyone. Treatment varies depending on the type of drug and the characteristics of the patients. Matching treatment settings, interventions, and services to an individual’s particular problems and needs is critical to his or her ultimate success 4-8 Medications for Opioid Use Disorder TIP 63 RESOURCE ALERT Recovery-Oriented Treatment Recovery-Oriented Methadone Maintenance: This guide by Bamber and White is the most thorough document on this topic currently available and is applicable to clients receiving other medications for OUD (www.williamwhitepapers.com/pr/2011%20Bamber-White%20Dialogue%20on%20Recovery- Oriented%20Methadone%20Maintenace.pdf). Supporting Recovery From Opioid Addiction: Community Care Best Practice Guidelines for Recovery-Oriented Methadone Maintenance (www.williamwhitepapers.com/pr/Recovery-oriented%20 Methadone%20Maintenance%20Best%20Practice%20Guidelines%202014%20-%20CCBHO.pdf) and Supporting Recovery From Opioid Addiction: Community Care Best Practice Guidelines for Buprenorphine and Suboxone (www.williamwhitepapers.com/pr/Community%20Care%20Best%20 Practice%20Guidelines%20for%20Buprenorphine%20and%20Suboxone%202014.pdf) outline phase- specifc tasks and accompanying strategies for programs that provide services to clients who take these medications. Yet those trials: − Relied on well-structured medical manage- ment sessions that may not be typical in practice. − Excluded patients with certain co-occurring disorders or factors that complicated treatment. • Benefts from counseling may depend on factors such as the number of sessions and adherence.60 Using a Recovery-Oriented Approach to Treating Patients With OUD Counseling for OUD gives patients tools to manage their illness, achieve and sustain better health, and improve their quality of life. There are limits to how much medication alone can accomplish. OUD medication will improve quality of life,61 but many clients in addiction treatment have complex issues that may decrease quality of life, such as: • Other SUDs (e.g., alcohol use disorder, cannabis use disorder).62,63,64 • Mental distress65 (i.e., high levels of symptoms) and disorders66,67,68 (e.g., major depressive disorder, posttraumatic stress disorder). • Medical problems (e.g., hepatitis, diabetes).69 • History of trauma.70,71 • Poor diet, lack of physical activity, or both.72 • Lack of social support.73 • Unemployment.74 Acknowledge many pathways to recovery Recovery occurs via many pathways.75 OUD medication may play a role in the beginning, middle, or entire continuum of care. Support clients in making their own informed decisions about treatment. Counselors don’t need to agree with clients’ decisions but must respect them. Educate new clients about: • Addiction as a chronic disease infuenced by genetics and environment. • How medications for OUD work. • What occurs during dose stabilization. • The benefts of longer term medication use and the risks of abruptly ending treatment. 4-9 TIP 63 Part 4 of 5—Bringing Together Addiction Treatment Counselors, Clients, and Healthcare Professionals SAMHSA’S GUIDING PRINCIPLES OF RECOVERY76 • Recovery emerges from hope. • Recovery is person driven. • Recovery occurs via many pathways. • Recovery is holistic. • Recovery is supported by peers and allies. • Recovery is supported through relationships and social networks. • Recovery is culturally based and infuenced. • Recovery is supported by addressing trauma. • Recovery involves individual, family, and community strengths and responsibilities. • Recovery is based on respect. Promote recovery for clients with OUD Focus on addressing personal and practical problems of greatest concern to clients, which can improve their engagement in treatment.77 Recovery supports can sustain the progress clients made in treatment and further improve their quality of life. Addressing the full range of client needs can improve clients’ quality of life and lead to better long-term recovery outcomes. A recovery-oriented approach to traditional SUD counseling may help address client needs.78,79 Increasing recovery capital supports long-term abstinence and improved quality of life, espe- cially for clients who decide to stop medication. Clients with substantial periods of abstinence from illicit drugs identify these strategies for increasing recovery capital as helpful:80,81,82 • Forging new relationships with friends/family • Obtaining support from friends, family, partners, and communities • Using positive coping strategies • Finding meaning or a sense of purpose in life • Engaging in a church or in spiritual practices • Pursuing education, employment, or both • Engaging in new interests or activities (e.g., joining a community group, exercising) • Building confdence in ability to maintain RESOURCE ALERT Decision-Making Tool The Shared Decision-Making Tools page is a SAMHSA web-based resource (www.samhsa. gov/brss-tacs/recovery-support-tools/shared- decision-making) to help people with OUD make decisions about treatment and recovery. abstinence (i.e., increasing abstinence-related self-effcacy) • Finding ways to help other individuals who are new to recovery Help clients further grow recovery capital by offering or connecting them to a range of services, such as: • Ancillary services (e.g., vocational rehabilitation, supported housing). • Additional counseling. • Medical services. • Mental health services. Provide person-centered care Clients’ confdence in their ability to stay away from illicit substances, or self-effcacy, is an important factor in successful change. In person-centered care, also known as patient- centered care: • Clients control the amount, duration, and scope of services they receive. • They select the professionals they work with. • Care is holistic; it respects and responds to clients’ cultural, linguistic, and socioenviron- mental needs.83 • Providers implement services that recognize patients as equal partners in planning, devel- oping, and monitoring care to ensure that it meets each patient’s unique needs.84 4-10 Medications for Opioid Use Disorder TIP 63 The confrontational/expert model that characterized much of SUD treatment in the past may harm some patients and inhibit or prevent recovery.85 A person-centered approach to OUD treatment empowers clients in making decisions, such as:86 • Whether to take OUD medication. • Which medication to take. • Which counseling and ancillary services to receive. Fragmented healthcare services are less likely to meet the full range of patients’ needs. Integrated medical and behavioral healthcare delivery provides patient-focused, comprehensive treatment that meets the wide range of symptoms and service needs that patients with OUD may have. Signifcant demand remains for better integrated and coordinated SUD treatment (including OTP), medical, and mental health services.87 Such improvements are RESOURCE ALERT particularly important for the many individuals with co-occurring substance use and mental disorders who receive OUD medication.88,89 In a randomized trial of methadone patients with co-occurring mental disorders receiving onsite versus offsite mental health services, those receiving services onsite had less psychiatric distress at follow-up.90 Promote family and social support Support from family and friends can be the most important factor in long-term recovery, according to many people who have achieved long-term recovery from OUD.91,92 Support from intimate partners helps all clients, especially women, avoid return to opioid use.93,94 But the more people in clients’ social networks who use drugs, the more likely clients are to return to use.95,96 Most clients are willing to invite a substance- free family member or friend to support their recovery.97 Most have at least one nearby family member who does not use illicit drugs.98 A client’s community may provide a cultural context for their recovery and culturally specifc supports that may not otherwise be available in treatment.99 Help clients develop and support positive relations with their families by: • Suggesting that clients invite family and friends to aid in the recovery planning process (Exhibit 4.4). • Emphasizing the importance of relationships with family and friends who actively support recovery. • Supporting clients in mending broken relationships with loved ones. • Helping clients cut ties with individuals who still use drugs or enable clients’ drug use. • Encouraging clients to build new relationships that support recovery. Treatment Guidance for Co- Occurring Substance Use and Mental Disorders TIP 42, Substance Use Disorder Treatment for People With Co-Occurring Disorders, provides SUD treatment strategies for people with mental disorders (https://store.samhsa.gov/product/ tip-42-substance-abuse-treatment-persons-co- occurring-disorders/PEP20-02-01-004). Integrated Treatment for Co-Occurring Disorders Evidence-Based Practices KIT provides practical guidance for integrating mental health services and SUD treatment (https://store.samhsa.gov/product/Integrated- Treatment-for-Co-Occurring-Disorders- Evidence-Based-Practices-EBP-KIT/ SMA08-4366). 4-11 TIP 63 Part 4 of 5—Bringing Together Addiction Treatment Counselors, Clients, and Healthcare Professionals EXHIBIT 4.4. Engaging Reluctant Family Members in a Client’s Treatment If the client agrees and has signed the appropriate releases, help even reluctant family members engage in the client’s treatment to offer support. To reach out to family members who hesitate to engage, try to: • Recognize that they have been harmed by their family member’s substance use and that their participation in his or her recovery can help them heal, too. • Ask them to recall some positive experiences they have had with the client. • Introduce them to mutual-help groups and other supports for families (e.g., Nar-Anon, Learn to Cope, Parents of Addicted Loved Ones Group). Ensure that suggested groups don’t have a negative option medication bias. Provide trauma-informed care Trauma-informed service requires providers to realize the signifcance of trauma. According to SAMHSA,100 trauma-informed counselors know what trauma is and also: • Understand how trauma can affect clients, families, and communities. • Apply knowledge of trauma extensively and consistently in both practice and policy. • Know ways to promote recovery from trauma. • Recognize the signs and symptoms of trauma in clients, families, staff members, and others. • Resist things that may retraumatize or harm clients or staff. Incorporate trauma-informed principles of care into recovery promotion efforts, because: • Trauma histories and trauma-related disorders may increase clients’ risk for various problems, including early drop-out from treatment101 and greater problems with pain.102 • Childhood trauma is highly prevalent among people with OUD.103,104 • People often suffer multiple traumas during opioid misuse.105 • Help them understand OUD, the treatment process, and medication’s role in recovery. This knowledge can keep family members from pressuring the client to taper medication prematurely. • Hold multifamily therapy groups or informal discussion sessions for families (with or without clients present) so that family members can learn from one another and share their experiences. • Offer family or couples therapy as an option for additional support. • An intervention that integrated trauma treatment and standard care (which goes further than the trauma-informed care detailed here) had better outcomes than standard care alone in a diverse group of women treated in various settings, including an OTP.106 RESOURCE ALERT Trauma-Informed Care TIP TIP 57, Trauma-Informed Care in Behavioral Health Services, has more information on providing trauma-informed care in SUD treatment programs (https://store.samhsa .gov/product/TIP-57-Trauma-Informed-Care -in-Behavioral-Health-Services/SMA14-4816). 4-12 Medications for Opioid Use Disorder TIP 63 Quick Guide to Medications This section introduces the neurochemistry and biology of OUD and the medications that treat it. Reading this section will familiarize counselors with terminology healthcare profes- sionals may use in discussing patients who take OUD medication (see also Exhibit 4.1 and the comprehensive glossary in Part 5). Understanding the Neurobiology of OUD Opioid receptors are a part of the body’s natural endorphin system. Endorphins are chemicals our bodies release to help reduce our experience of pain. They can also contribute to euphoric feelings like the “runner’s high” that some people experience. When endorphins or opioids bind to opioid receptors, the receptors activate, causing a variety of effects. After taking opioids, molecules bind to and activate the brain’s opioid receptors and release dopamine in a brain area called the nucleus accumbens (NAc), causing euphoria. Like opioid receptors, the NAc has a natural, healthy function. For example, when a person eats, the NAc releases dopamine to reinforce this essential behavior. The NAc is a key part of the brain’s reward system. Opioid use leads to an above-normal release of dopamine, essentially swamping the natural reward pathway and turning the brain strongly toward continued use. The brain also learns environmental cues associated with this dopamine release. It associates specifc people, places, and things (e.g., music, drug parapherna- lia) with the euphoria; these environmental cues then become triggers for drug use. Intermittent opioid use causes periods of euphoria followed by periods of withdrawal. The brain’s strong draw toward euphoria drives repeated and continued use. Few people with OUD reexperience the euphoria they obtained early in their opioid use, yet they continue to seek it. Changes in brain function that result from repeated drug use cause a person who once took the drug for euphoria to seek it out of habit, then compulsion. People with OUD use opioids to stave off withdrawal. Without opioids, the person feels dysphoric and physically ill, only feeling normal by taking opioids again. At the same time, other areas of the brain begin to change:107 • The amygdala, which is associated with feelings of danger, fear, and anger, becomes overactive. • The frontal cortex, which is associated with planning and self-control, becomes underactive. • The ability to control impulses diminishes, and drug use becomes compulsive. • The need to escape the discomfort and intensely negative emotional states of withdrawal becomes the driving force of continued use. Even after opioid use stops, brain changes linger. A person’s ability to make plans and manage impulses stays underactive. That’s why return to substance use is very common even after a period of abstinence. Medications for OUD promote emotional, psychological, and behavioral stabilization. By acting directly on the same opioid receptors as misused opioids (but in different ways), medications can stabilize abnormal brain activity. Learning How OUD Medications Work The following sections describe how each of the OUD medications functions (Exhibit 4.5; see also Part 3 of this TIP for greater detail). Discuss questions or concerns about a patient’s medi- cation, side effects, or dosage with the patient’s prescriber after getting the patient’s consent. 4-13 TIP 63 Part 4 of 5—Bringing Together Addiction Treatment Counselors, Clients, and Healthcare Professionals EXHIBIT 4.5. FDA-Approved Medications Used To Treat OUD: Key Points MEDICATION HOW IT’S TAKEN WHY IT WORKS SIDE EFFECTS NOTES Buprenorphine Tablet dissolved under the tongue or flm dissolved under the tongue or against the inside of the cheek. Taken once daily, every other day, or 3 Partially activates the opioid receptor. Reduces craving and blocks the euphoric effect of opioids. Can cause constipation, headache, nausea, insomnia, excessive sweating, or opioid withdrawal. Overdose is possible but less likely than with methadone. Overdose death risk is increased if buprenorphine is taken with alcohol or intravenously in combination with benzodiazepines or other CNS depressants. Less sedating than methadone. Prescribers must have a special SAMHSA waiver but don’t need to be part of a federally certifed OTP. Can be prescribed through pharmacies or provided via times a week. It also comes as an implant that lasts 6 months or as an injection that lasts 1 month. Neonatal abstinence syndrome (NAS) OTPs. The implant and injection can only be prescribed by waivered providers who have completed REMS training. Methadone Liquid or tablet once daily. Dose may be divided for twice- daily dosing if medically necessary. Fully activates the opioid receptor. Reduces craving and blocks the euphoric effect of opioids. Can cause constipation, sleepiness, sweating, swelling of hands and feet, sexual dysfunction, heart arrhythmias, low blood pressure, fainting, and substance misuse. Can cause overdose death if increased too rapidly, taken in a much higher than usual dose, or taken concurrently with some substances and medications, particularly CNS depressants such as alcohol or benzodiazepines. NAS Initially requires visits 6 to 7 times per week to an OTP. Patients can decrease attendance gradually based on time in treatment and clinical stability. Naltrexone Daily tablet (can also be taken 3 times a week) or monthly injection in buttock. Occupies the opioid receptors. Reduces craving and blocks the euphoric effect of opioids. Can cause nausea, headache, dizziness, fatigue, liver toxicity, depression and suicidality, muscle cramps, fainting, and loss of or decreased appetite or other appetite disorders; in the extended- release injectable formulation, can cause pain, swelling, and other complications at the injection site. Patient must complete withdrawal and stay opioid abstinent for at least 7 days before starting naltrexone and longer (e.g., 10 or more days) for long-acting opioids, such as methadone. Tablets are rarely effective. Monthly injections are more effective than tablets. 4-14 Medications for Opioid Use Disorder TIP 63 Buprenorphine Buprenorphine reduces opioid misuse, HIV risk behaviors, and risk of overdose death.108,109,110,111 Buprenorphine only partially activates opioid receptors; it is a partial agonist. It binds to and activates receptors suffciently to prevent craving and withdrawal and to block the effects of illicit opioids. Appropriate doses of buprenorphine shouldn’t make patients feel euphoric, sleepy, or foggy headed. Buprenorphine has the beneft of a ceiling effect. Its effectiveness and sedation or respiratory effects don’t increase after a certain dosing level, even if more is taken. This lowers risk of overdose and misuse.112 Groups at particular risk for buprenorphine overdose include children who accidentally ingest the medication113 and patients who also use CNS depressants like benzodiazepines or alcohol.114,115 (See Part 3 of this TIP for more information on concurrent use of CNS depressants and buprenorphine.) Buprenorphine is available outside of OTPs, through non-OTP healthcare settings (e.g., physicians’ offces, outpatient drug treatment programs). Healthcare professionals (including nurse practitioners and physician assistants, per the Comprehensive Addiction and Recovery Act of 2016, and, until October 1, 2023, qualifed clinical nurse specialists, certifed registered nurse anesthetists, and certifed nurse midwives, per the SUPPORT for Patients and Communities Act of 2018) can prescribe it outside of an OTP, provided they have a specifc federal waiver. This is often referred to as “being waivered” to prescribe buprenorphine. Buprenorphine can cause opioid withdrawal in patients who have recently taken a full opioid agonist (e.g., heroin, oxycodone). This occurs because buprenorphine pushes the full opioid activator molecules off the receptors and replaces them with its weaker, partially activating effect. For this reason, patients must be in opioid withdrawal when they take their frst dose of buprenorphine. The most common buprenorphine formulation contains naloxone to reduce misuse. Naloxone is an opioid antagonist. It blocks rather than activates receptors and lets no opioids sit on receptors to activate them. Naloxone is poorly absorbed under the tongue/against the cheek, so when taking the combined medication as directed, it has no effect. If injected, naloxone causes sudden opioid withdrawal. Buprenorphine comes in two forms that melt on the inside of the cheek or under the tongue: flms (combined with naloxone) or tablets (bu- prenorphine/naloxone or buprenorphine alone). For treatment of OUD, patients take the flms or tablets once daily, every other day, or three times a week. Various companies manufacture these forms of the medication. Some are brand name, and some are generic. The different kinds vary in strength or number of milligrams, but they have been designed and tested to provide roughly the same amount of medication as the frst approved product (Exhibit 3A.5 in Part 3). Buprenorphine is also available in a long- acting implant and long-acting injection that specially trained healthcare professionals place under the skin (subdermal implant) and an ex- tended-release formulation that is administered under the skin (subcutaneous injection). The implant is appropriate for patients who have been stable on low doses of the flms or tablets. It lasts for 6 months and can be replaced once after 6 months. The extended release injection lasts for 1 month and can be repeated monthly. It is appro- priate for patients who have been stabilized on the flms or tablets for at least 7 days. Healthcare professionals with waivers can prescribe buprenorphine. Physicians who take an 8-hour training and get a waiver can prescribe buprenorphine. Nurse practitioners and physician assistants are eligible to apply for waivers after 24 hours of training. Until October 1, 2023, clinical nurse specialists, certifed registered nurse anesthetists, and certifed nurse midwives also are eligible to apply for waivers after 24 hours of training. Recent buprenorphine practice guide- lines provide an exemption to providers who are 4-15 TIP 63 Part 4 of 5—Bringing Together Addiction Treatment Counselors, Clients, and Healthcare Professionals state licensed, possess a valid DEA registration, and wish to treat no more than 30 patients with buprenorphine. The “traditional” pathway of obtaining a waiver by undergoing the 8-hour training still exists and is required for providers who wish to treat more than 30 patients.116 Providers who wish to deliver buprenorphine implants must receive special training on how to insert and remove them. Buprenorphine can cause side effects including constipation, headache, nausea, and insomnia. These often improve over time and can be managed with dosage adjustments or other approaches. Methadone Methadone is highly effective. Many studies over decades of research show that it:117,118,119 • Increases treatment retention. • Reduces opioid misuse. • Reduces drug-related HIV risk behavior. • Lowers risk of overdose death. Methadone is slow in onset and long acting, avoiding the highs and lows of short-acting opioids. It is a full agonist. Patients who take the same appropriate dose of methadone daily as prescribed will neither feel euphoric from the medication nor experience opioid withdrawal. Methadone is an oral medication that is taken daily under observation by a nurse or phar- macist and under the supervision of an OTP physician. Methadone is available as a liquid concentrate, a tablet, or an oral solution made from a dispersible tablet or powder. Methadone blunts or blocks the euphoric effects of illicit opioids because it occupies the opioid receptors. This “opioid blockade” helps patients stop taking illicit opioids because they no longer feel euphoric if they use illicit opioids. When on a proper dose of methadone, patients can: • Keep regular schedules. • Lead productive, healthy lives. • Meet obligations (family, social, work). Methadone can lead to overdose death in people who use a dose that’s considerably higher than usual, as methadone is a full agonist. People who don’t usually take opioids or have abstained from them for a while could overdose on a fairly small amount of methadone. Thus, patients start on low doses of methadone and gradually adjust upward to identify the optimal maintenance dose level. Patients must attend a clinic for dose adminis- tration 6 to 7 days per week during the start of treatment. Healthcare professionals can thus observe patients’ response to medication and discourage diversion to others. Visit frequency can lessen after patients spend time in treatment and show evidence of progress. Methadone can cause certain side effects. Common potential side effects of methadone include: • Constipation. • Sleepiness. • Sweating. • Sexual dysfunction. • Swelling of the hands and feet. Sleepiness can be a warning sign of potential overdose. Patients who are drowsy should receive prompt medical assessment to determine the cause and appropriate steps to take—which may require a reduction in methadone dose. Some patients may appear sleepy or have trouble staying awake when idle, even if there is no immediate danger of evolving overdose. These patients may need a lower dose or may be taking other prescribed or nonprescribed medications (e.g., benzodiazepines, clonidine) that are interacting with the methadone. Naltrexone Naltrexone stops opioids from reaching and activating receptors, preventing any reward from use. Naltrexone is an antagonist of the opioid receptors—it does not activate them at all. Instead, it sits on the receptors and blocks other opioids from activating them. 4-16 Medications for Opioid Use Disorder TIP 63 Naltrexone appears to reduce opioid craving120 but not opioid withdrawal (unlike buprenorphine and methadone, which reduce both craving and withdrawal). Someone starting naltrexone must be abstinent from short-acting opioids for at least 7 days and from long-acting opioids for 10 to 14 days before taking the frst dose. Otherwise, it will cause opioid withdrawal, which can be more severe than that caused by reducing or stopping opioid use. Naltrexone comes in two forms: tablet and injection. • Patients take oral naltrexone as tablets daily or three times per week. Tablets are rarely effective, as patients typically stop taking them after a short time.121,122,123 • Highly externally monitored populations in remission may do well with the tablet,124,125,126 such as physicians who have mandatory frequent urine drug testing and are at risk of losing their licenses. • The injected form is more effective than the tablet because it lasts for 1 month. Patients can come to a clinic to receive an intramuscu- lar injection in their buttock. Naltrexone can produce certain side effects, which may include: • Nausea. • Headache. • Dizziness. • Fatigue. For the extended-release injectable formulation, potential reactions at the injection site include: • Pain. • Bumps. • Blistering. • Skin lesions (may require surgery). Knowing What Prescribers Do The following sections will help explain the role healthcare professionals play in providing each OUD medication as part of collaborative care. Part 3 of this TIP offers more detailed clinical information. Administer buprenorphine Patients typically begin buprenorphine in opioid withdrawal. Patients may take their frst dose in the prescriber’s offce so the prescriber can observe its initial effects. Increasingly often, patients take their frst dose at home and follow up with prescribers by phone. Most people are stable on buprenorphine dosages between 8 mg and 24 mg each day. Patients who take buprenorphine visit their prescriber regularly to allow monitoring of their response to treatment and side effects and to receive supportive counseling. The visits may result in specifc actions, such as adjusting the dosage or making a referral for psychosocial services. Stable patients may obtain up to a 30-day prescription of this medication through community pharmacies. Visits may include urine drug testing. Early in treatment, patients typically see their prescribers at least weekly. Further along, they may visit prescribers every 1 to 2 weeks and then as infrequently as once a month or less. The prescriber will make dosage adjustments as needed, reducing for side effects or increasing for unrelieved withdrawal or ongoing opioid misuse. OTPs that provide buprenorphine will typically follow a similar process, with the principal difference being that the program will administer or dispense the medication rather than the patient flling a prescription at a pharmacy. Administer methadone Only SAMHSA-certifed OTPs may provide methadone by physician order for daily observed administration onsite or for self- administration at home by stable patients.127 The physician will start patients on a low dose of methadone. People in early methadone treatment are required by federal regulation to visit the OTP six to seven times per week to take their medication under observation. The physician will monitor patients’ initial response to the methadone and slowly increase the dose until withdrawal is completely relieved for 24 hours. 4-17 TIP 63 Part 4 of 5—Bringing Together Addiction Treatment Counselors, Clients, and Healthcare Professionals A prescriber can’t predict at the start of treatment what daily methadone dose will work for a patient. An effective dose is one that eliminates withdrawal symptoms and most craving and blunts euphoria from self- administered illicit opioids without producing sedation. On average, higher dosages of methadone (60 mg to 100 mg daily) are associated with better outcomes than lower dosages.128,129 That said, an effective dose of methadone for a particular patient can be above or below that range. The prescriber will continue to monitor the patient and adjust dosage slowly up or down to fnd the optimum dose level. The dose may need further adjustment if the patient returns to opioid use, experiences side effects such as sedation, starts new medications that may interact with methadone, or has a change in health that causes the previously effective dose to become inadequate or too strong. If patients taking methadone drink heavily or take sedatives (e.g., benzodiazepines), physicians may: • Treat the alcohol misuse. • Refer to a higher level of care. • Address comorbid anxiety or depression. • Decrease dosage to prevent overdose. Administer naltrexone To avoid severe withdrawal, prescribers will ensure that patients are abstinent from opioids at least 7 to 10 days before initiating or resuming naltrexone. Prescribers may require longer periods of abstinence for patients tran- sitioning from buprenorphine or methadone to naltrexone. Prescribers typically take urine drug screens to confrm abstinence before giving naltrex- one. Healthcare professionals can confrm absti- nence through a “challenge test” with naloxone, a short-acting opioid antagonist. Healthcare professionals manage withdrawal symptoms with nonopioid medication. Prescribers are prepared to handle withdrawal caused by naltrexone despite a period of abstinence.130 Ideally, they administer the frst injection before patients’ release from residential treatment or other controlled settings (e.g., prison) so qualifed individuals can monitor them for symptoms of withdrawal. Healthcare professionals typically see patients at least monthly to give XR-NTX injections. For those taking oral naltrexone, prescribers schedule visits at their discretion. Thus, urine drug testing may be less frequent for these patients than for patients taking buprenorphine. But periodic drug testing should occur. There is only one dose level for injected naltrexone,131 so prescribers cannot adjust the dose. However, they can slightly shorten the dosing interval if the medication’s effectiveness decreases toward the end of the monthly dosing interval. If the patient is having side effects or intense cravings, the prescriber may recommend switching to a different medication. Set expectations Ideally, prescribers will collaborate with counselors and other care providers involved in patients’ care to set reasonable patient expectations. Medications can effectively treat OUD, but they don’t treat other SUDs (save naltrexone, also FDA-approved to treat alcohol use disorder). Patients may still need: • Counseling for psychosocial issues. • Social supports/treatment to get back on track. • Medications, therapy, or both for co-occurring conditions. Collaboration between all involved healthcare providers helps patients understand the OUD treatment timeline, which generally lasts months or years. Courses of medically supervised withdrawal or tapering are considerably less Patients may still beneft from the counseling you can offer in addition to care from other providers, even if you can’t communicate with those providers directly. 4-18 Medications for Opioid Use Disorder TIP 63 effective than longer term maintenance treatment with buprenorphine or methadone and are often associated with return to substance use and a heightened risk of overdose.132,133,134,135 Counselor–Prescriber Communications OUD medication can support counselors’ work with clients who have OUD, and counseling supports the work prescribers do with them. Good communication facilitates mutually supportive work (Exhibit 4.6). A counselor will probably: • See patients more frequently than prescribers. • Have a more complete sense of patients’ issues. • Offer providers valuable context and perspective. • Help patients take medications appropriately. • Ensure that patients receive high-quality care from their other providers. Obtaining Consent Get written consent from patients allowing communication directly with their providers (unless the counselor and the providers work Good communication with prescribers and other treatment team members allows everyone to work together to: • Assess patient progress. • Change treatment plans if needed. • Make informed decisions about OUD medication. in the same treatment program). The consent must explicitly state that the patient allows the counselor to discuss substance-use-related issues. It should also specify which kinds of in- formation the counselor can share (e.g., medical records, diagnoses). Consent forms must comply with federal and state confdentiality laws that govern the sharing of information about patients with SUDs.136,137 Carefully protect any identifying informa- tion about patients and their medical and treatment information. Don’t send such infor- mation through unsecured channels, such as: • Text messaging. • Unsecure, unencrypted emails. • Faxes to unsecured machines. EXHIBIT 4.6. Example of Counselor–Prescriber Communication Counselor: Dr. Smith, thank you for referring Jeff to my counseling practice. I’d like to review with you the elements of the treatment plan we’ve developed. Prescriber: That would be really helpful. Counselor: We agreed to meet weekly while he’s getting stabilized on the buprenorphine. The initial focus of our sessions will be helping Jeff expand his recovery support network. Prescriber: I’m glad to hear that you’re following up on that. My nurse reported that he’s alone in the waiting room before his appointments, and he also mentioned to me that he doesn’t have anybody to talk with. Counselor: I suggested a support group for people taking buprenorphine that’s in his neighborhood. We’ve also begun talking about recreational activities that can help him fll the time he used to spend with drug-using friends. Prescriber: I’ll reinforce your suggestions when he comes in this Friday. Counselor: Also, he seems confused about where the flm goes in his mouth. I urged him to discuss that with you. Prescriber: I’ll make a note to go over that with him again on Friday. 4-19 TIP 63 Part 4 of 5—Bringing Together Addiction Treatment Counselors, Clients, and Healthcare Professionals Phone calls are the most secure way to discuss patient cases, although it may be more conve- nient to reach out to healthcare professionals frst through email. Structuring Communications With Prescribers Regular, structured communication can improve the fow of information between treatment teams. Some multidisciplinary programs produce regular reports for prescribers about patient progress. Exhibit 4.7 provides some strategies for discussing patient care with healthcare professionals. Helping Clients Overcome Challenges in Accessing Resources By collaborating with healthcare professionals in OUD care, counselors can help clients overcome challenges they face in obtaining treatment, such as: • Ability to pay for OUD medication. Counselors are often already skilled in helping clients address treatment costs (e.g., facil- itating Medicaid applications, linking them to insurance navigators). Try to refer clients who face diffculty meeting prescription costs or copays back to the agency’s fnancial department for sliding scale adjustments and ability-to-pay assessments. Also try to help patients fnd and apply for relevant pharma- ceutical company medication prescription plans. • Transportation. Options to offer clients may include: − Providing vouchers for public transportation. − Providing information on other subsidized transportation options. − Linking clients to peer support specialists and case managers who can arrange transportation. − Assisting eligible clients in navigating Medicaid to obtain transportation services. − If available, arranging for telehealth services to overcome clients’ transportation barriers. • Access to medication in disaster situations. Counselors can review options with patients for obtaining prescription replacements and reflls or daily medicine dosing under various scenarios. This could include if their usual clinic or primary pharmacy is closed or if they’re relocated without notice because of an unforeseen emergency. Also advise patients on the items to take with them in such scenarios to facilitate reflls from a new EXHIBIT 4.7. Tips for Discussing Patient Care With Prescribers • Identify the patient. Once the counselor has established secure communication through encrypted email or by phone, he or she should state the patient’s name, date of birth, and medical record number (if obtained). • Let prescribers know up front the purpose of the call. Begin by clearly describing the question or concern leading to the call. If it is simply to establish contact because of a shared patient, that’s fne. • Share any relevant information about the patient (if the patient has consented). If there is a concern about a side effect, for example, describe observed changes to the healthcare professional. If there is a concern about return to opioid use, describe which elements of the patient’s behavior are worrisome. • Work together to build a shared understanding of the patient’s situation. The counselor likely has key information about the patient that the prescriber does not have, and vice versa. • Discuss next steps with the healthcare provider before ending any communication to help coordinate patient care. Consider scheduling a check-in with each other to assess patient progress. 4-20 Medications for Opioid Use Disorder TIP 63 medication-dispensing facility. Key materials include: − Photo identifcation. − Medication containers of currently pre- scribed medications (even if empty). − Written prescriptions. − Packaging labels that contain dosage, prescriber, and refll information. − Any payment receipts that contain medication information. To overcome systemic barriers, help enact collaborative policies and procedures. Work with program management and the community at large to address the following issues: • Connection to treatment: Counselors may be able to participate in community efforts to ensure that information on how to obtain treatment for OUD is available wherever people with OUD: − Gather (e.g., all-night diners, bars, free health clinics, injection equipment exchanges). − Seek help (e.g., emergency departments, houses of worship, social service agencies). − Reveal a need for help (e.g., encounters with law enforcement and child welfare agencies). Encourage buprenorphine prescribers to make known their availability if they are prepared to accept new patients. Help disseminate lists of addiction treatment providers and share their information via peer recovery specialists (see Part 5). • Rapid assessment and treatment initiation: Try to help OUD medication providers, partic- ularly in OTPs, streamline counseling intake processes to help patients receive medication effciently. The expert panel of this TIP recog- nizes that same-day admission of patients with OUD may not be possible in all settings, but it’s a worthwhile goal. Every program should streamline its intake processes and expedite admissions. • Return to treatment: When patients dis- continue treatment prematurely and return to use of opioids, it can be hard for them to reengage in treatment because of the shame they feel or because there is a waiting list for admission. The waitlist problem may not be solvable because of capacity limitations, but all collaborative care team members— including counselors and prescribers—should: − Inform patients from intake onward that the program will readmit them even if they drop out. − Encourage patients to seek readmission if they return to opioid use or feel that they are at risk for returning to opioid use. − Inform patients of the importance of overdose prevention (see the “Counseling Patients on Overdose Prevention and Treatment” section). − Provide continued monitoring if possible; it can range from informal quarterly check-ins to regularly scheduled remote counseling or peer support (e.g., from a recovery coach). − Offer an expedited reentry process to encourage patients to return if they need to. − Engage in active outreach and reengage- ment with OTP patients, which can be effective.138,139 Try to contact patients who have dropped out to encourage them to return. Creation of a Supportive Counseling Experience Maintaining the Therapeutic Alliance The therapeutic alliance is a counselor’s most powerful tool for infuencing outcomes.140 It underlies all types and modalities of therapy and helping services. A strong alliance welcomes patients into treatment and creates a sense of safety. 4-21 TIP 63 Part 4 of 5—Bringing Together Addiction Treatment Counselors, Clients, and Healthcare Professionals COUNSELING PATIENTS WITH OUD WHO DON’T TAKE MEDICATION Patients who don’t take an OUD medication after withdrawal are at high risk of return to opioid use, which can be fatal given the loss of opioid tolerance. Provide these patients with overdose prevention education and the overdose-reversal medication naloxone, or educate them about naloxone and how they can obtain it in their community. Advise them to report a return to opioid use or a feeling that they are at risk of relapsing. Work with them and their care team to either resume medication for OUD or enter a more intensive level of behavioral care. Certain counselor skills help build and maintain a therapeutic alliance, including: • Projecting empathy and warmth. • Making patients feel respected and understood. • Not allowing personal opinions, anecdotes, or feelings to infuence the counseling process (unless done deliberately and with therapeutic intention).141 These skills are relevant for working with all patients, including those taking medication for OUD. Apply them consistently from the very frst interaction with a patient through the conclusion of services. For example, recognize and reconcile personal views about medication for OUD so that they don’t infuence counseling sessions. Educating Patients About OUD and a Chronic Care Approach to Its Treatment Help ensure that patients understand the chronic care approach to OUD and their: • Diagnosis. • Prognosis. • Treatment options. • Available recovery supports. • Prescribed medications. • Risk of overdose (and strategies to reduce it). Seek to understand patients’ preferences and goals. Doing so can help convey information meaningfully so patients understand the choices available to them. Also, help communicate patients’ preferences and goals to healthcare professionals and family members. Educate colleagues and other staff members so they can help create a supportive experience for patients with OUD: • Provide basic education to colleagues about medications for OUD and how they work. • Share evidence on how these medications reduce risky behavior, improve outcomes, and save lives. • Note that major U.S. and international guide- lines affrm use of medication to treat OUD. • Ask about and address specifc fears and concerns. • Provide resources for additional information. Counseling Patients on Overdose Prevention and Treatment Know how to use naloxone to treat opioid overdose; share this information with patients and their family members and friends. Available by prescription (or without a prescription in some states), naloxone is an opioid antagonist that has successfully reversed many thousands of opioid overdoses. It comes in auto-injector and nasal spray formulations easy for laypeople to administer immediately on the scene of an overdose, before emergency responders arrive. Ask patients if they have a naloxone pre- scription or help them get it without one if possible. Providers may prescribe naloxone in addition to OUD medication. Counselors should check state laws to learn their jurisdiction’s naloxone prescription and dispensation policies (see “Resource Alert: Overdose Prevention/ Treatment”). 4-22 Medications for Opioid Use Disorder TIP 63 Inform clients and their friends and families of any Good Samaritan laws in the jurisdiction, which protect against drug offenses for people who call for medical help while experiencing or observing overdose. Emphasize that a person given naloxone to reverse overdose must go to the emergency department, because overdose can start again when naloxone wears off. Consider working with the program admin- istrator to place a naloxone rescue kit in the offce, if one is not already available. To be ready for an emergency, learn: • The signs of overmedication (which may progress to overdose) and overdose itself. • What to do if an overdose is suspected. • How to administer naloxone. Consider working with the program admin- istrators to set up a program to distribute naloxone directly to patients. Many states allow organizations to do this under a standing RESOURCE ALERT Overdose Prevention/Treatment SAMHSA Opioid Overdose Prevention Toolkit (https://store.samhsa.gov/product/Opioid- Overdose-Prevention-Toolkit/SMA18-4742) National Conference of State Legislatures’ Drug Overdose Immunity and Good Samaritan Laws (www.ncsl.org/research/civil-and-criminal -justice/drug-overdose-immunity-good -samaritan-laws.aspx) Project Lazarus’ Naloxone: The Overdose Antidote (www.projectlazarus.org/naloxone) Prescription Drug Abuse Policy System’s: Interactive Map of Naloxone Overdose Prevention Laws (http://pdaps.org/datasets /laws-regulating-administration-of -naloxone-1501695139) order from a physician. Clients are more likely to access naloxone if their program provides it directly to them rather than sending them to another organization to get it. Learn more at Prescribe to Prevent (http://prescribetoprevent.org). Helping Patients Cope With Bias and Discrimination Patients taking medication for OUD must deal with people—including family members, friends, colleagues, employers, and community members—who are misinformed or biased about the nature of OUD and effective treatments for it (Exhibit 4.8). Wherever possible, such as in a counseling session or a community education forum, counter misunderstandings with accurate information. Emphasize the message that addiction is governed by more powerful brain forces than those that determine habits. As a result, having a lot of positive intent, wanting to quit, and working hard at it sometimes won’t be enough. Remind patients about building recovery capital and sticking with their treatment plan and goals. A particularly good opportunity to do so arises when patients ask how to “get off medication.” Statements such as “The longer you take medication, the more of your life you can get back and the less likely you are to return to opioid use” and “We usually recommend continuing medication long term because it helps people maintain recovery” can help clients understand that they are following medical rec- ommendations and doing a good job of caring for themselves (Exhibit 4.9). People may think that addiction is just a bad habit or willful self-destruction and that someone who has diffculty stopping opioid misuse is lazy. They may view OUD medication as “just another drug” and urge patients to stop taking it. 4-23 TIP 63 Part 4 of 5—Bringing Together Addiction Treatment Counselors, Clients, and Healthcare Professionals EXHIBIT 4.8. Conversation: Addressing Misinformation Mother of Patient: They want to put my son on methadone, but it’s going to rot his teeth. Father of Patient: Yeah. I don’t want him to look like he’s on drugs when he’s fnally off them. Counselor: You have the impression that people who use drugs have bad teeth. And in many cases, that’s true. But there are a lot of reasons why people with a substance use disorder develop teeth and gum problems—such as a high-sugar diet, co- occurring depression that prevents them from taking good care of themselves, poor health that allows oral disease to develop, and lack of access to preventive dental care or treatment. But if your son practices good oral hygiene, his mouth will stay healthy while he takes methadone. Mother of Patient: What do you mean by “oral hygiene”? Counselor: Like all of us, he’ll have to limit his sweets and brush and foss regularly. Methadone can reduce the fow of saliva, which means that not as much of the bacteria on his teeth will get washed away. So, he’ll want to get good dental advice on how to address dry mouth if that’s a problem for him. Regular dental checkups will be really important, too. Father of Patient: So, he won’t trade his teeth for his recovery. Thanks—that’s one less thing to worry about! Review a client’s motivation for tapering or quitting medication (Exhibit 4.10) and have a conversation about the best timing for such a change (Exhibit 4.11). If the client has consented to communication with other providers, inform the client’s prescriber about the client’s desires or intent so that shared decision making can take place. Be proactive in dispelling myths and providing facts about medications for OUD when coun- tering misconceptions and judgmental attitudes. Point out that multiple organizations consider individuals to be in recovery if they take OUD medication as prescribed, including: • The American Medical Association.142 • The American Society of Addiction Medicine.143 • The National Institute on Drug Abuse.144 • The Offce of the Surgeon General.145 • The World Health Organization.146 Explain that alcohol and opioids are different substances with different effects on the body and brain. This counters the mistaken belief that people receiving buprenorphine or methadone are always “high” and as impaired as if they drank alcohol all day. People acquire tolerance to impairments that drinking causes in motor control and cognition. But this tolerance is partial; alcohol consumption always results in some defcits. Opioids don’t have the same motor or cognitive effects. Complete tolerance develops to the psychoactive effects and related motor impairments opioids cause. If a person takes a therapeutic dose of opioid agonist medication as prescribed, he or she may be as capable as anyone else of driving, being emotionally open, and working produc- tively. Some people worry that OUD medication causes a “high” because they’ve seen patients taking OUD medication whose behavior was affected by other substances (e.g., benzodiaze- pines). Others may assume that someone is high 4-24 Medications for Opioid Use Disorder TIP 63 EXHIBIT 4.9. Addressing the Misconception That an Opioid Medication Is “Just Another Drug” Concerned Colleague: These patients are just replacing one drug with another. Instead of heroin, they’re using buprenorphine or methadone. Counselor: Actually, there’s substantial research that medication for opioid use disorder helps patients stop feeling withdrawal and craving and allows them to get their life back on track. These medications keep patients in treatment and reduce crime and HIV risk behavior. Concerned Colleague: Yeah, but aren’t they still addicted? Counselor: Physically dependent, yes; but addicted, no. There’s an important difference. Someone addicted to heroin has to take the drug several times a day to avoid withdrawal. This usually leads to craving, loss of control, and taking more than intended. Drug-seeking behavior causes loss of family and friends. It makes the person unable to perform daily roles and meet obligations. Concerned Colleague: Yes, I know how addiction works. But isn’t taking methadone an addiction, too? Counselor: Patients only take methadone once a day, and its makeup is different from heroin. Daily methadone lets the body stabilize so patients don’t have the highs and lows that come from heroin use. If patients use heroin, the methadone blocks its effects; they don’t get high. Methadone is taken orally, so there isn’t the same danger of infection that comes with injection drug use. Taking methadone as part of a treatment program lets patients feel normal and focus on changing the other aspects of their lives that led to drug use. Concerned Colleague: But you just said they take methadone every day. Counselor: Yes. That is true of most medications for any disease, if you think about it. Patients have a physical dependence on the medication but are in remission from addiction. on a medication for OUD who isn’t taking any such medication at all. Point out that many thousands of people are prescribed medication for OUD every year, are receiving appropriate treatment, and are indistinguishable from other people. People taking OUD medication rely on it to maintain daily function, like people with diabetes rely on insulin. Nevertheless, some people think that individuals taking buprenorphine or methadone are still addicted to opioids (Exhibit 4.9), even if they don’t use illicit drugs. For people with OUD, the medication addresses the compulsion and craving to use. It also blocks the euphoric effects of illicit opioids, which over time helps people stop attempting to use. For people with EXHIBIT 4.10. When a Patient Wants To Taper Medication or Stop Altogether • Review the decision with the patient to determine the motivation for tapering or quitting medication and the best timing for such a change. • Tell the prescriber that the patient wants to taper; shared decision making should guide the patient’s decision. • Avoid encouraging tapering, which can imply that recovery can only truly occur off of the medication. 4-25 TIP 63 Part 4 of 5—Bringing Together Addiction Treatment Counselors, Clients, and Healthcare Professionals EXHIBIT 4.11. Responding to a Patient’s Desire To Taper Medication for OUD Patient: I want to taper off the buprenorphine. Counselor: You’d like to taper—can you tell me why? Patient: I’m getting married. I want a fresh start. Counselor: You’re saying you’d like to have this all behind you for the new phase in your life. Patient: Yeah, that’s it. Counselor: Would it be alright if I share my concerns about that? Patient: Okay. Counselor: A big change—whether it’s having a baby, getting a new job, or getting married like you’re about to do—can be very exciting. But it can also be surprisingly stressful. You may want to consider staying on the medication during this transition to make sure you maintain your recovery. I’m just suggesting postponing a taper decision until you start getting settled into married life. Patient: I hear you. The last thing I want to do is mess up my marriage right away by using again. It would be inappropriate for a medical team to refuse radiation for cancer patients because the team believes chemotherapy is always needed, or to refuse chemotherapy because they believe that radiation is always needed, regardless of each patient’s diagnosis and condition. It would be just as inappropriate to refuse evidence- based treatment with medication for a patient with OUD, when that may be the most clinically appropriate course of treatment. diabetes, medication addresses the problems caused by inadequate production of insulin by the pancreas. Medication allows both popula- tions to live life more fully. Focus on common ground—all patients want a healthy recovery, and judging or isolating someone for return to use doesn’t aid anyone’s recovery. A divide may occur between patients in a group setting over return to opioid use. People in the OUD community typically are forgiving of return to opioid use and recognize that it can occur on the path to long-term recovery. However, some people in mutual-help communities judge those who return to use (see the “Helping Clients Find Accepting Mutual-Help Groups” section). Address judgmental attitudes through this analogy: People with diabetes whose blood sugar spikes aren’t condemned and ejected from treatment. Dispel the myth that OUD medications make people sick. In fact, methadone and buprenor- phine relieve opioid withdrawal, even if patients don’t feel complete relief in the frst few days. Taking naltrexone too soon after opioid use can cause opioid withdrawal, but withdrawal symptoms can generally be managed success- fully. Point out that people taking medication for OUD sometimes get colds, the fu, or other illnesses, like everyone else. A similar misconcep- tion is that OUD medications make all patients sleepy. Exhibit 4.12 offers a sample dialog for responding to this misconception. 4-26 Medications for Opioid Use Disorder TIP 63 EXHIBIT 4.12. Conversation: Redirecting a Concern to the Prescriber Concerned Colleague: A patient in my group was falling asleep. I think his methadone dose is too high. Counselor: That’s an important observation. That certainly is possible, although there are many other possible explanations. What makes you think it’s the medication and not lack of sleep or some other reason? Concerned Colleague: Because everyone taking methadone falls asleep in group. Counselor: Our medical staff members work hard to make sure that each patient is on the right dose. If a patient is falling asleep in group, you should alert the patient’s physician right away, regardless of what medication they’re taking. But I’m wondering if anything besides medication could be causing this issue. Concerned Colleague: Well, this patient is struggling with having an all-night job. Counselor: It may be helpful to talk to the patient about moving to a group that meets at a time when he can be more rested. In any case, to be safe, you should call the patient’s prescriber about reassessing him. When return to opioid use comes up in a group counseling setting, messages about getting back on track and avoiding shaming and blaming apply just as much to the patients taking OUD medication as to other participants. This topic is an opportunity to address the dangers of overdose, especially the dangers of using an opioid after a period of abstinence or together with other CNS depressants. Helping Patients Advocate for Themselves Educate clients so they can advocate for their treatment and personal needs. Key topics include: • Addiction as a chronic disease infuenced by genetics and environment. • The ways that medications for OUD work. • The process of dose stabilization. • The benefts of longer term medication use and risks of abrupt treatment termination. • The role of recovery supports (e.g., mutual- help groups) in helping achieve goals. family and friends know how important they are and how valuable their support is. Also urge patients to ask loved ones to help them express concerns or fears. Role-playing can help patients self-advocate. It allows them to practice what to say, what reactions to expect, and ways to respond. Coach patients in active listening and in focusing on solutions rather than problems. Exhibit 4.13 gives an example of a counselor helping a client self-advocate. Urge patients to advocate for themselves beyond one-on-one conversations. Options include sharing educational pamphlets, inviting loved ones to a counseling session, or referring them to websites. Addressing Discrimination Against Clients Who Take OUD Medication Patients can face discriminatory actions when dealing with individuals, organizations, or systems that make decisions based on mis- information about, or biases against, the use of medication for OUD. The following sectionsOffer clients’ family and friends education on highlight issues patients taking OUD medicationthese topics, as well, so that they can advocate may face and how counselors can help.for their loved ones. Encourage patients to let 4-27 TIP 63 Part 4 of 5—Bringing Together Addiction Treatment Counselors, Clients, and Healthcare Professionals EXHIBIT 4.13. Conversation: Helping a Client Self-Advocate Patient: My mom is driving me to my back surgery. I’m worried that she’ll fnd out I’m taking buprenorphine. Counselor: It sounds like you’re worried she’ll reject you and be upset if she knows you’re taking medication. Patient: I think she’ll be disappointed in me. She thinks people who take addiction medication are still on drugs. Counselor: What would you think about fnding a time before your surgery to tell your mother that you’re taking buprenorphine? You can explain how it works and remind her how well you’ve been doing maintaining your job, regaining custody of your children, and living a balanced and healthy life. That may help ease her fears. Patient: Thanks. I’ll give that a try. Counselor: If you want, you could invite her to one of our sessions so that I can answer any questions she has. Patient: Yeah, she may hear it better from you. I like the idea of having her come in after I’ve told her. Counselor: When would be a good time to bring up this topic? Patient: She’s driving me to my pre-op appointment on Friday. Maybe I’ll suggest we go for coffee after. Counselor: That’s a good idea. How about we practice that conversation? I’ll play the role of your mom. Help clients address employment- related issues Under the Americans With Disabilities Act, employers cannot discriminate against patients taking medication for OUD.147 However, the law doesn’t always stop employers from taking such action. For example, some employers conduct workplace urine drug testing, either before offering employment or randomly during employment. The OUD medication they test for most frequently is methadone, but it’s possible to test for bu- prenorphine. Naltrexone is generally not tested for. The TIP expert panel concludes, based on multiple patient experiences, that patients who take OUD medication fnd it intimidating to explain to their employers why their urine test results are positive for opioids. Yet if they offer no explanation, they don’t get the callback for the job or are let go from the job they have. Direct patients to legal resources and help them consider how to respond to discrimina- tion at work based on misinterpreted drug tests. Offer to speak with their prospective/ current employers to address concerns and misperceptions about OUD medication and its effect on their ability to do work tasks. RESOURCE ALERT Becoming a Certifed Medication- Assisted Treatment Advocate The National Alliance for Medication Assisted Recovery has a training and credentialing program for interested people—not just those who receive medication for OUD—to become Certifed Medication-Assisted Treatment Advocates (www.methadone.org/certifcation /faq.html). 4-28 Medications for Opioid Use Disorder TIP 63 Understand potential legal issues This section describes issues that can affect access to care for patients involved in the justice system who take buprenorphine or methadone for OUD. These issues usually don’t apply for naltrexone. Many jails (short term) and prisons (long term) restrict or disallow access to OUD medication despite the federal mandate that people who are incarcerated have access to medical care.148,149 For example: • A jail may not continue methadone treatment or allow methadone delivery by patients’ OTPs. • Patients’ medication may be seized upon arrest. • Jail health offcials may deny patients’ bu- prenorphine prescriptions. Help negotiate patient access to OUD medication during incarceration. Negotiating access to OUD medication can be problematic and often requires multiple meetings between care providers and jail staff members to resolve successfully. Patients taking OUD medication may be forced to go without medication during incarceration. This increases their risk for opioid overdose if they return to use after reentering the community, given the decreased tolerance that results from interrupted treatment. Encourage patients to reengage in treatment as soon as they’re released. People with OUD released from prison or jail who don’t take OUD medication have higher risk of overdose death during their frst few weeks in the community. Early after release, they are at very high risk of overdose, given possible: • Decrease in opioid tolerance while incarcerated. • Lack of appropriate OUD therapy while incarcerated. • OUD medication initiation right before release. • Release without coordination or a slot for community-based treatment. Patients who aren’t opioid tolerant need a lower starting dose that prescribers will increase more slowly than usual. Extended-release injectable naltrexone can be an effective alternative for these patients. OPIOID ADDICTION is linked with high rates of ILLEGAL ACTIVITY and INCARCERATION.150,151 Support patients in getting legal advice or counsel via their OUD medication prescribers’ healthcare organization. Members of the TIP expert panel have observed situations in which law enforcement personnel arrested patients leaving methadone clinics and charged them with driving under the infuence or arrested them after fnding buprenorphine prescription bottles in their cars. Discussions among treatment orga- nizations and local law enforcement leadership can help address such situations. Address concerns and advocate for addiction specialists to select treatments best suited for each patient. Sometimes, authorities insist that patients enter a particular kind of treatment or follow particular rules related to their OUD. To ensure a patient-centered focus, help involve addiction specialists in determining what kind of treatment best meets patients’ needs. This kind of advocacy works best when counselors and the programs for which they work have preexisting relationships with personnel in local employ- ment, law enforcement, drug court, and child welfare facilities. Address issues in dealing with healthcare providers Misunderstandings about OUD and its treatment aren’t rare among healthcare providers: • Patients admitted to the hospital for medical issues may face prejudice from hospital staff members. • Providers may not know how to manage patients’ OUD medication during their hospital stay. 4-29 TIP 63 Part 4 of 5—Bringing Together Addiction Treatment Counselors, Clients, and Healthcare Professionals • Some providers don’t know how to manage pain in someone taking medication for OUD. Help communicate issues to patients’ prescribers, who can advocate for proper handling of OUD medication. It is also possible to help hospital staff members see the patient as a whole person who deserves respect and to provide them with essential information about treatment for OUD. Inpatient SUD treatment facilities may refuse admission until patients are off buprenorphine or methadone. Sometimes, patients taking OUD medication seek admission to inpatient facilities for treatment of an additional SUD, a mental disorder, or both. If a facility won’t accept someone on OUD medication, call on local or state regulatory authorities (e.g., the State Opioid Treatment Authority) and patients’ healthcare professionals to intervene with the facility’s professional staff and management. Demonstrate awareness of pregnancy and parenting issues Healthcare professionals may be unaware of current guidelines for treating pregnant women with OUD (Exhibit 4.14). As a result, they may inappropriately: • Deny OUD medication to pregnant women. • Discourage breastfeeding by mothers taking OUD medication. Treatment of Pain in Patients With OUD SAMHSA’s TIP 54, Managing Chronic Pain in Adults With or in Recovery From Substance Use Disorders (https://store.samhsa.gov/product/TIP -54-Managing-Chronic-Pain-in-Adults-With-or -in-Recovery-From-Substance-Use-Disorders /SMA13-4671) • Direct women who become pregnant while taking OUD medication to undergo with- drawal from their medication and attempt abstinence. Hospital policies on screening infants for prenatal substance exposure vary considerably. A positive screen may trigger involvement of Child Protective Services. This may occur even when the positive screen results from treatment with OUD medication under a physician’s care rather than opioid misuse. Help pregnant and postnatal clients in these situations by: • Educating them and encouraging them to share pertinent information and resources with healthcare professionals involved in their care. • Coordinating with their prescribers to help them get prenatal and postnatal care from well-informed healthcare professionals. • Getting involved in efforts to educate the local healthcare community about best practices for the care of pregnant and postnatal women with OUD. Legal problems can arise if Child Protective Services or legal personnel don’t understand that parents receiving OUD medication are fully capable of caring for children and con- tributing to their families. Judges, probation or parole offcers, or Child Protective Services workers may inappropriately request that patients discontinue medication as a condition of family Pregnancy- and Parenting-Related Issues SAMHSA’s Clinical Guidance for Treating Pregnant and Parenting Women With Opioid Use Disorder and Their Infants (https://store .samhsa.gov/product/SMA18-5054) RESOURCE ALERT RESOURCE ALERT 4-30 Medications for Opioid Use Disorder TIP 63 EXHIBIT 4.14. Summary of Current Guidance for the Treatment of Pregnant Women With OUD • An obstetrician and an addiction treatment provider should comanage care, and the woman should receive counseling and supportive services as needed to assist her in achieving a stable life. • Treatment with methadone or buprenorphine without naloxone during pregnancy is recommended. Treatment with naltrexone is not recommended during pregnancy. • Medically supervised withdrawal during pregnancy is typically not advisable. If not done with great care in a controlled setting, it can cause premature labor, fetal distress, and miscarriage. Attempts at abstinence from opioids without the support of medication are generally not advised because of the risk of return to opioid use, which can adversely affect both mother and fetus. • Newborns of women who take OUD medication often show symptoms of NAS, which is treatable. NAS from opioid agonist treatment is not as harmful to the fetus as continued use of illicit opioids during pregnancy. • Mothers stabilized on medication for OUD are encouraged to breastfeed. Summarized from SAMHSA’s publication A Collaborative Approach to the Treatment of Pregnant Women With Opioid Use Disorders (https://store.samhsa.gov/product/A-Collaborative-Approach-to -the-Treatment-of-Pregnant-Women-with-Opioid-Use-Disorders/SMA16-4978).152 reunifcation. Such orders are medically inappro- priate and should be challenged. Possible ways to help: • Write letters to judges and lawyers explaining how effective OUD medication can be. • Send judges and lawyers literature about current medical recommendations (including this TIP). • Testify in court, if necessary. Helping Clients Find Accepting Mutual- Help Groups Voluntary participation in 12-Step groups can improve abstinence and recovery-related skills and behaviors for some people with SUDs. Greater involvement (e.g., being a 12-Step sponsor) can increase these benefts.153,154,155,156 However, not much research has explored less widespread types of groups (e.g., groups that follow a given religion’s principles, secular groups that downplay the spiritual aspects of 12-Step groups). Research exploring longitudinal outcomes for people with OUD who attend NA is limited, but fndings link more frequent atten- dance with abstinence.157,158,159 Clients taking medication for OUD may face challenges in attending mutual-help groups. For example: • NA, the most widely available program, treats illicit opioids and OUD medications equally in gauging abstinence and recovery. NA doesn’t consider people taking OUD medication “clean and sober.”160 • Local chapters of NA may decide not to allow people taking OUD medication to participate at meetings or may limit their participation (e.g., not allowing service work). • Clients attending some NA meetings may encounter hostile attitudes toward the use of medication. • AA’s offcial policy is more accepting of the use of prescribed medication, but clients may still encounter negative attitudes toward their use of medications for OUD. • Other groups, such as some religious mutual- help programs, SMART Recovery, and LifeRing Secular Recovery, also have policies that could challenge clients for taking medication for OUD. 4-31 TIP 63 Part 4 of 5—Bringing Together Addiction Treatment Counselors, Clients, and Healthcare Professionals RESOURCE ALERT Addressing Bias and Discrimination Are You in Recovery From Alcohol or Drug Problems? Know Your Rights: Rights for Individuals on Medication-Assisted Treatment: SAMHSA publication explaining patient rights and federal laws that protect people receiving OUD medication. Describes whom these laws protect and what they cover, including employment, housing, services, and public accommodations (www.samhsa.gov/sites/ default/fles/programs_campaigns/medication_ assisted/Know-Your-Rights-Brochure.pdf) Medication-Assisted Treatment for Opioid Addiction: Myths and Facts: Legal Action Center publication that dispels myths and provides facts about OUD medication (www.lac.org/assets/fles/Myth-Fact-for-MAT. pdf) Methadone Maintenance Myths and Resources: Missouri Department of Mental Health factsheet (https://dmh.mo.gov/media/pdf/ methadone-maintenance-myths-and-resources) Prepare clients who take medication for OUD to attend mutual-help meetings Clients will be better able to fnd supportive mutual-help groups if their counselor and program: • Evaluate attitudes toward medication for OUD among local mutual-help groups. • Keep on hand information about all mutual- help options available in the clients’ area. • Recruit volunteers from mutual-help groups to help clients fnd and attend meetings (e.g., by providing transportation, serving as “sponsors,” introducing clients). • Do not mandate meeting attendance. Recommending participation is just as effective.161 • Keep track of clients’ experiences at different groups to ensure that meetings remain welcoming. • Help clients start onsite mutual-help groups. • Ask staff members to evaluate their own feelings and beliefs about mutual-help groups.162 Facilitate positive mutual-help group experiences • Educate clients about mutual-help groups. Explore group types, risks and benefts of participation, and limitations of research in support of those risks and benefts. • Suggest buddying up. Clients can attend meetings with other people who take medica- tion for OUD. • Review with clients their understanding of and prior experience with mutual help. • Explore clients’ understanding of the benefts and risks of disclosure about taking OUD medication. • Develop a risk-reduction plan for disclosure if clients want to share their use of OUD medication (e.g., talking with an individual group member instead of disclosing to the entire group). • Help clients anticipate and learn to handle negative responses: − Develop sample scripts clients can use when questioned about their medication. − Role-play scenarios in which clients respond to questions about their use of medication. • Respect the privacy of clients’ participation in mutual-help groups and recognize that some groups ask that participants not discuss what occurs in meetings. 4-32 Medications for Opioid Use Disorder TIP 63 • Make sure clients know they can talk about their experiences in mutual-help groups but don’t pressure them to disclose in these groups that they take OUD medication. • Consider mutual-help participation using groups more open to OUD medication (e.g., attending AA even if the client has no alcohol use disorder; attending groups for co- occurring substance use and mental disorders, such as Dual Recovery Anonymous or Double Trouble in Recovery). Clients with OUD who attend AA and not NA have similar recovery- related outcomes and retention rates.163 RESOURCE ALERT How To Use Technology-Based Tools in Behavioral Health Services SAMHSA’s TIP 60, Using Technology-Based Therapeutic Tools in Behavioral Health Services, is available from the SAMHSA Store (https://store.samhsa.gov/product/TIP-60 -Using-Technology-Based-Therapeutic-Tools -in-Behavioral-Health-Services/SMA15-4924). In addition to discussing online mutual-help groups, this TIP can help counselors implement technology-assisted care for patients with OUD. It highlights the importance of using technology- based assessments and interventions and discusses how technology reduces barriers to treatment. Online mutual-help groups Before recommending an online group, check its content and tone on the use of medication. Mutual help using the Internet (either through real-time chat rooms or discussion boards where one posts and waits for responses) has been growing in popularity. This is an especially valuable resource for clients living in rural and remote areas. Groups range from general meetings for people with a particular SUD (e.g., online AA meetings) to those that are very specifc (e.g., Moms on Methadone). Moderated groups are preferable to unmoderated groups. TIP 60, Using Technology-Based Therapeutic Tools in Behavioral Health Services, addresses many of the pros and cons of online support groups.164 Part 5 of this TIP gives links for several groups that the TIP expert panel has identifed as helpful. RESOURCE ALERT Mutual Help for Clients With OUD William White’s Narcotics Anonymous and the Pharmacotherapeutic Treatment of Opioid Addiction in the United States: Publication that gives more information on the pros and cons of 12-Step groups for people receiving medication for OUD and how to prepare them for meetings165 (http://atforum.com/documents /2011NAandMedication-assistedTreatment.pdf) White, Galanter, Humphreys, and Kelly’s “The Paucity of Attention to Narcotics Anonymous in Current Public, Professional, and Policy Responses to Rising Opioid Addiction”: Peer- reviewed journal article on the benefts of NA and the need to include it among the options offered to people receiving medication for OUD166 (www.tandfonline.com/doi/abs/10.1080/0734732 4.2016.1217712) 4-33 TIP 63 Part 4 of 5—Bringing Together Addiction Treatment Counselors, Clients, and Healthcare Professionals Mutual-help groups specifc to OTPs Although these meetings occur mostly on the premises of OTPs, it may be possible to use the models developed by OTPs in more general SUD treatment settings. Because they serve only patients receiving medication to treat OUD, OTPs can create and sustain onsite mutual- help groups specifc to this population. Such groups include Methadone Anonymous (MA),167 other variations on a 12-Step model,168,169 and the mutual-help component of Medication- Assisted Recovery Services (MARS). MARS is a recovery community organization, not just a mutual-help program. MARS members design, implement, and evaluate a variety of peer- delivered recovery support services in addition to providing meetings. More information on these programs is in the articles cited and online resources presented in Part 5. Facilitating Groups That Include Patients Taking OUD Medication Foster acceptance via attitude and behavior when facilitating groups that include patients taking OUD medication: • Establish ground rules about being respect- ful, avoiding negative comments about group members, and keeping statements made in the group confdential—as with any group. • Be proactive. State up front that ground rules apply to everyone, regardless of a given person’s decisions about whether to include OUD medication in his or her path to recovery. • Ask members to discuss how to address any negative comments, should they occur. This is especially important for mixed groups. • Ask group members to affrm that they will abide by the rules. • Provide consistent reminders throughout each session about the ground rules. Group members may still make negative comments about medication for OUD. Avoid feeding the negativity with attention, which can worsen the situation. Reframe negative comments to express underlying motivations, often based on fear or misunderstanding. Remain positive; model expected behavior, which can beneft the person who made the negative remark (Exhibit 4.15). Additional tips for leading mixed groups include the following: • Treat patients taking OUD medication the same as other patients in the group. Patients taking medication can participate in and beneft from individual and group counseling just like other patients. There is no need to have separate counseling tracks EXHIBIT 4.15. Redirecting Negative Comments Petra: How can you say Joni is in recovery when she’s still taking a drug every day? I struggled every day and never took anything for 10 years. Counselor: I hear your concern for Joni. You want her recovery to follow the same path you took in yours. Petra: Right! And she’s taking methadone, which is an opioid. People use opioids to get high. Counselor: In this treatment program, we see addiction as a brain disease. Methadone treats the brain disease part of addiction. It stabilizes the brain and allows the person to focus on learning new ways of thinking and reacting. It works by blocking the effects of other opioids. Patients on a proper dose can’t get high even if they try to use. This helps discourage future drug use. Joni, would you like to add anything? Joni: Petra, it’s great that you stopped using opioids and stayed in recovery without medication—but everyone has a different path to recovery. For me, medication helps me hold a job, take care of my kids, stay focused in my counseling sessions, and feel normal. 4-34 Medications for Opioid Use Disorder TIP 63 based on OUD medication status, nor should that status limit a participant’s responsibilities, leadership role, or level of participation. • Meet with patients taking OUD medication in advance to prepare them for mixed- group settings. Advise them that they don’t have to disclose their medication status to the group, just as they don’t have to disclose any other health issues. Counsel them that if they choose to talk about their medication status, it helps to talk about how medication has helped shape their personal recovery. • Don’t single out patients taking OUD medication. Let participants decide whether to tell the group about any issue they want to share, including medication status. If a patient chooses to disclose that status, follow up after the session to ensure that he or she is in a positive space and feels supported. • Keep the session’s focus on the topic and not on the pros and cons of medication for OUD. If the person receiving medication for OUD or other group members have specifc questions about such medications, have them ask their healthcare professionals. • Reinforce messages of acceptance. During the wrap-up discussion at the end of a session, members may comment on points that stood out for them. This is a chance to restate information accurately and model respect for each patient’s road to recovery, whether it includes OUD medication or not. • Review confdentiality rules. Affrm that patients’ OUD medication status will not be shared with other group members. Remind participants to think carefully before sharing personal details such as their medication status with the group, because other partic- ipants may not respect confdentiality even if they have agreed to do so as part of the group guidelines. Other Common Counseling Concerns Patients must sign releases to permit ongoing conversations between care providers in accordance with federal regulations on con- fdentiality of medical records for patients in treatment for an SUD (42 CFR Part 2). When patients’ primary care providers, prescribers of medication for OUD, and addiction-specifc counselors don’t work for the same entity, patients must consent for them to share information. It can be challenging when a patient refuses to consent to collaborative communication among his or her healthcare team members. In these cases, the professionals involved must decide whether they will continue to provide either medication or counseling services without permission to collaborate. In other words, is cross-communication among all providers required for collaborative care? The answer to this complicated question depends on each patient’s circumstances. The TIP expert panel recommends communication among providers as the standard of care for OUD treatment and recovery support. Carefully consider deviations from this standard, which should occur only rarely. That said, individualize decisions about collaborative communication among providers to each patient’s unique preferences, needs, and circumstances. 4-35 TIP 63 Part 4 of 5—Bringing Together Addiction Treatment Counselors, Clients, and Healthcare Professionals Patients may not consent to communication among providers if they: • Have experienced discrimination in health- care systems. • Have developed OUD after taking opioid pain medication. • Have legitimate cause not to trust providers (e.g., perceiving themselves as having been abused by a healthcare professional).170 • Are not ready to make primary care providers aware of their disorder, even (or especially) if those providers have been prescribing opioid pain medication. • Encounter problems in making progress toward recovery. After typically consenting to communication among providers, a patient’s sudden revocation may signal trouble in recovery. Exhibit 4.16 lists common collaborative care issues and responses counselors can consider. Suggested responses assume that patients have consented to open exchange of information among all providers. EXHIBIT 4.16. Common Collaborative Care Issues and Possible Counselor Responses POTENTIAL MEDICATION- RELATED ISSUE COUNSELOR RESPONSE The patient complains of Talk with the patient about his or her medication adherence. Review continued cravings. with the patient strategies for overcoming cravings using a CBT model. Communicate with the prescriber to see whether dosage can be adjusted to subdue the cravings. A patient taking methadone Ask the patient whether drowsiness is caused by lack of sleep, does not appear engaged disturbed sleep, substance use, or overmedication. Consider in counseling sessions obtaining a spot urine test (if available). and seems drowsy during conversations. In all cases of drowsiness, alert the prescriber immediately so that the cause can be determined. This is particularly important during the frst few weeks of treatment. The patient is at risk for Inform the prescriber if the patient appears at risk for return to use return to opioid use. given cravings, life stressors, changes in social circumstances, new triggers, or the like. This alerts the prescriber to monitor the patient more closely and consider medication changes to reduce likelihood of return to use. The patient has recently returned to opioid misuse after a period of abstinence. Gather details about circumstances surrounding the incident of use and, in collaboration with the prescriber and the patient, adjust the treatment plan accordingly. Reinforce the patient’s understanding of the increased risk of opioid overdose given altered levels of tolerance. Continued on next page 4-36 Medications for Opioid Use Disorder TIP 63 EXHIBIT 4.16. Common Collaborative Care Issues and Possible Counselor Responses (continued) POTENTIAL MEDICATION- RELATED ISSUE COUNSELOR RESPONSE The patient is discussing Direct the patient to a healthcare professional for assessment of pain chronic pain with the and medical treatment as necessary. counselor. If indicated as appropriate by a healthcare professional, provide CBT for dealing with pain or instruct the patient in adjunct methods for pain relief (e.g., meditation, exercise, physical therapy). The patient is asking the Answer questions based on your knowledge of medications for counselor for medical advice treatment of OUD but don’t provide medical advice. Refer the patient on what dose to take, side to the prescriber for that. effects, how long to stay on the medication, and the like. As appropriate, contact the prescriber with the patient to have a three-way discussion. The counselor or patient is concerned that the prescriber is not giving quality care. As appropriate, advocate for the patient with the prescribing medical team. The patient discloses use of Use motivational interviewing techniques to have a collaborative other drugs. conversation about the details of this drug use. For example, give a response like “Tell me more about this,” followed by questions about the specifc drugs used, why they were used, and what the patient’s thoughts are about changing that drug use. The patient discloses that Advise the patient to contact her prescriber immediately no matter she is pregnant. what medication she is taking. Work with her to help her get access to prenatal care (if she doesn’t have it already) and other health services related to pregnancy as needed. The patient has a positive Using motivational interviewing tools, discuss with the patient the urine screen. context of the substance use and what implications this use may have for the treatment plan. 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Long-term outcomes of offce-based buprenorphine/ naloxone maintenance therapy. Drug and Alcohol Dependence, 106(1), 56–60. 4-44 Medications for Opioid Use Disorder TIP 63 160Narcotics Anonymous World Services. (2016). Narcotics Anonymous and persons receiving medication-assisted treatment. Chatsworth, CA: Author. 161Monico, L. B., Gryczynski, J., Mitchell, S. G., Schwartz, R. P., O’Grady, K. E., & Jaffe, J. H. (2015). Buprenorphine treatment and 12-step meeting attendance: Conficts, compatibilities, and patient outcomes. Journal of Substance Abuse Treatment, 57, 89–95. 162White, W., Galanter, M., Humphreys, K., & Kelly, J. (2016). The paucity of attention to Narcotics Anonymous in current public, professional, and policy responses to rising opioid addiction. Alcoholism Treatment Quarterly, 34(4), 437–462. 163Kelly, J. F., Greene, M. C., & Bergman, B. G. (2014). Do drug-dependent patients attending Alcoholics Anonymous rather than Narcotics Anonymous do as well? 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MEDICATIONS FOR OPIOID USE DISORDERTIP 63 Substance Abuse and Mental Health Services Administration Part 5: Resources Related to Medications for Opioid Use Disorder For Healthcare and Addiction Professionals, Policymakers, Patients, and Families Part 5 of this Treatment Improvement Protocol (TIP) provides a collection of resources by audience and a glossary of key terms to help readers better understand how Food and Drug Administration (FDA)-approved medications can be used to treat opioid use disorder (OUD). TIP Navigation Executive Summary For healthcare and addiction professionals, policymakers, patients, and families Part 1: Introduction to Medications for Opioid Use Disorder Treatment For healthcare and addiction professionals, policymakers, patients, and families Part 2: Addressing Opioid Use Disorder in General Medical Settings For healthcare professionals Part 3: Medications for Opioid Use Disorder For healthcare professionals Part 4: Bringing Together Addiction Treatment Counselors, Clients, and Healthcare Professionals For healthcare and addiction professionals Part 5: Resources Related to Medications for Opioid Use Disorder For healthcare and addiction professionals, policymakers, patients, and families KEY MESSAGES • Practice guidelines and decision-making tools can help healthcare professionals with OUD screening, assessment, diagnosis, treatment planning, and referral. • Patient- and family-oriented resources provide information about opioid addiction in general; the role of medication, behavioral and supportive services, and mutual-help groups in the treatment of OUD; how-tos for identifying recovery support services; and how- tos for locating medical and behavioral health service providers who specialize in treating OUD or other substance use disorders (SUDs). 5-ii TIP 63 MEDICATIONS FOR OPIOID USE DISORDER—Part 5 of 5 Contents General Resources 5-1 Facts and Figures 5-1 Groups and Organizations 5-2 SAMHSA Publications 5-3 General Information 5-4 Practice Guidelines and Decision-Support Tools 5-8 Assessment Scales and Screening Tools 5-9 Resources for Counselors and Peer Providers 5-10 Organizations 5-10 Publications and Other Resources 5-11 Resources for Clients and Families 5-12 Organizations 5-12 Publications and Other Resources 5-13 Treatment Locators 5-14 Patient Success Stories 5-15 Online Boards and Chat Rooms 5-15 Provider Tools and Sample Forms 5-16 Provider Screening and Assessment Tools and Aids 5-16 TAPS Tool Part I 5-25 TAPS Tool Part 2 5-26 Provider Informational, Educational, and Decision-Making Tools 5-30 Sample Provider Forms 5-41 Pharmacy Tablet/Film Count Form 5-45 Glossary of TIP Terminology 5-56 Notes 5-59 5-1 MEDICATIONS FOR OPIOID USE DISORDERTIP 63 PART 5 of 5 Resources Related to Medications for Opioid Use Disorder There are numerous resources to help healthcare professionals and behavioral health service providers better understand the use of FDA-approved medications for OUD. Many other resources are available to help patients, their families and friends, and the general public better understand OUD and the medications available to treat it and support recovery from it. Part 5 of this TIP provides an audience-segmented collection of resources and a glossary of key terms related to OUD. It is of use to all interested readers. General Resources Facts and Figures American Association for the Treatment of Opioid Dependence (AATOD), Frequently Asked Questions (www.aatod.org/resources /frequently-asked-questions). Centers for Disease Control and Prevention (CDC), Smoking & Tobacco Use (www.cdc.gov /tobacco/index.htm). Legal Action Center (LAC), Medication- Assisted Treatment for Opioid Addiction: Myths and Facts (www.lac.org/assets/fles/Myth- Fact-for-MAT.pdf). Missouri Department of Mental Health, Methadone Maintenance Myths and Resources (https://dmh.mo.gov/media/pdf/methadone- maintenance-myths-and-resources). National Institute on Drug Abuse (NIDA) (www.drugabuse.gov): • Addiction Science (www.drugabuse.gov /related-topics/addiction-science). Provides two short videos that explain the nature Opioid overdose caused 49,860 DEATHS nationwide in 2019— this exceeded the # caused by motor vehicle crashes.1,2 of addiction. These are useful in educating people in primary care who suffer from addiction. This site has links to publications for professionals that explain the nature of addiction. • NIDAMED, Medical and Health Professionals (www.drugabuse.gov/nidamed-medical -health-professionals). Disseminates science- based resources to healthcare professionals on the causes and consequences of drug use and addiction and advances in pain management. 5-2 Medications for Opioid Use Disorder TIP 63 Offce of National Drug Control Policy, Medication-Assisted Treatment for Opioid Addiction (https://adai.uw.edu/pubs/infobriefs/ ondcpMATbrief.pdf): Offers a factsheet with a useful summary of medication for OUD and its effectiveness. Partnership for Drug-Free Kids, Commentary: Countering the Myths About Methadone (www.drugfree.org/news-service/commentary -countering-the-myths-about-methadone). Substance Abuse and Mental Health Services Administration (SAMHSA): • Addiction Technology Transfer Center (ATTC) (http://attcnetwork.org/home). Network with 10 regional centers across the country that provide training and information on evidence-based practices to practitioners. The ATTC website contains information and resources about OUD medication for clinicians, patients, and family members (https://attcnetwork.org/centers/global-attc/ taking-action-address-opioid-misuse). • State Opioid Treatment Authorities (SOTAs) (https://dpt2.samhsa.gov/regulations/smalist .aspx). United States Surgeon General’s Report, Facing Addiction in America: The Surgeon General’s Report on Alcohol, Drugs, and Health (https://addiction.surgeongeneral.gov). Groups and Organizations AATOD (www.aatod.org): Works with federal and state agencies on opioid treatment policy throughout the United States. Convenes con- ferences every 18 months on evidence-based clinical practice, current research, and organiza- tional developments related to OUD treatment. AATOD develops publications that serve as resources for addiction counselors and peer support providers. American Academy of Addiction Psychiatry (AAAP) (www.aaap.org): Offers education and training materials on addiction psychiatry (e.g., webinars, continuing medical education courses). American Society of Addiction Medicine (ASAM) (www.asam.org): Provides medical education and resources on the treatment of SUDs, including OUD. LAC (https://lac.org): Offers information about the rights of people with criminal records, HIV/AIDS, and SUDs. National Alliance for Medication Assisted Recovery (NAMA Recovery) (www.methadone .org): Supports quality opioid agonist treatment through its many U.S. chapters and its interna- tional network of affliate chapters. Thousands of methadone clients and healthcare professionals belong to the organization. National Alliance of Advocates for Buprenorphine Treatment (www.naabt.org): Aims to educate the public about opioid addiction and buprenorphine as a treatment option, to reduce prejudice and discrimination against clients who have SUDs, and to connect clients in need to qualifed treatment providers. SAMHSA (www.samhsa.gov): • Buprenorphine Practitioner Verifcation for Pharmacists (www.samhsa.gov/bupe /lookup-form) • National Recovery Month (https://recovery month.gov) • Opioid Treatment Program (OTP) Directory (https://dpt2.samhsa.gov/treatment) • SOTAs (https://dpt2.samhsa.gov/regulations /smalist.aspx) 5-3 TIP 63Part 5 of 5—Resources Related to Medications for Opioid Use Disorder SAMHSA Publications • Clinical Guidance for Treating Pregnant All publications listed in this section are available for free from SAMHSA’s publications ordering webpage (https://store.samhsa.gov) or by calling 1-877-SAMHSA-7 (1-877-726-4727): • TIP 42: Substance Use Disorder Treatment for People With Co-Occurring Disorders (https://store.samhsa.gov/product /TIP-42-Substance-Abuse-Treatment-for -Persons-With-Co-Occurring-Disorders /SMA13-3992) • TIP 54: Managing Chronic Pain in Adults With or in Recovery From Substance Use Disorders (https://store.samhsa.gov/product/TIP-54 -Managing-Chronic-Pain-in-Adults-With-or -in-Recovery-From-Substance-Use-Disorders /SMA13-4671) • TIP 57: Trauma-Informed Care in Behavioral Health Services (https://store.samhsa.gov /product/TIP-57-Trauma-Informed-Care-in -Behavioral-Health-Services/SMA14-4816) • Advisory: An Introduction to Extended- Release Injectable Naltrexone for the Treatment of People With Opioid Dependence (https://store.samhsa.gov /product/An-Introduction-to-Extended -Release-Injectable-Naltrexone-for-the -Treatment-of-People-with-Opioid -Dependence/SMA12-4682) • Advisory: Sublingual and Transmucosal Buprenorphine for Opioid Use Disorder: Review and Update (https://store.samhsa.gov/product/ Advisory-Sublingual-and-Transmucosal- Buprenorphine-for-Opioid-Use-Disorder-/ SMA16-4938) • Buprenorphine Quick Start Guide (www.samhsa.gov/sites/default/fles/quick- start-guide.pdf) • Buprenorphine Quick Start Pocket Guide (www.samhsa.gov/sites/default/fles/quick- start-pocket.pdf) and Parenting Women With Opioid Use Disorder and Their Infants (https://store. samhsa.gov/product/Clinical-Guidance-for- Treating-Pregnant-and-Parenting-Women- With-Opioid-Use-Disorder-and-Their-Infants/ SMA18-5054) • Clinical Use of Extended-Release Injectable Naltrexone in the Treatment of Opioid Use Disorder: A Brief Guide (https://store.samhsa.gov/product/ Clinical-Use-of-Extended-Release- Injectable-Naltrexone-in-the-Treatment- of-Opioid-Use-Disorder-A-Brief-Guide/ SMA14-4892R) • A Collaborative Approach to the Treatment of Pregnant Women With Opioid Use Disorders (https://store.samhsa.gov/product/A -Collaborative-Approach-to-the-Treatment -of-Pregnant-Women-with-Opioid-Use -Disorders/SMA16-4978) • Decisions in Recovery: Treatment for Opioid Use Disorders, Handbook (https://store .samhsa.gov/product/SMA16-4993) • Integrated Treatment for Co-Occurring Disorders Evidence-Based Practices (EBP) Kit (https://store.samhsa.gov/product/ Integrated-Treatment-for-Co-Occurring- Disorders-Evidence-Based-Practices-EBP-KIT/ SMA08-4366) • Technical Assistance Publication 32: Clinical Drug Testing in Primary Care (https://store.samhsa.gov/product/tap- 32-clinical-drug-testing-primary-care/ sma12-4668) • What Are Peer Recovery Support Services? (https://store.samhsa.gov/product/What- Are-Peer-Recovery-Support-Services-/ sma09-4454) 5-4 Medications for Opioid Use Disorder TIP 63 General Information Agency for Healthcare Research and Quality: • Medication-Assisted Treatment Models of Care for Opioid Use Disorder in Primary Care Settings (www.ncbi.nlm.nih.gov/books /NBK402352) • Academy for Integrating Behavioral Health and Primary Care (https://integrationacademy .ahrq.gov) American Academy of Family Physicians: • Chronic Pain Management and Opioid Misuse: A Public Health Concern (Position Paper) (www.aafp.org/about/policies/all/pain -management-opioid.html) • Pain Management and Opioid Use Resources (www.aafp.org/patient-care/public-health /pain-opioids/resources.html) ATTC Network (http://attcnetwork.org/home): This nationwide network of SAMHSA-sponsored regional centers is a multidisciplinary resource for professionals in the addiction treatment and recovery services felds. The network has many valuable resources and projects of interest to people involved in treating SUDs. Of particular interest to readers of this TIP are the training programs produced as part of the NIDA/ SAMHSA-ATTC Blending Initiative: • Buprenorphine Treatment: Training for Multidisciplinary Addiction Professionals (https://attcnetwork.org/centers/global-attc/ product/buprenorphine-treatment-train- ing-multidisciplinary-addiction) • Buprenorphine Treatment for Young Adults (https://attcnetwork.org/centers/ network-coordinating-offce/product/ buprenorphine-treatment-young-adults) • Prescription Opioid Addiction Treatment Study (POATS) (https://attcnetwork.org/ centers/network-coordinating-offce/ product/prescription-opioid-addiction-treat- ment-study-poats) BupPractice.com Federal Recordkeeping Requirements for Buprenorphine Treatment (https://docs.clinicaltools.com/pdf/Buppractice/ V5-Bup-How-To-Comply.pdf): Provides informa- tion about federal recordkeeping requirements. CDC Smoking & Tobacco Use (www.cdc.gov /tobacco/index.htm): Includes resource links for clinicians on smoking and the treatment of tobacco use. Centers for Medicare & Medicaid Services (www.cms.gov/Medicare/Medicare-General -Information/Telehealth/index.html): Gives guidance on the delivery of telehealth. Department of Health and Human Services (HHS): • Centers for Medicare & Medicaid Services Clinical Laboratory Improvement Amendments Application for Certifcation (www.cms.gov/Medicare/CMS-Forms/CMS -Forms/downloads/cms116.pdf) • Medication Assisted Treatment for Opioid Use Disorders: Final Rule (www.federalregister .gov/documents/2016/07/08/2016-16120 /medication-assisted-treatment-for-opioid -use-disorders) Drug Enforcement Administration (DEA): • DEA Requirements for DATA Waived Physicians (www.deadiversion.usdoj.gov/pubs/ docs/index.html). Lists DEA requirements for Drug Addiction Treatment Act of 2000 (DATA 2000)-waivered healthcare professionals. • Form DEA-106, Report of Theft or Loss of Controlled Substances (https://apps .deadiversion.usdoj.gov/webforms/dtlLogin .jsp). Provides instructions for completing form DEA-106, which must be fled when stored buprenorphine is lost or stolen. Drugs.com: • Buprenorphine Drug Interactions (www.drugs .com/drug-interactions/buprenorphine-index .html?flter=3&generic_only=) • Drug Interactions Checker (www.drugs.com /drug_interactions.php) 5-5 TIP 63Part 5 of 5—Resources Related to Medications for Opioid Use Disorder FDA: • Approved Risk Evaluation and Mitigation Strategy (REMS): Buprenorphine Transmucosal Products for Opioid Dependence (www .accessdata.fda.gov/scripts/cder/rems/index .cfm?event=RemsDetails.page&REMS=9) • REMS: Probuphine (buprenorphine hydro- chloride) (www.accessdata.fda.gov/scripts /cder/rems/index.cfm?event=IndvRemsDetails .page&REMS=356) • REMS: Sublocade (extended-release injectable buprenorphine) (www.accessdata.fda.gov /scripts/cder/rems/index.cfm?event =IndvRemsDetails.page&REMS=376) • REMS: Suboxone/Subutex (buprenorphine and naloxone/buprenorphine) (www.accessdata .fda.gov/scripts/cder/rems/index.cfm?event =IndvRemsDetails.page&REMS=352) • REMS: Vivitrol (extended-release naltrexone [XR-NTX]) (www.vivitrolrems.com) LAC (https://lac.org): LAC attorneys provide legal advice by phone to service providers and government agencies. They assist dozens of agencies annually with questions about conf- dentiality of treatment records, discrimination, and other issues. LAC’s confdentiality hotline provides information about the federal law protecting the confdentiality of drug and alcohol treatment and prevention records (42 CFR Part 2). The hotline is free to New York treatment providers and government agencies. Outside New York, the hotline is accessible if the state alcohol/drug oversight agency subscribes to LAC’s Actionline service. To speak with a hotline attorney, call LAC Monday through Friday 1−5 p.m. (Eastern Time Zone) at 1-212-243-1313, or toll-free at 1-800-223-4044. National Alliance of Advocates for Buprenorphine Treatment 30−100 Patient Limit (www.naabt.org/30_patient_limit.cfm): Summarizes the DATA 2000 law. National Association of State Controlled Substances Authorities State Profles (www .nascsa.org/stateprofles.htm): Contains a directory of each state’s prescription drug monitoring program (PDMP). National Conference of State Legislatures Drug Overdose Immunity and Good Samaritan Laws (www.ncsl.org/research/civil-and-criminal -justice/drug-overdose-immunity-good-samaritan -laws.aspx): Provides information about naloxone and Good Samaritan immunity. National Institute on Alcohol Abuse and Alcoholism (NIAAA) Professional Education Materials (www.niaaa.nih.gov/publications /clinical-guides-and-manuals): Provides professional education materials; offers links to screening, treatment planning, and general information for clinicians in outpatient programs. National Library of Medicine’s DailyMed: • FDA label information for methadone (https:// dailymed.nlm.nih.gov/dailymed/search .cfm?labeltype=all&query=METHADONE) • FDA label information for XR-NTX (https:// dailymed.nlm.nih.gov/dailymed/drugInfo.cfm ?setid=cd11c435-b0f0-4bb9-ae78 -60f101f3703f) NIDA: • Available Treatments for Marijuana Use Disorders (www.drugabuse.gov/publications /research-reports/marijuana/available -treatments-marijuana-use-disorders). Provides information about treatment options for individuals with marijuana use disorder. • Naloxone for Opioid Overdose: Life-Saving Science (www.drugabuse.gov/publications/ naloxone-opioid-overdose-life-saving-science). Contains naloxone information for providers. • NIDAMED, Clinical Resources (www. drugabuse.gov/nidamed-medical-health- professionals). Provides practice-related and professional education-related resources. 5-6 Medications for Opioid Use Disorder TIP 63 • Medications To Treat Opioid Addiction (www .drugabuse.gov/publications/research-reports /medications-to-treat-opioid-addiction /overview). Provides an overview of the need for and effcacy of OUD medications and discusses common misconceptions, impacts on outcome, and use of OUD medications with certain specifc populations. • Effective Treatments for Opioid Addiction (www.drugabuse.gov/publications /effective-treatments-opioid-addiction /effective-treatments-opioid-addiction). • Therapeutic Communities (www.drugabuse .gov/publications/research-reports /therapeutic-communities/what-are -therapeutic-communities). Gives a brief overview of OUD medications and links to additional information. • Principles of Drug Addiction Treatment: A Research-Based Guide (www.drugabuse.gov /publications/principles-drug-addiction -treatment-research-based-guide-third -edition/preface). Discusses how OUD affects the brain and covers the state of addiction treatment in the United States, principles of effective treatment, frequently asked questions about OUD medication, evi- dence-based approaches to treatment, and additional resources. • Principles of Adolescent Substance Use Disorder Treatment: A Research-Based Guide (www.drugabuse.gov/publications/principles -adolescent-substance-use-disorder-treatment -research-based-guide/introduction). Discusses principles of SUDs in adolescents, addresses frequently asked questions, summa- rizes treatment settings and evidence-based treatment approaches, and provides treatment referral resources. • Treating Opioid Use Disorder During Pregnancy (www.drugabuse.gov/publications /treating-opioid-use-disorder-during -pregnancy/treating-opioid-use-disorder -during-pregnancy). Addresses the risks of OUD to the pregnant woman and the fetus, briefy summarizes OUD pharmacotherapies for use during pregnancy, and provides links to additional information. North American Syringe Exchange Program (https://nasen.org/directory): Provides a national directory of syringe exchange programs in the United States. Prescription Drug Abuse Policy System’s Naloxone Overdose Prevention Laws (http://pdaps.org/datasets/laws-regulating -administration-of-naloxone-1501695139): Provides a map with a link to each state’s naloxone overdose prevention laws, including policies on prescribing, dispensing, and civil and criminal immunity. Project Lazarus’s Naloxone: The Overdose Antidote (www.projectlazarus.org/naloxone): Provides guidance on administering naloxone. Providers’ Clinical Support System’s (PCSS’s) How To Prepare for a Visit From the Drug Enforcement Agency Regarding Buprenorphine Prescribing (http://pcssmat .org/wp-content/uploads/2014/02/FINAL-How -to-Prepare-for-a-DEA-Inspection.pdf): Provides a description of the DEA inspection process and how to comply with its requirements. SAMHSA: • Understanding the Final Rule for a Patient Limit of 275 (www.samhsa.gov/medication-as- sisted-treatment/training-materials-resources/ apply-for-practitioner-waiver). Provides infor- mation about the fnal rule and how to use it to increase patient access to medication for OUD and associated reporting requirements. 5-7 TIP 63Part 5 of 5—Resources Related to Medications for Opioid Use Disorder • Buprenorphine Quick Start Guide (www. samhsa.gov/sites/default/fles/quick-start- guide.pdf). Provides a checklist to guide healthcare professionals in prescribing buprenorphine, managing withdrawal, and providing maintenance therapy. • Buprenorphine Quick Start Pocket Guide (www.samhsa.gov/sites/default/fles/quick- start-pocket.pdf): Provides a one-page fow chart for induction onto buprenorphine. • Buprenorphine Practice Guidelines (www. federalregister.gov/documents/2021/04/ 28/2021-08961/practice-guidelines-for-the-ad- ministration-of-buprenorphine-for-treat- ing-opioid-use-disorder). Provides information about how providers may become exempt from training and psychosocial service attesta- tion requirements for obtaining a SAMHSA X waiver. • Buprenorphine Waiver Management (www. samhsa.gov/medication-assisted-treatment/ training-materials-resources/apply-for-prac- titioner-waiver). Provides information on the buprenorphine waiver, including links to the buprenorphine waiver application and an explanation of the processes, requirements, and recordkeeping strategies associated with prescribing buprenorphine. • Qualify for Nurse Practitioners (NPs) and Physician Assistants (PAs) Waiver (www. samhsa.gov/medication-assisted-treatment/ training-materials-resources/apply-for- practitioner-waiver). Provides information for NPs and PAs about the buprenorphine waiver training, with links to trainings and the appli- cation process. • Buprenorphine Training for Physicians (www. samhsa.gov/medication-assisted-treatment/ training-materials-resources/apply-for-prac- titioner-waiver). Offers links to organizations that provide buprenorphine training for physicians. • SAMHSA Opioid Overdose Prevention Toolkit (https://store.samhsa.gov/product/Opioid- Overdose-Prevention-Toolkit/SMA18-4742). Prepares healthcare professionals, communi- ties, and local governments with material to develop practices and policies to help prevent opioid-related overdoses and deaths. It addresses issues for healthcare professionals, frst responders, treatment providers, and those recovering from opioid overdose. • Federal Guidelines for Opioid Treatment Programs (https://store.samhsa.gov/product /Federal-Guidelines-for-Opioid-Treatment -Programs/PEP15-FEDGUIDEOTP). Provides updated guidelines for how OTPs can satisfy the federal regulations. • Form SMA-168 Opioid Treatment Exception Request (www.samhsa.gov/medication -assisted-treatment/opioid-treatment -programs/submit-exception-request). Provides instructions for physicians on how to request exceptions to federal standards for opioid treatment. • Laws and Regulations (www.samhsa.gov /about-us/who-we-are/laws-regulations). Provides an overview and summary of the most frequent questions about disclosure and patient records pertaining to substance use treatment that federal programs maintain. • Substance Abuse in Brief Fact Sheet: Introduction to Mutual-Support Groups for Alcohol and Drug Abuse (http://www. williamwhitepapers.com/pr/CSAT%20 Mutual%20Support%20Groups%202008.pdf). Provides information to help medical and behavioral health service providers understand mutual-help groups and how to make referrals to such groups. 5-8 Medications for Opioid Use Disorder TIP 63 • SAMHSA has developed several resources to guide healthcare professionals in their use of telehealth and telemedicine approaches for OUD: − In Brief: Rural Behavioral Health: Telehealth Challenges and Opportunities (https://store.samhsa.gov/product/ In-Brief-Rural-Behavioral-Health- Telehealth-Challenges-and-Opportunities/ SMA16-4989) − Certifed Community Behavioral Health Clinics (CCBHCs) Using Telehealth or Telemedicine (www.samhsa.gov/section -223/care-coordination/telehealth -telemedicine) Practice Guidelines and Decision- Support Tools ASAM: • Appropriate Use of Drug Testing in Clinical Addiction Medicine (http:// download.lww.com / wolterskluwer_vitalstream_com/PermaLink /JAM/A/JAM_11_3_2017_06_02_SAFARIAN _JAM-D-17-00020_SDC1.pdf). Details the ASAM consensus statement on drug testing in addiction treatment. • The ASAM National Practice Guideline: For the Use of Medication in the Treatment of Addiction Involving Opioid Use (www.asam .org/docs/default-source/practice-support /guidelines-and-consensus-docs/asam -national-practice-guideline-supplement .pdf). Provides information on prescribing methadone, buprenorphine, naltrexone, and naloxone. The document also discusses the needs of special populations, including women during pregnancy, patients with chronic pain, adolescents, individuals in the criminal justice system, and patients with co-occurring psychiatric conditions. CDC: • CDC Guideline for Prescribing Opioids for Chronic Pain (www.cdc.gov/drugoverdose /prescribing/guideline.html). • Guideline Resources: Clinical Tools (www.cdc .gov/drugoverdose/prescribing/clinical-tools .html). Provides links and tools to help clinicians prevent opioid overdose deaths. Credible Meds (www.crediblemeds.org): Maintains a list of medications that may increase QTc intervals. Free registration is required to access the most up-to-date list. HHS: • BeTobaccoFree.gov News and Resources (https://betobaccofree.hhs.gov/quit-now /index.html#professionals). Offers links for clinicians that provide guidance on the care for patients with nicotine addiction. The Resources section is at the bottom of the page linked here. • BeTobaccoFree.gov Nicotine Addiction and Your Health (https://betobaccofree.hhs.gov/). Provides information on nicotine addiction and its health effects. Institute for Research, Evaluation, and Training in Addictions’ Management of Benzodiazepines in Medication-Assisted Treatment (https://ireta.org/wp-content/ uploads/2018/03/BP_Guidelines_for_ Benzodiazepines.pdf): Provides information on managing benzodiazepine use in patients taking medications for OUD. PCSS for Medication Assisted Treatment (https://pcssnow.org/): Provides buprenorphine waiver training for clinicians (physicians, NPs, and PAs). PCSS Mentoring Program (https://pcssnow. org/mentoring/): Gives providers guidance on prescribing OUD medications. This national network of experienced providers is available at no cost. Mentors provide support by telephone, email, or in person if possible. 5-9 TIP 63Part 5 of 5—Resources Related to Medications for Opioid Use Disorder PCSS Models of Buprenorphine Induction (http://pcssmat.org/wp-content/uploads/ 2015/02/Buprenorphine-Induction-Online- Module.pdf): Provides information about various buprenorphine induction approaches including in-offce, non-OTP, and at-home dosing. Prescribe To Prevent (http://prescribeto prevent.org): Provides information about naloxone prescribing for overdose prevention, including educational patient handouts and videos. SAMHSA: • Buprenorphine (www.samhsa.gov/medication -assisted-treatment/treatment/buprenorphine). • Naltrexone (www.samhsa.gov/medication -assisted-treatment/treatment/naltrexone). • Decisions in Recovery: Treatment for Opioid Use Disorder, Planning for Success (https:// store.samhsa.gov/product/Decisions- in-Recovery-Treatment-for-Opioid-Use- Disorders/SMA16-4993). Provides assistance in developing a recovery plan. • Bringing Recovery Supports to Scale Technical Assistance Center Strategy (www.samhsa.gov /brss-tacs) and Shared Decision-Making Tools (www.samhsa.gov/brss-tacs/recovery-support -tools/shared-decision-making). Offers training and technical assistance on many topics related to medication for OUD, including recovery- oriented systems of care, mutual-support groups, capacity building, leadership by people in recovery and family members, certifcation requirements for peer specialists and mutual- support group coaches, and core competencies for recovery-oriented behavioral health workers. • Pharmacologic Guidelines for Treating Individuals With Post-Traumatic Stress Disorder and Co-Occurring Opioid Use Disorders (https://store.samhsa.gov/ product/pharmacologic-guidelines- treating-individuals-post-traumatic-stress- disorder-co-occurring). Veterans Administration (VA)/Department of Defense (DoD) Clinical Practice Guideline for the Management of Substance Use Disorders (www.healthquality.va.gov/guidelines/MH/ sud/VADoDSUDCPGRevised22216.pdf): Provides information on screening, assessment, and treatment of OUD as well as other SUDs. It is primarily for VA and DoD healthcare providers and others involved in the care of service members or veterans with an SUD. Assessment Scales and Screening Tools AAAP, Education & Training (www.aaap.org/ education/educational-opportunities/): Provides Performance-in-Practice Clinical Modules for alcohol use disorder and tobacco use disorder. American Psychiatric Nurses Association, Tobacco & Nicotine Use Screening Tools & Assessments (www.apna.org/i4a/pages/index .cfm?pageID=6150): Provides the Fagerström screening tools for nicotine dependence and smokeless tobacco and a screening checklist for adolescent tobacco use. ASAM Appropriate Use of Drug Testing in Clinical Addiction Medicine (www.asam.org/ Quality-Science/quality/drug-testing): Gives in- formation on the appropriate use of drug testing in identifying, diagnosing, and treating people with or at risk for SUDs. Clinical Institute Narcotic Assessment Scale for Withdrawal Symptoms (www.ncpoep.org /wp-content/uploads/2015/02/Appendix_7 _Clinical_Institute_Narcotic_Assessment_CINA _Scale_for_Withdrawal_Symptoms.pdf). • General Principles for the Use of Pharmacological Agents To Treat Individuals With Co-Occurring Mental and Substance Use Disorders (https://store.samhsa.gov/ sites/default/files/d7/priv/sma12-4689.pdf). 5-10 Medications for Opioid Use Disorder TIP 63 NIDA, Screening Tools and Prevention (www. drugabuse.gov/nidamed-medical-health- professionals/screening-tools-prevention): Gives resources such as an evidence-based screening tool chart for adolescents and adults and drug use screening tool supports; also has a clinician resource and quick reference guide for drug screening in general medical settings. U.S. Preventive Services Task Force Final Recommendation Statement— Unhealthy Drug Use: Screening (https:// uspreventiveservicestaskforce.org/uspstf/ recommendation/drug-use-illicit-screening): Includes recommendations about the screening of adults in primary care for illicit drug use and prescription medication misuse. World Health Organization Guidelines for the Psychosocially Assisted Pharmacological Treatment of Opioid Dependence (www.ncbi .nlm.nih.gov/books/NBK143183): Includes links to the Clinical Opiate Withdrawal Scale (www.drugabuse.gov/sites/default/fles/fles /ClinicalOpiateWithdrawalScale.pdf) and other opioid withdrawal scales from Annex 10 of the guidelines. Resources for Counselors and Peer Providers Organizations Community Care Behavioral Health Organization (www.ccbh.com): A provider network focused on recovery that has published Supporting Recovery From Opioid Addiction: Community Care Best Practice Guidelines for Recovery-Oriented Methadone Maintenance (www.williamwhitepapers.com/pr/Recovery- oriented%20Methadone%20Maintenance%20 Best%20Practice%20Guidelines%202014%20 -%20CCBHO.pdf), a set of recovery-orient- ed practice implementation guidelines for methadone programs. Faces & Voices of Recovery (https://facesand voicesofrecovery.org): Dedicated to organizing and mobilizing the millions of Americans in recovery from addiction to alcohol and drugs, their families and friends, and other allies into recovery community organizations and networks. Faces & Voices of Recovery promotes the right resources to recover through advocacy, education, and demonstration of the power and proof of long-term recovery. Medication-Assisted Recovery Services (MARS) Project (www.marsproject.org): A peer-initiated, peer-based recovery support project sponsored by NAMA Recovery that offers, among other resources, an educational video about the MARS peer support program and an online network for MARS peer support personnel: • MARS Project Video (www.marsproject.org). • New York State Peer Recovery Network, Peers Organizing for Results Through Advocacy and Leadership (PORTAL) (http://marsproject. org/). Created to help peers in recovery more effectively organize their communities, communicate with each other, and create a stronger voice for advocacy efforts. National Association of Peer Supporters (www. inaops.org/): An organization for mental health and addiction peer recovery support specialists, recovery coaches, recovery educators and trainers, administrators of consumer-operated or peer-run organizations, and others. Pillars of Peer Support Services (www.pillarsof peersupport.org): Develops and fosters the use of Medicaid funding to support peer recovery services in state mental health systems of care. Recovery Community Services Program— Statewide Network (www.samhsa.gov/grants /grant-announcements/ti-14-001): A SAMHSA grant program for peer-to-peer recovery support services that help people initiate and sustain recovery from SUDs. 5-11 TIP 63Part 5 of 5—Resources Related to Medications for Opioid Use Disorder Publications and Other Resources ATTC’s Recovery-Oriented Methadone Maintenance (http://www.williamwhitepa- pers.com/pr/2011%20Bamber-White%20 Dialogue%20on%20Recovery-Oriented%20 Methadone%20Maintenace.pdf): This guide is the most thorough document on this topic currently available and is applicable to clients receiving other medications for OUD. Community Care Behavioral Health Organization: These publications outline phase- specifc tasks and accompanying strategies for programs that serve clients who take methadone or buprenorphine: • Supporting Recovery From Opioid Addiction: Community Care Best Practice Guidelines for Recovery-Oriented Methadone Maintenance (www.williamwhitepapers.com/pr/Recovery -oriented%20Methadone%20Maintenance %20Best%20Practice%20Guidelines%20 2014%20-%20CCBHO.pdf). • Supporting Recovery From Opioid Addiction: Community Care Best Practice Guidelines for Buprenorphine and Suboxone (http://www. williamwhitepapers.com/pr/Community%20 Care%20Best%20Practice%20Guidelines%20 for%20Buprenorphine%20and%20 Suboxone%202014.pdf). Narcotics Anonymous (NA) (www.na.org): The organization’s most recent statement on medi- cations for treating OUD—Narcotics Anonymous and Persons Receiving Medication-Assisted Treatment—is available online (www.na.org /admin/include/spaw2/uploads/pdf/pr/2306 _NA_PRMAT_1021.pdf). SAMHSA (https://store.samhsa.gov): This agency oversees medications to treat opioid addiction, including methadone, buprenorphine, and naltrexone; sets regulations; guides policy; and offers information and resources for the feld. SAMHSA has many recovery-oriented publications for providers: • Medication-Assisted Recovery: Medication Assisted Peer Recovery Support Services Meeting Report (www.samhsa.gov/sites /default/fles/programs_campaigns /medication_assisted/dear_colleague _letters/2015-prss-summary-report.pdf). • Financing Recovery Support Services: Review and Analysis of Funding Recovery Support Services and Policy Recommendations (https://facesandvoicesofrecovery.org/wp- content/uploads/2019/06/Financing- Recovery-Support-Services.pdf). • SAMHSA’s Working Defnition of Recovery (https://store.samhsa.gov/product/ SAMHSA-s-Working-Defnition-of-Recovery/ PEP12-RECDEF). • Access to Recovery Approaches to Recovery- Oriented Systems of Care (http://www.william- whitepapers.com/pr/ATR%20Approaches%20 to%20ROSC%202009.pdf). • Building Bridges—Co-Occurring Mental Illness and Addiction: Consumers and Service Providers, Policymakers, and Researchers in Dialogue (https://permanent.access.gpo.gov/ lps80206/SMA04-3892.pdf). Selected Papers of William L. White (www .williamwhitepapers.com): Contains papers, monographs, and presentations on recovery, including recovery-oriented methadone main- tenance, methadone and anti-medication bias, discrimination and methadone, NA and the pharmacotherapeutic treatment of OUD, and co-participation in 12-Step mutual-support groups and methadone maintenance. 5-12 Medications for Opioid Use Disorder TIP 63 Resources for Clients and Families Organizations AATOD (www.aatod.org): Offers a variety of resources, news releases about medication for the treatment of OUD, and information about its national conferences. Al-Anon Family Groups (www.al-anon.org): Describes group meetings where friends and family members of people with substance use issues share their experiences and learn how to apply the principles of the Al-Anon program to their individual situations. Sponsorship gives members the chance to get personal support from more experienced individuals in the program. Alcoholics Anonymous (AA) (www.aa.org): Offers group meetings for people who have problems relating to drinking and wish to stop. AA sponsors provide members with more personal support from experienced individuals. Many people who are taking medication to treat OUD fnd AA increasingly receptive to their decisions about medication, and AA meetings are more widely available to these individuals. ASAM: Provides patient and family education tools about addiction in general and OUD specifcally: • Patient Resources (www.asam.org/resources /patientresources) • Opioid Addiction Treatment: A Guide for Patients, Families, and Friends (http://eguideline.guidelinecentral.com /i/706017-asam-opioid-patient-piece/0?) Double Trouble in Recovery (http://www.bhevo- lution.org/public/doubletroubleinrecovery.page): Describes a fellowship of people who support each other in recovering from substance use and mental disorders. Dual Recovery Anonymous (www.draonline.org): Presents information on mutual-help organiza- tion that follows 12-Step principles in supporting people recovering from addiction and emotional or mental illness. Focuses on preventing relapse and actively improving members’ quality of life through a community of mutual support. Faces & Voices of Recovery (https://facesand voicesofrecovery.org): Offers recovery stories, news, events information, publications, and webinars. Heroin Anonymous (https://heroinanonymous. org/): Describes a nonproft fellowship of individuals in recovery from heroin addiction committed to helping each other stay sober. This organization holds local support meetings, a directory of which can be found on its website. LAC (https://lac.org): Offers information about the rights of people with criminal records, HIV/AIDS, and SUDs. Learn to Cope (www.learn2cope.org): Describes a secular mutual-help group that offers education, resources, and peer support for the families of people with SUDs (although the focus is primarily on OUD). The organization maintains an online forum, but groups are only available in a few states. NA (www.na.org): Provides a global, community- based organization with a multilingual, multi- cultural membership that supports addiction recovery via a 12-Step program, including regular group meeting attendance. Members hold nearly 67,000 meetings weekly in 139 countries. NA is an ongoing support network for maintaining a drug-free lifestyle. NA doesn’t focus on a particular addictive substance. NAMA Recovery (www.methadone.org): Offers an education series, provides training and certifcation for Certifed MAT Advocates, and has local chapters and international affliates that act to advocate for methadone patients. It has a helpful webpage titled FAQs About Advocate Training and Certifcation (www.methadone.org /certifcation/faq.html). 5-13 TIP 63Part 5 of 5—Resources Related to Medications for Opioid Use Disorder Nar-Anon Family Groups (www.nar-anon.org): Provides group meetings where friends and family of people with drug use problems can share their experiences and learn to apply the 12-Step Nar-Anon program to their lives. Nar-Anon groups also offer more individualized support from experienced individuals in the program who act as sponsors. National Alliance on Mental Illness (NAMI) (www.nami.org): Describes the largest grassroots educational, peer support, and mental health advocacy organization in the United States. Founded in 1979 by a group of family members of people with mental disorders, NAMI has developed into an association of hundreds of local affliates, state organizations, and volunteers. Parents of Addicted Loved Ones (https:// palgroup.org): Presents a secular support group for parents who have a child with an SUD. The organization has meetings in only some states but also hosts telephone meetings. Pills Anonymous (www.pillsanonymous.org): Offers a 12-Step mutual-support group that holds regular meetings in which individuals in recovery from addiction to pills share their expe- riences, build their strengths, and offer hope for recovery to one another. Self-Management for Addiction Recovery (SMART Recovery) (www.smartrecovery.org): Is a self-empowering addiction recovery support group; participants learn science-based tools for addiction recovery and have access to an international recovery community of mutual-help groups. Stop Stigma Now (www.stopstigmanow.org): Describes an advocacy organization that works to eradicate prejudice associated with taking medication to treat OUD and offers resources and a media library. Women for Sobriety (https://womenfor- sobriety.org/): Offers an abstinence-based mutual-help group that helps women fnd their individual paths to recovery by acknowledging the unique needs women have in recovery. This organization is not affliated with any other recovery organization. It offers recovery tools to help women in recovery develop coping skills focused on emotional growth, spiritual growth, self-esteem, and a healthy lifestyle. Publications and Other Resources AAAP Patient Resources (www.aaap.org /patient-resources/helpful-links): Offers resources and publications for patients and their families. Addiction Treatment Forum, Narcotics Anonymous and the Pharmacotherapeutic Treatment of Opioid Addiction in the United States (http://atforum.com/documents /2011NAandMedication-assistedTreatment.pdf): Presents William White’s publication for people receiving medication for OUD that gives infor- mation on the pros and cons of 12-Step groups and how to prepare for meetings. ASAM, Opioid Addiction Treatment: A Guide for Patients, Families, and Friends (http:// eguideline.guidelinecentral.com/i/706017-asam -opioid-patient-piece): Provides a guide about the treatment of OUD for patients, families, and friends. HHS: • Smokefree.gov (https://smokefree.gov). Provides useful information that helps indi- viduals in planning and maintaining tobacco cessation. • BeTobaccoFree.gov (https://betobaccofree. hhs.gov/): Provides information for individuals struggling with nicotine addiction and links for clinicians that provide guidance on the care for patients with nicotine addiction. LAC (https://lac.org/resources/substance-use -resources/medication-assisted-treatment -resources). Maintains a library of documents related to medication for the treatment of OUD and other resources, including an advocacy toolkit, sample support letter form, training materials, and webinars: 5-14 Medications for Opioid Use Disorder TIP 63 • Driving on Methadone or Buprenorphine (Suboxone): DUI? (www.lac.org/assets/fles/ Driving-on-Methadone-or-Suboxone-DUI.pdf) factsheet. • Medication-Assisted Treatment for Opioid Addiction: Myths and Facts (www.lac.org/ assets/fles/Myth-Fact-for-MAT.pdf) factsheet. NAMA Recovery (www.methadone.org): Offers many resources and training opportunities to become a certifed advocate for medication for OUD and provides links to resources related to medication for the treatment of OUD. National Council on Alcoholism and Drug Dependence’s Consumer Guide to Medication- Assisted Recovery (www.williamwhitepapers. com/pr/NCADD%20Consumer%20Guide%20 to%20Medication-assisted%20Recovery%20 2011.pdf). NIAAA’s Rethinking Drinking (www.rethinking drinking.niaaa.nih.gov/help-links): Provides links to patient and family education, help lines, and other recovery resources. SAMHSA (https://store.samhsa.gov): Provides patient and family educational tools about OUD and medication treatment for OUD. The resources below are available in several languages, including Spanish and Russian: • Decisions in Recovery: Treatment for Opioid Use Disorders (https://store.samhsa.gov /product/Decisions-in-Recovery-Treatment -for-Opioid-Use-Disorders/SMA16-4993). Helps clients identify an appropriate path of recovery from OUD. • The Facts About Buprenorphine for Treatment of Opioid Addiction (https://store.samhsa.gov/product/ The-Facts-about-Buprenorphine- for-Treatment-of-Opioid-Addiction/ SMA15-4442). • The Facts About Naltrexone for Treatment of Opioid Addiction (https://permanent.access. gpo.gov/gpo20171/naltrexone-facts.pdf). Treatment Locators Faces & Voices of Recovery Guide to Mutual Aid Resources (http://facesandvoicesof recovery.org/resources/mutual-aid-resources): Offers a comprehensive list of 12-Step and non- 12-Step recovery support groups throughout the United States and online. National Alliance of Advocates for Buprenorphine Treatment (www.treatment match.org/TM_index.php): Offers a free, 24/7 anonymous treatment-matching service for patients and providers. Probuphine Healthcare Provider Locator (https://probuphinerems.com/fnd-probu- phine/): Offers a list of healthcare professionals who prescribe, insert, and/or remove buprenor- phine implants. • Know Your Rights: Rights for Individuals on Medication-Assisted Treatment (www.samhsa. gov/sites/default/files/programs_campaigns/ medication_assisted/Know-Your-Rights- Brochure.pdf). • Medication-Assisted Treatment for Opioid Addiction: Facts for Families and Friends (https://portal.ct.gov/-/media/DMHAS/ Opioid-Resources/MATInfoFamilyFriendspdf. pdf). • What Every Individual Needs To Know About Methadone Maintenance Treatment (https://roar.nevadaprc.org/system/ documents/3100/original/NPRC.168. WhatEveryIndividualNeedsToKnow. pdf?1435165554). • What Is Substance Abuse Treatment? A Booklet for Families (https://store. samhsa.gov/product/What-Is-Substance- Abuse-Treatment-A-Booklet-for-Families/ SMA14-4126). 5-15 TIP 63Part 5 of 5—Resources Related to Medications for Opioid Use Disorder SAMHSA: • Behavioral Health Treatment Services Locator is a directory of inpatient treatment providers (https://fndtreatment.samhsa.gov). • Behavioral Health Treatment Services Locator: Self-Help, Peer Support, and Consumer Groups (Addiction) provides a directory for consumers (https://fndtreatment.samhsa. gov/). • Buprenorphine Treatment Practitioner Locator provides an interactive treatment locator of providers who prescribe buprenorphine (www .samhsa.gov/medication-assisted-treatment /physician-program-data/treatment-physician -locator). • Opioid Treatment Program Directory provides an interactive SAMHSA OTP treatment locator (https://dpt2.samhsa.gov/treatment/directory .aspx). VA Substance Use Disorder Program Locator (www.va.gov/directory/guide/SUD.asp): Provides an interactive treatment locator for VA SUD treatment programs. Patient Success Stories Patients’ success stories highlight the powerful ways in which medication for the treatment of OUD can help people achieve remission and recovery. Examples of patient success stories include the following: • Carol (https://vimeo.com/105287902) • Brandon (https://vimeo.com/105078010) • Archie (www.youtube/iHJ6K4VQvrw?list =PLGV_2NAg58zkUOZRupfKc6_Z7jaBf7h-V) • MARS Project Video (www.marsproject.org) Online Boards and Chat Rooms 12-Step Forums: A variety of NA and AA meetings are available online, each with its own perspective on medication: • The AA online intergroup directory lists numerous online AA meetings, which occur at specifc times (https://aa-intergroup.org/). • The NA chatroom asks that participants not talk about medication (www.nachatroom.net). Online Forums and Groups: Many medication- assisted recovery organizations maintain an online presence for creating online mutual- support and chat opportunities: • Heroin Anonymous (https://heroinanonymous. org/). • NAMA Recovery (http://www.methadone. org/). • Stop Stigma Now (http://www.stopstigmanow. org/). SMART Recovery Online Forum (www.smart recovery.org/community/forum.php): An online group that welcomes new members. We Speak Methadone (and Buprenorphine) (www.methadone.org/wespeakmethadone): A discussion forum for medication-assisted treatment patients, their families, and advocates. 5-16 Medications for Opioid Use Disorder TIP 63 Provider Tools and Sample Forms Provider Screening and Assessment Tools and Aids Alcohol Use Disorders Identifcation Test (AUDIT) 1. How often do you have a drink containing alcohol? (0) Never [Skip to Questions 9–10] (1) Monthly or less (2) 2 to 4 times a month (3) 2 to 3 times a week (4) 4 or more times a week 6. How often during the last year have you needed an alcoholic drink frst thing in the morning to get yourself going after a night of heavy drinking? (0) Never (1) Less than monthly (2) Monthly (3) Weekly (4) Daily or almost daily 2. How many drinks containing alcohol do you have on a typical day when you are drinking? (0) 1 or 2 (1) 3 or 4 (2) 5 or 6 (3) 7, 8, or 9 (4) 10 or more 7. How often during the last year have you had a feeling of guilt or remorse after drinking? (0) Never (1) Less than monthly (2) Monthly (3) Weekly (4) Daily or almost daily 3. How often do you have six or more drinks on one occasion? (0) Never (1) Less than monthly (2) Monthly (3) Weekly (4) Daily or almost daily Skip to Questions 9 and 10 if total score for Questions 2 and 3 = 0 8. How often during the last year have you been unable to remember what happened the night before because you had been drinking? (0) Never (1) Less than monthly (2) Monthly (3) Weekly (4) Daily or almost daily 4. How often during the last year have you found that you were not able to stop drinking once you had started? (0) Never (1) Less than monthly (2) Monthly (3) Weekly (4) Daily or almost daily 9. Have you or someone else been injured as a result of your drinking? (0) No (2) Yes, but not in the last year (4) Yes, during the last year 5. How often during the last year have you failed to do what was normally expected from you because of drinking? (0) Never (1) Less than monthly (2) Monthly (3) Weekly (4) Daily or almost daily 10. Has a relative, friend, doctor, or another health professional expressed concern about your drinking or suggested you cut down? (0) No (2) Yes, but not in the last year (4) Yes, during the last year Note: Add up the points associated with answers. A score of 8 or more is considered a positive test for unhealthy drinking. Adapted from material in the public domain.3 Available online (http://auditscreen.org). 5-17 TIP 63Part 5 of 5—Resources Related to Medications for Opioid Use Disorder Stable Resource Toolkit Audit-C – Overview The AUDIT-C is a 3-item alcohol screen that can help identify persons who are hazardous drinkers or have active alcohol use disorders (including alcohol abuse or dependence). The AUDIT-C is a modifed version of the 10 question AUDIT instrument. Clinical Utility The AUDIT-C is a brief alcohol screen that reliably identifes patients who are hazardous drinkers or have active alcohol use disorders. Scoring The AUDIT-C is scored on a scale of 0-12. Each AUDIT-C question has 5 answer choices. Points allotted are: a = 0 points, b = 1 point, c = 2 points, d = 3 points, e = 4 points • In men, a score of 4 or more is considered positive, optimal for identifying hazardous drinking or active alcohol use disorders. • In women, a score of 3 or more is considered positive (same as above). • However, when the points are all from Question #1 alone (#2 & #3 are zero), it can be assumed that the patient is drinking below recommended limits and it is suggested that the provider review the patient’s alcohol intake over the past few months to confrm accuracy. • Generally, the higher the score, the more likely it is that the patient’s drinking is affecting his or her safety. Psychometric Properties For identifying patients with heavy/hazardous drinking and/or Active-DSM alcohol abuse or dependence MEN1 WOMEN2 ≥3 Sens: 0.95 / Spec. 0.60 Sens: 0.66 / Spec. 0.94 ≥4 Sens: 0.86 / Spec. 0.72 Sens: 0.48 / Spec. 0.99 For identifying patients with active alcohol abuse or dependence MEN1 WOMEN2 ≥3 Sens: 0.90 / Spec. 0.45 Sens: 0.80 / Spec. 0.87 ≥4 Sens: 0.79 / Spec. 0.56 Sens: 0.67 / Spec. 0.94 1. Bush K, Kivlahan DR, McDonell MB, et al. The AUDIT Alcohol Consumption Questions (AUDIT-C): An effective brief screening test for problem drinking. Arch Internal Med. 1998 (3): 1789-1795. 2. Bradley KA, Bush KR, Epler AJ, et al. Two brief alcohol-screening tests from the Alcohol Use Disorders Identifcation Test (AUDIT): Validation in a female veterans affairs patient population. Arch Internal Med Vol 165, April 2003: 821-829. Continued on next page 5-18 Medications for Opioid Use Disorder TIP 63 AUDIT-C Questionnaire Patient Name: _____________________________________________________ Dates of Visit: ______________________ 1. How often do you have a drink containing alcohol? □ a. Never □ b. Monthly or less □ c. 2-4 times a month □ d. 2-3 times a week □ e. 4 or more times a week 2. How many standard drinks containing alcohol do you have on a typical day? □ a. 1 or 2 □ b. 3 or 4 □ c. 5 or 6 □ d. 7 to 9 □ e. 10 or more 3. How often do you have six or more drinks on one occasion? □ a. Never □ b. Less than monthly □ c. Monthly □ d. Weekly □ e. Daily or almost daily AUDIT-C is available for use in the public domain. Reprinted from material in the public domain.4 5-19 TIP 63Part 5 of 5—Resources Related to Medications for Opioid Use Disorder Drug Abuse Screening Test (DAST-10) General Instructions “Drug use” refers to (1) the use of prescribed or over-the-counter drugs in excess of the directions, and (2) any nonmedical use of drugs. The various classes of drugs may include cannabis (i.e., marijuana, hashish), solvents (e.g., paint thinner), tran- quilizers (e.g., Valium), barbiturates, cocaine, stimulants (e.g., speed), hallucinogens (e.g., LSD), or narcotics (e.g., heroin). The questions do not include alcoholic beverages. Please answer every question. If you have trouble with a question, then choose the response that is mostly right. Segment: ____________ Visit Number: ___________ Date of Assessment: ______/_______/________ These questions refer to drug use in the past 12 months. Please answer No or Yes. 1. Have you used drugs other than those required for medical reasons? □ No □ Yes 2. Do you use more than one drug at a time? □ No □ Yes 3. Are you always able to stop using drugs when you want to? □ No □ Yes 4. Have you had “blackouts” or “fashbacks” as a result of drug use? □ No □ Yes 5. Do you ever feel bad or guilty about your drug use? □ No □ Yes 6. Does your spouse (or parents) ever complain about your involvement with drugs? □ No □ Yes 7. Have you neglected your family because of your use of drugs? □ No □ Yes 8. Have you engaged in illegal activities to obtain drugs? □ No □ Yes 9. Have you ever experienced withdrawal symptoms (i.e., felt sick) when you stopped □ No □ Yes taking drugs? 10. Have you had medical problems as a result of your drug use (e.g., memory loss, □ No □ Yes hepatitis, convulsions, bleeding)? Comments: Scoring Score 1 point for each “Yes,” except for question 3, for which a “No” receives 1 point. DAST Score: __________ Interpretation of Score: Score Degree of Problems Related to Drug Abuse Suggested Action 0 No problems reported None at this time 1–2 Low level Monitor, reassess at a later date 3–5 Moderate level Further investigation 6–8 Substantial level Intensive assessment 9–10 Severe level Intensive assessment Adapted with permission.5,6 5-20 Medications for Opioid Use Disorder TIP 63 DSM-5 Opioid Use Disorder Checklist7 Patient’s Name: ___________________________________________________________ Date of Birth: ______________________ Worksheet for DSM-5 Criteria for Diagnosis of Opioid Use Disorder DIAGNOSTIC CRITERIA (Opioid use disorder requires that at least 2 criteria be met within a 12-month period.) MEETS CRITERIA? Yes OR No NOTES/SUPPORTING INFORMATION 1. Opioids are often taken in larger amounts or over a longer period of time than intended. 2. There is a persistent desire or unsuccessful efforts to cut down or control opioid use. 3. A lot of time is spent in activities necessary to obtain the opioid, use the opioid, or recover from its effects. 4. Craving, or a strong desire to use opioids. 5. Recurrent opioid use resulting in failure to fulfll major role obligations at work, school, or home. 6. Continued opioid use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of opioids. 7. Important social, occupational, or recreational activities are given up or reduced because of opioid use. 8. Recurrent opioid use in situations in which it is physically hazardous. 9. Continued use despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by opioids. 10. Tolerance,* as defned by either of the following: (a) a need for markedly increased amounts of opioids to achieve intoxication or desired effect (b) markedly diminished effect with continued use of the same amount of an opioid 11. Withdrawal,* as manifested by either of the following: (a) the characteristic opioid withdrawal syndrome (b) the same (or a closely related) substance is taken to relieve or avoid withdrawal symptoms *This criterion is not met for individuals taking opioids solely under appropriate medical supervision. Severity: mild = 2–3 symptoms; moderate = 4–5 symptoms; severe = 6 or more symptoms Signed: _____________________________________________________ Date: _______________________ 5-21 TIP 63Part 5 of 5—Resources Related to Medications for Opioid Use Disorder Heaviness of Smoking Index Ask these two questions of current or recent smokers: 1. How soon after waking do you smoke your frst cigarette? • Within 5 minutes (3 points) • 5–30 minutes (2 points) • 31–60 minutes (1 point) • 61 or more minutes (no points) 2. How many cigarettes a day do you smoke? • 10 or less (no points) • 11–20 (1 point) • 21–30 (2 points) • 31 or more (3 points) Total score: 1 to 2 points = very low dependence; 3 points = low to moderate dependence; 4 points = moderate dependence; 5 or more points = high dependence Adapted with permission.8 NIAAA Single-Item Screener How many times in the past year have you had fve or more drinks in a day (four drinks for women and all adults older than age 65)? A response of one or more times is considered a positive screen. Patients who screen positive should have an assessment for alcohol use disorder. Adapted with permission.9 5-22 Medications for Opioid Use Disorder TIP 63 Opioid Overdose: Risk, Prevention, Identifcation, and Response Overdose Risk • Using heroin (possibly mixed with illicitly manufactured fentanyl or fentanyl analogs) • Using prescription opioids that were not prescribed • Using prescription opioids more frequently or at higher doses than prescribed • Using opioids after a period of abstinence or reduced use (e.g., after medically supervised withdrawal or incarceration) • Using opioids with alcohol, benzodiazepines, or both Overdose Prevention • Don’t use opioids that were not prescribed. • Take medications only as prescribed. • Don’t use drugs when you are alone. • Don’t use multiple substances at once. • Have naloxone available and make sure others know where it is and how to use it. • Use a small “test dose” if returning to opioid use after a period of abstinence, if the substance appears altered or has been acquired from an unfamiliar source. Beware: This doesn’t guarantee safety; illicitly manufactured fentanyl or other substances may be present in the drug, and any use may be fatal. Overdose Identifcation • Fingernails or lips are blue or purple. • Breathing or heartbeat is slow or stopped. • The person is vomiting or making gurgling noises. • The person can’t be awakened or is unable to speak. Overdose Response • Call 9-1-1. • Administer naloxone (more than one dose may be needed to restore adequate spontaneous breathing). • Perform rescue breathing. If certifed to provide cardiopulmonary resuscitation, perform chest compressions if there is no pulse. • Put the person in the “recovery position,” on his or her side and with the mouth facing to the side to prevent aspiration of vomit, if he or she is breathing independently. • Stay with the person until emergency services arrive. Naloxone’s duration of action is 30–90 minutes. The person should be observed after this time for a return of opioid overdose symptoms. Adapted from material in the public domain.10 5-23 TIP 63Part 5 of 5—Resources Related to Medications for Opioid Use Disorder Physical Signs of Opioid Withdrawal and Time to Onset STAGE GRADE PHYSICAL SIGNS/SYMPTOMS Early Withdrawal Short-acting opioids: 8–24 hours after last use Long-acting opioids: Up to 36 hours after last use Grade 1 Lacrimation, rhinorrhea, or both Diaphoresis Yawning Restlessness Insomnia Early Withdrawal Short-acting opioids: 8–24 hours after last use Long-acting opioids: Up to 36 hours after last use Grade 2 Dilated pupils Piloerection Muscle twitching Myalgia Arthralgia Abdominal pain Fully Developed Withdrawal Short-acting opioids: 1–3 days after last use Long-acting opioids: 72–96 hours after last use Grade 3 Tachycardia Hypertension Tachypnea Fever Anorexia or nausea Extreme restlessness Fully Developed Withdrawal Short-acting opioids: 1–3 days after last use Long-acting opioids: 72–96 hours after last use Grade 4 Diarrhea, vomiting, or both Dehydration Hyperglycemia Hypotension Curled-up position Total duration of withdrawal: • Short-acting opioids: 7–10 days. • Long-acting opioids: 14 days or more. Signs of Opioid Intoxication Physical Findings Drowsy but arousable Sleeping intermittently (“nodding off”) Constricted pupils Mental Status Findings Slurred speech Impaired memory or concentration Normal to euphoric mood Single-Item Drug Screener How many times in the past year have you used an illegal drug or used a prescription medication for nonmedical reasons? (A positive screen is 1 or more days.) Reprinted with permission.11 5-24 Medications for Opioid Use Disorder TIP 63 Substance Misuse and SUD Screening Substance misuse screening Negative Positive Reinforce healthy behavior Assess substance use and comorbidities Substance misuse Substance use disorder Brief counseling Brief counseling and treatment referral Monitoring/follow up - Consider medication If misuse continues, negotiate a plan and refer to treatment Ongoing assessment and support Adapted with permission.12 5-25 TIP 63Part 5 of 5—Resources Related to Medications for Opioid Use Disorder TAPS Tool Part I Directions: The TAPS Tool Part 1 is a 4-item screening for tobacco use, alcohol use, prescription medication misuse, and illicit substance use in the PAST YEAR. Question 2 should be answered by males, and Question 3 should be answered by females. Each of the four multiple-choice items has fve possible responses to choose from. Check the box to select your answer. In the PAST 12 MONTHS: 1. How often have you used any tobacco product (for example, cigarettes, ecigarettes, cigars, pipes, or smokeless tobacco)? □ Never □ Less than monthly □ Monthly □ Weekly □ Daily or almost daily 2. How often have you had 5 or more drinks containing alcohol in 1 day? One standard drink is about 1 small glass of wine (5 oz), 1 beer (12 oz), or 1 single shot of liquor. (Note: This question should only be answered by males.) □ Never □ Less than monthly □ Monthly □ Weekly □ Daily or almost daily 3. How often have you had 4 or more drinks containing alcohol in 1 day? One standard drink is about 1 small glass of wine (5 oz), 1 beer (12 oz), or 1 single shot of liquor. (Note: This question should only be answered by females.) □ Never □ Less than monthly □ Monthly □ Weekly □ Daily or almost daily 4. How often have you used any drugs including marijuana, cocaine or crack, heroin, methamphetamine (crystal meth), hallucinogens, or ecstasy/MDMA? □ Never □ Less than monthly □ Monthly □ Weekly □ Daily or almost daily 5. How often have you used any prescription medications just for the feeling, more than prescribed, or that were not prescribed for you? Prescription medications that may be used this way include opiate pain relievers (for example, OxyContin, Vicodin, Percocet, or methadone), medications for anxiety or sleeping (for example, Xanax, Ativan, or Klonopin), or medications for ADHD (for example, Adderall or Ritalin). □ Never □ Less than monthly □ Monthly □ Weekly □ Daily or almost daily 5-26 Medications for Opioid Use Disorder TIP 63 TAPS Tool Part 2 Directions: The TAPS Tool Part 2 is a brief assessment for tobacco use, alcohol use, illicit substance use, and prescription medication misuse in the PAST 3 MONTHS ONLY. Each of the following questions and subquestions has two possible answers, yes or no. Check the box to select your answer. In the PAST 3 MONTHS: 1. Did you smoke a cigarette containing tobacco? □ Yes □ No If “Yes,” answer the following questions: • Did you usually smoke more than 10 cigarettes each day? • Did you usually smoke within 30 minutes after waking? □ Yes □ Yes □ No □ No 2. Did you have a drink containing alcohol? □ Yes □ No If “Yes,” answer the following questions: • Did you have 4 or more drinks containing alcohol in a day?* □ Yes □ No (Note: This question should only be answered by females.) • Did you have 5 or more drinks containing alcohol in a day?* □ Yes □ No (Note: This question should only be answered by males.) • Have you tried and failed to control, cut down, or stop drinking? • Has anyone expressed concern about your drinking? □ Yes □ Yes □ No □ No 3. Did you use marijuana (hash, weed)? □ Yes □ No If “Yes,” answer the following questions: • Have you had a strong desire or urge to use marijuana at least once a week or more often? □ Yes □ No • Has anyone expressed concern about your use of marijuana? □ Yes □ No 4. Did you use cocaine, crack, or methamphetamine (crystal meth)? □ Yes □ No If “Yes,” answer the following questions: • Did you use cocaine, crack, or methamphetamine (crystal meth) at least once a week or more often? □ Yes □ No • Has anyone expressed concern about your use of cocaine, crack, or methamphetamine (crystal meth)? □ Yes □ No 5. Did you use heroin? □ Yes □ No If “Yes,” answer the following questions: • Have you tried and failed to control, cut down, or stop using heroin? □ Yes □ No • Has anyone expressed concern about your use of heroin? □ Yes □ No 6. Did you use a prescription opiate pain reliever (for example Percocet or Vicodin) not as □ Yes □ No prescribed or that was not prescribed for you? If “Yes,” answer the following questions: • Have you tried and failed to control, cut down, or stop using an opiate pain reliever? □ Yes □ No • Has anyone expressed concern about your use of an opiate pain reliever? □ Yes □ No *One standard drink is about 1 small glass of wine (5 oz), 1 beer (12 oz), or 1 single shot of liquor. Continued on next page 5-27 TIP 63Part 5 of 5—Resources Related to Medications for Opioid Use Disorder 7. Did you use medication for anxiety or sleep (for example, Xanax, Ativan, or Klonopin) not as prescribed or that was not prescribed for you? If “Yes,” answer the following questions: • Have you had a strong desire or urge to use medications for anxiety or sleep at least once a week or more often? • Has anyone expressed concern about your use of medication for anxiety or sleep? □ Yes □ Yes □ Yes □ No □ No □ No 8. Did you use medication for ADHD (for example, Adderall or Ritalin) not as prescribed or that was not prescribed for you? If “Yes,” answer the following questions: • Did you use a medication for ADHD (for example, Adderall or Ritalin) at least once a week or more often? • Has anyone expressed concern about your use of medication for ADHD (for example, Adderall or Ritalin)? □ Yes □ Yes □ Yes □ No □ No □ No 9. Did you use any other illegal or recreational drugs (for example, ecstasy, molly, GHB, □ Yes □ No poppers, LSD, mushrooms, special K, bath salts, synthetic marijuana [“spice”], whip-its)? If “Yes,” answer the following question: • What were the other drug(s) you used? (write in response) The complete tool is available online (https://cde.drugabuse.gov/instrument/29b23e2e-e266-f095-e050-bb89ad43472f). Adapted from material in the public domain.13 Two-Item Drug Use Disorder Screener for Primary Care Clinics Serving U.S. Veterans Question 1: How many days in the past 12 months have you used drugs other than alcohol? (A positive screen is 7 or more days.) If <7, proceed with Question 2. Question 2: How many days in the past 12 months have you used drugs more than you meant to? (A positive screen is 2 or more days.) Adapted with permission.14 5-28 Medications for Opioid Use Disorder TIP 63 Urine Drug Testing Window of Detection15,16 DRUG POSITIVE TEST WINDOW OF DETECTION* COMMENTS Amphetamine; methamphetamine; 3,4-methylenedioxy- methamphetamine Amphetamine 1–2 days False positives w/ bupropion, chlorpromazine, desipramine, fuoxetine, labetalol, promethazine, ranitidine, pseudoephedrine, trazadone, and other common medications. Confrm unexpected positive results with the laboratory. Barbiturates Barbiturates Up to 6 weeks N/A Benzodiazepines Benzodiazepines 1–3 days; up to 6 weeks with heavy use of long-acting benzodiazepines Immunoassays may not be sensitive to therapeutic doses, and most immunoassays have low sensitivity to clonazepam and lorazepam. Check with your laboratory regarding sensitivity and cutoffs. False positives with sertraline or oxaprozin. Buprenorphine Buprenorphine 3–4 days Will screen negative on opiate screen. Tramadol can cause false positives. Can be tested for specifcally. Cocaine Cocaine, benzoylecgonine 2–4 days; 10–22 days with heavy use N/A Codeine Morphine, codeine, high-dose hydrocodone 1–2 days Will screen positive on opiate immunoassay. Fentanyl Fentanyl 1–2 days Will screen negative on opiate screen. Can be tested for specifcally. May not detect all fentanyl-like substances.17 Heroin Morphine, codeine 1–2 days Will screen positive on opiate immunoassay. 6-monoacetylmorphine, a unique metabolite of heroin, is present in urine for about 6 hours. Can be tested for specifcally to distinguish morphine from heroin, but this is rarely clinically useful. Hydrocodone Hydrocodone, hydromorphone 2 days May screen negative on opiate immunoassay. Can be tested for specifcally. Hydromorphone May not be detected 1–2 days May screen negative on opiate immunoassay. Can be tested for specifcally. Continued on next page 5-29 TIP 63Part 5 of 5—Resources Related to Medications for Opioid Use Disorder Methadone Comfort Zone Serum Level 0 2 4 6 8 10 12 14 16 18 20 22 24 Opioid Overmedication Signs: Pinpoint pupils, drowsy or nodding off, listless mental status, itching/scratching, fushing, decreased body temperature, slowed heartbeat and/or respirations Opioid Withdrawal—Subjective Symptoms: Drug craving, anxious feelings or depression, irritability, fatigue, insomnia, hot/cold fashes, aching muscles/joints, nausea, disorientation, restlessness Severe Opioid Withdrawal—Objective Signs: Dilated pupils, illicit opioid use, “goose fesh,” perspiring, shaking, diarrhea, vomiting, runny nose, sneezing, yawning, fever, hypertension, increased heartbeat and/or respirations Peak Trough No Illicit Opioid Use No Withdrawal or Overmedication Hours Urine Drug Testing Window of Detection (continued) DRUG POSITIVE TEST WINDOW OF DETECTION* COMMENTS Marijuana Tetrahydrocan- nabinol Infrequent use of 1–3 days; chronic use of up to 30 days False positives possible with efavirenz, ibuprofen, and pantoprazole. Methadone Methadone 2–11 days Will screen negative on opiate screen. Can be tested for specifcally. Morphine Morphine, hydromorphone 1–2 days Will screen positive on opiate immunoassay. Ingestion of poppy plant/ seed may screen positive. Oxycodone Oxymorphone 1–1.5 days Typically screens negative on opiate immunoassay. Can be tested for specifcally. *Detection time may vary depending on the cutoff. Using Signs and Symptoms To Determine Optimal Methadone Level Adapted with permission.18 5-30 Medications for Opioid Use Disorder TIP 63 Provider Informational, Educational, and Decision-Making Tools Key Elements of an OBOT Clinic Diversion Control Plan19 New Patients Ongoing Patients Periodically check the state’s PDMP. Conduct random urine tests that include a wide spectrum of opioids—including morphine, oxycodone, and buprenorphine—and periodically include buprenorphine metabolites. This will help monitor response to treatment and determine whether patients are taking at least some of their prescribed buprenorphine. Use unobserved specimen collection to preserve patient privacy and dignity: • Do not let patients bring backpacks, jackets, or other items into the bathroom. • Do not let others enter bathrooms with patients. • Temperature test the urine sample. Use observed specimen collection (obtained by a staff member of the same gender) or oral fuid testing if there is reason to suspect tampering or falsifcation. Contact patients at random; ask them to bring in their medication within a reasonable period (24 to 48 hours) to count the tablets/flms to ensure that all medication is accounted for. Provide a limited number of days of medication per prescription without reflls (e.g., several days or 1 week per prescription) until the patient has demonstrated stability and lowered diversion risk. Check the state’s PDMP before admission to determine whether patients are receiving opioids or benzodiazepine prescriptions from other providers. Ask patients to sign a release of information to speak with the other prescribers. Patients who are unwilling to sign a release of information are poor candidates for outpatient treatment. Review the clinic diversion control policy with new patients. This should include counseling patients to: • Keep buprenorphine locked up and out of children’s reach. • Never share medication with anyone. • Never sell medication to anyone. • Acknowledge giving or selling medication to others as illegal. • Take medication only as prescribed. • Review, understand, and agree to the practice’s buprenorphine treatment agreement before they start. Prescribe buprenorphine/naloxone when possible, rather than monoproduct. Exceptions would include prescribing the monoproduct for pregnant women with OUD. Prescribe an adequate but not excessive dose. Most patients respond to doses at or below 24 mg per day. Carefully evaluate requests for higher doses and confrm, document, and assess medication adherence continuously. 5-31 TIP 63Part 5 of 5—Resources Related to Medications for Opioid Use Disorder Key Points of Patient Education for Buprenorphine Before starting OUD treatment with buprenorphine, patients should: • Tell providers the prescribed and over-the-counter medications they take, to allow drug interaction assessment. • Understand the goal of the frst week of treatment: To improve withdrawal symptoms without oversedation. • Tell providers if they feel sedated or euphoric within 1 to 4 hours after their dose. • Be given the appropriate buprenorphine medication guide. • Know possible side effects, including: - Headache. - Dizziness. - Nausea. - Vomiting. - Sweating. - Constipation. - Sexual dysfunction. • Agree to store medication securely and out of the reach of others. • Alert providers if they discontinue medications, start new ones, or change their medication dose. • Understand that discontinuing buprenorphine increases risk of overdose death upon return to illicit opioid use. • Know that use of alcohol or benzodiazepines with buprenorphine increases the risk of overdose and death. • Understand the importance of informing providers if they become pregnant. • Tell providers if they are having a procedure that may require pain medication. • Be aware of resources through which to obtain further education for: - Themselves (https://store.samhsa.gov/product /SMA16-4993). - Their families and friends (https://portal.ct.gov/ DMHAS/Programs-and-Services/Opioid- Treatment/Medication-Assisted-Treatment). Key Points of Patient Education for Methadone Before starting OUD treatment with methadone, patients should: • Be told that the methadone dose is started low and increased slowly over days and weeks with monitoring, because it takes 4 or more days for the body to adjust to a dose change. This is necessary to avoid the risk of overdose. • Understand that the goal of the frst weeks of treatment is to improve withdrawal symptoms without oversedation. Patients should tell providers if they feel sedated or high within the frst 4 hours after their dose. • Learn the symptoms of methadone intoxication and how to seek emergency care. The frst 2 weeks of treatment have the highest risk of overdose. • Be aware that rescue naloxone does not last very long, so they should remain in emergency care for observation if they are treated for opioid overdose. • Know that concurrent alcohol, benzodiazepine, or other sedative use with methadone increases the risk of overdose and death. • Inform OTP nursing/medical staff about prescribed and over-the-counter medications and herbs (e.g., St. John’s wort) they are taking, stopping, or changing doses of to allow assessment of potential drug–drug interactions. • Inform other treating healthcare professionals that they are receiving methadone treatment. • Plan to avoid driving or operating heavy machinery until their dose is stabilized. • Learn about other possible side effects of methadone, including dizziness, nausea, vomiting, sweating, constipation, edema, and sexual dysfunction. • Agree to keep take-home doses locked up and out of the reach of others. Understand that giving methadone, even small amounts, to others may be fatal. • Inform providers if they become pregnant. • Understand that stopping methadone increases their risk of overdose death if they return to illicit opioid use. 5-32 Medications for Opioid Use Disorder TIP 63 Key Points of Patient Education for Naltrexone • Do not use any opioids in the 7 to 10 days (for short acting) or 10 to 14 days (for long acting) before starting XR-NTX, to avoid potentially serious opioid withdrawal symptoms. Opioids include: - Heroin. - Prescription opioid analgesics (including tramadol). - Cough, diarrhea, or other medications that contain codeine or other opioids. - Methadone. - Buprenorphine. • Seek immediate medical help if symptoms of allergic reaction or anaphylaxis occur, such as: - Itching. - Swelling. - Hives. - Shortness of breath. - Throat tightness. • Do not try to override the opioid blockade with large amounts of opioids, which could result in overdose. • Understand the risk of overdose from using opioids near the time of the next injection, after missing a dose, or after stopping medications. • Report injection site reactions including: - Pain. - Hardening. - Lumps. - Blisters. - Blackening. - Scabs. - An open wound. Some of these reactions could require surgery to repair (rarely). • Report signs and symptoms of hepatitis. • Report depression or suicidal thoughts. Seek immediate medical attention if these symptoms appear. • Seek medical help if symptoms of pneumonia appear (e.g., shortness of breath, fever). • Tell providers of naltrexone treatment, as treatment differs for various types of pneumonia. • Inform all healthcare professionals of XR-NTX treatment. • Report pregnancy. • Inform providers of any upcoming medical procedures that may require pain medication. • Understand that taking naltrexone may result in diffculty achieving adequate pain control if acute medical illness or trauma causes severe acute pain. • Wear medical alert jewelry and carry a medical alert card indicating you are taking XR-NTX. A patient wallet card or medical alert bracelet can be ordered at 1-800-848-4876. 5-33 TIP 63Part 5 of 5—Resources Related to Medications for Opioid Use Disorder Medication Management for Patients With Respiratory or Hepatic Impairment Who Take Buprenorphine CONTRAINDICATION/CAUTION MANAGEMENT Compromised respiratory function (e.g., chronic obstructive pulmonary disease, decreased respiratory reserve, hypoxia, hypercapnia [abnormally elevated blood levels of carbon dioxide], preexisting respiratory depression). Hepatic impairment Buprenorphine and naloxone are extensively metabolized by the liver. Moderate to severe impairment results in decreased clearance, increased overall exposure to both medications, and higher risk of buprenorphine toxicity and precipitated withdrawal from naloxone. These effects have not been observed in patients with mild hepatic impairment.21,22 • Prescribe with caution; monitor closely. • Warn patients about the risk of using benzodiazepines or other depressants while taking buprenorphine.20 • Support patients in their attempts to discontinue tobacco use. • Mild impairment (Child-Pugh score of 5–6):23 No dose adjustment needed. • Moderate impairment (Child-Pugh score of 7–9):24 Combination products are not recommended; they may precipitate withdrawal. *Use combination products cautiously for maintenance treatment in patients who’ve been inducted with a monoproduct;25,26 monitor for signs and symptoms of buprenorphine toxicity or overdose.27 Naloxone may interfere with buprenorphine’s effcacy.28,29 • Severe impairment (Child-Pugh score of 10–15):30 Do not use the combination product.31 For monoproduct, consider halving the starting and titration doses used in patients with normal liver function; monitor for signs and symptoms of toxicity or overdose caused by increased buprenorphine levels.32 *Moderate to severe impairment results in much more reduced clearance of naloxone than of buprenorphine. Nasser et al.33 found that moderate impairment doubled or tripled exposure (compared with subjects with no or mild impairment) for both medications. In subjects with severe impairment, buprenorphine exposure was two to three times higher; naloxone exposure increased more than tenfold. Adapted from material in the public domain.34 Monitoring Recovery Activities At medical management visits, do not simply ask about attendance at recovery support meetings; explore the level of participation and engagement in those activities. Some activities include: • Finding and working closely with a sponsor. • “Working” the 12 Steps at 12-Step meetings and with a sponsor. • Doing service at meetings (e.g., setting up chairs, making coffee, going on a “commitment” to speak at a meeting in a jail or an inpatient drug and alcohol program). • Having and frequently attending a regular “home” group.35 Remember this statement from recovery experts A. Thomas McLellan and William White: “Recovery status is best defned by factors other than medication status. Neither medication-assisted treatment of opioid addiction nor the cessation of such treatment by itself constitutes recovery. Recovery status instead hinges on broader achievements in health and social functioning—with or without medication support.”36 5-34 Medications for Opioid Use Disorder TIP 63 OUD Medications: An Overview37,38 CATEGORY BUPRENORPHINE* METHADONE XR-NTX** A p p ro p ri at e p at ie n ts Typically for patients with OUD who are physiologically dependent on opioids Typically for patients with OUD who are physiologically dependent on opioids and who meet federal criteria for OTP admission Typically for patients with OUD who have abstained from short-acting opioids for at least 7–10 days and long-acting opioids for at least 10–14 days P h ar m ac ol og y Opioid receptor partial agonist Reduces opioid withdrawal and craving; blunts or blocks euphoric effects of self-administered illicit opioids through cross-tolerance and opioid receptor occupancy. Opioid receptor agonist Reduces opioid withdrawal and craving; blunts or blocks euphoric effects of self-administered illicit opioids through cross- tolerance and opioid receptor occupancy. Opioid receptor antagonist Blocks euphoric effects of self-administered illicit opioids through opioid receptor occupancy. Causes no opioid effects. P at ie n t E d u ca ti on Tell patients: • That they will need to be in opioid withdrawal to receive their frst dose to avoid buprenorphine- precipitated opioid withdrawal. • About the risk of overdose with concurrent benzodiazepine or alcohol use, with injecting buprenorphine, and after stopping the medication. Tell patients: • That their dose will start low and build up slowly to avoid oversedation; it takes several days for a given dose to have its full effect. • About overdose risk in the frst 2 weeks of treatment, especially with concurrent benzodiazepine or alcohol use, and after stopping the medication. Tell patients: • That they will need to be opioid free for at least 7–10 days for short- acting and at least 10–14 days for long-acting opioids before their frst dose to avoid XR-NTX- precipitated opioid withdrawal (which may require hospitalization). • About the risk of overdose after stopping the medication. A d m in is tr at io n Daily (or off-label less-than-daily dosing regimens) administration of sublingual or buccal tablet or flm. Subdermal implants every 6 months, for up to 1 year, for stable patients. Monthly subcutaneous injection of extended-release formulation in abdominal region for patients treated with transmucosal buprenorphine for at least 1 week. Daily oral administration as liquid concentrate, tablet, or oral solution from dispersible tablet or powder (unless patients can take some home). Every 4 weeks or once- per-month intramuscular injection. P re sc ri b in g Physicians, NPs, PAs, and, until October 1, 2023, clinical nurse specialists, certifed registered nurse anesthetists, and certifed nurse midwives need a waiver to prescribe. Any pharmacy can fll a prescription for sublingual or buccal formulations. OTPs can administer/ dispense by OTP physician order without a waiver. SAMHSA-certifed OTPs can provide methadone for daily onsite administration or at-home self- administration for stable patients. Physicians, NPs, PAs, and, until October 1, 2023, clinical nurse specialists, certifed registered nurse anesthetists, and certifed nurse midwives prescribe or order administration by qualifed healthcare professionals. *Long-acting buprenorphine implants (every 6 months) for patients on a stable dose of buprenorphine are also available through implanters and prescribers with additional training and certifcation through the Probuphine REMS Program. Extended-release buprenorphine monthly subcutaneous injections are available only through prescribers and pharmacies registered with the Sublocade REMS Program. **Naltrexone hydrochloride tablets (50 mg each) are also available for daily oral dosing but have not been shown to be more effective than treatment without medication or placebo because of poor patient adherence. 5-35 TIP 63Part 5 of 5—Resources Related to Medications for Opioid Use Disorder OUD Medications: Comparison To Guide Shared Decision Making CATEGORY BUPRENORPHINE METHADONE NALTREXONE Appropriate Typically for patients Typically for patients Typically for patients with patients with OUD who are with OUD who are OUD who are abstinent physiologically dependent physiologically dependent from short-acting opioids on opioids on opioids and who meet for 7 days and long-acting federal criteria for OTP opioids for 10–14 days admission Outcome: Higher than treatment Higher than treatment For XR-NTX, treatment Retention in without medication and without OUD medication retention is higher than treatment treatment with placebo39 and treatment with for treatment without placebo40 OUD medication and treatment with placebo, but treatment retention with oral naltrexone is no better than with placebo or no medication 41 ,42,43 Outcome: Suppression of illicit opioid use Effective Effective Effective Outcome: Overdose mortality Lower for people in treatment than for those not in it Lower for people in treatment than for those not in it Unknown Location/ Offce/clinic: Begins daily OTP only: 6–7 days/week Offce/clinic: Varies from frequency of to weekly, then tailored initially; take-homes are weekly to monthly offce visits to patient’s needs OTP: Can treat with buprenorphine 6–7 days/ allowed based on time in treatment and patient progress week initially; take-homes are allowed without the time-in-treatment requirements of methadone Who can Physicians, NPs,* PAs, OTP physicians order the Physicians, NPs,* PAs, prescribe/order? and, until October 1, 2023, clinical nurse specialists, certifed registered nurse anesthetists, and certifed nurse midwives possessing a federal waiver can prescribe and dispense; can be dispensed by a community pharmacy or an OTP medication; nurses and pharmacists administer and dispense it and, until October 1, 2023, clinical nurse specialists, certifed registered nurse anesthetists, and certifed nurse midwives **NPs, PAs, clinical nurse specialists, certifed registered nurse anesthetists, and certifed nurse midwives should check with their state to determine whether prescribing buprenorphine, naltrexone, or both is within their allowable scope of practice. Continued on next page 5-36 Medications for Opioid Use Disorder TIP 63 OUD Medications: Comparison To Guide Shared Decision Making (continued) CATEGORY BUPRENORPHINE METHADONE NALTREXONE Administration Sublingual/buccal; injection implant by specially trained provider, and only for stabilized patients Oral Oral or intramuscular (Note: Oral naltrexone is less effective than the other OUD medications.) Misuse/diversion Low in OTPs or other Low in OTPs with directly None potential settings with observed dose administration; moderate for take- home doses; risk can be mitigated by providing take-homes to stable patients and a diversion control plan observed therapy; moderate for take- home doses; risk can be mitigated by a diversion control plan Sedation Low unless concurrent substances are present (e.g., alcohol, benzodiazepines) Low unless dose titration is too quick or dose is not adjusted for the presence of concurrent substances (e.g., alcohol, benzodiazepines) None Risk of medication- induced respira- tory depression Very rare; lower than methadone Rare, although higher than buprenorphine; may be elevated during the frst 2 weeks of treatment or in combination with other sedating substances None Risk of Can occur if started too None Severe withdrawal is precipitated prematurely after recent possible if period of withdrawal use of other opioids abstinence is inadequate when starting before starting medication medication Withdrawal symptoms on discontinuation Present; lower than methadone if abruptly discontinued Present; higher than buprenorphine if abruptly discontinued None Most common Constipation, vomiting, Constipation, vomiting, Diffculty sleeping, anxiety, side effects headache, sweating, insomnia, blurred vision sweating, dizziness, sedation nausea, vomiting, low energy, joint and muscle pain, headache, liver enzyme elevation XR-NTX: Injection site pain, nasopharyngitis, insomnia, toothache D. Coffa, December 2017 (personal communication). Adapted with permission. 5-37 TIP 63Part 5 of 5—Resources Related to Medications for Opioid Use Disorder OUD Medications: Formulations44,45 GENERIC/ TRADE NAME FORMULATIONS ACTION AT THE RECEPTOR FDA INDICATIONS DOSING REGIMEN Methadone Orally as liquid Mu-opioid receptor Medically supervised Once daily (also (Methadose, concentrate, full agonist withdrawal and off-label dosing Dolophine) tablet, or oral solution of powder or dispersible tablet maintenance treatment of opioid dependence; additional formulations FDA- approved for pain are not a focus of this TIP regimens if appropriate, such as split dose twice daily) Generic Sublingual tablet Mu-opioid receptor Treatment of opioid Once daily (also buprenorphine partial agonist dependence; additional alternative off-label monoproduct formulations FDA- approved for pain are not a focus of this TIP regimens) Generic combination product (buprenorphine/ naloxone) Sublingual tablet, flm Mu-opioid receptor partial agonist combined with mu-opioid receptor antagonist; the latter is not absorbed sublingually Treatment of opioid dependence Once daily (also alternative off-label regimens) Buprenorphine/ Sublingual tablet Mu-opioid receptor Treatment of opioid Once daily (also naloxone partial agonist dependence alternative off-label (Zubsolv) combined with mu-opioid receptor antagonist; the latter is not absorbed sublingually regimens) Buprenorphine/ Buccal flm Mu-opioid receptor Treatment of opioid Once daily (also naloxone partial agonist dependence alternative off-label (Bunavail) combined with mu-opioid receptor antagonist; the latter is not absorbed sublingually regimens) Buprenorphine/ Sublingual flm; Mu-opioid receptor Treatment of opioid Once daily (also naloxone may also be partial agonist dependence alternative off-label (Suboxone) administered buccally combined with mu-opioid receptor antagonist; the latter is not absorbed sublingually regimens) Continued on next page 5-38 Medications for Opioid Use Disorder TIP 63 OUD Medications: Formulations (continued) GENERIC/ TRADE NAME FORMULATIONS ACTION AT THE RECEPTOR FDA INDICATIONS DOSING REGIMEN Buprenorphine (Probuphine) Implants Mu-opioid receptor partial agonist Maintenance treatment of opioid dependence in clinically stable patients taking 8 mg/ day or less of Suboxone equivalents Implants last for 6 months and are then removed, after which a second set can be inserted Extended- release injection buprenorphine (Sublocade) Subcutaneous injection in the abdominal region Mu-opioid receptor partial agonist Treatment of moderate-to-severe OUD among patients initiated and taking transmucosal buprenorphine for at least 7 days Monthly Oral naltrexone (Naltrexone hydrochloride) Oral tablet Mu-opioid receptor antagonist Block the effects of administered opioid agonists Once daily (also alternative off-label regimens) XR-NTX (Vivitrol) Intramuscular injection Mu-opioid receptor antagonist Prevent return to opioid dependence after medically supervised opioid withdrawal Once monthly by injection 5-39 TIP 63Part 5 of 5—Resources Related to Medications for Opioid Use Disorder Referring Patients Who Receive OUD Medications to Behavioral Health Therapies Case management Vocational training Yes No Yes No Is the patient willing to engage in additional behavioral health therapies? Is the patient entering an OTP for methadone or intensive treatment? Offer best advice and ongoing motivational interviewing; revisit offer for behavioral health therapies. Counseling, peer support, and case management will likely be provided through the OTP. Identify specifc needs, and refer appropriately to one or more of the following: Counseling: Individual, family, and/or group Peer support groups: Alcoholics Anonymous, Narcotics Anonymous, SMART Recovery, buprenorphine groups Housing, transportation, food, legal, and other support programs 5-40 Medications for Opioid Use Disorder TIP 63 Strategies for Managing Benzodiazepine Use by Patients in OUD Treatment • Carefully assess the patient’s benzodiazepine use, including: - Intent of use. - Source (check the state’s PDMP). - Amount and route of use. - Binge use. - Prior overdoses. - Harms (e.g., car crashes, criminal acts, sleep trouble). - Co-use with other substances that further increase risk for respiratory depression and overdose. - Withdrawal history (e.g., seizures, delirium). • Also assess the following: - Psychiatric and medical comorbidity - Motivation for change - Psychosocial support system (obtain history from a signifcant other if the patient permits) • Gauge level of care and setting needed (e.g., residential, outpatient). Inpatient treatment may be best for patients with poor motivation, limited psychosocial support, serious or complicated comorbidity, or injection or binge use. • Coordinate with other prescribers. Some patients may have taken appropriately prescribed benzodiazepines for years with limited or no evidence of misuse. For such patients, tapering benzodiazepines may be contraindicated and unrealistic. • Address comorbid mental disorders (e.g., anxiety, depression) with other medications or psychosocial treatments, when feasible. • Provide medically supervised withdrawal from benzodiazepines or refer to specialty care for same. • Create a treatment plan with built-in conditions (e.g., urine testing, more frequent visits, short medication supply). • Frequently review patient progress and objective outcomes, such as: - Urine drug testing. - PDMP reports. - Psychosocial functioning. - Reports from signifcant others. • Revise treatment plans as needed, and document the rationale for treatment decisions. Adapted with permission.46 5-41 TIP 63Part 5 of 5—Resources Related to Medications for Opioid Use Disorder Sample Provider Forms General forms Goal-Setting Form Patient’s Name: ________________________________________________________________ Date: _________________________ GOAL CATEGORY CURRENT SITUATION SCORE 10 = major problems and 0 = no problems What would need to change to decrease this score? PRIORITY SCORE 10 = highest priority (“I really want to work on this”) and 1 = lowest priority (“I really do not want to work on this”) Opioid use Other illicit drug use: ______________ Alcohol use Tobacco use Physical health Mental health Legal/court issues Finances Job/employment Hobbies Family relations Partner relations Supportive drug-free network Education Keeping medication safe (e.g., not giving it away, selling it, having it stolen) Other Other M. Lofwall, February 27, 2017 (personal communication). Adapted with permission. 5-42 Medications for Opioid Use Disorder TIP 63 Goal Sheet and Coping Strategies Form Goals are things you would like to accomplish. Patient’s Name: _______________________________________________________________ Date: _________________________ 3-MONTH 1 GOALS 2 3 6-MONTH 1 GOALS 2 3 1-YEAR 1 GOALS 2 3 List of Triggers to Using Drugs People To Stay Away From Places To Stay Away From Ways To Cope or Manage Stress Without Using Drugs M. Lofwall, February 27, 2017 (personal communication). Adapted with permission. 5-43 TIP 63Part 5 of 5—Resources Related to Medications for Opioid Use Disorder ________________________________________________________________________________________________________________ ________________________________________________________________________________________________________________ ________________________________________________________________________________________________________________ ________________________________________________________________________________________________________________ Medical Management Visit Form Patient’s Name: ___________________________________________________________ ID#____________________________ Date: ____________________ Week#: _________ Dose: ________ mg □ No Show Heroin/cocaine or other illicit drug use since last visit? Symptoms or signs that might indicate return to use (e.g., changes in mood, physical appearance)? Since the last visit, are there any problems with the following: If yes, explain Drug Use □ Yes □ No Alcohol Use □ Yes □ No Psychiatric □ Yes □ No Medical □ Yes □ No Employment □ Yes □ No Social/Family □ Yes □ No Legal □ Yes □ No Any new problem to add to Treatment Plan Review? □ Yes □ No Plan to address any new problem _________________________________________________________________________________ Participation in Narcotics Anonymous or Alcoholics Anonymous since last visit? □ Yes □ No Length of Session: ________________ Healthcare Professional Signature: ___________________________________________ D. Fiellin, December 3, 2016 (personal communication). Adapted with permission. 5-44 Medications for Opioid Use Disorder TIP 63 Patient Urine Drug Screen and Medication Count Monitoring Form Patient’s Name: ______________________________________________________ Dates To Be Called: ____________________ Called for: □ Urine Drug Screen □ Medication Count at □Offce or □Pharmacy FOR: _____________________________________________________________ □ Buprenorphine/Naloxone □ Other (list drug: ___________________________, ___________________________, ___________________________) Documentation of Phone Call to Patient Patient was called at _____________________________ (insert phone #) on ____________________ (date) at _____:_____ (time) and informed of monitoring required (described above) within the next _______ hours. Check One: □ I spoke with patient □ Message left on answering machine/voicemail □ Message left with ________________________________________________ □ Other __________________________________________________________ Signature of Staff Member Making Phone Call: _______________________________________________________ M. Lofwall, February 27, 2017 (personal communication). Adapted with permission. 5-45 TIP 63Part 5 of 5—Resources Related to Medications for Opioid Use Disorder ________________________________________________ Pharmacy Tablet/Film Count Form (Note: Before sending this form, discuss with the pharmacist frst to explain goals and procedures and to ensure agreement and understanding.) Date: ___________________ To: Pharmacists @ ________________________________________ Pharmacy From: Healthcare Provider: ____________________________________________ Clinic Address: _________________________________________________ Phone Number: ________________________________________________ My patient, __________________________________, is starting offce-based buprenorphine treatment for opioid dependence. As part of monitoring this treatment, we ask the patient to do buprenorphine tablet/flm counts at random times (we call the patient when it’s time for a pill/flm count). The above-named patient lives much closer to your pharmacy than to our treatment clinic. It would be a big help to me and this patient if you would be able to perform periodic tablet/flm counts on his/her buprenorphine and then fax this form to us. On the days we call the patient for a random tablet/flm count, the patient would come to your pharmacy with his or her pill bottle. When we call the patient to go for a random tablet/flm count, we will fax this form to you. We would appreciate if you could record the tablet/flm count results on this form and fax it back to us the same day. This would be a real help to me in monitoring my patient’s treatment and also a great service to the patient. Thank you very much for your help with this! Sincerely, Signature Buprenorphine/naloxone formulation: _________________________________________ Dose per tablet/flm: _______________ Total # of tablets/flms remaining in bottle: ______________ Fill date on bottle: ___________________ Total # of tablets/flms dispensed on fll date: ____________ Tablet/flm count correct? □Yes □No Please fax this back to: _____________________________________ Thank You! M. Lofwall, February 27, 2017 (personal communication). Adapted with permission. 5-46 Medications for Opioid Use Disorder TIP 63 Standard Consent to Opioid Maintenance Treatment Form for OTPs CONSENT TO PARTICIPATE IN METHADONE OR BUPRENORPHINE TREATMENT Patient’s Name: _____________________________________________________ Date: ________________ I authorize and give voluntary consent to _________________________________ [insert name of program] to dispense and administer medications—including methadone or buprenorphine—to treat my opioid use disorder. Treatment procedures have been explained to me, and I understand that I should take my medication at the schedule determined by the program physician, or his/her designee, in accordance with federal and state regulations. I understand that, like all other medications, methadone or buprenorphine can be harmful if not taken as prescribed. It has been explained to me that I must safeguard these medications and not share them with anyone because they can be fatal to children and adults if taken without medical supervision. I also understand that methadone and buprenorphine produce physical opioid dependence. Like all medications, they may have side effects. Possible side effects, as well as alternative treatments and their risks and benefts, have been explained to me. I understand that it is important for me to inform any medical and psychiatric provider who may treat me that I am enrolled in an opioid treatment program. In this way, the provider will be aware of all the medications I am taking, can provide the best possible care, and can avoid prescribing medications that might affect my treatment with methadone or buprenorphine or my recovery. I understand that I may withdraw voluntarily from this treatment program and discontinue the use of these medications at any time. If I choose this option, I understand I will be offered medically supervised withdrawal. For women of childbearing age: Pregnant women treated with methadone or buprenorphine have better outcomes than pregnant women not in treatment who continue to use opioid drugs. Newborns of mothers who are receiving methadone or buprenorphine treatment may have opioid withdrawal symptoms (i.e., neonatal abstinence syndrome). The delivery hospital may require babies who are exposed to opioids before birth to spend a number of days in the hospital for monitoring of withdrawal symptoms. Some babies may also need medication to stop withdrawal. If I am or become pregnant, I understand that I should tell the medical staff of the OTP right away so I can receive or be referred to prenatal care. I understand that there are ways to maximize the healthy course of my pregnancy while I am taking methadone or buprenorphine. Signature of Patient: ___________________________________________________ Date of Birth: ________________ Date: ________________ Witness: ______________________________________________________________________ Adapted from material in the public domain.47 5-47 TIP 63Part 5 of 5—Resources Related to Medications for Opioid Use Disorder Buprenorphine Forms Buprenorphine Diversion Control Policy XYZ Medical Practice Offce-Based Opioid Use Disorder Policy and Procedure Manual Policy Title: Diversion Control for Patients Prescribed Transmucosal (Sublingual) Buprenorphine Effective Date: ______________________ (Month, Day, Year) This Diversion Control Policy is provided for educational and informational purposes only. It is intended to offer healthcare professionals guiding principles and policies regarding best practices in diversion control for patients who are prescribed buprenorphine. This policy is not intended to establish a legal or medical standard of care. Healthcare professionals should use their personal and professional judgment in interpreting these guidelines and applying them to the particular circum- stances of their individual patients and practice arrangements. The information provided in this Policy is provided “as is” with no guarantee as to its accuracy or completeness. Preamble: Healthcare professionals can now treat up to 275 patients with buprenorphine. This increased access may contrib- ute to increased diversion, misuse, and related harms. Signs that a patient is misusing or diverting buprenorphine include (1) missed appointments; (2) requests for early reflls because pills were lost, stolen, or other reasons; (3) urine screens negative for buprenorphine, positive for opioids; (4) claims of being allergic or intolerant to naloxone and requesting monotherapy; (5) nonhealing or fresh track marks; or (5) police reports of selling on the streets. Likewise, there are a range of reasons for diversion and misuse (e.g., diverting to family/friends with untreated opioid addiction with the intent of trying to “help” convince them to also get treatment; diverting to family/friends on a treatment waiting list; selling some or all of the medication to pay off old drug debts/purchase preferred opioid of misuse/pay for treatment in places where there are inadequate addiction treatment professionals taking private insurance or Medicaid for such reasons as inadequate reim- bursement/no reimbursement/burdensome prior authorization process). The safety and health of patients and others in the community could be at risk if misuse and diversion are not addressed proactively throughout treatment. The reputation of XYZ Medical Practice may also be put at risk. Defnitions: Diversion is defned as the unauthorized rerouting or misappropriation of prescription medication to someone other than for whom it was intended (including sharing or selling a prescribed medication); misuse includes taking medica- tion in a manner, by route or by dose, other than prescribed.48 Purpose: Misuse and diversion should be defned and discussed with patients at the time of treatment entry; periodically throughout treatment, particularly when there have been returns to illicit drug use; and when suspected (e.g., incorrect buprenorphine pill/flm count) or confrmed. These procedures will establish the steps to be taken to prevent, monitor, and respond to misuse and diversion of buprenorphine. The response should be therapeutic and matched to the patients’ needs, as untreated opioid use disorder and treatment dropout/administrative discharges may lead to increased patient morbidity and mortality and further use of diverted medications or illicit opioids associated with overdose death. Procedures for Prevention: • Use buprenorphine/naloxone combination products when medically indicated and cost is not an issue. Reserve the daily buprenorphine monoproducts for pregnant patients and patients who could not afford treatment if the combination product were required, who have a history of stability in treatment and low diversion risk, or who have arrangements for observed dosing. Buprenorphine monoproducts are recommended for pregnant women. • Counsel patients on safe storage of, and nonsharing of, medications. Patients must agree to safe storage of their medication. This is even more critical if there are children in the home where the patient lives. Counsel patients about acquiring locked devices and avoiding storage in parts of the home frequented by visitors (e.g., do not recommend storage in the kitchen or common bathrooms). Proactively discuss how medication should be stored and transported when traveling to minimize risk of unintended loss. • Counsel patients on taking medication as instructed and not sharing medication. Explicitly explain to patients the defnitions of diversion and misuse, with examples. Patients are required to take medication as instructed by the healthcare professional; for example, they may not crush or inject the medication. • Check the prescription drug monitoring program for new patients and check regularly thereafter. Prescription drug monitoring program reports can be a useful resource when there is little history available or when there is a concern based on observation. Check for prescriptions that interact with buprenorphine and for other buprenorphine prescribers. 5-48 Medications for Opioid Use Disorder TIP 63 • Prescribe a therapeutic dose that is tailored to the patient’s needs. Do not routinely provide an additional supply “just in case.” Question patients who say they need a signifcantly higher dose, particularly when they are already at 24 mg per day of buprenorphine equivalents. • Make sure the patient understands the practice’s treatment agreement and prescription policies. The XYZ Medical Practice’s treatment agreement and other documentation are clear about policies regarding number of doses in each prescription, reflls, and rules on “lost” prescriptions. Review the policies in person with the patient. Offer an opportunity for questions. Patient and provider must sign the agreement. Review the policies again with the patient at subsequent appointments. See Sample Buprenorphine Treatment Agreement or Sample XR-NTX Treatment Agreement as needed. Procedures for Monitoring: • Request random urine tests. The presence of buprenorphine in the urine indicates that the patient has taken some portion of the prescribed dose. Absence of buprenorphine in the urine supports nonadherence. Testing for bu- prenorphine metabolites (which are present only if buprenorphine is metabolized) should periodically be included to minimize the possibility that buprenorphine is added directly to the urine sample. Dipstick tests can be subverted or replaced. A range of strategies can be used to minimize falsifed urine collections, including (1) observed collection; (2) disallowing carry-in items (e.g., purses, backpacks) in the bathroom; (3) turning off running water and coloring toilet water to eliminate the possibility of dilution; (4) monitoring the bathroom door so that only one person can go in; and (5) testing the temperature of the urine immediately after voiding. • Schedule unannounced pill/flm counts. Periodically ask patients who are at high risk at initial or subsequent appoint- ments to bring in their medication containers for a pill/flm count. • With unannounced monitoring (both pill/flm counts and urine tests), the patient is contacted and must appear within a specifed time period (e.g., 24 hours) after the phone call. If the patient doesn’t show, then the provider should consider this as a positive indicator of misuse or diversion. • Directly observe ingestion. Patients take medication in front of the healthcare professional or another qualifed clinician and are observed until the medication dissolves in the mouth (transmucosal [sublingual or buccal] absorp- tion). Patients who are having diffculty adhering to their buprenorphine can have their medication provided under direct observation in the offce for a designated frequency (e.g., three times/week). • Limit medication supply. When directly observed doses in the offce are not practical, short prescription time spans can be used (e.g., weekly, 3 days at a time). Procedures To Respond to Misuse or Diversion: Misuse or diversion doesn’t mean automatic discharge from the practice. However, it will require consideration of one or more of the following procedures: • Evaluate the misuse and diversion. For instance, describe the incident of misuse (e.g., “the patient took the pre- scribed dose on three or more occasions by intravenous route immediately after starting treatment, stating that she believed the dose would not be adequate by sublingual route; she has just initiated treatment”) or diversion (“the patient gave half of dose to his wife, who is still using heroin and was withdrawing, because he did not want her to have to buy heroin off the street; she is on a waiting list for treatment”) and tailor the response to the behavior (e.g., reeducation of the patient on buprenorphine pharmacology in the frst example above; assistance with treatment entry for the spouse in the second example). Reassess the treatment plan and patient progress. Strongly consider smaller supplies of medication and supervised dosing for any patient who is taking medication intravenously or in- tranasally or diverting, regardless of reason. Treatment structure may need to be increased, including more frequent appointments, supervised administration, and increased psychosocial support. • Intensify treatment or level of care, if needed. Some patients may require an alternative treatment setting or pharma- cotherapy such as methadone. The clinician will discuss these alternatives with the patient to ensure optimal patient outcome. This should be discussed at treatment onset so the patient is aware of the consequences of misuse and diversion. • Document and describe the misuse and diversion incident. Also document the clinical thinking that supports the clinical response, which should be aimed at minimizing risk of diversion and misuse and treating the patient’s opioid use disorder at the level of care needed. Policy adapted from ASAM’s Offce-Based Opioid Use Disorder Policy and Procedure Manual, which is updated periodically; the most current version is available online (www.asam.org/docs/default-source/advocacy/sample-diversion-policy .pdf?sfvrsn=6). Adapted with permission.49 5-49 TIP 63Part 5 of 5—Resources Related to Medications for Opioid Use Disorder Buprenorphine Induction and Maintenance Appropriate Use Checklists Continued on next page 5-50 Medications for Opioid Use Disorder TIP 63 Available online (www.accessdata.fda.gov/drugsatfda_docs/rems/BTOD_2017-01-23_Appropriate_Use_Checklist.pdf). Reprinted from material in the public domain.50 5-51 TIP 63Part 5 of 5—Resources Related to Medications for Opioid Use Disorder Buprenorphine Treatment Agreement This form is for educational/informational purposes only. It doesn’t establish a legal or medical standard of care. Healthcare professionals should use their judgment in interpreting this form and applying it in the circumstances of their individual patients and practice arrangements. The information provided in this form is provided “as is” with no guarantee as to its accuracy or completeness. TREATMENT AGREEMENT I agree to accept the following treatment contract for buprenorphine offce-based opioid addiction treatment: 1. The risks and benefts of buprenorphine treatment have been explained to me. 2. The risks and benefts of other treatment for opioid use disorder (including methadone, naltrexone, and nonmedication treatments) have been explained to me. 3. I will keep my medication in a safe, secure place away from children (for example, in a lockbox). My plan is to store it [describe where and how _____________________________________________________________________]. 4. I will take the medication exactly as my healthcare provider prescribes. If I want to change my medication dose, I will speak with my healthcare provider frst. Taking more medication than my healthcare provider prescribes or taking it more than once daily as my healthcare provider prescribes is medication misuse and may result in supervised dosing at the clinic. Taking the medication by snorting or by injection is also medication misuse and may result in supervised dosing at the clinic, referral to a higher level of care, or change in medication based on my healthcare provider’s evaluation. 5. I will be on time to my appointments and respectful to the offce staff and other patients. 6. I will keep my healthcare provider informed of all my medications (including herbs and vitamins) and medical problems. 7. I agree not to obtain or take prescription opioid medications prescribed by any other healthcare provider without consulting my buprenorphine prescriber. 8. If I am going to have a medical procedure that will cause pain, I will let my healthcare provider know in advance so that my pain will be adequately treated. 9. If I miss an appointment or lose my medication, I understand that I will not get more medication until my next offce visit. I may also have to start having supervised buprenorphine dosing. 10. If I come to the offce intoxicated, I understand that my healthcare provider will not see me, and I will not receive more medication until the next offce visit. I may also have to start having supervised buprenorphine dosing. 11. I understand that it’s illegal to give away or sell my medication; this is diversion. If I do this, my treatment will no longer include unsupervised buprenorphine dosing and may require referral to a higher level of care, supervised dosing at the clinic, and/or a change in medication based on my healthcare provider’s evaluation. 12. Violence, threatening language or behavior, or participation in any illegal activity at the offce will result in treatment termination from the clinic. 13. I understand that random urine drug testing is a treatment requirement. If I do not provide a urine sample, it will count as a positive drug test. 14. I understand that I will be called at random times to bring my medication container into the offce for a pill or flm count. Missing medication doses could result in supervised dosing or referral to a higher level of care at this clinic or potentially at another treatment provider based on my individual needs. 15. I understand that initially I will have weekly offce visits until I am stable. I will get a prescription for 7 days of medication at each visit. 16. I can be seen every 2 weeks in the offce starting the second month of treatment if I have two negative urine drug tests in a row. I will then get a prescription for 14 days of medication at each visit. 17. I will go back to weekly visits if I have a positive drug test. I can go back to visits every 2 weeks when I have two negative drug tests in a row again. 18. I may be seen less than every 2 weeks based on goals made by my healthcare provider and me. 19. I understand that people have died by mixing buprenorphine with alcohol and other drugs like benzodiazepines (drugs like Valium, Klonopin, and Xanax). Continued on next page 5-52 Medications for Opioid Use Disorder TIP 63 20. I understand that treatment of opioid use disorder involves more than just taking medication. I agree to comply with my healthcare provider’s recommendations for additional counseling and/or for help with other problems. 21. I understand that there is no fxed time for being on buprenorphine and that the goal of treatment is for me to stop using all illicit drugs and become successful in all aspects of my life. 22. I understand that I may experience opioid withdrawal symptoms when I stop taking buprenorphine. 23. I have been educated about the other two FDA-approved medications used for opioid dependence treatment, methadone and naltrexone. 24. I have been educated about the increased chance of pregnancy when stopping illicit opioid use and starting buprenorphine treatment and been informed about methods for preventing pregnancy. Other specifc items unique to my treatment include: Patient’s Name (print): _____________________________________________________ Patient’s Signature: ________________________________________________________ Date: ____________________ This form is adapted from the American Society of Addiction Medicine’s Sample Treatment Agreement, which is updated periodically; the most current version of the agreement is available online (www.asam.org/docs /default-source/advocacy/sample-treatment-agreement30fa159472bc604ca5b7ff000030b21a.pdf?sfvrsn =bd4675c2_0). Adapted with permission.51 5-53 TIP 63Part 5 of 5—Resources Related to Medications for Opioid Use Disorder Naltrexone forms Key Techniques for Reducing Injection Site Reactions52 To reduce severe injection site reactions when administering XR-NTX via intramuscular injection, use the following techniques: • Use one of the administration needles provided with the XR-NTX kit to ensure that the injection reaches the gluteal muscle. Use the 2-inch needle for patients who have more subcuta- neous adipose tissue. Use the 1.5-inch needle for patients with less subcutaneous adipose tissue. Either needle is appropriate for use with patients who have average amounts of subcutaneous adipose tissue. • Use aseptic technique when administering intramuscularly. Using a circular motion, clean the injection site with an alcohol swab. Let the area dry before administering the injection. Do not touch this area again before administration. • Use proper deep intramuscular injection technique into the gluteal muscle. XR-NTX must not be injected intravenously, subcutaneously, or into adipose tissue. Accidental subcutaneous injection may increase the risk of severe injection site reactions. − Administer the suspension by deep intramuscular injection into the upper outer quadrant of gluteal muscle, alternating buttocks per monthly injection. − Remember to aspirate for blood before injection. If blood aspirates or the needle clogs, do not inject. Change to the spare needle provided in the package and administer into an adjacent site in the same gluteal region, again aspirating for blood before injection. − Inject the suspension in a smooth, continuous motion. A patient counseling tool is available to help you counsel your patients before administration about the serious risks associated with XR-NTX. The above information is a selection of key safety information about the XR-NTX injection. For complete safety information, refer to the directions for use and the prescribing information provided in the medication kit. You can also obtain this information online (www.vivitrolrems.com) or by calling 1-800-VIVITROL. Available online (www.vivitrolrems.com/content/pdf/patinfo-injection-poster.pdf). 5-54 Medications for Opioid Use Disorder TIP 63 Patient Counseling Tool for XR-NTX Risk of sudden opioid withdrawal during initiation and re-initiation of VIVITROL Using any type of opioid including street drugs, prescription pain medicines, cough, cold or diarrhea medicines that contain opioids, or opioid dependence treatments buprenorphine or methadone, in the 7 to 14 days before starting VIVITROL may cause severe and potentially dangerous sudden opioid withdrawal. Risk of opioid overdose Patients may be more sensitive to the effects of lower amounts of opioids: Patients should tell their family and people close to them about the increased sensitivity to opioids and the risk of overdose even when using lower doses of opioids or amounts that they used before treatment. Using large amounts of opioids, such as prescription pain pills or heroin, to overcome effects of VIVITROL can lead to serious injury, coma, and death. Risk of severe reactions at the injection site Remind patients of these possible symptoms at the injection site: Some of these injection site reactions have required surgery. Tell your patients to contact a healthcare provider if they have any reactions at the injection site. Risk of liver injury, including liver damage or hepatitis Remind patients of the possible symptoms of liver damage or hepatitis. Patients may not feel the therapeutic effects of opioid-containing medicines for pain, cough or cold, or diarrhea while taking VIVITROL. Patients should carry written information with them at all times to alert healthcare providers that they are taking VIVITROL, so they can be treated properly in an emergency. A Patient Wallet Card or Medical Alert Bracelet can be ordered from: 1-800-848-4876, Option #1. Patient Counseling Tool VIVITROL® (naltrexone for extended-release injectable suspension) • After stopping opioids (detoxifcation) • If a dose of VIVITROL is missed • When the next VIVITROL dose is due • After VIVITROL treatment stops • Intense pain • Blisters • The area feels hard • Open wound • Large areas of swelling • Dark scab • Lumps • Stomach area pain lasting more than a few days • Yellowing of the whites of eyes • Dark urine • Tiredness PLEASE SEE PRESCRIBING INFORMATION AND MEDICATION GUIDE. Alkermes® and VIVITROL® are registered trademarks of Alkermes, Inc. ©2013 Alkermes, Inc. All rights reserved VIV-001317 Printed in U.S.A w w w.vivitrol.com Available online (www.vivitrolrems.com/content/pdf/patinfo-counseling-tool.pdf). Reprinted with permission.53 5-55 TIP 63Part 5 of 5—Resources Related to Medications for Opioid Use Disorder Sample XR-NTX Treatment Agreement This form is for educational/informational purposes only. It doesn’t establish a legal or medical standard of care. Healthcare professionals should use their judgment in interpreting this form and applying it in the circumstances of their individual patients and practice arrangements. The information provided in this form is provided “as is” with no guarantee as to its accuracy or completeness. TREATMENT AGREEMENT I agree to accept the following treatment agreement for extended-release injectable naltrexone (XR-NTX) offce-based opioid use disorder treatment: 1. The risks and benefts of XR-NTX treatment have been explained to me, and I understand the information provided. 2. The risks and benefts of other treatment for opioid use disorder (including methadone, buprenorphine, and nonmedication treatments) have been explained to me. 3. I will be on time to my appointments and respectful to the offce staff and other patients. 4. I will keep my healthcare provider informed of all my medications (including herbs and vitamins) and medical problems. 5. I agree not to obtain or take prescription opioid medications prescribed by any other healthcare provider. 6. If I am going to have a medical procedure that will cause pain, I will let my healthcare provider know in advance so that my pain will be adequately treated. 7. If I miss a scheduled appointment for my next XR-NTX injection, I understand that I should reschedule the appointment as soon as possible because it is important to receive the medication on time to reduce the risk of opioid overdose should I return to use. 8. If I come to the offce intoxicated, I understand that my healthcare provider will not see me. 9. Violence, threatening language or behavior, or participation in any illegal activity at the offce will result in treatment termination from the clinic. 10. I understand that random urine drug testing is a treatment requirement. If I do not provide a urine sample, it will count as a positive drug test. 11. I understand that initially I will have weekly offce visits until my condition is stable. 12. I can be seen every 2 weeks in the offce starting the second month of treatment if I have two negative urine drug tests in a row. 13. I may be seen less than every 2 weeks based on goals made by my healthcare provider and me. 14. I understand that people have died trying to overcome the opioid blockade by taking large amounts of opioids. 15. I understand that treatment of opioid use disorder involves more than just taking medication. I agree to follow my healthcare provider’s recommendations for additional counseling and/or for help with other problems. 16. I understand that there is no fxed time for being on XR-NTX and that the goal of treatment is for me to stop using all illicit drugs and become successful in all aspects of my life. 17. I understand that my risk of overdose increases if I go back to using opioids after stopping XR-NTX. 18. I have been educated about the other two FDA-approved medications used to treat opioid use disorder, methadone and buprenorphine, and I prefer to receive treatment with XR-NTX. 19. I have been educated about the increased chance of pregnancy when stopping illicit opioid use and starting XR- NTX treatment and have been informed about methods for preventing pregnancy. 20. I have been informed that if I become pregnant during naltrexone treatment, I should inform my provider and have a discussion about the risks and benefts of continuing to take XR-NTX. Other specifc items unique to my treatment include: Patient Name (print): _____________________________________________________ Patient Signature: ________________________________________________________ Date: ____________________ This form is adapted from ASAM’s Sample Treatment Agreement, which is updated periodically; the most current version of the agreement is available online (www.asam.org/docs/default-source/advocacy/sample-treatment-agreement30fa159472bc604ca5b7ff0 00030b21a.pdf?sfvrsn=0). Adapted with permission.54 5-56 Medications for Opioid Use Disorder TIP 63 Glossary of TIP Terminology Abuse liability: The likelihood that a medication with central nervous system activity will cause desirable psychological effects, such as euphoria or mood changes, that promote the medication’s misuse. Addiction: As defned by ASAM,55“a primary, chronic disease of brain reward, motivation, memory, and related circuitry.” It is characterized by inability to consistently abstain, impairment in behavioral control, craving, diminished recognition of signifcant problems with one’s behaviors and interpersonal relationships, and a dysfunctional emotional response. Like other chronic diseases, addiction often involves cycles of relapse and remission. The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition56 (DSM-5), does not use the term for diagnostic purposes, but it commonly describes the more severe forms of opioid use disorder. Bioavailability: Proportion of medication administered that reaches the bloodstream. Care provider: Encompasses both healthcare professionals and other professionals who do not provide medical services, such as counselors or providers of supportive services. Often shortened to “provider.” Cross-tolerance: Potential for people tolerant to one opioid (e.g., heroin) to be tolerant to another (e.g., methadone). Dissociation: Rate at which a drug uncouples from the receptor. A drug with a longer dissoci- ation rate will have a longer duration of action than a drug with a shorter dissociation rate. Half-life: Rate of removal of a drug from the body. One half-life removes 50 percent from the plasma. After a drug is stopped, it takes fve half-lives to remove about 95 percent from the plasma. If a drug is continued at the same dose, its plasma level will continue to rise until it reaches steady state concentrations after about fve half-lives. Healthcare professionals: Physicians, nurse practitioners, physician assistants, and other medical service professionals who are eligible to prescribe medications for and treat patients with OUD (i.e., until October 1, 2023, clinical nurse specialists, certifed registered nurse anesthetists, certifed nurse midwives). The term “prescribers” also refers to these healthcare professionals. Induction: Process of initial dosing with medica- tion for OUD treatment until the patient reaches a state of stability; also called initiation. Intrinsic activity: The degree of receptor activation attributable to drug binding. Full agonist, partial agonist, and antagonist are terms that describe the intrinsic activity of a drug. Maintenance treatment: Providing medications to achieve and sustain clinical remission of signs and symptoms of OUD and support the individual process of recovery without a specifc endpoint (as with the typical standard of care in medical and psychiatric treatment of other chronic illnesses). Medically supervised withdrawal (formerly called detoxifcation): Using an opioid agonist (or an alpha-2 adrenergic agonist if opioid agonist is not available) in tapering doses or other med- ications to help a patient discontinue illicit or prescription opioids. Medical management: Process whereby health- care professionals provide medication, basic brief supportive counseling, monitoring of drug use and medication adherence, and referrals, when necessary, to addiction counseling and other services to address the patient’s medical, mental health, comorbid addiction, and psycho- social needs. 5-57 TIP 63Part 5 of 5—Resources Related to Medications for Opioid Use Disorder Mutual-help groups: Groups of people who work together on obtaining and maintaining recovery. Unlike peer support (e.g., the use of recovery coaches), mutual-help groups consist entirely of people who volunteer their time and typically have no offcial connection to treatment programs. Most are self-supporting. Although 12-Step groups such as AA and NA are the most widespread and well-researched type of mutual- help groups, other groups may be available in some areas. They range from groups affliated with a religion or church (e.g., Celebrate Recovery, Millati Islami) to purely secular groups (e.g., SMART Recovery, Women for Sobriety). Offce-based opioid treatment (OBOT): Providing medication for OUD in settings other than certifed OTPs. Opiates: A subclass of opioids derived from opium (e.g., morphine, codeine, thebaine). Opioid misuse: The use of prescription opioids in any way other than as directed by a prescriber; the use of any opioid in a manner, situation, amount, or frequency that can cause harm to self or others.57 Opioid receptor agonist: A substance that has an affnity for and stimulates physiological activity at cell receptors in the central nervous system that are normally stimulated by opioids. Mu-opioid receptor full agonists (e.g., methadone) bind to the mu-opioid receptor and produce actions similar to those produced by the endogenous opioid beta-endorphin. Increasing the dose increases the effect. Mu-opioid receptor partial agonists (e.g., buprenorphine) bind to the mu-opioid receptor. Unlike with full agonists, increasing their dose may not produce additional effects once they have reached their maximal effect. At low doses, partial agonists may produce effects similar to those of full agonists. Opioid receptor antagonist: A substance that has an affnity for opioid receptors in the central nervous system without producing the physi- ological effects of opioid agonists. Mu-opioid receptor antagonists (e.g., naltrexone) can block the effects of exogenously administered opioids. Opioid receptor blockade: Blunting or blocking of the euphoric effects of an opioid through opioid receptor occupancy by an opioid agonist (e.g., methadone, buprenorphine) or antagonist (e.g., naltrexone). Opioids: All natural, synthetic, and semisynthetic substances that have effects similar to morphine. They can be used as medications having such effects (e.g., methadone, buprenorphine, oxycodone). Opioid treatment program (OTP): An accredited treatment program with SAMHSA certifcation and DEA registration to administer and dispense opioid agonist medications that are approved by FDA to treat opioid addiction. Currently, these include methadone and buprenorphine products. Other pharmacother- apies, such as naltrexone, may be provided but are not subject to these regulations. OTPs must provide adequate medical, counseling, voca- tional, educational, and other assessment and treatment services either onsite or by referral to an outside agency or practitioner through a formal agreement.58 Opioid use disorder (OUD): Per DSM-5,59 a disorder characterized by loss of control of opioid use, risky opioid use, impaired social functioning, tolerance, and withdrawal. Tolerance and withdrawal do not count toward the diagnosis in people experiencing these symptoms when using opioids under appropriate medical supervision. OUD covers a range of severity and replaces what the DSM-IV termed “opioid abuse” and “opioid dependence.” An OUD diagnosis is applicable to a person who uses opioids and experiences at least 2 of the 11 symptoms in a 12-month period. (See Exhibit 2.11 in Part 2 for full DSM-5 diagnostic criteria for OUD.) 5-58 Medications for Opioid Use Disorder TIP 63 Peer support: The use of peer support spe- cialists in recovery to provide nonclinical (i.e., not requiring training in diagnosis or treatment) recovery support services to individuals in recovery from addiction and to their families. Peer support specialist: Someone in recovery who has lived experience in addiction plus skills learned in formal training. Peer support spe- cialists may be paid professionals or volunteers. They are distinguished from members of mutual- help groups because they maintain contact with treatment staff. They offer experiential knowledge that treatment staff often lack. Prescribers: Healthcare professionals who are eligible to prescribe medications for OUD. Psychosocial support: Ancillary services to enhance a patient’s overall functioning and well-being, including recovery support services, case management, housing, employment, and educational services. Psychosocial treatment: Interventions that seek to enhance a patient’s social and mental functioning, including addiction counseling, contingency management, and mental health services. Receptor affnity: Strength of the bond between a medication and its receptor. A medication with high mu-opioid receptor affnity requires lower concentrations to occupy the same number of mu-opioid receptors as a drug with lower mu-opioid receptor affnity. Drugs with high mu-opioid receptor affnity may displace drugs with lower affnity. Recovery: A process of change through which individuals improve their health and wellness, live a self-directed life, and strive to reach their full potential. Even individuals with severe and chronic SUDs can, with help, overcome their SUDs and regain health and social function. Although abstinence from all substance misuse is a cardinal feature of a recovery lifestyle, it is not the only healthy, prosocial feature. Patients taking FDA-approved medication to treat OUD can be considered in recovery. Recovery capital: The sum of the internal (e.g., motivation, self-effcacy, spirituality) and external (e.g., access to health care, employment, family support) resources that an individual can draw on to begin and sustain recovery from SUDs. Recovery-oriented care: A service orientation that supports individuals with behavioral health conditions in a process of change through which they can improve their health and wellness, live self-directed lives, and strive to reach their full potential. Relapse: A process in which a person with OUD who has been in remission experiences a return of symptoms or loss of remission. A relapse is different from a return to opioid use in that it involves more than a single incident of use. Relapses occur over a period of time and can be interrupted. Relapse need not be long lasting. The TIP uses relapse to describe relapse preven- tion, a common treatment modality. Remission: A medical term meaning a disappearance of signs and symptoms of the disease.60 DSM-5 defnes remission as present in people who previously met OUD criteria but no longer meet any OUD criteria (with the possible exception of craving).61 Remission is an essential element of recovery. Return to opioid use: One or more instances of opioid misuse without a return of symptoms of OUD. A return to opioid use may lead to relapse. Tolerance: Alteration of the body’s responsive- ness to alcohol or other drugs (including opioids) such that higher doses are required to produce the same effect achieved during initial use. See also medically supervised withdrawal. 5-59 TIP 63Part 5 of 5—Resources Related to Medications for Opioid Use Disorder Notes 1 Centers for Disease Control and Prevention, National Center for Health Statistics. (2020). Multiple Cause of Death 2018-2019 on CDC WONDER Online Database, released in 2020. Retrieved April 29, 2021, from https:// wonder.cdc.gov/mcd.html 2 National Highway Traffc Safety Administration. (2020). NHTSA Releases 2019 Crash Fatality Data. Retrieved April 29, 2021, from www.nhtsa.gov/press-releases/ nhtsa-releases-2019-crash-fatality-data 3 Babor, T. F., Higgins-Biddle, J. C., Saunders, J. B., & Monteiro, M. G. (2001). The Alcohol Use Disorders Identifcation Test. Guidelines for use in primary care (2nd ed.). Geneva, Switzerland: The World Health Organization. 4 Bush, K., Kivlahan, D. R., McDonell, M. B., Fihn, S. D., & Bradley, K. A. (1998). The AUDIT alcohol consumption questions (AUDIT-C): An effective brief screening test for problem drinking. Ambulatory Care Quality Improvement Project (ACQUIP). Alcohol Use Disorders Identifcation Test. Archives of Internal Medicine, 158(16), 1789–1795. 5 Skinner, H. A. (1982). The Drug Abuse Screening Test. Addictive Behavior, 7(4), 363–371. 6 Yudko, E., Lozhkina, O., & Fouts, A. (2007). A comprehensive review of the psychometric properties of the Drug Abuse Screening Test. Journal of Substance Abuse Treatment, 32, 189–198. 7 American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed., p. 541). Arlington, VA: American Psychiatric Publishing. 8 Heatherton, T. F., Kozlowski, L. T., Frecker, R. C., Rickert, W., & Robinson, J. (1989). Measuring the heaviness of smoking: Using self-reported time to the frst cigarette of the day and number of cigarettes smoked per day. British Journal of Addiction, 84(7), 791–799. 9 Smith, P. C., Schmidt, S. M., Allensworth-Davies, D., & Saitz, R. (2009). Primary care validation of a single- question alcohol screening test. Journal of General Internal Medicine, 24(7), 783–788. doi:10.1007/ s11606-009-0928-6 10 Substance Abuse and Mental Health Services Administration. (2016). SAMHSA opioid overdose prevention toolkit. HHS Publication No. (SMA) 16-4742. Rockville, MD: Substance Abuse and Mental Health Services Administration. 11 Smith, P. C., Schmidt, S. M., Allensworth-Davies, D., & Saitz, R. (2010). A single-question screening test for drug use in primary care. Archives of Internal Medicine, 170(13), 1155–1160. 12 Shapiro, B., Coffa, D., & McCance-Katz, E. F. (2013). A primary care approach to substance misuse. American Family Physician, 88(2), 113–121. 13 McNeely, J., Wu, L. T., Subramaniam, G., Sharma, G., Cathers, L. A., Svikis, D., … Schwartz, R. P. (2016). Performance of the Tobacco, Alcohol, Prescription Medication, and Other Substance Use (TAPS) Tool for substance use screening in primary care patients. Annals of Internal Medicine, 165(10), 690–699. 14 Tiet, Q. Q., Leyva, Y. E., Moos, R. H., Frayne, S. M., Osterberg, L., & Smith, B. (2015). Screen of drug use: Diagnostic accuracy of a new brief tool for primary care. JAMA Internal Medicine, 175(8), 1371–1377. 15 Lynch, K. (2014). San Francisco General Hospital laboratory protocol. San Francisco, CA: San Francisco General Hospital. 16 Warner, E., & Lorch, E. (2014). Laboratory diagnosis. In R. K. Ries, D. A. Fiellin, S. C. Miller, & R. Saitz (Eds.), Principles of addiction medicine (5th ed., pp. 332–343). Philadelphia, PA: Wolters Kluwer. 17 Milone, M. C. (2012). Laboratory testing for prescription opioids. Journal of Medical Toxicology,8(4), 408–416. doi:10.1007/s13181-012-0274-7 18 Leavitt, S. B., Shinderman, M., Maxwell, S., Eap, C. B., & Paris, P. (2000). When “enough” is not enough: New perspectives on optimal methadone maintenance dose. Mount Sinai Journal of Medicine, 67(5–6), 404–411. 19 American Society of Addiction Medicine. (2016). Sample offce-based opioid use disorder policy and procedure manual. Retrieved October 19, 2017, from www.asam. org/docs/default-source/advocacy/sample -diversion-policy.pdf?sfvrsn=0 20 Roxane Laboratories. (2015). Buprenorphine HCl sublingual tablets: Full prescribing information. Retrieved October 16, 2017, from http://dailymed.nlm .nih.gov/dailymed/drugInfo.cfm?setid=1bf8b35a -b769-465c-a2f8-099868dfcd2f 21 Roxane Laboratories. (2015). Buprenorphine HCl sublingual tablets: Full prescribing information. Retrieved October 16, 2017, from http://dailymed.nlm .nih.gov/dailymed/drugInfo.cfm?setid=1bf8b35a -b769-465c-a2f8-099868dfcd2f 22 Nasser, A. F., Heidbreder, C., Liu, Y., & Fudala, P. J. (2015). Pharmacokinetics of sublingual buprenorphine and naloxone in subjects with mild to severe hepatic impairment (Child-Pugh classes A, B, and C), in hepatitis C virus-seropositive subjects, and in healthy volunteers. Clinical Pharmacokinetics, 54(8), 837–849. 23 Durand, F., & Valla, D. (2008). Assessment of prognosis of cirrhosis. Seminars in Liver Disease, 28(1), 110–122. 5-60 Medications for Opioid Use Disorder TIP 63 24 Durand, F., & Valla, D. (2008). Assessment of prognosis of cirrhosis. Seminars in Liver Disease, 28(1), 110–122. 25 Indivior. (2015). Suboxone (buprenorphine and naloxone) sublingual flm: Full prescribing information. Retrieved October 16, 2017, from www.suboxone.com/pdfs/ prescribing-information.pdf 26 Nasser, A. F., Heidbreder, C., Liu, Y., & Fudala, P. J. (2015). Pharmacokinetics of sublingual buprenorphine and naloxone in subjects with mild to severe hepatic impairment (Child-Pugh classes A, B, and C), in hepatitis C virus-seropositive subjects, and in healthy volunteers. Clinical Pharmacokinetics, 54(8), 837–849. 27 Roxane Laboratories. (2015). Buprenorphine HCl sublingual tablets: Full prescribing information. Retrieved October 16, 2017, from http://dailymed.nlm .nih.gov/dailymed/drugInfo.cfm?setid=1bf8b35a -b769-465c-a2f8-099868dfcd2f 28 Indivior. (2015). Suboxone (buprenorphine and naloxone) sublingual flm: Full prescribing information. Retrieved October 16, 2017, from www.suboxone.com/pdfs/ prescribing-information.pdf 29 Nasser, A. F., Heidbreder, C., Liu, Y., & Fudala, P. J. (2015). Pharmacokinetics of sublingual buprenorphine and naloxone in subjects with mild to severe hepatic impairment (Child-Pugh classes A, B, and C), in hepatitis C virus-seropositive subjects, and in healthy volunteers. Clinical Pharmacokinetics, 54(8), 837–849. 30 Durand, F., & Valla, D. (2008). Assessment of prognosis of cirrhosis. Seminars in Liver Disease, 28(1), 110–122. 31 Nasser, A. F., Heidbreder, C., Liu, Y., & Fudala, P. J. (2015). Pharmacokinetics of sublingual buprenorphine and naloxone in subjects with mild to severe hepatic impairment (Child-Pugh classes A, B, and C), in hepatitis C virus-seropositive subjects, and in healthy volunteers. Clinical Pharmacokinetics, 54(8), 837–849. 32 Roxane Laboratories. (2015). Buprenorphine HCl sublingual tablets: Full prescribing information. Retrieved October 16, 2017, from http://dailymed.nlm .nih.gov/dailymed/drugInfo.cfm?setid=1bf8b35a -b769-465c-a2f8-099868dfcd2f 33 Nasser, A. F., Heidbreder, C., Liu, Y., & Fudala, P. J. (2015). Pharmacokinetics of sublingual buprenorphine and naloxone in subjects with mild to severe hepatic impairment (Child-Pugh classes A, B, and C), in hepatitis C virus-seropositive subjects, and in healthy volunteers. Clinical Pharmacokinetic, 54(8), 837–849. 34 Substance Abuse and Mental Health Services Administration. (2016). Sublingual and transmucosal buprenorphine for opioid use disorder: Review and update. Advisory, Vol. 15, Issue 1. Rockville, MD: Substance Abuse and Mental Health Services Administration. 35 Donovan, D. M., Ingalsbe, M. H., Benbow, J., & Daley, D. C. (2013). 12-step interventions and mutual support programs for substance use disorders: An overview. Social Work in Public Health, 28(3–4), 313–332. 36 McLellan, A. T., & White, W. (2012). Opioid maintenance and recovery-oriented systems of care: It is time to integrate (p. 2). London, England: National Treatment Agency for Substance Misuse. 37 Substance Abuse and Mental Health Services Administration. (2016). Pocket guide: Medication-assisted treatment of opioid use disorder. HHS Publication No. (SMA) 16-4892PG. Rockville, MD: Substance Abuse and Mental Health Services Administration. 38 Substance Abuse and Mental Health Services Administration. (2015). Clinical use of extended-release injectable naltrexone in the treatment of opioid use disorder: A brief guide. HHS Publication No. (SMA) 14-4892R. Rockville, MD: Substance Abuse and Mental Health Services Administration. 39 Mattick, R. P., Breen, C., Kimber, J., & Davoli, M. (2014). Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. Cochrane Database of Systematic Reviews, 2014(2), 1–84. 40 Mattick, R. P., Breen, C., Kimber, J., & Davoli, M. (2009). Methadone maintenance therapy versus no opioid replacement therapy for opioid dependence. Cochrane Database of Systematic Reviews, 2009(3), 1–19. 41 Minozzi, S., Amato, L., Vecchi, S., Davoli, M., Kirchmayer, U., & Verster, A. (2011). Oral naltrexone maintenance treatment for opioid dependence. Cochrane Database Systems Review, 4, CD001333. 42 Krupitsky, E., Zvartau, E., Blokhina, E., Verbitskaya, E., Wahlgren, V., Tsoy-Podosenin, M., … Woody, G. E. (2012.) Randomized trial of long-acting sustained-release naltrexone implant vs oral naltrexone or placebo for preventing relapse to opioid dependence. Archives of General Psychiatry, 69(9), 973–981. 43 Lee, J. D., Friedmann, P. D., Kinlock, T. W., Nunes, E. V., Boney, T. Y., Hoskinson, R. A., Jr., … O’Brien, C. P. (2016). Extended-release naltrexone to prevent opioid relapse in criminal justice offenders. New England Journal of Medicine, 374(13), 1232–1242. 44 Minozzi, S., Amato, L., Vecchi, S., Davoli, M., Kirchmayer, U., & Verster, A. (2011). Oral naltrexone maintenance treatment for opioid dependence. Cochrane Database of Systematic Reviews, 2, CD001333. 45 Substance Abuse and Mental Health Services Administration. (2016). Sublingual and transmucosal buprenorphine for opioid use disorder: Review and update. Advisory, Vol. 15, Issue 1. Rockville, MD: Substance Abuse and Mental Health Services Administration. 5-61 TIP 63Part 5 of 5—Resources Related to Medications for Opioid Use Disorder 46 Lintzeris, N., & Nielsen, S. (2010). Benzodiazepines, methadone and buprenorphine: Interactions and clinical management. American Journal on Addictions, 19(1), 59–72. 47 Substance Abuse and Mental Health Services Administration. (2015). Federal guidelines for opioid treatment programs. HHS Publication No. (SMA) PEP15-FEDGUIDEOTP. Rockville, MD: Substance Abuse and Mental Health Services Administration. 48 Lofwall, M. & Walsh, S. (2014). A review of buprenorphine diversion and misuse: The current evidence base and experiences from around the world (p. 316). Journal of Addiction Medicine, 8(5), 315–326. 49 American Society of Addiction Medicine. (2016). Sample offce-based opioid use disorder policy and procedure manual. Retrieved October 19, 2017, from www.asam.org/docs/default-source/advocacy/sample -diversion-policy.pdf?sfvrsn=0 50 Food and Drug Administration (2017, May). Appropriate use checklist: Buprenorphine-containing transmucosal products for opioid dependence. Silver Spring, MD: Food and Drug Administration. 51 American Society of Addiction Medicine. (2017). Sample treatment agreement. Retrieved October 19, 2017, from www.asam.org/docs/default-source /advocacy/sample-treatment-agreement30fa159472bc 604ca5b7ff000030b21a.pdf?sfvrsn=0 52 Alkermes. (2015). Key techniques to reduce severe injection site reactions: VIVITROL (naltrexone for extended release injectable suspension) intramuscular injection. Retrieved January 9, 2018, from www .vivitrolrems.com/content/pdf/patinfo-injection -poster.pdf 53 Alkermes. (2013). Patient counseling tool: VIVITROL (naltrexone for extended-release injectable suspension). Retrieved January 9, 2018, from www.vivitrolrems.com /content/pdf/patinfo-counseling-tool.pdf 54 American Society of Addiction Medicine. (2017). Sample treatment agreement. Retrieved October 19, 2017, from www.asam.org/docs/default-source /advocacy/sample-treatment-agreement30fa159472bc60 4ca5b7ff000030b21a.pdf?sfvrsn=0 55 American Society of Addiction Medicine. (2011). Defnition of addiction. Retrieved October 30, 2017, from www.asam.org/resources/defnition-of-addiction 56 American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Arlington, VA: American Psychiatric Publishing. 57 Department of Health and Human Services, Offce of the Surgeon General. (2016). Facing addiction in America: The Surgeon General’s report on alcohol, drugs, and health. Washington, DC: Department of Health and Human Services. 58 Substance Abuse and Mental Health Services Administration. (2015). Federal guidelines for opioid treatment programs. HHS Publication No. (SMA) PEP15- FEDGUIDEOTP. Rockville, MD: Substance Abuse and Mental Health Services Administration. 59 American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Arlington, VA: American Psychiatric Publishing. 60 National Cancer Institute. (n.d.). NCI dictionary of cancer terms: Remission. Retrieved November 22, 2017, from www.cancer.gov/publications/dictionaries /cancer-terms?cdrid=45867 61 American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Arlington, VA: American Psychiatric Publishing. This page intentionally left blank. Available TIPs TIPs may be ordered or downloaded for free from SAMHSA’s Publications Ordering webpage at https:// store.samhsa.gov. Or, please call SAMHSA at 1-877-SAMHSA-7 (1-877-726-4727) (English and Español). TIP 24 A Guide to Substance Abuse Services for TIP 46 Substance Abuse: Administrative Issues in Primary Care Clinicians Outpatient Treatment TIP 25 Substance Abuse Treatment and Domestic TIP 47 Substance Abuse: Clinical Issues in Intensive Violence Outpatient Treatment TIP 26 Treating Substance Use Disorder in Older TIP 48 Managing Depressive Symptoms in Adults Substance Abuse Clients During Early TIP 27 Comprehensive Case Management for Recovery Substance Abuse Treatment TIP 49 Incorporating Alcohol Pharmacotherapies TIP 29 Substance Use Disorder Treatment for Into Medical Practice People With Physical and Cognitive TIP 50 Addressing Suicidal Thoughts and Behaviors Disabilities in Substance Abuse Treatment TIP 30 Continuity of Offender Treatment for TIP 51 Substance Abuse Treatment: Addressing the Substance Use Disorders From Institution to Specifc Needs of Women Community TIP 52 Clinical Supervision and Professional TIP 31 Screening and Assessing Adolescents for Development of the Substance Abuse Substance Use Disorders Counselor TIP 34 Brief Interventions and Brief Therapies for TIP 53 Addressing Viral Hepatitis in People With Substance Abuse Substance Use Disorders TIP 35 Enhancing Motivation for Change in TIP 54 Managing Chronic Pain in Adults With or in Substance Abuse Treatment Recovery From Substance Use Disorders TIP 36 Substance Abuse Treatment for Persons with TIP 55 Behavioral Health Services for People Who Child Abuse and Neglect Issues Are Homeless TIP 37 Substance Abuse Treatment for Persons TIP 56 Addressing the Specifc Behavioral Health With HIV/AIDS Needs of Men TIP 38 Integrating Substance Abuse Treatment and TIP 57 Trauma-Informed Care in Behavioral Health Vocational Services Services TIP 39 Substance Use Disorder Treatment and TIP 58 Addressing Fetal Alcohol Spectrum Family Therapy Disorders (FASD) TIP 41 Substance Abuse Treatment: Group Therapy TIP 59 Improving Cultural Competence TIP 42 Substance Abuse Treatment for Persons TIP 60 Using Technology-Based Therapeutic Tools With Co-Occurring Disorders in Behavioral Health Services TIP 44 Substance Abuse Treatment for Adults in TIP 61 Behavioral Health Services for American the Criminal Justice System Indians and Alaska Natives TIP 45 Detoxifcation and Substance Abuse TIP 63 Medications for Opioid Use Disorder Treatment Publication No. PEP21-02-01-002 First released 2018. Revised 2019, 2020, and 2021. U.S. Department of Health and Human Services Substance Abuse and Mental Health Services Administration Center for Substance Abuse Treatment TIP 63_Comp FrontMatter TIP 63_ExecutiveSummary TIP 63_Part1 TIP 63_Part2 TIP 63_Part3 TIP 63_Part4 TIP 63_Part5