Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction

A Treatment Improvement Protocol TIP 40

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES BP Substance Abuse and Mental Health Services Administration Buprenorphine Center for Substance Abuse Treatment Clinical Guide www.samhsa.gov e de i hin p Gu l ca

renor Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction TIP 40 p lini C Bu BP BP BP Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction

Laura McNicholas, M.D., Ph.D. Consensus Panel Chair

A Treatment Improvement Protocol TIP 40

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Substance Abuse and Mental Health Services Administration Center for Substance Abuse Treatment

1 Choke Cherry Road Rockville, MD 20857 Acknowledgments described in this document are intended or should be inferred. The guidelines in this Numerous people contributed to the document should not be considered development of this TIP (see pp. ix, xi, and substitutes for individualized client care and appendix J). This publication was produced treatment decisions. by the American Institutes for Research® (AIR) under the Center for Substance Abuse Treatment (CSAT) contract, task order Public Domain Notice number 277-00-6401 under the Substance All materials appearing in this volume except Abuse and Mental Health Services those taken directly from copyrighted sources Administration (SAMHSA) contract, Number are in the public domain and may be 277-99-6400, U.S. Department of Health and reproduced or copied without permission from Human Services (DHHS). CAPT Susanne SAMHSA/CSAT or the authors. Do not Caviness, Ph.D., SR SURG Angel A. reproduce or distribute this publication for a González, M.D., and Raymond Hylton, Jr., fee without specific, written authorization R.N., M.S.N., served as the CSAT from SAMHSA’s Office of Communications. Government Project Officers. Anton C. Bizzell, M.D., and Alan Trachtenberg, M.D., M.P.H., served as the CSAT Medical Editors. Electronic Access and Copies Christina Currier served as the CSAT TIPs of Publication Task Leader. Elizabeth F. Howell, M.D., served as the Senior Medical Editor. Wayne Copies may be obtained free of charge from SAMHSA’s National Clearinghouse for Alcohol Brandes, D.O., M.P.H., served as the AIR and Drug Information (NCADI), Medical Editor and Project Director. Janet (800) 729-6686 or (301) 468-2600; TDD (for Carrese served as the AIR Deputy Project the hearing impaired), (800) 487-4889; or Director. Other AIR personnel included Susan electronically through the following site: Bratten, Senior Editor; Susan Keller, M.P.H., http://www.kap.samhsa.gov/products/ M.S., B.S.N., Quality Assurance Editor; and manuals/index.htm. Patricia Louthian, Document Production Specialist. In addition, Center for Health Policy Studies (CHPS) Consulting staff Roy Recommended Citation Walker, M.B.A., Kimberly Stern, M.H.A., Center for Substance Abuse Treatment. Elly Gilbert, M.S., R.N., C.H.E.S., and Ji Clinical Guidelines for the Use of Kim served as the original support team for Buprenorphine in the Treatment of Opioid the consensus and field review panels. Writers Addiction. Treatment Improvement Protocol were Margaret Boone, Ph.D.; Nancy J. (TIP) Series 40. DHHS Publication No. (SMA) Brown; Mary A. Moon; Deborah J. Schuman; 04-3939. Rockville, MD: Substance Abuse and Josephine Thomas, M.F.A.; and Denise L. Mental Health Services Administration, 2004. Wright, Ph.D.

Disclaimer Originating Office The opinions expressed herein are the views of Division of Pharmacologic Therapies, Center the consensus panel members and do not for Substance Abuse Treatment, Substance Abuse and Mental Health Services necessarily reflect the official position of Administration, 1 Choke Cherry Road, CSAT, SAMHSA, or DHHS. No official Rockville, MD 20857. support of or endorsement by CSAT, SAMHSA or DHHS for these opinions or for DHHS Publication No. (SMA) 04-3939 particular instruments, software, or resources Printed 2004

ii Contents

What Is a TIP? ...... vii Consensus Panel ...... ix Buprenorphine Expert Panel ...... xi Foreword ...... xiii Executive Summary ...... xv Chapter 1 Introduction ...... 1 Practical Guidelines for Physicians ...... 1 Opioid Addiction Today in the United States ...... 3 Current State of Opioid Addiction Treatment ...... 4 Current Pharmacotherapy Treatment Options for Opioid Addiction ...... 5 Buprenorphine: A New Treatment Option for Opioid Addiction ...... 6 Summary and Overview of the Guidelines ...... 9 Chapter 2 Pharmacology ...... 11 Overview ...... 11 General Opioid Pharmacology ...... 11 Pharmacology of Buprenorphine ...... 14 Buprenorphine Safety, Adverse Reactions, and Drug Interactions ...... 18 Effectiveness of Buprenorphine Treatment ...... 20 The Buprenorphine/Naloxone Combination ...... 23 Diversion and Misuse of Either Buprenorphine Alone or the Buprenorphine/Naloxone Combination Product ...... 23 Summary ...... 24 Chapter 3 Patient Assessment ...... 25 Overview ...... 25 Screening and Assessment of Opioid Use Disorders ...... 25 Determining Appropriateness for Buprenorphine Treatment ...... 41 Chapter 4 Treatment Protocols ...... 49 Overview ...... 49 Maintenance Treatment With Buprenorphine ...... 51 Opioid Detoxification With Buprenorphine ...... 58 Patient Management ...... 63

iii Chapter 5 Special Populations ...... 67 Overview ...... 67 Patients With Medical Comorbidities ...... 67 Pregnant Women and Neonates ...... 68 Adolescents/Young Adults ...... 71 Geriatric Patients ...... 73 Patients With Significant Psychiatric Comorbidity ...... 73 Polysubstance Abuse ...... 74 Patients With Pain ...... 74 Patients Recently Discharged From Controlled Environments ...... 77 Healthcare Professionals Who Are Addicted to Opioids ...... 78 Chapter 6 Policies and Procedures ...... 79 Overview ...... 79 The DATA 2000 Waiver ...... 79 Preparing for Office-Based Opioid Treatment ...... 81 Confidentiality and Privacy ...... 83 Buprenorphine Use in OTPs ...... 84 Appendix A Bibliography ...... 87 Appendix B Assessment and Screening Instruments ...... 101 Appendix C DSM-IV-TR Material ...... 115 Appendix D Consent to Release of Information Under Title 42, Part 2, Code of Federal Regulations ...... 119 Appendix E Clinical Toolbox: Chapter 3 Supplemental Information ...... 121 Appendix F Federation of State Medical Boards—Model Policy Guidelines for Opioid Addiction Treatment in the Medical Office ...... 131 Appendix G Stages of Change ...... 139 Appendix H Sample Treatment Agreement/Contract ...... 147 Appendix I Glossary ...... 149 Appendix J Field Reviewers ...... 153 Index ...... 163

iv Contents Figures 1–1 Dosage Forms of Buprenorphine Available in the United States ...... 8 2–1 Conceptual Representation of Opioid Effect Versus Log Dose for Opioid Full Agonists, Partial Agonists, and Antagonists ...... 13 2–2 Bioavailability of Buprenorphine ...... 16 2–3 Partial List of Medications Metabolized by Cytochrome P450 3A4 ...... 21 3–1 Attributes of an Effective Addiction Treatment Provider ...... 28 3–2 Targeted, Open-Ended Questions About Drug and Alcohol Use ...... 28 3–3 Quantifiable Interview Questions ...... 29 3–4 Components of a Complete Substance Abuse Assessment History ...... 29 3–5 Examination Findings Suggestive of Addiction or Its Complications ...... 30 3–6 Signs of Opioid Intoxication and Overdose ...... 31 3–7 Staging and Grading Systems of Opioid Withdrawal ...... 32 3–8 Mental Status Examination Checklist ...... 32 3–9 Recommended Baseline Laboratory Evaluation of Patients Who Are Addicted to Opioids ...... 34 3–10 DSM-IV-TR Opioid Use Disorders (ICD-9 Code) ...... 36 3–11 Selected Medical Disorders Related to Alcohol and Other Drug Use ...... 38 3–12 Buprenorphine Treatment Checklist ...... 44 3–13 Conditions and Circumstances That May Preclude a Patient as a Candidate for Office-Based Buprenorphine Treatment ...... 45 4–1 Induction Days 1–2 ...... 53 4–2 Induction Day 2 Forward ...... 55 4–3 Stabilization Phase ...... 57 4–4 Detoxification From Short-Acting Opioids ...... 60 4–5 Discontinuation of OAT Using Buprenorphine ...... 62 5–1 Clinical Features Distinguishing Opioid Use in Patients With Pain Versus Patients Who Are Addicted to Opioids ...... 75 6–1 Policies, Procedures, and Items for Medical Practices To Establish Prior to Initiating Office-Based Opioid Addiction Treatment ...... 83 6–2 Privacy and Confidentiality Issues in Addiction Treatment ...... 84

Contents v vi What Is a TIP?

Treatment Improvement Protocols (TIPs) are best-practice guidelines for the treatment of substance use disorders, provided as a service of the Substance Abuse and Mental Health Services Administration’s (SAMHSA’s) Center for Substance Abuse Treatment (CSAT). CSAT’s Office of Evaluation, Scientific Analysis and Synthesis draws on the experience and knowledge of clinical, research, and administrative experts to produce the TIPs, which are distributed to a growing number of facilities and individuals across the country. As alcoholism and other substance use disorders are increasingly recognized as major problems, the audience for the TIPs is expanding beyond public and private substance use disorder treatment facilities.

After selecting a topic, CSAT invites staff from pertinent Federal agencies and national organizations to a resource panel that recommends specific areas of focus as well as resources that should be considered in developing the content of the TIP. Then recommendations are communicated to a consensus panel composed of experts who have been nominated by their peers. This panel participates in a series of discussions; the information and recommendations on which they reach consensus become the foundation of the TIP. The members of each consensus panel represent substance use disorder treatment programs, hospitals, community health centers, counseling programs, criminal justice and child welfare agencies, and private practitioners. A panel chair (or cochairs) ensures that the guidelines mirror the results of the group’s collaboration.

A large and diverse group of experts reviews the draft document closely. The Buprenorphine Expert Panel, a distinguished group of substance abuse experts and professionals in such related fields as primary care, mental health, and social services, worked with the Consensus Panel Chair and the CSAT Division of Pharmacologic Therapies to generate new and updated changes to the subject matter for this TIP based on the field’s current needs for information and guidance. Once the changes recommended by the field reviewers have

vii been incorporated, the TIP is prepared for a new option for the treatment of opioid publication in print and online. addiction. The goal of this TIP is to provide information that physicians can use to make The TIPs can be accessed via the Internet at practical and informed decisions about the use http://www.kap.samhsa.gov/products/ of buprenorphine to treat opioid addiction. manuals/index.htm. The use of electronic The Guidelines address a number of topic media also means that the TIPs can be areas related to this goal, including the physi- updated more easily so that they can continue ology and pharmacology of opioids, opioid to provide the field with state-of-the-art addiction, and treatment with buprenorphine; information. Although each TIP includes an the screening and assessment of opioid addic- evidence base for the practices its panel tion problems; detailed protocols for opioid recommends, CSAT recognizes that the field addiction treatment with buprenorphine; of substance use disorder treatment is management of special populations; and evolving continuously and that research policies and procedures related to office-based frequently lags behind the innovations opioid addiction treatment under the para- pioneered by those in the field. A major goal digm established by the Drug Addiction Treatment Act of 2000. This TIP represents of each TIP is to convey “front line” another step by CSAT toward its goal of information quickly but responsibly. For this bringing national leaders together to improve reason, recommendations in the TIP are substance use disorder treatment in the attributed either to panelists’ clinical experi- United States. ence or to the appropriate literature. If there is research to support a particular approach, Other TIPs may be ordered by contacting the citations are provided. National Clearinghouse for Alcohol and Drug Information (NCADI), (800) 729-6686 or This TIP, Clinical Guidelines for the Use of (301) 468-2600; TDD (for the hearing Buprenorphine in the Treatment of Opioid impaired), (800) 487-4889. See http:// Addiction, provides consensus- and evidence- www.kap.samhsa.gov/products/manuals/ based guidance on the use of buprenorphine, index.htm.

viii What is a TIP? Consensus Panel

Chair George De Leon, Ph.D. Director Laura McNicholas, M.D., Ph.D. Center for Therapeutic Community Clinical Assistant Professor Research of The National Development Department of Psychiatry and Research Institutes University of Pennsylvania Treatment New York, New York Research Center Philadelphia, Pennsylvania Elizabeth F. Howell, M.D. Panelists Senior Medical Editor Atlanta, Georgia Tony Aguilar, L.M.F.T. Legislative Consultant Martin Iguchi, Ph.D. California Department of Social Services Senior Behavioral Scientist Sacramento, California Director Drug Policy Research Center Daniel Alford, M.D., M.P.H. Rand Corporation Association for Medical Education and Santa Monica, California Research in Substance Abuse (AMERSA) Assistant Professor of Medicine Herbert D. Kleber, M.D. Boston University School of Medicine Professor of Psychiatry Clinical Addiction Research and Education Unit Director Boston, Massachusetts The Division on Substance Abuse Columbia University Catherine T. Baca, M.D. New York, New York Clinical Supervisor Center on Alcoholism, Substance Abuse, Ervin Lewis, M.D. and Addictions Area Chief Medical Officer Albuquerque, New Mexico Albuquerque Area Indian Health Service Albuquerque, New Mexico Thomas J. Croce, Jr., R.Ph. (replacing Jann B. Skelton) Senior Manager James J. Manlandro, D.O. Strategic Alliances Medical Director American Pharmaceutical Association Family Addiction Treatment Services Philadelphia, Pennsylvania Rio Grande, New Jersey

ix Andrew J. Saxon, M.D. Jann B. Skelton, R.Ph., M.B.A. Professor Vice President Department of Psychiatry and Behavioral U.S. Wellness, Inc. Sciences University of Washington Gaithersburg, Maryland Center of Excellence in Substance Abuse Treatment and Education David E. Smith, M.D. VA Puget Sound Health Care System President and Founder Seattle, Washington Haight Ashbury Free Clinic San Francisco, California Charles R. Schuster, Ph.D. Professor Department of Psychiatry and Behavioral Eric C. Strain, M.D. Neuroscience Professor Wayne State University School of Medicine Johns Hopkins University School of Medicine Detroit, Michigan Baltimore, Maryland Audrey Sellers, M.D. Medical Director Joycelyn Woods, M.A. Bay Area Addiction Research and President Treatment, Inc. National Alliance of Methadone Advocates San Francisco, California New York, New York

x Consensus Panel Buprenorphine Expert Panel

Chair James J. Manlandro, D.O. Eric C. Strain, M.D. Medical Director Professor Family Addiction Treatment Services Johns Hopkins University School of Medicine Rio Grande, New Jersey Baltimore, Maryland Elinore F. McCance-Katz, M.D., Ph.D. Leslie Amass, Ph.D. Professor of Psychiatry and Chair Principal Investigator Friends Research Institute, Inc. Addiction Psychiatry Los Angeles, California Medical College of Virginia Virginia Commonwealth University David Fiellin, M.D. Richmond, Virginia Associate Professor of Medicine Yale University School of Medicine Joe Merrill, M.D., M.P.H. Primary Care Center Yale-New Haven Hospital Research Scientist New Haven, Connecticut Division of General Medicine Harborview Medical Center R. E. Johnson, Pharm.D. Seattle, Washington Professor Department of Psychiatry and Behavioral Geoff Mumford, Ph.D. Sciences Behavioral Pharmacology Research Unit American Psychological Association Johns Hopkins University School of Medicine Washington, District of Columbia Baltimore, Maryland Richard T. Suchinsky, M.D. Thomas R. Kosten, M.D. Associate Director for Addictive Disorders Professor of Psychiatry and Psychiatric Rehabilitation Yale University School of Medicine Deputy Chief of Psychiatry Research U.S. Department of Veterans Affairs VA Connecticut Healthcare System Veterans Health Administration West Haven, Connecticut Washington, District of Columbia

xi xii Foreword

Our Nation has made great strides in recent years in achieving recovery for persons with substance use disorders. We know much more about how to deliver recovery-oriented substance abuse treatment, improve service quality, achieve desired improvements in quality-of-life outcomes, and implement needed care systems in each community in the United States. Our vision is of a life in the community for everyone. The Treatment Improvement Protocol (TIP) series promotes resilience and facilitates recovery from substance use disorders. The TIPs add to our knowledge base and provide best practice guidance to clinicians, program administrators, and payors. They are the result of careful consideration of all relevant clinical and health services research findings, demonstration experience, and implementation requirements. For each TIP topic, an expert panel of non-Federal clinical researchers, clinicians, program administrators, and patient advocates debates and discusses best practices until its members reach a consensus. The talent, dedication, and hard work that TIPs panelists and reviewers bring to this highly participatory process have bridged the gap between the promise of research and the needs of practicing clinicians and administrators. We are grateful to all who have joined with us to contribute to advances in the substance use disorder treatment field. We hope you will find many uses for the information contained in this volume and that you will join in our goal of helping all Americans with substance use disorders realize healthy, contributing lives in their communities nationwide. Charles G. Curie, M.A., A.C.S.W. Administrator Substance Abuse and Mental Health Services Administration H. Westley Clark, M.D., J.D., M.P.H., CAS, FASAM Director, Center for Substance Abuse Treatment Substance Abuse and Mental Health Services Administration

xiii xiv Executive Summary

Federal statute, the Drug Addiction Treatment Act of 2000 (DATA 2000), has established a new paradigm for the medication-assisted treatment of opioid addiction in the United States (Drug Addiction Treatment Act of 2000). Prior to the enactment of DATA 2000, the use of opioid medications to treat opioid addiction was permissible only in federally approved Opioid Treatment Programs (OTPs) (i.e., methadone clinics), and only with the Schedule II opioid medications methadone and levo-alpha-acetyl-methadol (LAAM), which could only be dispensed, not prescribed.* Now, under the provisions of DATA 2000, qualifying physicians in the medical office and other appropriate settings outside the OTP system may prescribe and/or dispense Schedule III, IV, and V opioid medications for the treatment of opioid addiction if such medications have been specifically approved by the Food and Drug Administration (FDA) for that indication. (The text of DATA 2000 can be viewed at http://www.buprenorphine.samhsa.gov/ fulllaw.html.) In October 2002, FDA approved two sublingual formulations of the Schedule III opioid partial agonist medication buprenorphine for the treatment of opioid addiction. These medications, Subutex® (buprenorphine) and Suboxone® (buprenorphine/naloxone), are the first and, as of this writing, the only Schedule III, IV, or V medications to have received such FDA approval and, thus, to be eligible for use under DATA 2000. Office-based treatment with buprenorphine promises to bring opioid addiction care into the mainstream of medical practice, thereby greatly expanding access to treatment and bringing new hope to thousands.

DATA 2000 directs the Substance Abuse and Mental Health Services Administration (SAMHSA) to develop a Treatment Improvement

*Due to a number of factors, including the association of LAAM with cardiac arrhythmias in some patients, as of January 1, 2004, the sole manufacturer has ceased production of the drug.

xv Protocol (TIP) containing best practice individuals who are addicted to opioids and guidelines for the treatment and maintenance who may be candidates for treatment with of opioid-dependent patients. This TIP, buprenorphine. Clinical Guidelines for the Use of Buprenor- phine in the Treatment of Opioid Addiction, is Chapter 4, Treatment Protocols, provides the product of that mandate. The TIP was detailed protocols on the use of buprenor- developed by SAMHSA and a team of inde- phine for the treatment of opioid addiction, pendent substance abuse treatment profes- including both maintenance and withdrawal sionals, in consultation with the National treatment approaches. Institute on Drug Abuse, the Drug Chapter 5, Special Populations, discusses Enforcement Administration (DEA), and several special populations whose circum- FDA. The purpose of this TIP is to provide stances require careful consideration as they physicians with science-based clinical practice begin buprenorphine treatment. Treating guidelines on the use of buprenorphine in the these special populations requires an under- treatment of opioid addiction. The primary standing of available resources and often audience of this TIP is physicians who are involves collaboration with specialists in other interested in providing buprenorphine for the areas of care. treatment of opioid addiction. Chapter 6, Policies and Procedures, discusses In developing this TIP, the consensus panel, legal and regulatory issues pertaining to the made up of research and clinical experts in provision of opioid addiction treatment, the field of opioid addiction treatment, recog- including the procedures and physician nized that while buprenorphine offers new qualifications necessary to obtain the required hope to many individuals, pharmacotherapy waiver under DATA 2000 to provide office- alone is rarely sufficient for the long-term based opioid addiction treatment, recom- successful treatment of opioid addiction. As a mended office practice policies and result, these guidelines emphasize that procedures, the security and confidentiality of optimally effective and comprehensive opioid opioid addiction care information, and the use addiction care is achieved when attention is of buprenorphine in OTPs. provided to all of an individual’s medical and psychosocial comorbidities. The following sections summarize the content of this TIP and are grouped by chapter. This TIP is composed of 6 chapters and 10 appendices, including a complete list of references (Appendix A, Bibliography). Chapter 1, Chapter 1, Introduction, describes the basic Introduction facts regarding opioid addiction, the traditional approaches to its treatment, and Chapter 1 provides an overview of opioid the new DATA 2000 treatment paradigm. addiction in the United States today, including the historical context of the current treatment Chapter 2, Pharmacology, addresses, environment, the scope of the opioid addiction in-depth, the physiology and pharmacology problem, the traditional approaches to treat- of opioids in general, and of buprenorphine in ment, and an introduction to buprenorphine particular. The chapter also provides a review as an opioid addiction treatment. of the research literature regarding the safety and effectiveness of buprenorphine for the Opioid addiction includes not only misuse and treatment of opioid addiction. abuse of heroin, but also the less commonly recognized issue of misuse and abuse of Chapter 3, Patient Assessment, summarizes prescription opioid pain medications, such as an approach to screening and assessment of hydrocodone, oxycodone, and meperidine.

xvi Executive Summary Rates of addiction to prescription opioids Chapter 2, have been increasing. The incidence of emergency department visits related to prescrip- Pharmacology tion opioid pain medications has more than Buprenorphine has unique pharmacological doubled between 1994 and 2001. Recent data properties that make it an effective and well- show that in at least 15 metropolitan areas, tolerated addition to the available pharm- two or more narcotic pain medications— acological treatments for opioid addiction. primarily oxycodone, hydrocodone, and This chapter reviews the general pharma- codeine—were ranked among the 10 most cology of opioid agonists and antagonists, as common drugs involved in drug abuse deaths well as the opioid partial agonist properties of (SAMHSA 2002b). buprenorphine.

The prevalence of heroin addiction in the Drugs that activate opioid receptors on United States also has been increasing and neurons are termed opioid agonists. Heroin and methadone are opioid agonists. The currently is believed to be the highest it has repeated administration of opioid agonists been since the 1970s. According to the Office results in dose-dependent physical depen- of National Drug Control Policy (ONDCP), an dence and tolerance. Physical dependence is estimated 810,000 to 1,000,000 individuals in manifested as a characteristic set of with- the United States were addicted to heroin in drawal signs and symptoms upon reduction, the year 2000 (ONDCP 2003). cessation, or loss of an active compound at its receptors. Addiction, conversely, is a Well-run methadone maintenance programs behavioral syndrome characterized by the (with programming that includes counseling repeated, compulsive seeking or use of a services, vocational resources, referrals, and substance, despite adverse social, psycho- appropriate drug monitoring) have been logical, and/or physical consequences. Opioid shown to decrease opioid use and related addiction often, but not always, is accom- crime, increase employment, and decrease the panied by tolerance, physical dependence, incidence of human immunodeficiency virus and opioid withdrawal symptoms. (HIV) related to needle sharing. In addition, Opioids that bind to opioid receptors but treatment in such programs improves physical block them, rather than activating them, are and mental health and decreases overall termed opioid antagonists. Examples of opioid mortality from opioid addiction. Unfortu- antagonists are naltrexone and naloxone. nately, despite these results, methadone maintenance treatment system capacity has Opioid partial agonists are drugs that activate not kept pace with the rise in the prevalence receptors, but not to the same degree as full of opioid addiction. agonists. Increasing the dose of a partial agonist does not produce as great an effect as More than 20 years ago, buprenorphine was does increasing the dose of a full agonist. The identified as a viable option for the mainte- agonist effects of a partial agonist reach a nance treatment of individuals addicted to ceiling at moderate doses and do not increase from that point, even with increases in dosage. opioids. Research conducted over the past two Buprenorphine is an opioid partial agonist. It decades has documented the safety and is the partial agonist properties of buprenor- effectiveness of buprenorphine for this phine that make it a safe and an effective indication. The enactment of DATA 2000 has option for the treatment of opioid addiction. now enabled physicians in the United States to Buprenorphine has sufficient agonist prop- offer specifically approved forms of buprenor- erties such that when it is administered to phine for the treatment of opioid addiction. individuals who are not opioid dependent but

Executive Summary xvii who are familiar with the effects of opioids, treatment setting, and level of treatment they experience subjectively positive opioid intensity, based on a patient’s preferences, effects. These subjective effects aid in main- addiction history, presence of medical or taining compliance with buprenorphine dosing psychiatric comorbidities, and readiness to in patients who are opioid dependent. change. Buprenorphine is a treatment option for many, but not for all. Buprenorphine occupies opioid receptors with great affinity and thus blocks opioid full agonists from exerting their effects. Buprenor- Screening phine dissociates from opioid receptors at a The Clinical Guidelines for the Use of Bupre- slow rate. This enables daily or less frequent norphine in the Treatment of Opioid Addic- dosing of buprenorphine, as infrequently as tion Consensus Panel recommends that three times per week in some studies. physicians periodically and regularly screen Buprenorphine is abusable, consistent with its all patients for substance use and substance- agonist action at opioid receptors. Its abuse related problems, not just those patients who potential, however, is lower in comparison fit the stereotypical picture of addiction. with that of opioid full agonists. A formulation Several validated addiction screening instru- containing buprenorphine in combination with ments are discussed. The full text of selected naloxone has been developed to decrease the screening instruments is provided in potential for abuse via the injection route. Appendix B, Assessment and Screening Physicians who prescribe or dispense bupre- Instruments. norphine or buprenorphine/naloxone should monitor for diversion of the medications. Assessment Due to the potential for serious drug–drug If screening indicates the presence of an interactions, buprenorphine must be used opioid use disorder, further assessment is cautiously with certain other types of medica- indicated to thoroughly delineate the patient’s tions, particularly benzodiazepines, other problem, to identify comorbid or complicating sedative drugs, opioid antagonists, medi- medical or emotional conditions, and to cations metabolized by the cytochrome determine the appropriate treatment setting P450 3A4 system, and opioid agonists. and level of treatment intensity for the patient. Complete assessment may require several office visits, but initial treatment Chapter 3, Patient should not be delayed during this period. Assessment The Guidelines document provides recom- This chapter provides an approach to the mendations on effective interviewing tech- screening, assessment, and diagnosis of opioid niques and on the components of the complete addiction problems, and for determining when history, physical examination, and recom- buprenorphine is an appropriate option for mended initial laboratory evaluation of treatment. The necessary first steps in the patients with opioid addiction. medical management of opioid addiction are The consensus panel recommends that initial (1) the use of validated screening tools to and ongoing drug screening should be used to identify patients who may have an opioid use detect or confirm the recent use of drugs (e.g., problem and (2) further assessment to clearly alcohol, benzodiazepines, barbiturates), delineate the scope of an opioid addiction which could complicate patient management. problem when one is identified. When treat- Urine screening is the most commonly used ment is indicated, consideration must be given and generally most cost-effective testing to the appropriate treatment approach, method.

xviii Executive Summary Diagnosis of Opioid-Related individuals whose circumstances or conditions Disorders include After a thorough assessment of a patient has • Comorbid dependence on high doses of been conducted, a formal diagnosis can be benzodiazepines or other central nervous made. As a general rule, to be considered for system depressants (including alcohol) buprenorphine maintenance, patients should • Significant untreated psychiatric have a diagnosis of opioid dependence, as comorbidity defined in the Diagnostic and Statistical • Active or chronic suicidal or homicidal Manual of Mental Disorders, Fourth Edition, ideation or attempts Text Revision (DSM-IV-TR) (American • Multiple previous treatments for drug abuse Psychiatric Association 2000). This diagnosis with frequent relapses (except that multiple is based not merely on physical dependence previous detoxification attempts followed by on opioids but rather on opioid addiction relapse are a strong indication for long-term with compulsive use despite harm. (See DSM- maintenance treatment) IV-TR diagnostic criteria in Appendix C, DSM-IV-TR Material.) • Poor response to previous treatment attempts with buprenorphine • Significant medical complications Determining Appropriateness for Buprenorphine Treatment Chapter 4, Treatment A detailed approach to determining the suitability of buprenorphine as a treatment Protocols option for patients with opioid addiction is This chapter provides detailed protocols for included in the Guidelines. The evaluation the use of buprenorphine in the treatment includes determining if appropriate patient of opioid addiction. A variety of clinical motivation exists and ruling out contraindi- cating medical and psychiatric comorbidities. scenarios are addressed, including whether patients are addicted to long- versus short- Patients for whom buprenorphine may be an acting opioids, and whether the approach appropriate treatment option are those who selected is maintenance treatment or medically supervised withdrawal (which must be fol- • Are interested in treatment for opioid lowed by long-term drug-free or naltrexone addiction treatment to be useful to the patient). • Have no contraindications to buprenorphine treatment • Can be expected to be reasonably compliant Maintenance Treatment with such treatment Maintenance treatment with buprenorphine • Understand the benefits and risks of for opioid addiction consists of three phases: buprenorphine treatment (1) induction, (2) stabilization, and (3) main- • Are willing to follow safety precautions for tenance. Induction is the first stage of bupre- buprenorphine treatment norphine treatment and involves helping patients begin the process of switching from • Agree to buprenorphine treatment after a the opioid of abuse to buprenorphine. The review of treatment options goal of the induction phase is to find the Patients less likely to be appropriate minimum dose of buprenorphine at which the candidates for buprenorphine treatment of patient discontinues or markedly diminishes opioid addiction in an office-based setting are use of other opioids and experiences no

Executive Summary xix withdrawal symptoms, minimal or no side The goal of using buprenorphine for medically effects, and no craving for the drug of abuse. supervised withdrawal from opioids is to The consensus panel recommends that the provide a transition from the state of physical buprenorphine/naloxone combination be used dependence on opioids to an opioid-free state, for induction treatment (and for stabilization while minimizing withdrawal symptoms (and and maintenance) for most patients. The avoiding side effects of buprenorphine). consensus panel further recommends that initial induction doses be administered as Medically supervised withdrawal with bupre- observed treatment; further doses may be norphine consists of an induction phase and a provided via prescription thereafter. dose-reduction phase. The consensus panel recommends that patients dependent on short- To minimize the chances of precipitated acting opioids (e.g., hydromorphone, oxyco- withdrawal, patients who are transferring done, heroin) who will be receiving medically from long-acting opioids (e.g., methadone, supervised withdrawal be inducted directly sustained release morphine, sustained release onto buprenorphine/naloxone tablets. The use oxycodone) to buprenorphine should be of buprenorphine (either as buprenorphine inducted using buprenorphine monotherapy, monotherapy or buprenorphine/naloxone but switched to buprenorphine/naloxone soon combination treatment) to taper off long- thereafter. Because of the potential for acting opioids should be considered only for naloxone to precipitate withdrawal in both those patients who have evidence of sustained mother and fetus, pregnant women who are medical and psychosocial stability, and should deemed to be appropriate candidates for be undertaken in conjunction and in buprenorphine treatment should be inducted coordination with patients’ OTPs. and maintained on buprenorphine monotherapy. Nonpharmacological The stabilization phase has begun when a patient is experiencing no withdrawal symp- Interventions toms, is experiencing minimal or no side Pharmacotherapy alone is rarely sufficient effects, and no longer has uncontrollable treatment for drug addiction. For most cravings for opioid agonists. Dosage adjust- patients, drug abuse counseling—individual ments may be necessary during early stabili- or group—and participation in self-help zation, and frequent contact with the patient programs are necessary components of com- increases the likelihood of compliance. prehensive addiction care. As part of training in the treatment of opioid addiction, physi- The longest period that a patient is on bupre- cians should at a minimum obtain some norphine is the maintenance phase. This knowledge about the basic principles of brief period may be indefinite. During the main- intervention in case of relapse. Physicians tenance phase, attention must be focused on considering providing opioid addiction care the psychosocial and family issues that have should ensure that they are capable of pro- been identified during the course of treatment viding psychosocial services, either in their as contributing to a patient’s addiction. own practices or through referrals to reputable behavioral health practitioners in their Medically Supervised communities. In fact, DATA 2000 stipulates Withdrawal that when physicians submit notification to SAMHSA to obtain the required waiver to (“Detoxification”) practice opioid addiction treatment outside Buprenorphine can be used for the medically the OTP setting, they must attest to their supervised withdrawal of patients from both capacity to refer such patients for appropriate self-administered opioids and from opioid counseling and other nonpharmacological agonist treatment with methadone or LAAM. therapies.

xx Executive Summary Treatment Monitoring treatment, but this evidence is from case series, not from controlled studies. Methadone Patients and their physicians together need to is currently the standard of care in the United reach agreement on the goals of treatment and States for the treatment of opioid addiction in develop a treatment plan based on the pregnant women. Pregnant women who patient’s particular problems and needs. present for treatment of opioid addiction During the stabilization phase, patients should be referred to specialized services in receiving maintenance treatment should be methadone maintenance treatment programs. seen on at least a weekly basis. Once a stable If such specialized services are refused by a buprenorphine dose is reached and toxicologic patient or are unavailable in the community, samples are free of illicit opioids, the physician may determine that less frequent visits maintenance treatment with buprenorphine may be considered as an alternative. (biweekly or longer, up to 30 days) are acceptable. During opioid addiction treatment with buprenorphine, toxicology tests for relevant Adolescents/Young Adults illicit drugs should be administered at least monthly. Buprenorphine can be a useful option for the treatment of adolescents with opioid addiction problems. The treatment of addiction in Chapter 5, Special adolescents, however, is complicated by a number of medical, legal, and ethical con- Populations siderations. Physicians intending to treat This chapter discusses the approach to addiction in adolescents should be thoroughly patients who have certain life circumstances familiar with the laws in their States regarding or comorbid medical or behavioral conditions parental consent. Physicians who do not that warrant special consideration during the specialize in the treatment of opioid addiction assessment and treatment of opioid addiction. should strongly consider consulting with, or referring adolescent patients to, addiction specialists. Additionally, State child protection Patients With Medical agencies can be a valuable resource when Comorbidities determining the proper disposition for Patients who are addicted to opioids often adolescent patients addicted to opioids. have other medical comorbid problems as a consequence of both high-risk behaviors and Geriatric Patients of direct toxic effects of the active and inert ingredients in illicit drugs. In patients being Literature on the use of buprenorphine in treated with buprenorphine for opioid geriatric patients is extremely limited. Due to addiction, it is important to screen for and potential differences in rates of metabolism manage common comorbid medical conditions and absorption compared to younger indivi- and to anticipate known and potential drug duals, care should be exercised in the use of interactions. buprenorphine in geriatric patients.

Pregnant Women and Patients With Significant Neonates Psychiatric Comorbidity The scant evidence available does not show The presence and severity of comorbid psy- any causal adverse effects on pregnancy or chiatric conditions must be assessed prior to neonatal outcomes from buprenorphine initiating buprenorphine treatment, and a

Executive Summary xxi determination made whether referral to should not be transferred to an opioid main- specialized behavioral health services is tenance treatment program simply because necessary. The psychiatric disorders most they have become physically dependent on commonly encountered in patients addicted to prescribed opioids in the course of medical opioids are other substance abuse disorders, treatment. depressive disorders, posttraumatic stress disorder, substance-induced psychiatric Patients who are being treated for addiction also may experience pain due to illness or disorders, and antisocial and borderline injury unrelated to drug use. Pain in patients personality disorder. receiving buprenorphine treatment for opioid As with medical comorbidities, it is important addiction should be treated initially with to explore the medications used to treat the nonopioid analgesics when appropriate. other psychiatric conditions. Assessing for Patients maintained on buprenorphine whose drug interactions is a critical part of the acute pain is not relieved by nonopioid medi- process. cations should receive the usual aggressive pain management, which may include the use Polysubstance Abuse of short-acting opioid pain relievers. While patients are taking opioid pain medications, Abuse of multiple drugs (polysubstance abuse) the administration of buprenorphine generally by individuals addicted to opioids is common. should be discontinued. When restarting Pharmacotherapy with buprenorphine for buprenorphine, to prevent acutely precipi- opioid addiction will not necessarily have a tating withdrawal, administration generally beneficial effect on an individual’s use of other should not begin until sufficient time has drugs. Care in the prescribing of buprenor- elapsed for the opioid pain medication to have phine for patients who abuse alcohol and for cleared from the patient’s system, as demon- those who abuse sedative/hypnotic drugs strated by the onset of early withdrawal (especially benzodiazapines) must be exercised symptoms. Patients who are receiving because of the documented potential for fatal long-acting opioids for chronic severe pain interactions. may not be good candidates for buprenorphine treatment because of the ceiling effect Patients With Pain on buprenorphine’s analgesic properties. Physicians may encounter particular complex- ities with regard to abuse and addiction in the Patients Recently Discharged use of opioids to treat patients with pain. From Controlled Some patients move from needing prescription Environments opioids for the treatment of pain to abusing them. Physicians concerned about this A number of issues should be considered in changing diagnostic picture now may legally determining the most appropriate treatment use an opioid—buprenorphine—to help modalities for patients with addiction who are facilitate a controlled detoxification in order recently released from controlled environ- to manage the physical dependence of the ments (e.g., prison). Intensive buprenorphine patient who no longer has pain that requires monitoring activities are required, and an opioid, but who continues to take the treating physicians may be called upon to opioid for its mood-altering effects. verify and explain treatment regimens (e.g., to parole and probation officers); to document Patients who need treatment for pain but not patient compliance; and to interact with the for addiction should be treated within the legal system, employers, and others. If an context of a medical or surgical setting. They OTP alternative is available, physicians

xxii Executive Summary should determine if any patient factors at the SAMHSA Buprenorphine Web site at preclude referral. http://www.buprenorphine.samhsa.gov. Alternatively, the form can be printed out from the site and submitted via ground mail Healthcare Professionals Who or fax. (The site contains detailed information Are Addicted to Opioids about buprenorphine, the DATA 2000 para- There is a substantial problem of addiction to digm, and the physician waiver process.) prescription opioids among physicians and Physicians who meet the qualifications defined other health professionals, especially within in DATA 2000 are issued a waiver by certain specialties. Prescription opioid addic- SAMHSA and a special identification number tion in health professionals should be viewed by DEA. as an occupational hazard of the practice of To qualify for a DATA 2000 waiver, physicians medicine. Health professionals with substance must have completed at least 8 hours of abuse disorders often require specialized, approved training in the treatment of opioid extended care. addiction or have certain other qualifications as defined in the legislation (e.g., clinical research experience with the treatment Chapter 6, Policies and medication, certification in addiction med- Procedures icine) and must attest that they can provide or refer patients to the necessary, concurrent This chapter presents information on a psychosocial services. The consensus panel number of administrative and regulatory recommends that all physicians who plan to issues pertaining to the use of controlled practice opioid addiction treatment with substances in the treatment of opioid addic- buprenorphine attend a DATA 2000- tion that are beyond the general medico-legal qualifying 8-hour training program on responsibilities that govern most other types buprenorphine. SAMHSA maintains a list of of medical practice. Physicians should become upcoming DATA 2000-qualifying buprenor- thoroughly familiar with these issues prior to phine training sessions on the SAMHSA undertaking the treatment of opioid addiction. Buprenorphine Web site. Additional information about DATA 2000 and buprenor- The DATA 2000 Waiver phine also can be obtained by contacting the SAMHSA Buprenorphine Information Center To practice office-based treatment of opioid by phone at 866-BUP-CSAT (866-287-2728) or addiction under the auspices of DATA 2000, via e-mail at [email protected]. physicians must first obtain a waiver from the special registration requirements established in the Narcotic Addict Treatment Act of 1974 Preparing for Office-Based and its enabling regulations. To obtain a Opioid Treatment DATA 2000 waiver, a physician must submit notification to SAMHSA of his or her intent to Prior to embarking on the provision of office- begin dispensing and/or prescribing this based addiction treatment services, medical treatment. The Notification of Intent form practices that will be new to this form of care must contain information on the physician’s should undertake certain preparations to qualifying credentials and must contain ensure the highest quality experience for additional certifications, including that the patients, providers, and staff. Providers and physician (or the physician’s group practice) practice staff should have an appropriate level will not treat more than 30 patients for addic- of training, experience, and comfort with tion at any one time. Notification of Intent opioid addiction treatment. Linkages with forms can be filled out and submitted online other medical and mental health professionals

Executive Summary xxiii should be established to ensure continuity of requirement for signed patient consent treatment and the availability of comprehen- extends to activities such as telephoning or sive, community-based, psychosocial services. faxing addiction treatment prescriptions to pharmacies, as this information constitutes disclosure of the patient’s addiction treat- Privacy and Confidentiality ment. A sample consent form with all the The privacy and confidentiality of individ- elements required by 42 C.F.R. Part 2 is ually identifiable drug or alcohol treatment included as Appendix D, Consent to Release information is protected by SAMHSA confi- of Information Under 42 C.F.R. Part 2. dentiality regulation Title 42, Part 2 of the Code of Federal Regulations (42 C.F.R. Part 2). This regulation mandates that addiction Buprenorphine Use in OTPs treatment information in the possession of In May 2003, the Federal OTP regulations substance abuse treatment providers be (42 C.F.R. Part 8) were amended to add handled with a greater degree of confiden- Subutex® and Suboxone® to the list of tiality than general medical information. approved opioid medications that may be used Among other stipulations, regulation in federally certified and registered OTPs 42 C.F.R. Part 2 requires that physicians (i.e., methadone clinics). OTPs that choose to providing opioid addiction treatment obtain use Subutex® and Suboxone® in the treatment signed patient consent before disclosing of opioid addiction must adhere to the same individually identifiable addiction treat- Federal treatment standards established for ment information to any third party. The all medications under 42 C.F.R. Part 8.

xxiv Executive Summary 1 Introduction

Practical Guidelines for Physicians In This Physicians are invited to use the Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction to make practical Chapter… and informed decisions about the treatment of opioid addiction with buprenorphine. This document provides step-by-step guidance Practical Guidelines through the opioid addiction treatment decisionmaking process. Using for Physicians the materials provided in these guidelines, physicians should be able to (1) perform initial screening and assessment of patients with opioid Opioid Addiction Today addiction, (2) determine the appropriateness of buprenorphine treat- in the United States ment for patients with opioid addiction, (3) provide treatment of opioid addiction with buprenorphine according to established protocols, Current State of Opioid (4) assess for the presence of and arrange appropriate treatment Addiction Treatment services for comorbid medical and psychosocial conditions, and (5) determine when to seek specialty addiction treatment referral or Current Pharmacotherapy consultation. Treatment Options for Opioid Addiction The history of opioid addiction treatment forms an important back- drop for the decisions that physicians will make regarding their use of Buprenorphine: A New buprenorphine. Developing informed decisions about care should take into account the state of the art of opioid addiction treatment and Treatment Option for ancillary services that exist to support both the patient and physician. Opioid Addiction

Summary and Overview Historical Context of the Guidelines A significant breakthrough in the treatment of opioid addiction occurred with the introduction of methadone in the 1960s. Methadone maintenance proved safe and effective and enabled patients to lead functional lives—something that was often not possible using only drug-free approaches. Within a few years of its introduction, however, new laws and regulations in the United States, including the Methadone Regulations in 1972 and the Narcotic Addict Treatment Act of 1974, effectively limited methadone maintenance treatment to the context of the Opioid Treatment Program (OTP) (i.e., methadone clinic) setting. These laws and regulations established a closed distribution system for

1 methadone that required special licensing by 2000 (P.L. 106-310) was enacted into law. both Federal and State authorities. The new Title XXXV of the Act provides a “Waiver system made it very difficult for physicians to Authority for Physicians Who Dispense or use methadone to treat opioid addiction in an Prescribe Certain Narcotic Drugs for Mainte- office setting or even in a general drug nance Treatment or Detoxification Treatment rehabilitation program. To receive methadone of Opioid-Dependent Patients.” This part of maintenance, patients were required to attend the law is known as the Drug Addiction an OTP, usually on Treatment Act of 2000 (DATA 2000; Clark a daily basis. The 2003). The promise of DATA stigma and incon- venience associated Under the provisions of DATA 2000, quali- with receiving fying physicians may now obtain a waiver 2000 is to help methadone mainte- from the special registration requirements in nance in the OTP the Narcotic Addict Treatment Act of 1974, destigmatize opioid setting led, in part, and its enabling regulations, to treat opioid to the current sit- addiction with Schedule III, IV, and V opioid medications that have been specifically addiction treatment uation in the United States in approved by FDA for that indication, and to which it is esti- prescribe and/or dispense these medications and to enable mated that fewer in treatment settings other than licensed than 25 percent of OTPs, including in office-based settings. On qualified physicians the individuals October 8, 2002, two new sublingual formulations of the opioid partial agonist bupre- with opioid addic- ® tion receive any norphine, Subutex (buprenorphine) and to manage opioid Suboxone® (buprenorphine/naloxone), form of treatment became the first and, as of this writing, the for it (NIH Con- addiction in their only Schedule III, IV, or V medications to sensus Statement have received this FDA approval. own practices… 1997). Another result of the closed To qualify for a DATA 2000 waiver, physicians distribution system must have completed at least 8 hours of was that most U.S. approved training in the treatment of opioid physicians were prevented from gaining expe- addiction or have certain other qualifications rience and expertise in the treatment of opioid defined in the legislation (e.g., clinical addiction. The Food and Drug Administration research experience with the treatment (FDA) approval of the longer acting opioid medication, certification in addiction medi- agonist levo-alpha-acetyl-methadol (LAAM) in cine) and must attest that they can provide the 1990s did little to change the situation.* or refer patients to necessary, concurrent (Additional information about substance psychosocial services. (Chapter 6 provides a abuse statistics and treatment availability in detailed discussion of the qualifying criteria the United States can be found on the Sub- defined in DATA 2000 and of the procedure stance Abuse and Mental Health Services for obtaining a waiver.) Administration [SAMHSA] Office of Applied Studies [OAS] Web site at http:// Physicians who obtain DATA 2000 waivers www.oas.samhsa.gov/). may treat opioid addiction with Subutex® or Suboxone® in any appropriate clinical settings Efforts to return opioid addiction treatment to in which they are credentialed to practice the mainstream of medical care began to take medicine. The promise of DATA 2000 is to shape and gain momentum in the 1990s. In help destigmatize opioid addiction treatment October 2000, the Children’s Health Act of and to enable qualified physicians to manage

*Due to a number of factors, including the association of LAAM with cardiac arrhythmias in some patients, as of January 1, 2004, the sole manufacturer has ceased production of the drug.

2 Introduction opioid addiction in their own practices, thus Addiction is often (but not always) accom- greatly expanding currently available treat- panied by physical dependence, a withdrawal ment options and increasing the overall syndrome, and tolerance. Physical depend- availability of treatment. ence is defined as a physiological state of adaptation to a substance, the absence of New Guidelines which produces symptoms and signs of withdrawal. Withdrawal syndrome consists of a The new guidelines provide information about predictable group of signs and symptoms the medical use of buprenorphine, based on resulting from abrupt removal of, or a rapid (1) the evidence available from buprenorphine decrease in the regular dosage of, a psycho- studies and (2) clinical experience using active substance. The syndrome is often buprenorphine in the treatment of opioid characterized by overactivity of the physio- addiction. The guidelines are as complete as logical functions that were suppressed by the the expert members of the Consensus Panel on drug and/or depression of the functions that Clinical Guidelines for the Use of Buprenor- were stimulated by the drug. Tolerance is a phine in the Treatment of Opioid Addiction state in which a drug produces a diminishing could make them and should provide a rea- biological or behavioral response; in other sonable basis for current best practices in the words, higher doses are needed to produce the area. Physicians should note that the guide- same effect that the user experienced initially. lines are not intended to fully address all possible issues that can arise in the treatment It is possible to be physically dependent on a of patients who are addicted to opioids. Some drug without being addicted to it, and con- issues cannot be substantively addressed in versely, it is possible to be addicted without the guidelines because of the lack of controlled being physically dependent (Nelson et al. studies and the limited U.S. experience using 1982). An example of physical dependence on buprenorphine in office-based settings. opioids without addiction is a patient with Physicians are urged to seek the advice of cancer who becomes tolerant of and physically knowledgeable addiction specialists if their dependent on opioids prescribed to control questions are not answered fully by the pain. Such a patient may experience with- guidelines, and should keep themselves aware drawal symptoms with discontinuation of the of training and information on the use of usual dose but will not experience social, buprenorphine that becomes available after psychological, or physical harm from using the publication of this document. Such the drug and would not seek out the drug if it information will be posted regularly on the were no longer needed for analgesia (Jacox et SAMHSA Buprenorphine Web site at http:// al. 1994). An example of addiction to opioids www.buprenorphine.samhsa.gov. without physical dependence is a patient addicted to oxycodone who has been recently detoxified from the drug. In this situation, the Opioid Addiction patient may no longer be suffering from Today in the United withdrawal symptoms or tolerance but may continue to crave an opioid high and will States invariably relapse to active opioid abuse without further treatment.

Opioid Addiction Factors contributing to the development of Opioid addiction is a neurobehavioral opioid addiction include the reinforcing syndrome characterized by the repeated, properties and availability of opioids, family compulsive seeking or use of an opioid despite and peer influences, sociocultural environ- adverse social, psychological, and/or physical ment, personality, and existing psychiatric consequences. disorders. Genetic heritage appears to

Introduction 3 influence susceptibility to alcohol addiction Historically, heroin purity has been less than and, possibly, addiction to tobacco and other 10 percent. By the late 1990s, however, purity drugs as well (Goldstein 1994). was between 50 and 80 percent. The increase in purity has made heroin easier to use by noninjection routes, such as snorting and Addiction Rates smoking. Because individuals can become According to the January 2003 Drug Abuse addicted to or overdose from heroin taken via Warning Network (DAWN) Report published any route, the increase in the type and by SAMHSA’s OAS, the incidence of abuse of number of routes used has led to a rise in new prescription opioid pain medications (also cases of heroin addiction across all sociodemo- known as narcotic analgesics), such as hydro- graphic categories. codone, oxycodone, meperidine, and propoxy- phene, has risen markedly in recent years Many addicted individuals may switch to the (Crane 2003). The incidence of emergency injection route as their heroin use continues to department (ED) visits related to these medi- increase, or if heroin purity should decrease cations has been increasing since the 1990s again. An increase in rates of injection drug and has more than doubled between 1994 and use would have a significant effect on the 2001 (Crane 2003). In 2001, there were an incidence of human immunodeficiency virus estimated 90,232 ED visits related to opioid (HIV) infection, hepatitis B and C, and other analgesic abuse, infectious diseases. a 117 percent The rise of heroin use appears to be a nation- The rise of heroin increase since 1994. Nationally, wide phenomenon in the United States. Heroin overdose deaths have risen sharply, as use appears to be a opioid analgesics were involved in have ED admissions involving heroin. The 14 percent of all most recent data on such ED admissions come nationwide drug-abuse-related from SAMHSA’s DAWN reports, which can be ED visits in 2001 accessed via the Web at the following sites: phenomenon in the (SAMHSA 2002b). http://dawninfo.samhsa.gov/ or According to the http://www.nida.nih.gov/CEWG/DAWN.html. United States. DAWN Mortality Data Report for 2002 (SAMHSA Current State of 2002c), hydroco- Opioid Addiction done ranked among the 10 most common drugs related to deaths in 18 cities, including Treatment Detroit (63), Las Vegas (46), Dallas (36), There are two main modalities for the treat- New Orleans (33), and Oklahoma City (31). ment of opioid addiction: pharmacotherapy Oxycodone ranked among the 10 most and psychosocial therapy. Pharmacotherapies common drugs related to deaths in 19 cities, now available for opioid addiction include including Philadelphia (88), Baltimore (34), (1) agonist maintenance with methadone; Boston (34), Phoenix (34), and Miami (28). (2) partial-agonist maintenance with According to the Office of National Drug buprenorphine or buprenorphine plus Control Policy (ONDCP), there were an naloxone; (3) antagonist maintenance using estimated 810,000 to 1,000,000 individuals naltrexone; and (4) the use of antiwithdrawal addicted to heroin in the United States in the (“detoxification”) agents (e.g., methadone, year 2000—which is the highest number since buprenorphine, and/or clonidine) for brief the mid-to-late 1970s (ONDCP 2003). Several periods, and in tapering doses, to facilitate factors have contributed to this increase. entry into drug-free or antagonist treatment.

4 Introduction Psychosocial approaches (e.g., residential entry into treatment. A discussion of the new therapeutic communities), mutual-help treatment option using buprenorphine programs (e.g., Narcotics Anonymous), and follows. 12-Step- or abstinence-based treatment programs are important modalities in the treatment of addiction to heroin and other Agonist Pharmacotherapy opioids, either as stand-alone interventions or Methadone is the most commonly used medi- in combination with pharmacotherapy. cation for opioid addiction treatment in the United States. Well-run OTPs—with appro- In 2003, more than 200,000 individuals in the priate drug monitoring, counseling services United States were maintained on methadone (individual, group, family), and vocational or LAAM (SAMHSA 2002a). Although precise resources and referrals—have been demon- data are difficult to obtain, it is estimated that strated to decrease heroin use and related fewer than 5,000 individuals are maintained crime, increase employment, improve physical on naltrexone for opioid addiction. The and mental health (McLellan et al. 1993), and number of individuals in 12-Step programs is markedly reduce mortality (see the forth- unknown because of the undisclosed nature coming TIP Medication-Assisted Treatment of the programs and their assurance of ano- for Opioid Addiction [CSAT in develop- nymity. The number of patients in residential ment†]), as well as the incidence of needle therapeutic community treatment who identify sharing (Metzger et al. 1991) and HIV trans- opioids as their primary drugs of abuse is mission (Metzger et al. 1993). Methadone conservatively estimated at 3,000–4,000. suppresses opioid withdrawal, blocks the (This estimate is derived from various effects of other opioids, and decreases craving sources, both published, such as Drug Abuse for opioids. Treatment Outcome Studies [DATOS], and unpublished, such as Therapeutic Antagonist Pharmacotherapy Communities of America reports, found at http://www.drugabuse.gov/about/ Naltrexone is an opioid antagonist that blocks organization/despr/DATOS.html and http:// the effects of heroin and most other opioids. www.therapeuticcommunitiesofamerica.org.) It does not have addictive properties or produce physical dependence, and tolerance does not develop. It has a long half-life, and Current its therapeutic effects can last up to 3 days. Naltrexone is not a stigmatized treatment. It Pharmacotherapy also decreases the likelihood of alcohol relapse Treatment Options for when used to treat alcohol dependence. Opioid Addiction From a purely pharmacological point of view, naltrexone would appear to have the prop- Three traditional types of pharmacotherapy erties of a useful medication for the treatment for opioid addiction are described briefly in of opioid addiction. Its usefulness in the treat- this section: (1) agonist treatment (e.g., ment of opioid addiction, however, has been methadone pharmacotherapy), (2) antagonist limited because of certain disadvantages. treatment (e.g., naltrexone), and (3) the use of First, many addicted patients are not inter- these and other agents (e.g., clonidine) to help ested in taking naltrexone because, unlike withdrawal from opioid drugs as a means of methadone and LAAM, it has no opioid

†Some TIPs are available online at http://www.kap.samhsa.gov/products/manuals/index.htm. Others can be ordered from the National Clearinghouse for Alcohol and Drug Information (NCADI) by accessing its electronic catalog http://store.health.org/catalog/ or by calling 1-800-729-6686. Up to five free hard copies may be ordered using the NCADI order number.

Introduction 5 agonist effects; patients continue to experience increasing purity of street heroin, however, cravings and are thereby not motivated to physicians are reporting more difficulty maintain adherence to the medication regi- managing patients with the use of clonidine men. Second, a patient addicted to opioids and other alpha-adrenergic agonists during must be fully withdrawn for up to 2 weeks withdrawal. from all opioids before beginning naltrexone treatment. Unfortunately, during this with- Unfortunately, the majority of individuals drawal period, many patients relapse to use of addicted to opioids relapse to opioid use after opioids and are unable to start on naltrexone. withdrawal, regardless of the withdrawal Furthermore, once patients have started on method used. Too often, physicians and naltrexone, it may increase the risk for over- facilities use dose-reduction and withdrawal in dose death if relapse does occur. isolation without adequate arrangements for the appropriate treatment and support Naltrexone has demonstrated some utility services that decrease the likelihood of relapse among subgroups of addicted patients with and that are usually necessary for long-term strong motivation and psychosocial support recovery. (For more information about agents for treatment and medication adherence (e.g., used to assist with withdrawal, see the forth- healthcare professionals, business executives, coming TIP Medication-Assisted Treatment younger patients, patients involved in the for Opioid Addiction [CSAT in development].) criminal justice system). Because most addicted patients will not voluntarily take naltrexone, however, the number of indi- Buprenorphine: A New viduals maintained on it continues to be low. Treatment Option for Research is under way on a number of sustained-release, injectable forms of nal- Opioid Addiction trexone in an effort to increase adherence, Buprenorphine’s pharmacological and safety particularly in the early stages of treatment. profile (see chapter 2) makes it an attractive treatment for patients addicted to opioids as Agents Used To Assist With well as for the medical professionals treating them. Buprenorphine is a partial agonist at Withdrawal From Opioid the mu opioid receptor and an antagonist at Drugs the kappa receptor. It has very high affinity and low intrinsic activity at the mu receptor Medically supervised withdrawal (detoxifi- and will displace morphine, methadone, and cation) from opioids is an initial component of other opioid full agonists from the receptor. certain treatment programs but, by itself, Its partial agonist effects imbue bupre- does not constitute treatment of addiction. A norphine with several clinically desirable variety of agents and methods are available pharmacological properties: lower abuse for medically supervised withdrawal from potential, lower level of physical dependence opioids. These include methadone dose- (less withdrawal discomfort), a ceiling effect reduction, the use of clonidine and other at higher doses, and greater safety in overdose alpha-adrenergic agonists to suppress with- compared with opioid full agonists. drawal signs and symptoms, and rapid detoxification procedures (e.g., with a combination At analgesic doses, buprenorphine is 20–50 of naltrexone or naloxone and clonidine and, times more potent than morphine. Because of more recently, buprenorphine). Each of these its low intrinsic activity at the mu receptor, methods has strengths and weaknesses. When however, at increasing doses, unlike a full used properly, various pharmacological agents opioid agonist, the agonist effects of buprenor- can produce safe and less uncomfortable phine reach a maximum and do not continue opioid withdrawal. As a result of the to increase linearly with increasing doses of

6 Introduction the drug—the ceiling effect. One consequence tablet (Temgesic®). Until 2002, the only form of the ceiling effect is that an overdose of of buprenorphine approved and marketed in buprenorphine is less likely to cause fatal the United States was the parenteral form for respiratory depression than is an overdose of treatment of pain (Buprenex®). In 2002, two a full mu opioid agonist. sublingual tablet formulations of buprenorphine were approved by FDA as opioid In the pharmacotherapy of opioid addiction, addiction treatment medications: bupre- buprenorphine, as a partial opioid agonist, norphine alone (Subutex®) and a combination can be thought of as occupying a midpoint tablet containing buprenorphine plus nalox- between opioid full agonists (e.g., methadone, one in a 4:1 ratio (Suboxone®). Both of these LAAM) and opioid antagonists (e.g., naltrex- tablets are Schedule III opioids and therefore one, nalmefene). It has sufficient agonist eligible for use in the treatment of opioid properties such that individuals addicted to addiction under DATA 2000. Figure 1–1 shows opioids perceive a reinforcing subjective effect the dosage forms of buprenorphine currently from the medication, often described in terms available in the United States. Note that, as of of “feeling normal.” In higher doses, and the date of this publication, Subutex® and under certain circumstances, its antagonist Suboxone® are the only forms of buprenor- properties can cause the precipitation of acute phine that are indicated and can be legally withdrawal if administered to an individual used for the treatment of opioid addiction in who is physically dependent on opioids and the United States—neither Buprenex® nor its maintained on a sufficient dose of a full generic equivalent can be used legally to treat agonist. In this scenario, buprenorphine can opioid addiction. displace the full agonist from the mu receptors, yet not provide the equivalent degree of Many of the large clinical studies of buprenor- receptor activation, thereby leading to a net phine in the treatment of opioid addiction in decrease in agonist effect and the onset of the United States withdrawal. (See chapter 2 for more details have been on such effects.) Furthermore, because of the conducted under In 2002, two high affinity of buprenorphine for the opioid the joint spon- receptor, this precipitated abstinence syn- sorship of the sublingual tablet drome may be difficult to reverse. Buprenor- National Institute phine produces a blockade to subsequently on Drug Abuse formulations of administered opioid agonists in a dose- (NIDA) and responsive manner. This effect makes the Reckitt Benckiser, buprenorphine were drug particularly appealing to well-motivated the company patients, as it provides an additional disin- holding the bupre- approved by FDA as centive to continued opioid use. norphine patent. The most extensive Buprenorphine can produce euphoria, opioid addiction especially if it is injected. Buprenorphine does clinical experience with buprenor- produce physical dependence, although it treatment appears to do so to a lesser degree than do phine used for full opioid agonists, and it appears to be treatment of opioid easier to discontinue at the end of medication addiction is in medications… treatment. France, where the medication has Buprenorphine has several pharmaceutical been available for office-based treatment of uses. It is a potent analgesic, available in opioid addiction since February 1996. In many countries as a 0.3–0.4 mg sublingual France, buprenorphine can be prescribed for

Introduction 7 Figure 1–1 Dosage Forms of Buprenorphine Available in the United States (as of July 2004)

FDA-Approved for Opioid Addiction Medication Trade Name Dosage Form(s) Indication Company Treatment

Buprenorphine Subutex® 2- or 8-mg Opioid Reckitt Yes sublingual addiction Benckiser tablets

Buprenorphine/ Suboxone® 2- or 8-mg Opioid Reckitt Yes naloxone sublingual addiction Benckiser combination tablets with buprenorphine/ naloxone in 4:1 ratio

Buprenorphine Buprenex® Injectable ampules Moderate- Reckitt No to-severe pain Benckiser

Buprenorphine Buprenorphine Injectable ampules Moderate- Abbott No injectable to-severe pain Laboratories (generic)

maintenance treatment by both addiction Although buprenorphine has been abused and specialists and general practitioners. It is injected by individuals addicted to opioids in estimated that close to 70,000 patients are countries where the sublingual tablet is currently receiving maintenance treatment available as an analgesic, its abuse potential with buprenorphine in France. appears substantially less than that of full opioid agonists. To reduce the potential for Buprenorphine doses studied for opioid abuse even further, the sublingual tablet addiction treatment have ranged from 1–2 mg dosage form combining buprenorphine with to 16–32 mg, depending upon the formulation naloxone was developed by NIDA and Reckitt (solution versus tablet), with duration of Benckiser. treatment lasting from a few weeks to years. Using the outcome measures of illicit opioid The buprenorphine/naloxone combination use, retention in treatment, and assessment tablet appears to have reduced abuse poten- for adverse events, studies have shown that tial compared with buprenorphine alone when buprenorphine treatment reduces opioid use, studied in opioid-dependent populations. It retains patients in treatment, has few side works on the principle that naloxone is effects, and is acceptable to most patients approximately 10–20 times more potent by (Johnson 1992; Johnson 2000; Ling 1996; injection than by the sublingual route. There- Ling 1998; O’Connor 2000). fore, if the combination is taken sublingually,

8 Introduction as directed, the small amount of naloxone controlled environments (e.g., prison), and available should not interfere with the desired healthcare professionals who are addicted. effects of buprenorphine. If the combination Chapter 6 provides important information on form is dissolved and injected by an individual policies and procedures relevant to opioid physically dependent on opioids, however, the addiction treatment under the DATA 2000 increased bioavailability of naloxone via the paradigm. References (see appendix A) are parenteral route should precipitate an opioid provided so that physicians can consult them withdrawal syndrome. to develop the best fit for each patient’s treatment plan. Summary and As of the date of this publication, Subutex® (buprenorphine) and Suboxone® (bupre- Overview of the norphine/naloxone) are the only forms of Guidelines buprenorphine that have received FDA approval for use in opioid addiction treat- Buprenorphine as a medication, and the ment. Throughout the remainder of this doc- circumstances under which it can be used, ument, use of the term buprenorphine will together provide a new means to treat opioid apply to both sublingual formulations of bup- addiction in the United States. Buprenor- renorphine and to any similarly formulated phine’s usefulness stems from its unique generic products that may receive FDA pharmacological and safety profile, which approval in the future. When information is encourages treatment adherence and reduces presented that is specific to either the bupre- the possibilities for both abuse and overdose. norphine monotherapy formulation or to the Because buprenorphine has unusual phar- buprenorphine/naloxone combination, the macological properties, physicians may want specific designation will be employed, either to consult with addiction specialists to under- by the trade name of the currently approved stand more fully the partial opioid agonist products (which will be meant to include any effects of buprenorphine and how these similar generic equivalents that may be properties are useful in opioid addiction treatment. Although buprenorphine offers approved in the future) or by the full formula designation. special advantages to many patients, it is not for everyone. Care must be taken to assess The consensus panel notes that these guide- each patient fully and to develop a realistic lines represent one approach, but not neces- treatment plan for each patient accepted for sarily the only approach, to the treatment of buprenorphine treatment. opioid addiction with buprenorphine. The Chapter 2 provides additional information on panel considers these guidelines not as the pharmacological properties of opioids in inflexible rules that must be applied in every general and of buprenorphine in particular, instance, but rather as guidance to be con- along with safety considerations (especially sidered in the evaluation and treatment of drug interactions). Chapter 3 provides individual patients. Because each patient is important screening guidelines and specific unique, and because scientific knowledge and tools for initially assessing patients. Chapter 4 clinical best practices change over time, the provides a step-by-step guide for initiating application of these guidelines to the treat- and maintaining treatment and developing a ment of an individual patient must be treatment plan. Chapter 5 provides guidelines informed by the needs of the patient, the on the use of buprenorphine with special pop- changing body of scientific and clinical ulations, including, for example, pregnant knowledge, and the clinical judgment of the women, adolescents, individuals leaving physician.

Introduction 9 10 2 Pharmacology

Overview Five topics related to the general pharmacology of opioids are reviewed In This in the first part of this chapter: (1) opioid receptors; (2) functions of Chapter… opioids at receptors; (3) consequences of repeated administration and withdrawal of opioids; (4) the affinity, intrinsic activity, and dissociation of opioids from receptors; and (5) general characteristics of General Opioid abused opioids. These topics are followed by a detailed review of the Pharmacology general and applied pharmacology of buprenorphine. Pharmacology of Buprenorphine General Opioid Pharmacology Buprenorphine Safety, Adverse Reactions, and Opioid Receptors Drug Interactions Opioid receptors are molecules on the surfaces of cells to which opioid compounds attach and through which they exert their effects. Different Effectiveness of types of opioid receptors are present in the brain. The receptor most Buprenorphine relevant to opioid abuse and treatment is the mu receptor. It is through Treatment activation of the mu receptor that opioids exert their analgesic, euphorigenic, and addictive effects. The roles of other types of opioid The Buprenorphine/ receptors in the brain (that is, non-mu opioid receptors) in the Naloxone Combination addictive process are not well defined.

Diversion and Misuse of Either Buprenorphine The Functions of Opioids at Receptors Alone or the Opioids can interact with receptors in different ways. For purposes of Buprenorphine/Naloxone this discussion, three types of drug/receptor interactions are Combination Product described: agonists (or full agonists), antagonists, and partial agonists. Summary Full Agonists Drugs that activate receptors in the brain are termed agonists. Agonists bind to receptors and turn them on—they produce an effect

11 in the organism. Full mu opioid agonists acti- Consequences of Repeated vate mu receptors. Increasing doses of full agonists produce increasing effects until a Administration and maximum effect is reached or the receptor is Withdrawal of Opioid Drugs fully activated. Opioids with the greatest The repeated administration of a mu opioid abuse potential are full agonists (e.g., agonist results in tolerance and dose- morphine, heroin, methadone, oxycodone, dependent physical dependence. Tolerance is hydromorphone). characterized by a decreased subjective and objective response to the same amount of Antagonists opioids used over time or by the need to keep increasing the amount used to achieve the Antagonists also bind to opioid receptors, but desired effect. In the case of abuse or addic- instead of activating receptors, they effec- tion, the desired effect typically is euphoria. tively block them. Antagonists do not activate Physical dependence is manifested as a receptors, and they prevent receptors from characteristic set of withdrawal signs and being activated by agonist compounds. An symptoms in response to reduction, cessation, antagonist is like a key that fits in a lock but or loss of the active compound at receptors does not open it and prevents another key (withdrawal syndrome). from being inserted to open the lock. Examples of opioid antagonists are naltrexone Typical signs and symptoms of the opioid and naloxone. withdrawal syndrome include lacrimation, diarrhea, rhinorrhea, piloerection, yawning, Partial Agonists cramps and aches, pupillary dilation, and Partial agonists possess some of the properties sweating. Not all of these signs and symptoms are necessarily present in any single individual of both antagonists and full agonists. Partial agonists bind to receptors and activate them, experiencing the opioid withdrawal syndrome. but not to the same degree as do full agonists. Withdrawal, characterized by marked distress, may include drug craving and drug At lower doses and in individuals who are not dependent on opioids, full agonists and partial seeking and is frequently associated with agonists produce effects that are indistinguish- relapse to drug use in a patient with opioid addiction. In an individual who otherwise is in able. As doses are increased, both full and partial agonists produce increasing effects. At good general health (e.g., with no history of a certain point, however, as illustrated in significant cardiovascular disease), opioid withdrawal is not life threatening. Patients figure 2–1, the increasing effects of partial agonists reach maximum levels and do not with cardiovascular disease or other severe increase further, even if doses continue to conditions will need comanagement involving the appropriate specialist, as well as con- rise—the ceiling effect. The figure represents any effect mediated by mu opioid receptors sultation with an addiction specialist. (e.g., analgesia, euphoria, respiratory depres- Two types of withdrawal are associated with sion). As higher doses are reached, partial mu opioid agonists: spontaneous withdrawal agonists can act like antagonists—occupying and precipitated withdrawal. receptors but not activating them (or only partially activating them), while at the same time displacing or blocking full agonists from Spontaneous Withdrawal receptors. Buprenorphine is an example of a Spontaneous withdrawal can occur when an mu opioid partial agonist, and its properties individual who is physically dependent on as such are discussed in detail below. mu agonist opioids (e.g., has been using

12 Pharmacology Figure 2–1 Conceptual Representation of Opioid Effect Versus Log Dose for Opioid Full Agonists, Partial Agonists, and Antagonists*

Full Agonist (Methadone)

Effect

Opioid Partial Agonist (Buprenorphine )

Antagonist (Naloxone)

Log Dose *Conceptual representation only, not to be used for dosing purposes.

opioids on a daily basis) suddenly discontinues half-lives have a longer period before the that opioid use. It also can occur if an indi- onset of spontaneous withdrawal (e.g., 24– vidual who is physically dependent markedly 72 hours for methadone) and a longer period decreases his or her daily opioid use. before peak withdrawal is experienced.

In an individual who is physically dependent on heroin, spontaneous withdrawal usually Precipitated Withdrawal begins 6–12 hours after the last dose and Precipitated withdrawal also occurs in indi- peaks in intensity 36–72 hours after the last viduals who are physically dependent on use. The spontaneous withdrawal syndrome mu agonist opioids. Precipitated withdrawal from heroin lasts approximately 5 days, usually occurs when an individual physically although a milder, protracted withdrawal may dependent on opioids is administered an last longer. Other short-acting opioids, such opioid antagonist. In an individual who is not as oxycodone and hydrocodone, have kinetic physically dependent upon opioids, the acute profiles that are similar to heroin, and the administration of an antagonist typically time course of spontaneous withdrawal for produces no effects. In an individual who is these agents should be similar to that doc- physically dependent on opioids, however, an umented for heroin. Opioids with longer antagonist produces a syndrome of withdrawal

Pharmacology 13 that is qualitatively similar to that seen with agonists, partial agonists, and antagonists can spontaneous withdrawal (although the onset is vary in their affinity. faster and the syndrome is shorter, depending on the half-life of the antagonist). One way to In addition to variations in affinity and conceptualize precipitated withdrawal is that intrinsic activity, drugs also vary in their rate the antagonist displaces agonists from recep- of dissociation from receptors. Dissociation is tors, but because the antagonist does not a measure of the disengagement or uncoupling activate the receptor, there is a net decrease of the drug from the receptor. Dissociation is in agonist effect, resulting in withdrawal. not the same as affinity—a drug can have high affinity for a receptor (it is difficult to displace It is also possible for partial agonists to pre- it from the receptor with another drug once cipitate withdrawal. If an individual who is the first drug is present), but it still dissociates physically dependent on opioids receives an or uncouples from the receptor with some acute dose of a partial agonist, the partial regularity. Buprenorphine’s slow dissociation agonist can displace the full agonist from the contributes to its long duration of action. receptors yet not activate the receptors as much as the full agonist had. The net effect would be a decrease in agonist effect and a Characteristics of Abused precipitated withdrawal syndrome. Precipi- Drugs tated withdrawal with a partial agonist is more The rate of onset of the pharmacological likely to occur in effects of a drug, and thereby its abuse poten- an individual who tial, is determined by a number of factors. has a high level of Buprenorphine has Important among these are the drug’s route of physical depend- administration, its half-life, and its lipophili- ence (e.g., high city (which determines how fast the drug high affinity for, but use of opioids each reaches the brain). A faster route of drug day), who takes administration (e.g., injection, smoking), a low intrinsic activity the partial agonist shorter half-life, and a faster onset of action soon after a dose all are associated with a higher abuse potential at, mu receptors. of full agonist, of a drug. With all classes of drugs of abuse, it and/or who takes has been shown that the likelihood of abuse is a high dose of the related to the ease of administration, the cost partial agonist. of the drug, and how fast the user experiences These points, the desired results after the drug’s administra- discussed in more detail below, are directly tion. In this respect, heroin is highly abusable, relevant to the initiation of buprenorphine as it currently is inexpensive; can be snorted, treatment. smoked, or injected; and produces a rapid euphorigenic response. Affinity, Intrinsic Activity, and Dissociation Pharmacology of The strength with which a drug binds to its Buprenorphine receptor is termed its affinity. The degree to which a drug activates its receptors is termed its intrinsic activity. Affinity for a receptor Overview and activation of the receptor are two differ- Buprenorphine is a thebaine derivative that is ent qualities of a drug. A drug can have high legally classified as a narcotic. It is available affinity for a receptor but not activate the in numerous countries for use as an analgesic. receptor (e.g., an antagonist). Mu opioid When used as an analgesic, buprenorphine is

14 Pharmacology usually given by injection, via a sublingual sublingual buprenorphine-alone tablet was tablet, or as a transdermal patch, and doses more effective than the 8-mg dose in blocking are relatively low (compared with doses used the reinforcing effects of heroin. Similarly, it is in the treatment of opioid addiction). The difficult for opioid antagonists (e.g., naloxone) typical analgesic dose of buprenorphine is to displace buprenorphine and precipitate 0.3–0.6 mg (intramuscular or intravenous), withdrawal. and its analgesic effects last about 6 hours. Buprenorphine has a slow dissociation rate Buprenorphine is a partial agonist that exerts from the mu opioid receptor, which gives rise significant actions at the mu opioid receptor. to its prolonged suppression of opioid with- As reviewed in the previous section, however, drawal and blockade of exogenous opioids. its maximal opioid effects are less than that of This enables buprenorphine dosing to occur on full agonists, and reach a ceiling where higher a less frequent basis than full opioid agonists doses do not result in increasing effect. (Amass et al. 1994a,b, 1998, 2000, 2001). Because it is a partial agonist, higher doses of Buprenorphine can be given as infrequently as buprenorphine can be given with fewer three times per week (Amass et al. 2001; Perez adverse effects (e.g., respiratory depression) de los Cobos et al. 2000; and Schottenfeld et al. than are seen with higher doses of full agonist 2000). Buprenorphine’s effectiveness as a opioids. Past a certain point, dose increases of medication for the treatment of opioid addic- buprenorphine do not further increase the tion on a daily or less-than-daily basis con- pharmacological effects of the drug but do trasts with its relatively short duration of increase its duration of withdrawal suppres- action as an analgesic. sion and opioid blockade.

At low doses, buprenorphine is many times Bioavailability more potent than morphine. Individuals who Buprenorphine has poor gastrointestinal (GI) are not dependent on opioids but who are bioavailability (Brewster et al. 1981; Walter familiar with the effects of opioids experience and Inturrisi 1995), and fair sublingual a subjectively positive opioid effect when they bioavailability. (See figure 2–2.) FDA- receive an acute dose of buprenorphine. approved formulations of the drug for treat- These subjective effects aid in maintaining ment of opioid addiction are in the form of compliance with buprenorphine dosing in sublingual tablets that are held under the patients who are addicted to opioids. tongue and absorbed through the sublingual mucosa. Studies of sublingually administered Affinity, Intrinsic Activity, buprenorphine have employed either an alcohol-based solution or a tablet formulation and Dissociation of the drug. Confusion may result when Buprenorphine has high affinity for, but low reviewing the literature on the effectiveness of intrinsic activity at, mu receptors. Buprenor- buprenorphine at various doses because most phine displaces morphine, methadone, and early trials and clinical studies of buprenor- other full opioid agonists from receptors. It phine were performed with a sublingually also can block the effects of other opioids administered liquid preparation, whereas the (Bickel et al. 1988; Rosen et al. 1994; Strain et oral formulations marketed in the United al. 2002). Because of buprenorphine’s higher States are sublingual tablets. Studies have affinity for the mu receptor, full agonists shown that the bioavailability of buprenor- cannot displace it and therefore will not exert phine in sublingual tablet form is significantly an opioid effect on receptors already occupied less than via sublingual liquid solution—about by buprenorphine. This effect is dose related, 50–70 percent that of the liquid form (Nath as shown by Comer et al. (2001) in a study et al. 1999; Schuh and Johanson 1999), so the demonstrating that the 16-mg dose of the dosages of buprenorphine sublingual tablets

Pharmacology 15 Figure 2–2 Bioavailability of Buprenorphine

Buprenorphine Buprenorphine Buprenorphine Bioavailability Bioavailability Bioavailability Relative to Relative to Relative to Sublingual Solution Route of Intravenous Route Intramuscular Route Route of Administration of Administration of Administration Administration

Intravenous 100% — —

Intramuscular 70% 100% —

Sublingual Solution 49% 70% 100%

Sublingual Tablet 29% 42% 50–70%

Sources: Brewster et al. 1981; Kuhlman et al. 1996; Lloyd-Jones et al. 1980; Nath 1999; Schuh and Johanson 1999; Strain and Stitzer 1999; Weinberg et al. 1988

must be significantly higher than those used in Abuse of buprenorphine has been reported the liquid form to achieve the same therapeu- to occur via the sublingual and intranasal tic effect. routes but primarily via diversion of sublingual tablets to the injection route. In a study from France (Obadia et al. 2001), Abuse Potential sublingual, buprenorphine-only tablets Epidemiological studies and human laboratory (Subutex®), marketed for the treatment of studies indicate that buprenorphine is abus- opioid addiction, were diverted to the injec- able. This is consistent with its action at the tion route. mu opioid receptor. The abuse potential, however, is lower in comparison with the Laboratory studies with inpatient subjects abuse potential of full opioid agonists. This is have examined the effects of buprenorphine consistent with buprenorphine’s partial relevant to abuse potential in two populations: (1) subjects who have a history of opioid abuse agonist effects and the resultant ceiling in maximal effects produced. Still, abuse of the but are not physically dependent on opioids, and (2) subjects who are physically dependent analgesic form of buprenorphine through on opioids. diversion to the injectable route has been reported internationally: Abuse Potential in • England (Strang 1985) Nonphysically Dependent • Ireland (O’Connor et al. 1988) Opioid Users • Scotland (Gray et al. 1989; Morrison 1989; In nonphysically dependent opioid users, Sakol et al. 1989) acute parenteral doses of buprenorphine • India (Chowdhury and Chowdhury 1990; produce typical mu agonist opioid effects Singh et al. 1992) (e.g., pupillary constriction, mild euphoria), • New Zealand (Robinson et al. 1993) suggesting that this population could abuse

16 Pharmacology buprenorphine (Jasinski et al. 1978, 1989; Time Interval. The abuse potential of bupre- Pickworth et al. 1993). Similar effects can norphine in opioid-dependent individuals also occur in this population when buprenorphine varies as a function of the time interval is administered via other routes, including the between the dose of agonist and the dose of sublingual route (Jasinski et al. 1989; Johnson buprenorphine. At relatively short time et al. 1989; Walsh et al. 1994). Strain et al. intervals (e.g., 2 hours after a dose of meth- (2000) recently reconfirmed the opioid-like adone), buprenorphine can precipitate effects of sublingually administered buprenor- withdrawal—even when the level of physical phine in this population. These researchers dependence is relatively low (Strain et al. further found that, in nondependent 1995). At longer time intervals, it becomes subjects, the addition of naloxone (in the more likely that buprenorphine will exhibit buprenorphine/naloxone combination tablet) either no effects (i.e., similar to placebo did not attentuate buprenorphine’s opioid [Strain et al. 1992]) or effects similar to opioid effects via the sublingual route. The onset of agonists. effects via the sublingual route is slower than Acute Dose of Buprenorphine. Finally, the that seen with parenteral administration, dose of buprenorphine administered also can suggesting that the abuse potential by this influence its abuse potential. Low doses of route is lower than via the parenteral route. injected buprenorphine (e.g., <2 mg) produce minimal effects in opioid-dependent patients Abuse Potential in Physically and are primarily identified as similar to Dependent Opioid Users placebo (Strain et al. 1992) although there has been at least one report of more precipitated The abuse potential of buprenorphine in abstinence (Banys et al. 1994). individuals who are physically dependent on opioids varies as a function of three factors: Higher doses can be identified as opioid (1) level of physical dependence, (2) time agonist-like, especially as the time interval interval between administration of the full since the dose of agonist increases (e.g., 24 or agonist and of buprenorphine, and (3) the more hours) and if the individual has a lower dose of buprenorphine administered. level of physical dependence (e.g., 30 mg per day of methadone or the equivalent). Level of Physical Dependence. In individuals with a high level of physical dependence (e.g., Although buprenorphine can precipitate those using substantial amounts of opioids on withdrawal under certain circumstances, it is a daily basis), buprenorphine may precipitate worth noting that it does not usually produce withdrawal when taken during the time of severe precipitated withdrawal symptoms. opioid intoxication or receptor occupancy. The relationship between level of physical dependence and buprenorphine-related Potential for Physical precipitated withdrawal has been investigated Dependence primarily in subjects maintained on metha- Repeated administration of buprenorphine done. For example, patients maintained on produces or maintains opioid physical 60 mg of methadone daily can experience dependence; however, because buprenorphine precipitated withdrawal from acute doses of is a partial agonist, the level of physical sublingual buprenorphine (Walsh et al. 1995). dependence appears to be less than that Conversely, in individuals with a low level of produced by full agonists (Eissenberg et al. physical dependence (e.g., patients main- 1996). Furthermore, the withdrawal syn- tained on <30 mg per day of methadone), drome associated with buprenorphine dis- buprenorphine could produce opioid agonist continuation may be significantly milder in effects, thus suggesting a potential for abuse. intensity, and the onset of withdrawal signs

Pharmacology 17 and symptoms slower, than that seen with full Preclinical studies suggest that high acute mu agonists (Eissenberg et al. 1997; Jasinski doses of buprenorphine (analogous to an et al. 1978; Mello et al. 1982; San et al. 1992). overdose) produce no significant respiratory The reason for the slower onset of withdrawal depression or other life-threatening sequelae symptoms is not completely understood but is (e.g., circulatory collapse). Overdose of likely related to buprenorphine’s slow disso- buprenorphine combined with other medica- ciation from the mu receptor. Gradual dose tions, however, may increase morbidity and reduction of buprenorphine results in an even mortality, as described further below. milder withdrawal syndrome. Respiratory Depression Metabolism and Excretion In contrast to full mu agonists, overdose of A high percentage of buprenorphine is bound buprenorphine (by itself) does not appear to to plasma protein and is metabolized in the cause lethal respiratory depression in non- liver by the cytochrome P450 3A4 enzyme compromised individuals. Consistent with this system into norbuprenorphine and other clinical observation, a preclinical study of products (Iribarne et al. 1997; Kobayashi et buprenorphine showed initial dose-related al. 1998). First-pass effects account for its increases in pCO2 (arterial carbon dioxide relatively low GI bioavailability and its short level) followed by decreases in pCO2 com- plasma half-life. (See the buprenorphine patible with buprenorphine’s bell-shaped package inserts for a more detailed explana- dose-response curve (Cowan et al. 1977). tion of its metabolism and excretion.) However, although none of the outpatient clinical trials comparing buprenorphine to Side Effects methadone or placebo reported adverse events of respiratory depression, some cases The primary side effects of buprenorphine are have been reported of respiratory depression similar to other mu opioid agonists (e.g., induced by buprenorphine in individuals not nausea, vomiting, constipation), but the physically dependent on opioids (Gal 1989; intensity of these side effects may be less than Thörn et al. 1988). In addition, buprenor- that produced by full agonist opioids. phine, in combination with other sedative drugs, has been reported to produce respira- Buprenorphine Safety, tory depression. (See “Drug Interactions” below.) Adverse Reactions, and Drug Interactions Cognitive and Psychomotor Effects Accidental Ingestion and Available evidence in patients maintained on Overdose buprenorphine indicates no clinically signifi- Because of buprenorphine’s poor GI bioavail- cant disruption in cognitive and psychomotor ability, swallowing the tablets will result in a performance (Walsh et al. 1994). milder effect compared with administering them sublingually. (By extrapolation, bupre- Hepatic Effects norphine tablets are approximately one-fifth as potent when swallowed versus when taken Elevation in liver enzymes (AST and ALT) has sublingually.) Buprenorphine’s ceiling effect been reported in individuals receiving bupre- also adds to its safety in accidental or inten- norphine (Lange et al. 1990; Petry et al. tional overdose. 2000). There also appears to be a possible

18 Pharmacology association between intravenous buprenor- Drug Interactions phine misuse and liver toxicity (Berson et al. 2001). See Johnson et al. 2003b for further Benzodiazepines and Other details. Mild elevations in liver enzymes have been noted in patients with hepatitis who Sedative Drugs received long-term buprenorphine dosing There have been case reports of deaths appar- (Petry 2000). ently associated with injections of buprenorphine combined with benzodiazepines and/or other central nervous system (CNS) depres- Perinatal Effects sants (e.g., alcohol) (Reynaud et al. 1998a,b). There is limited clinical experience with bup- Gaulier et al. (2000) reported a case of fatal renorphine maintenance in pregnant women overdose in which buprenorphine and its who are addicted to opioids. The literature in metabolites, as well as the metabolites of this area is limited to case reports, prospective flunitrazepam, were very high at the time of studies, and open-labeled controlled studies; death. Although it is not known if this is a however, no randomized controlled studies pharmacodynamic interaction, have been reported (Johnson et al. 2003b). Ibrahim et al. See “Pregnant Women and Neonates” in …overdose of (2000) and chapter 5 for a detailed discussion of the Kilicarslan and available clinical and research evidence. Sellers (2000) sug- buprenorphine (by gest that, because Buprenorphine-Induced of buprenor- itself) does not appear Precipitated Withdrawal phine’s weak ability to inhibit to cause lethal Administration of buprenorphine can precipi- the cytochrome tate an opioid withdrawal syndrome. Although P450 3A4 system, respiratory there is much variability in response to bupre- the effect is more likely pharmaco- norphine, precipitated withdrawal symptoms depression in tend to be milder than those produced by dynamic. This antagonist-precipitated withdrawal, and interaction, intervention is rarely required. In controlled however, under- noncompromised studies in which buprenorphine was given to scores the individuals who were physically dependent on importance for individuals. opioids, the precipitated withdrawal syn- physicians to be drome was both mild in intensity and easily cautious in pre- tolerated (Strain et al. 1995). However, at scribing buprenorphine in conjunction with benzodiazepines, as well as in prescribing least one open-label small-sample trial of buprenorphine to patients who are addicted to low-dose buprenorphine caused a patient to opioids and also are abusing or are addicted experience pronounced, precipitated, and to benzodiazepines. It is prudent to assume poorly tolerated withdrawal of severe intensity that these cautions also should be applied to (Banys et al. 1994). The probability of pre- buprenorphine combined with other CNS cipitating a withdrawal syndrome is minimized depressants, including alcohol and by reducing the dose of mu agonist before barbiturates. buprenorphine treatment is initiated, by allowing a longer elapsed interval between last agonist dose and first buprenorphine dose, Opioid Antagonists and by starting treatment with a lower bup- Buprenorphine treatment should not be renorphine dose. combined with opioid antagonists (e.g.,

Pharmacology 19 naltrexone). It is common for individuals who mu agonists for analgesia can be effective. If are addicted to opioids to be concurrently the necessity should arise for the use of a full dependent on alcohol. Although naltrexone mu agonist for pain relief in a patient main- may decrease the likelihood of relapse to tained on buprenorphine, the buprenorphine drinking, patients maintained on opioids should be discontinued until the pain can be should not be given naltrexone to prevent controlled without the use of opioid pain alcohol relapse since the naltrexone can medications. It must be recognized that precipitate an opioid withdrawal syndrome in treatment with full mu agonists for pain relief buprenorphine-maintained patients. Thus, will produce increased opioid tolerance and a physicians should not prescribe naltrexone for higher degree of physical dependence. See patients being treated with buprenorphine for “Patients With Pain” in chapter 5 for a opioid addiction. detailed discussion of the treatment of pain in patients maintained on buprenorphine. Medications Metabolized by Cytochrome P450 3A4 Effectiveness of Buprenorphine is metabolized by the cyto- Buprenorphine chrome P450 3A4 enzyme system. Other medications that interact with this enzyme Treatment system should be used with caution in patients Buprenorphine can be used for either long- taking buprenorphine. No controlled term maintenance or for medically supervised studies, however, have examined these withdrawal (detoxification) from opioids. The pharmacokinetic interactions. Figure 2–3 preponderance of research evidence and lists some of the drugs known to be metab- clinical experience, however, indicates that olized by cytochrome P450 3A4. In some opioid maintenance treatments have a much cases, these drugs may either enhance or higher likelihood of long-term success than do decrease buprenorphine’s effects through any forms of withdrawal treatment. In any * actions on the cytochrome P450 3A4 system. event, the immediate goals in starting buprenorphine should be stabilization of the patient Opioid Agonists and abstinence from illicit opioids, rather Clinical situations may arise in which a full than any arbitrary or predetermined schedule agonist may be required for patients who of withdrawal from the prescribed medication. currently are being treated with buprenorphine, such as in the treatment of acute pain. Maintenance Treatment Although this medication interaction has not been studied systematically, the pharmaco- A number of clinical trials have established logical characteristics of buprenorphine the effectiveness of buprenorphine for the suggest that it may be difficult to obtain maintenance treatment of opioid addiction. adequate analgesia with full agonists in These have included studies that compared patients stabilized on maintenance buprenorphine to placebo (Johnson et al. buprenorphine. 1995; Ling et al. 1998; Fudala et al. 2003), as well as comparisons to methadone (e.g., Data nonspecific to buprenorphine suggest Johnson et al. 1992; Ling et al. 1996; Pani et that, in patients maintained chronically on al. 2000; Petitjean et al. 2001; Schottenfeld et methadone, the acute administration of full al. 1997; Strain et al. 1994a, 1994b) and to

*It is important to understand that in vitro findings may not be predictive of what occurs in humans, underscoring the need for clinicians to monitor patients for potential drug interactions and associated adverse events.

20 Pharmacology Figure 2–3 Partial List of Medications Metabolized by Cytochrome P450 3A4

Inhibitors (potentially Inducers (potentially increasing blood levels decreasing blood levels of buprenorphine) Substrates of buprenorphine) Amiodarone Alprazolam Loratadine Carbamazepine Clarithromycin Amlodipine Losartan Dexamethasone Delavirdine Astemizole Lovastatin Efavirenz Erythromycin Atorvastatin Miconazole Ethosuximide Fluconazole Carbamazepine Midazolam Nevirapine Fluoxetine Cisapride Navelbine Phenobarbital Fluvoxamine Clindamycin Nefazadone Phenytoin Grapefruit Juice Clonazepam Nelfinavir Primadone Indinavir Cyclobenzaprine Nicardipine Rifampin Itraconazole Cyclosporine Nifedipine Ketoconazole Dapsone Nimodipine Metronidazole Delavirdine Ondansetron Miconazole Dexamethasone Oral Nefazadone Diazepam Contraceptives Nelfinavir Diltiazem Paclitaxel Nicardipine Disopyramide Prednisone Norfloxacin Doxorubicin Progestins Omeprozol Erythromycin Quinidine Paroxetine Estrogens Rifampin Ritonavir Etoposide Ritonavir Saquinavir Felodipine R-Warfarin Sertraline Fentanyl Saquinavir Verapamil Fexofenadine Sertraline Zafirlukast Glyburide Simvastatin Zileuton Ifosfamide Tacrolimus Indinavir Tamoxifen Ketoconazole Verapamil Lansoprazole Vinblastine Lidocaine Zileuton For a continuously updated list of cytochrome P450 3A4 drug interactions, visit http://medicine.iupui.edu/flockhart/table.htm. methadone and levo-alpha-acetyl-methadol A meta-analysis comparing buprenorphine to (LAAM) (Johnson et al. 2000). Results from methadone (Barnett et al. 2001) concluded these studies suggest that buprenorphine in a that buprenorphine was more effective than dose range of 8–16 mg a day sublingually is as 20–35 mg of methadone but did not have as clinically effective as approximately 60 mg a robust an effect as 50–80 mg methadone— day of oral methadone, although it is unlikely much the same effects as the individual studies to be as effective as full therapeutic doses of have concluded. methadone (e.g., 120 mg per day) in patients requiring higher levels of full agonist activity Buprenorphine’s partial mu agonist for effective treatment. properties make it mildly reinforcing, thus

Pharmacology 21 encouraging patient compliance with regular the literature on opioid withdrawal can be administration. This is in contrast to medica- used to guide recommendations in this regard. tions such as naltrexone, which also blocks This literature suggests that using buprenor- the effects of opioid agonists but lacks any phine for gradual detoxification is more agonist effects. Because a medication such as effective than its use for rapid detoxification naltrexone is not reinforcing, adherence in in terms of patient compliance and relapse to therapeutic use is poor. Naltrexone also may opioid use. These findings are analogous to increase the risk for overdose death in the those seen with methadone which show that event of relapse following its discontinuation. patients undergoing a 10-week methadone dose reduction (i.e., 10 percent per week) had a higher rate of opioid-positive urine samples Medically Supervised than those receiving a 30-week dose reduction Withdrawal (i.e., 3 percent per week) and asked for more Although controlled clinical studies of the use schedule interruptions (Senay et al. 1977). of buprenorphine as an agent for treating Moderate-Period Withdrawal. Few studies of opioid withdrawal (detoxification) are scarce, withdrawal from illicit opioids have been some clinical conducted using buprenorphine for moderate research on its use periods (>3 days, but <30 days). Moderate- The safety and for this indication period withdrawal using buprenorphine has been con- suppresses signs and symptoms of withdrawal, efficacy profile of ducted (Parran is tolerated by patients, and is safe. For et al. 1994). In example, a study comparing 10 days of bupre- sublingual general, buprenorphine versus clonidine for the inpatient norphine has been treatment of opioid withdrawal found bupre- used in three ways buprenorphine/ norphine superior to clonidine in relieving for withdrawal withdrawal signs and symptoms (Nigam et al. from opioids: long- naloxone appears to 1993). Outcomes with moderate-period with- period withdrawal drawal, however, are unlikely to be as positive (>30 days), usually as those seen with long-period withdrawal be equivalent to that on an outpatient (Amass et al. 1994a,b). basis; moderate- of buprenorphine period withdrawal Short-Period Withdrawal. The liquid form (>3 days but of buprenorphine has been studied for the alone.… <30 days), again withdrawal from opioids over short periods on an outpatient (e.g., 3 days) (Armenian et al. 1999). In these basis; and short- studies, the doses of buprenorphine admin- period withdrawal (<3 days), which often has istered were low (compared to maintenance been conducted on an inpatient basis. The doses) and typically were administered two or available evidence from buprenorphine and three times per day, either by injection or by methadone research suggests that long-period having the patient hold the liquid under his or buprenorphine withdrawal probably would be her tongue. (Note that this off-label use of the more effective than moderate- or short-period liquid form of buprenorphine is unlawful withdrawals but that all forms of withdrawal outside an approved study setting and is now are less effective compared with ongoing unnecessary due to the FDA approval of opioid maintenance (Amass et al. 1994a,b; Subutex® and Suboxone®.) Sees et al. 2000). Reports have indicated that buprenorphine is Long-Period Withdrawal. Although few data well accepted by patients for short-period are available on the use of buprenorphine for withdrawal and that opioid withdrawal signs gradual withdrawal over a period of months, and symptoms are suppressed (DiPaula et al.

22 Pharmacology 2002; and Bickel et al. 1988). When compared treatment is elected for a pregnant woman, with clonidine for the treatment of short- the monotherapy product should be used. period withdrawal, buprenorphine is better (See “Pregnant Women and Neonates” in accepted by patients and more effective in chapter 5.) relieving withdrawal symptoms (Cheskin et al. 1994). Long-term outcomes from short-period opioid withdrawal using buprenorphine have Diversion and not been reported, however, and studies of other withdrawal modalities have shown that Misuse of Either brief withdrawal periods do not produce Buprenorphine Alone measurable long-term benefits (Simpson and Sells 1989); patients usually relapse to opioid or the Buprenorphine/ use. Naloxone Combination Product The Buprenorphine/ As with any prescription opioid, physicians Naloxone Combination prescribing or dispensing buprenorphine or the buprenorphine/naloxone combination There have been reports from several should monitor patients for diversion of these countries of abuse of buprenorphine by medications. As noted above, naloxone is injection. Because of this buprenorphine combined with buprenorphine to decrease abuse, a sublingual tablet form containing the potential for abuse of the combination via naloxone has been developed for the U.S. injection. Four types of individuals might market to decrease the potential for abuse of attempt to abuse buprenorphine or the combination product via the injection buprenorphine/naloxone tablets parenterally: route. Sublingual naloxone has relatively low bioavailability (Preston et al. 1990), while 1. Those using diverted tablets who are sublingual buprenorphine has good bioavail- physically dependent on illicit opioids ability. (Both naloxone and buprenorphine (e.g., heroin). Parenteral use of the have poor GI bioavailability.) Thus, if a tablet combination buprenorphine/naloxone containing buprenorphine plus naloxone is tablet by these individuals would result in taken as directed—sublingually—the patient precipitated withdrawal more reliably will experience a predominant buprenorphine than injection of buprenorphine alone. effect. However, if an opioid-dependent 2. Those using diverted tablets who are individual dissolves and injects the combi- taking therapeutic full agonist opioids nation tablet, then the antagonistic effect of (e.g., oxycodone, methadone). Parenteral naloxone predominates because of its high use of the combination buprenorphine/ parenteral bioavailability (Stoller et al. 2001). naloxone tablet by these individuals also Under such circumstances, the individual would result in a precipitated withdrawal should experience a precipitated withdrawal syndrome more reliably than injection of syndrome. This should decrease the likelihood buprenorphine alone. of misuse and abuse of the combination tablet 3. Those receiving prescription buprenor- by the injection route. phine or buprenorphine/naloxone tablets The safety and efficacy profile of sublingual who dissolve and inject their own medi- buprenorphine/naloxone appears to be equiv- cation. This population would experience alent to that of buprenorphine alone (Harris an agonist effect from buprenorphine but et al. 2000). Currently, no special safety or no antagonist effect from naloxone, as side-effect considerations exist for the combi- large doses of opioid antagonists are nation formulation, but it is not recommended needed to precipitate withdrawal in for use in pregnant women. If buprenorphine buprenorphine-maintained subjects

Pharmacology 23 (Eissenberg et al. 1996). Although some of Summary the agonist effects of buprenorphine may be attenuated by the simultaneous An understanding of both the general injection of naloxone, acute agonist effects pharmacology of opioids and the specific will still be experienced whether the pharmacological properties of buprenorphine combination or the monotherapy product is essential for physicians who intend to treat is injected. opioid addiction with buprenorphine. 4. Those who abuse opioids but who are not Buprenorphine has unique qualities that make physically dependent on them. In this it an effective and safe addition to the group, neither naloxone nor buprenor- available pharmacological treatments for phine will produce precipitated with- opioid addiction. The combination of drawal. Sublingual or injected use of buprenorphine with the opioid antagonist either buprenorphine product will naloxone further increases its safety and produce opioid agonist effects; however, decreases—but does not eliminate—the the euphoric effects would be mild. likelihood of diversion and misuse.

24 Pharmacology 3 Patient Assessment

Overview In This This chapter presents guidance on screening for the presence of Chapter… opioid use disorders and for the further assessment of patients in whom screening indicates the potential presence of a problem. Guidelines are provided for determining when buprenorphine is an Screening and Assessment appropriate treatment option for patients who have an opioid addic- of Opioid Use Disorders tion. Additional information about many of the topics discussed in this chapter can be found in appendix E. Determining Appropriateness for Buprenorphine Treatment Screening and Assessment of Opioid Use Disorders

Screening The consensus panel that developed the Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction recommends that physicians periodically and regularly screen all patients for substance use and substance-related problems, not just those patients who fit the stereotypical picture of addiction. Although addiction to drugs and alcohol is common, currently fewer than one- third of physicians in the United States carefully screen for addiction (National Center on Addiction and Substance Abuse 2000). Conducting ongoing, regular substance abuse screening as part of medical care facilitates the early identification, intervention, and treatment of addiction. Periodic assessments for abuse, addiction, or other adverse effects are particularly helpful when the primary care physician or specialist is prescribing opioids for the treatment of pain. Office-based physicians may conduct further assessment and provide primary opioid addiction treatment for those patients who are determined to be appropriate candidates for office-based treatment. Alternatively, when indicated, patients may be referred for treatment in another setting.

25 Goals of Screening Examples of addiction screening instruments include The goals of addiction screening and assessment are to • Drugs: • Identify individuals who are at risk for – COWS (Clinical Opiate Withdrawal developing drug- or alcohol-related Scale) (Wesson et al. 1999) problems – SOWS (Subjective Opiate Withdrawal • Identify individuals who may have devel- Scale) (Bradley et al. 1987; Gossop 1990; oped drug- or alcohol-related problems or Handelsman et al. 1987) addiction – DAST-10 (Drug Abuse Screening Test) • Identify individuals who require further (Skinner 1982) medical or addiction assessment – CINA (Clinical Institute Narcotic • Diagnose addiction or other substance- Assessment Scale for Withdrawal related disorders Symptoms) (Peachey and Lei 1988) • Develop recommendations and plan for – CAGE-AID (CAGE Adapted to Include appropriate addiction treatment Drugs) (Brown and Rounds 1995) • Assess the biopsychosocial needs of patients – Narcotic Withdrawal Scale (Fultz and with addictions Senay 1975) Initial Screening • Alcohol: – CAGE (Maisto et al. 2003) Initial screening should consist of a combination of objective screening instruments, – AUDIT (Alcohol Use Disorders laboratory evaluations, and interview(s). If Identification Test) (Babor et al. 2001) the physician suspects an addiction problem – MAST (Michigan Alcohol Screening Test) after reviewing (Selzer 1971) the initial results, – SMAST (Short Michigan Alcohol further assess- Screening Test) (Selzer et al. 1975) To determine the ment is indicated. In-depth For more information about such tools, see appropriateness of interviews and appendix B. The reader also can review the standardized Substance Abuse and Mental Health Serv- office-based or other assessments are ices Administration (SAMHSA) Center for the most effective Substance Abuse Treatment (CSAT) TIP 24, means of gather- opioid agonist A Guide to Substance Abuse Services for ing further Primary Care Clinicians (CSAT 1997). See information. http://www.kap.samhsa.gov/products/ treatment, a manuals/index.htm. Several validated comprehensive addiction screening instruments Assessment are available. In patient assessment is addition, many If screening indicates the presence of an physicians opioid use disorder, further assessment is essential. develop their own indicated to thoroughly delineate the set of screening patient’s problem, to identify comorbid or questions for complicating medical or emotional condi- medical illnesses. Screening questionnaires tions, and to determine the appropriate may be given to all patients in a physician’s treatment setting and level of treatment practice, not just to those patients intensity for the patient. To determine the considered to be “at risk” for drug or appropriateness of office-based or other alcohol problems. opioid agonist treatment, a comprehensive

26 Patient Assessment patient assessment is essential. The assess- Medicine Patient Placement Criteria ment may be accomplished in stages over a (ASAM PPC) and the categories of the 3- to 4-week period, during initiation of Addiction Severity Index (ASI) (Mee-Lee treatment and gradual acquisition of 2001; McLellan et al. 1992). The ASAM increasingly detailed information. Several PPC may be ordered from ASAM at office visits may be required to obtain all the http://www.asam.org. The full text of the information necessary to make a compre- ASI can be downloaded from the hensive set of diagnoses and to develop an Treatment Research Institute Web site appropriate treatment plan, although these at http://www.tresearch.org. efforts also can be completed in a single, extended visit if so desired. Treatment should not be delayed, however, pending Complete History Taking— complete patient assessment. Interviewing Patients Who Are Addicted Goals of Assessment Attitude of the Physician. The approach The goals of the medical assessment of a and attitude the physician shows to patients patient who is addicted to opioids are to who have an addiction are of paramount • Establish the diagnosis or diagnoses importance. Patients are often hesitant or reluctant to disclose their drug use or • Determine appropriateness for treatment problems. Patients who are addicted report • Make initial treatment recommendations discomfort, shame, fear, distrust, hopeless- • Formulate an initial treatment plan ness, and the desire to continue using drugs • Plan for engagement in psychosocial as reasons they do not discuss addiction treatment openly with their physicians (National Center on Addiction and Substance Abuse • Ensure that there are no contraindications 2000). Patients in treatment for pain may to the recommended treatments fear the loss of their opioid pain medications • Assess other medical problems or con- should they disclose to a physician their ditions that need to be addressed during concerns about their possible addiction. early treatment Physicians need to approach patients who • Assess other psychiatric or psychosocial have an addiction in an honest, respectful, problems that need to be addressed during matter-of-fact way, just as they would early treatment approach patients with any other medical illness or problem. A physician’s responsi- Components of Assessment bility is to deal appropriately with his or her The components of the assessment of a own attitudes and emotional reactions to a patient who is addicted to opioids should patient. For evaluation to be effective, include personal biases and opinions about drug use, individuals who have addictions, sexual • Complete history behavior, lifestyle differences, and other • Physical examination emotionally laden issues must be set aside or dealt with openly and therapeutically. • Mental status examination • Relevant laboratory testing Certain characteristics of treatment • Formal psychiatric assessment (if providers facilitate effective evaluation and indicated) treatment of addiction, and these characteristics should be cultivated by In forming a framework for assessment, physicians who plan to treat patients who physicians may include questions and have addictions (CSAT 1999b; Miller et al. evaluations pertinent to the most recent 1993; Najavits and Weiss 1994). These edition of the American Society of Addiction attributes are listed in figure 3–1.

Patient Assessment 27 Figure 3–1 Attributes of an Effective Addiction Treatment Provider

• Ability to establish a helping • Respect alliance • Affirmation • Good interpersonal skills • Empathy • Nonpossessive warmth • Supportive style • Friendliness • Patient-centered approach • Genuineness • Reflective listening

Targeted, open-ended questions, such as use, patterns and consequences of use, past those presented in figure 3–2, about the use attempts to deal with problems, medical and of drugs and alcohol will elicit more infor- psychiatric history (the “what, who, when, mation than simple, closed-ended, “yes” or where, how”)—not on the reasons (the “no” or single-answer questions. Refer to “why”) for addiction problems. Questions TIP 34, Brief Interventions and Brief Ther- should be asked in a direct and straight- apies for Substance Abuse (CSAT 1999a) at forward manner, using simple language and http://www.kap.samhsa.gov/products/ avoiding street terms. Assumptive or manuals/index.htm for specific examples of quantifiable questions, such as those in interview questions. figure 3–3, yield more accurate responses in the initial phases of the interview. Most patients are willing and able to provide reliable, factual information regarding their Components of the Complete History. A drug use; however, many cannot articulate thorough and comprehensive medical, their reasons or motivation for using drugs. social, and drug use history should be taken An effective interview should focus on drug on all patients being evaluated for substance

Figure 3–2 Targeted, Open-Ended Questions About Drug and Alcohol Use

• “How has heroin use affected your life?” • “How has hydrocodone affected your life?” • “In the past, what factors have helped you stop using?” • “What specific concerns do you have today?”

28 Patient Assessment Figure 3–3 Quantifiable Interview Questions • “At what age did you first use • “When was the last time you alcohol or other drugs?” were high?” • “How many days of the week do you • “How many times did you use drink alcohol?” last month?” • “How often do you use heroin?”

use disorders. The components of a com- screening results. Figure 3–5 lists physical plete history are shown in figure 3–4. examination findings that suggest addiction or its complications. The physical complica- Physical Examination tions of opioid addiction should be identified and addressed as part of the overall treat- The physical examination should focus on ment plan. physical findings related to addiction. Several physical findings may lead the Assessing Intoxication and Overdose. It is physician to suspect addiction in patients vitally important to assess for signs of opioid who deny drug use or have equivocal intoxication, overdose, or withdrawal during

Figure 3–4 Components of a Complete Substance Abuse Assessment History

• Substance use history (e.g., age of first • Medical history (e.g., detailed review of use; substances used; change in effects systems, past medical/surgical history, over time; history of tolerance, sexual history [for women, determine overdose, withdrawal; attempts to quit; likelihood of pregnancy], current and current problems with compulsivity or past medications, pain history) cravings) • Social history (e.g., quality of recovery • Addiction treatment history (e.g., environment, family/living previous treatments for addiction, environment, substance use by types of treatments tried, outcomes of members of support network) treatment attempts) • Readiness to change (e.g., patient’s • Psychiatric history (e.g., patient’s understanding of his or her substance diagnoses, psychiatric treatments use problem, Stage of Change the recommended/attempted, outcomes of patient is in [see appendix G], patient’s treatments) interest in treatment now, whether • Family history (e.g., substance use treatment is coerced or voluntary) disorders in family, family medical and psychiatric history)

Patient Assessment 29 Figure 3–5 Examination Findings Suggestive of Addiction or Its Complications • General: • Gastrointestinal: Odor of alcohol on breath Hepatomegaly Odor of marijuana on clothing Liver tenderness Odor of nicotine or smoke on breath Positive stool hemoccult or clothing • Immune: Poor nutritional status Lymphadenopathy Poor personal hygiene • Cardiovascular: • Behavior: Hypertension Intoxicated behavior during exam Tachycardia Slurred speech Cardiac arrhythmia Staggering gait Heart murmurs, clicks Scratching Edema • Skin:* Swelling Signs of physical injury • Pulmonary: Bruises Wheezing, rales, rhonchi Lacerations Cough Scratches Respiratory depression Burns • Female reproductive/endocrine: Needle marks Pelvic tenderness Skin abscesses Vaginal discharge Cellulitis • Male reproductive/endocrine: Jaundice Testicular atrophy Palmar erythema Penile discharge Hair loss Gynecomastia Diaphoresis • Neurologic: Rash Sensory impairment Puffy hands Memory impairment • Head, Eyes, Ears, Nose, Throat (HEENT): Motor impairment Conjunctival irritation or injection Ophthalmoplegia Inflamed nasal mucosa Myopathy Perforated nasal septum Neuropathy Blanched nasal septum Tremor Sinus tenderness Cognitive deficits Gum disease, gingivitis Ataxia Gingival ulceration Pupillary dilation or constriction Rhinitis Sinusitis Pale mucosae Burns in oral cavity

*For additional information, see the CSAT publication entitled Classifying Skin Lesions of Injection Drug Users: A Method for Corroborating Disease Risk, NCADI Order No. AVD 154, DHHS Publication No. (SMA) 02-3753, Printed 2002. Order from: http://store.health.org/.

30 Patient Assessment the physical examination. Opioid overdose Assessing Other Drug Intoxication or should be treated as a medical emergency. Withdrawal Syndromes. Instruments for Figure 3–6 lists the signs of opioid intoxica- assessing withdrawal from alcohol and tion and overdose. benzodiazepines include Assessing Opioid Withdrawal. Opioid with- • CIWA-Ar (Clinical Institute Withdrawal drawal can be objectively assessed by using Assessment for Alcohol, Revised) (Sullivan one of the following several instruments: et al. 1989) • COWS (Clinical Opiate Withdrawal Scale) • CIWA-B (Clinical Institute Withdrawal (Wesson et al. 1999) Assessment for Benzodiazepines) (Busto et al. 1989) • SOWS (Short Opiate Withdrawal Scale) (Bradley et al. 1987; Gossop 1990; Handelsman et al. 1987) Mental Status Examination • CINA (Clinical Institute Narcotic In addition to observing a patient’s behavior Assessment Scale for Withdrawal during history taking and the physical exam- Symptoms) (Peachey and Lei 1988) ination, a formal mental status examination • Narcotic Withdrawal Scale (Fultz and (MSE) should be performed, including the Senay 1975) components shown in figure 3–8. Full text and/or links to these instruments Information from the interview and MSE are included in appendix B. Figure 3–7 may reveal significant current or past psy- shows methods of staging and grading opioid chiatric problems. Depending on the physi- withdrawal. cian’s expertise and comfort in managing

Figure 3–6 Signs of Opioid Intoxication and Overdose

Syndrome Physical Findings

Opioid Intoxication Conscious Sedated, drowsy Slurred speech “Nodding” or intermittently dozing Memory impairment Mood normal to euphoric Pupillary constriction

Opioid Overdose Unconscious Pinpoint pupils Slow, shallow respirations; respirations below 10 per minute Pulse rate below 40 per minute Overdose triad: apnea, coma, pinpoint pupils (with terminal anoxia: fixed and dilated pupils)

Patient Assessment 31 Figure 3–7 Staging and Grading Systems of Opioid Withdrawal

Stage Grade Physical Signs/Symptoms

Early Withdrawal Grade 1 Lacrimation and/or rhinorrhea (8–24 hours after last use) Diaphoresis Yawning Restlessness Insomnia Grade 2 Dilated pupils Piloerection Muscle twitching Myalgia Arthralgia Abdominal pain Grade 3 Tachycardia Fully Developed Withdrawal Hypertension (1–3 days after last use) Tachypnea Fever Anorexia or nausea Extreme restlessness Grade 4 Diarrhea and/or vomiting Dehydration Hyperglycemia Hypotension Curled-up position

Figure 3–8 Mental Status Examination Checklist • General appearance • Motivation and readiness to change • Behavior and interaction with interviewer – Patient’s stated goals and • Speech and voice expectations • Motor activity • Cognitive function • Mood and affect – Orientation • Perceptions – Memory – Hallucinations – Attention • Thought process – Concentration • Thought content – Fund of information – Suicidal ideation – Literacy skills – Homicidal ideation – Abstraction – Delusions – Intelligence • Insight • Personality characteristics • Judgment • Defense mechanisms

32 Patient Assessment psychiatric disorders, referral to an addic- Several findings may alert physicians to tion psychiatrist or psychologist for a full potential complications to treatment with mental health evaluation and/or formal buprenorphine. Alcohol use may complicate psychiatric diagnosis may be indicated buprenorphine treatment; indirect indica- before starting treatment for addiction. tors of excess alcohol use include elevated mean corpuscular volume (MCV) and Laboratory Evaluations gamma glutamyl transpeptidase (GGT). Liver enzyme abnormalities also may Laboratory testing is an important part of suggest liver disease from toxicity, infection, the assessment and evaluation of patients or other factors. Additional biomedical who have an addiction. Laboratory tests markers such as Carbohydrate-Deficient cannot make a diagnosis of addiction, but a Transferrin (CDT) may provide further variety of laboratory evaluations are useful objective information on screening and in the comprehensive assessment of patients confirmation of acute or recent alcohol who have an addiction. consumption, relapse to use, heavy or The recommended baseline laboratory harmful use, and alcohol-related organ evaluation of patients who are addicted to dysfunction. Guidance on liver disease in opioids is shown in figure 3–9. patients who are addicted to opioids will be available from SAMHSA’s Division of The following additional laboratory eval- Pharmacologic Therapies (DPT) Web site at uations should be considered and offered as http://www.dpt.samhsa.gov. indicated: As described elsewhere, pregnancy, HIV • Blood alcohol level (using a breath testing treatment, and active hepatitis or liver instrument or a blood sample) disease also may complicate treatment with • Infectious disease evaluation: buprenorphine. Pregnant women may not be optimal candidates for buprenorphine – HIV antibody testing treatment. HIV-positive status does not – Hepatitis B virus (HBV) and hepatitis C preclude buprenorphine treatment, but virus (HCV) screens as-yet-unrecognized antiretroviral medication interactions with buprenorphine may – Serology test for syphilis—Venereal potentially interfere with treatment. Posi- Disease Research Laboratories (VDRL) tive results on hepatitis B surface antigen – Purified protein derivative (PPD) test testing indicate active HBV infection, for tuberculosis, preferably with possibly associated with active hepatitis. control skin tests Further testing (e.g., serial enzymes) may be indicated to determine whether HBV infec- In addition, other laboratory evaluations tion complicates buprenorphine treatment. may be indicated by the patient’s history or Hepatitis B information for health pro- physical examination. Appropriate coun- fessionals can be accessed on the Centers for seling should be provided, and consent Disease Control and Prevention (CDC) Web obtained, before testing for certain infec- site at http://www.cdc.gov/ncidod/diseases/ tious diseases (e.g., HIV, hepatitis C). hepatitis/b/index.htm. Abnormalities or medical problems detected by laboratory evaluation should be A confirmed positive hepatitis C antibody addressed as they would be for patients test indicates current or past infection with who are not addicted. HCV. Patients who test positive for HCV

Patient Assessment 33 Figure 3–9 Recommended Baseline Laboratory Evaluation of Patients Who Are Addicted to Opioids

• Serum electrolytes • Lipid profile • BUN and creatinine • Urinalysis • CBC with differential and platelet • Pregnancy test (for women of count childbearing age) • Liver function tests (GGT, AST, • Toxicology tests for drugs of abuse ALT, PT or INR, albumin) • Hepatitis B and C screens

should be further evaluated and treated are posted on the CDC Web site at http:// according to the most up-to-date recom- www.cdc.gov/std/. mendations. Training for health professionals on HCV is available on the CDC Web A positive PPD skin test may indicate past site at http://www.cdc.gov/ncidod/diseases/ or current infection with tuberculosis. Any hepatitis/c_training/edu/default.htm. The patient with a positive PPD test should be 2002 National Institutes of Health (NIH) referred to a local health department for Consensus Statement regarding the man- further evaluation and treatment. Addi- agement of hepatitis C is available on the tional information on tuberculosis and its Web at http://consensus.nih.gov/cons/116/ treatment is found on the CDC Web site at 116cdc_intro.htm. Materials about http://www.cdc.gov/nchstp/tb/links.htm. hepatitis C also are available on the Agency Physicians should be familiar with all for Healthcare Research and Quality Web site reporting requirements for infectious at http://www.ahrq.gov/clinic/epcsums/ diseases in their State. hepcsum.htm. Evaluations of Drug Use Positive serology tests for syphilis may Tests for illicit drugs are not sufficient to indicate active or past infection with diagnose addiction and cannot substitute for Treponema pallidum. All patients with such a clinical interview and medical evaluation positive test results should be treated onsite or referred to a local health department for of the patient (Casavant 2002). Hammett- further evaluation and treatment. It should Stabler et al. (2002) point out that the term be noted, however, that biologic false posi- drug screen is a misnomer, because not all tive results on serology tests for syphilis are drugs are, and cannot be, tested for rou- common in individuals who abuse drugs tinely. Physicians must decide which drug intravenously. Only those with confirmatory tests are necessary in each clinical setting, fluorescent treponemal antibody absorption including office-based buprenorphine treat- (FTA-ABS) tests are likely to have actual ment. Physicians and laboratory personnel treponemal infection. The most current must understand the limitations of the treatment recommendations for syphilis and assays used, the pharmacokinetic charac- other sexually transmitted diseases (STDs) teristics of the drugs assayed, the parent

34 Patient Assessment compound–metabolite relationships, and Several manufacturers produce combination how to interpret laboratory results urine collection and test kits that facilitate (Hammett-Stabler et al. 2002). Testing for in-office urine testing. In-office testing facil- drugs can be performed on a number of itates prompt evaluation of clinical param- bodily fluids and tissues, including urine, eters and allows the physician to present the blood, saliva, sweat, and hair. Urine screen- results to the patient and to make immediate ing is the method most commonly employed. therapeutic use of the information. However, A comprehensive discussion of urine drug physicians who do not work in a setting with testing in the primary care setting can be an onsite, federally regulated laboratory found in Urine Drug Testing in Primary must ensure that they are using in-office Care: Dispelling the Myths & Designing testing kits waived from regulatory over- Strategies (Gourlay et al. 2002). When sight under the Clinical Laboratory selecting drug tests, physicians should Improvement Amendments (CLIA) law of consider the cost to patients, as testing for 1988. See the CLIA pages on the Food and all possible drugs of abuse can be costly. Drug Administration (FDA) Web site at In buprenorphine treatment, appropriate http://www.fda.gov/cdrh/clia/cliawaived.html tests for illicit drug use should be admin- for more information about the law and istered as part of patient assessment. Physi- CLIA-waived point-of-care testing kits. For cians should explain the role of drug testing the current listing of CLIA-waived urine at the beginning of treatment for addiction. drug tests, refer to the FDA Web site at The literature supports the therapeutic http://www.accessdata.fda.gov/scripts/cdrh/ utility of random drug testing in clinical cfdocs/cfClia/testswaived.cfm or search settings (Preston et al. 2002). Laboratory the FDA CLIA database at http:// test results can be used in the physician– www.accessdata.fda.gov/scripts/cdrh/cfdocs/ patient interaction to further treatment cfCLIA/search.cfm. objectives, to address patient denial, and to reinforce abstinence from other drugs. Toxicology testing for drugs of abuse that Initial and ongoing drug screening should be takes place at scheduled visits cannot be truly used to detect or confirm the recent use of random; nevertheless, it is clinically drugs (e.g., alcohol, benzodiazepines, worthwhile. Urine samples should be col- barbiturates) that could complicate lected in a room where they cannot be management of a patient on buprenorphine. diluted or otherwise adulterated and where patients are not permitted to bring brief- When a patient requests treatment with cases, purses, bags, or containers of any buprenorphine, a toxicology screen can help sort. If these conditions are not feasible, to establish that the patient is indeed using temperature-sensitive strips, specific gravity, either a proscribed substance such as heroin and creatinine can be used to minimize the or a prescribed substance such as oxyco- possibility of false or adulterated urine done. A negative test does not necessarily specimens. If the physician’s office cannot mean that the patient is not using an opioid. provide this service, patients can be referred It may mean that the patient has not used an to a facility that is equipped to perform opioid within a period of time sufficient to monitored specimen collection. Another produce measurable metabolic products or option that is sometimes feasible is to collect that the patient was not using the drug for a sample of oral fluid (saliva) to be sent to a which he or she was tested. Thus, as with laboratory for testing. any patient, the physician is alerted to a spectrum of possibilities and works with the Timely shipment of samples for testing and patient using the information collected from rapid turnaround time for the results are the toxicology screen. also important issues that should be resolved

Patient Assessment 35 before undertaking office-based treatment Fourth Edition, Text Revision (DSM-IV-TR) of opioid addiction. If a patient needs drug (American Psychiatric Association 2000) test results for employment or for legal (see Appendix C) or the International monitoring, strict chain-of-custody pro- Classification of Diseases—Ninth Edition— cedures must be followed, and samples Clinical Modification (ICD-9-CM), should be should be evaluated by a SAMHSA-certified used to document a diagnosis of opioid laboratory. If a patient subsequently wants dependence. (This diagnosis is not merely to use the drug test result for other pur- physical dependence on opioids but corres- poses, both the physician and the patient ponds to opioid addiction, classically defined should understand the limits of the office as compulsive use despite harm.) testing and other requirements for the test. DSM-IV-TR defines several opioid-related Other than for U.S. Department of Health disorders. (See figure 3–10.) A DSM-IV-TR and Human Services and U.S. Department diagnosis of either opioid dependence or of Transportation, private-sector testing abuse is based on a cluster of behaviors and requirements may be less rigorous. Further physiological effects occurring within a information about the detection of drugs in specific timeframe. The diagnosis of opioid urine and other biological samples is found dependence always takes precedence over in appendix E. that of opioid abuse (i.e., a diagnosis of abuse is made only if DSM-IV-TR criteria Diagnosis of Opioid-Related for dependence have never been met). As a Disorders general rule, to be considered for buprenorphine maintenance, patients should meet the After a thorough assessment of a patient has DSM-IV-TR criteria for a diagnosis of opioid been conducted, a formal diagnosis can be dependence. (See full diagnostic criteria in made. Criteria for substance dependence, appendix C.) In rare instances, a patient such as those set forth in the Diagnostic and may be physiologically dependent on opioids Statistical Manual of Mental Disorders, and meet DSM-IV-TR criteria for abuse, but

Figure 3–10 DSM-IV-TR Opioid Use Disorders (ICD-9 Code)

• Opioid Abuse (305.50) • Opioid-Induced Psychotic Disorder, • Opioid Dependence (304.00) With Hallucinations (292.12) • Opioid Intoxication (292.89) • Opioid-Induced Mood Disorder (292.84) • Opioid Withdrawal (292.0) • Opioid-Induced Sexual Dysfunction • Opioid Intoxication Delirium (292.89) (292.81) • Opioid-Induced Sleep Disorder • Opioid-Induced Psychotic (292.89) Disorder, With Delusions (292.11) • Opioid-Related Disorder NOS (292.9)

Source: International Classification of Diseases, 9th Rev., Clinical Modification: ICD-9-CM. Volumes 1 and 2. Salt Lake City, UT; Ingenix, Medicode, 2003. 810 pages.

36 Patient Assessment not for dependence. In such a case, a short also at increased risk of engaging in high- course of buprenorphine may be considered risk sexual behavior (e.g., exposure to for detoxification. Maintenance treatment multiple partners, inconsistent use of safe with buprenorphine is not recommended for sexual practices) and of contracting syphilis, patients who do not meet DSM-IV-TR cri- gonorrhea, and other STDs. teria for opioid dependence. Among individuals who are opioid addicted, other common medical conditions are Common Comorbid Medical related to the use of other drugs and to the Conditions life disruptions that often accompany addiction. These conditions include nutri- Individuals addicted to opioids may have the same chronic diseases seen in the general tional deficiencies and anemia caused by population and should be evaluated as poor eating habits; chronic obstructive appropriate for diseases that require pulmonary disease secondary to cigarette treatment (e.g., diabetes, hypertension). In smoking; impaired hepatic function or addition, a number of medical conditions moderately elevated liver enzymes from are commonly associated with opioid and various forms of chronic hepatitis (particu- other drug addictions. During the course of larly hepatitis B and C) and alcohol con- a medical history and physical examination, sumption; and cirrhosis, neuropathies, or the possible existence of these conditions cardiomyopathy secondary to alcohol should be evaluated. Refer to figure 3–11 dependence. for a detailed list of selected medical disorders related to drug and alcohol use. Summary Infectious diseases are more common among After completing a comprehensive assess- individuals who are addicted to opioids, indi- ment of a candidate for treatment, the viduals who are addicted to other drugs, and physician should be prepared to individuals who inject drugs. For example, in some areas, more than 50 percent of • Establish the diagnosis or diagnoses injection drug users may be HIV positive. • Determine appropriate treatment options There are wide variations in the epidemiol- for the patient ogy of HIV infection, however, and in other • Make initial treatment recommendations areas the prevalence of HIV infection among injection drug users may be less than • Formulate an initial treatment plan 10 percent. Because of the potential impact • Plan for engagement in psychosocial of HIV on the lives of affected patients and treatment the availability of effective treatments, it is • Ensure that there are no absolute important to screen for HIV infection contraindications to the recommended among patients who present for bupre- treatments norphine treatment. • Assess other medical problems or Tuberculosis is also a major problem among conditions that need to be addressed substance abusers. In 2001, 2.3 percent of during early treatment tuberculosis cases in the United States • Assess other psychiatric or psychosocial occurred in injection drug users, 7.2 percent problems that need to be addressed during in noninjection drug users, and 15.2 percent early treatment in individuals with excessive alcohol use in the past 12 months (CDC 2002; http:// The next section describes methods for www.cdc.gov/nchstp/tb/surv/surv2001/ determining the appropriateness of default.htm. See tables 28, 29, and 30). buprenorphine treatment for patients who Individuals who abuse drugs and alcohol are have an opioid addiction.

Patient Assessment 37 Figure 3–11 Selected Medical Disorders Related to Alcohol and Other Drug Use

Cardiovascular Alcohol: Cardiomyopathy, atrial fibrillation (holiday heart), hypertension, dysrhythmia, masks angina symptoms, coronary artery spasm, myocardial ischemia, high-output states, coronary artery disease, sudden death. Cocaine: Hypertension, myocardial infarction, angina, chest pain, supraventricular tachycardia, ventricular dysrhythmias, cardiomyopathy, cardiovascular collapse from body-packing rupture, moyamoya vasculopathy, left ventricular hypertrophy, myocarditis, sudden death, aortic dissection. Tobacco: Atherosclerosis, stroke, myocardial infarction, peripheral vascular disease, cor pulmonale, erectile dysfunction, worse control of hypertension, angina, dysrhythmia. Injection drug use: Endocarditis, septic thrombophlebitis. Cancer Alcohol: Aerodigestive (lip, oral cavity, tongue, pharynx, larynx, esophagus, stomach, colon), breast, hepatocellular and bile duct cancers. Tobacco: Oral cavity, larynx, lung, cervical, esophagus, pancreas, kidney, stomach, bladder. Injection drug use or high-risk sexual behavior: Hepatocellular carcinoma related to hepatitis C. Endocrine/ Alcohol: Hypoglycemia and hyperglycemia, diabetes, ketoacidosis, Reproductive hypertriglyceridemia, hyperuricemia and gout, testicular atrophy, gynecomastia, hypocalcemia and hypomagnesemia because of reversible hypoparathyroidism, hypercortisolemia, osteopenia, infertility, sexual dysfunction. Cocaine: Diabetic ketoacidosis. Opiates: Osteopenia, alteration in gonadotropins, decreased sperm motility, menstrual irregularities. Tobacco: Graves disease, azoospermia, erectile dysfunction, osteopenia, osteoporosis, fractures, estrogen alterations, insulin resistance. Any addiction: Amenorrhea. Hepatic Alcohol: Steatosis (fatty liver), acute and chronic hepatitis (infectious [that is, B or C] or toxic [that is, acetaminophen]), alcoholic hepatitis, cirrhosis, portal hypertension and varices, spontaneous bacterial peritonitis. Cocaine: Ischemic necrosis, hepatitis. Opiates: Granulomatosis. Injection drug use or high-risk sexual behavior: Infectious hepatitis B and C (acute and chronic) and delta. Hematologic Alcohol: Macrocytic anemia, pancytopenia because of marrow toxicity and/or splenic sequestration, leukopenia, thrombocytopenia, coagulopathy because of liver disease, iron deficiency, folate deficiency, spur cell anemia, burr cell anemia. Tobacco: Hypercoagulability. Injection drug use or high-risk sexual behavior: Hematologic consequences of liver disease, hepatitis C-related cryoglobulinemia and purpura.

38 Patient Assessment Figure 3–11 Selected Medical Disorders Related to Alcohol and Other Drug Use, Continued

Infectious Alcohol: Hepatitis C, pneumonia, tuberculosis (including meningitis), HIV, sexually transmitted diseases, spontaneous bacterial peritonitis, brain abscess, meningitis. Opiates: Aspiration pneumonia. Tobacco: Bronchitis, pneumonia, upper respiratory tract infections. Injection drug use: Endocarditis, cellulitis, pneumonia, septic thrombophlebitis, septic arthritis (unusual joints, that is, sternoclavicular), osteomyelitis (including vertebral), epidural and brain abscess, mycotic aneurysm, abscesses and soft tissue infections, mediastinitis, malaria, tetanus. Injection or high-risk sexual behavior: Hepatitis B, C, and delta; HIV; sexually transmitted diseases. Neurologic Alcohol: Peripheral and autonomic neuropathy, seizure, hepatic encephalopathy, Korsakoff dementia, Wernicke syndrome, cerebellar dysfunction, Marchiafava-Bignami syndrome, central pontine myelinolysis, myopathy, amblyopia, stroke, withdrawal, delirium, hallucinations, toxic leukoencephalopathy, subdural hematoma, intracranial hemorrhage. Cocaine: Stroke, seizure, status epilepticus, headache, delirium, depression, hypersomnia, cognitive deficits. Opiates: Seizure (overdose and hypoxia), compression neuropathy. Tobacco: Stroke, small vessel ischemia and cognitive deficits. Any addiction: Compression neuropathy.

Nutritional Alcohol: Vitamin and mineral deficiencies (B1, B 6, riboflavin, niacin, vitamin D, magnesium, calcium, folate, phosphate, zinc). Any addiction: Protein malnutrition. Other Alcohol: Gastritis, esophagitis, pancreatitis, diarrhea, malabsorption (because Gastrointestinal of pancreatic exocrine insufficiency, or folate or lactase deficiency), parotid enlargement, malignancy, colitis, Barrett esophagus, gastroesophageal reflux, Mallory-Weiss syndrome, gastrointestinal bleeding. Cocaine: Ischemic bowel and colitis. Opiates: Constipation, ileus, intestinal pseudo-obstruction. Tobacco: Peptic ulcers, gastroesophageal reflux, malignancy (pancreas, stomach). Any addiction: Overdose from body-packing. Prenatal and Alcohol: Fetal alcohol effects and syndrome. Perinatal Cocaine: Placental abruption, teratogenesis, neonatal irritability. Opiates: Neonatal abstinence syndrome, including seizures. Tobacco: Teratogenesis, low birth weight, spontaneous abortion, abruptio placentae, placenta previa, perinatal mortality, sudden infant death syndrome, neurodevelopmental impairment. Perioperative Alcohol: Withdrawal, perioperative complications (delirium, infection, bleeding, pneumonia, delayed wound healing, dysrhythmia), hepatic decompensation, hepatorenal syndrome, death. Cocaine: Hypersomnia and depression in withdrawal, mimicking of postoperative neurologic complications, complications from underlying drug- induced cardiopulmonary disease. Opiates: Withdrawal, inadequate analgesia. Tobacco: Pulmonary infection, difficulty weaning, respiratory failure, reactive airways exacerbations.

Patient Assessment 39 Figure 3–11 Selected Medical Disorders Related to Alcohol and Other Drug Use, Continued

Pulmonary Alcohol: Aspiration, sleep apnea, respiratory depression, apnea, chemical or infectious pneumonitis. Cocaine: Nasal septum perforation, gingival ulceration, perennial rhinitis, sinusitis, hemoptysis, upper airway obstruction, fibrosis, hypersensitivity pneumonitis, epiglottitis, pulmonary hemorrhage, pulmonary hypertension, pulmonary edema, emphysema, interstitial fibrosis, hypersensitivity pneumonia. Inhalants: Pulmonary edema, bronchospasm, bronchitis, granulomatosis, airway burns. Opiates: Respiratory depression/failure, emphysema, bronchospasm, exacerbation of sleep apnea, pulmonary edema. Tobacco: Lung cancer, chronic obstructive pulmonary disease, reactive airways, pneumonia, bronchitis, pulmonary hypertension, interstitial lung disease, pneumothorax. Injection drug use: Pulmonary hypertension, talc granulomatosis, septic pulmonary embolism, pneumothorax, emphysema, needle embolization. Renal Alcohol: Hepatorenal syndrome, rhabdomyolysis and acute renal failure, volume depletion and prerenal failure, acidosis, hypokalemia, hypophosphatemia. Cocaine: Rhabdomyolysis and acute renal failure, vasculitis, necrotizing angiitis, accelerated hypertension, nephrosclerosis, ischemia. Opiates: Rhabdomyolysis, acute renal failure, factitious hematuria. Tobacco: Renal failure, hypertension. Injection drug use or high-risk sexual behavior: Focal glomerular sclerosis (HIV, heroin), glomerulonephritis from hepatitis or endocarditis, chronic renal failure, amyloidosis, nephrotic syndrome (hepatitis C). Sleep Alcohol: Apnea, periodic limb movements of sleep, insomnia, disrupted sleep, daytime fatigue. Cocaine: Hypersomnia in withdrawal. Opiates: Insomnia. Tobacco: Insomnia, increased sleep latency. Trauma Alcohol: Motor vehicle crash, fatal and nonfatal injury, physical and sexual abuse. Cocaine: Death during “Russian Roulette.” Opiates: Motor vehicle crash, other violent injury. Tobacco: Burns, smoke inhalation. Any addiction: Sexual and physical abuse. Musculoskeletal Alcohol: Rhabdomyolysis, compartment syndromes, gout, saturnine gout, fracture, osteopenia, osteonecrosis. Cocaine: Rhabdomyolysis. Opiates: Osteopenia. Any addiction: Compartment syndromes, fractures.

Source: Saitz 2003. Overview of medical and surgical complications. In Graham, A.W.; Schultz, T.K.; Mayo-Smith, M.F.; Ries, R.K.; and Wilford, B.B. (eds.) Principles of Addiction Medicine, Third Edition. Copyright 2003, American Society of Addiction Medicine, Chevy Chase, MD. All rights reserved. Reprinted with permission.

40 Patient Assessment Determining illicit opioid use should be able to receive this treatment, if it is clinically indicated. Appropriateness for Buprenorphine Evaluation Questions Treatment To thoroughly evaluate a patient for appropriateness for opioid addiction treatment with Several issues should be considered in eval- buprenorphine, the physician should ask the uating whether a patient is an appropriate candidate for buprenorphine treatment of following questions: opioid addiction in the office or other 1. Does the patient have a diagnosis of setting. opioid dependence? Candidates for First, a candidate for buprenorphine treat- buprenorphine treatment should have a ment for opioid addiction should have an diagnosis of opioid dependence. Bupre- objectively ascertained diagnosis of opioid norphine treatment is not indicated for addiction (compulsive use of opioids despite other disorders. harm), otherwise known as opioid depend- 2. Are there current signs of intoxication ence as defined in the latest edition of the or withdrawal? Is there a risk for DSM-IV-TR of the APA (2000). Refer to severe withdrawal? The physician appendix C for DSM-IV-TR diagnostic should assess the patient for current criteria for opioid dependence and opioid signs of intoxication or withdrawal from abuse. In rare instances, a patient may be opioids or other drugs as well as for the physiologically dependent on opioids and risk of severe withdrawal. The risk of meet DSM-IV-TR criteria for abuse, but not severe opioid withdrawal is not a for dependence. In such a case, a short contraindication to buprenorphine course of buprenorphine may be considered treatment. The risk of withdrawal from for detoxification. Maintenance treatment sedative-hypnotics, however, may with buprenorphine is not recommended for initially preclude the use of bupre- patients who do not meet DSM-IV-TR cri- norphine in an office setting. teria for opioid dependence. 3. Is the patient interested in bupre- Second, a candidate for buprenorphine norphine treatment? If a patient with treatment should, at a minimum opioid addiction has not heard of or presented specifically for buprenorphine • Be interested in treatment for opioid treatment, buprenorphine treatment addiction should be discussed as a treatment • Have no absolute contraindication (i.e., option. known hypersensitivity) to buprenorphine 4. Does the patient understand the risks (or to naloxone if treating with the bup- and benefits of buprenorphine treat- renorphine/naloxone combination) ment? (Refer to chapter 2 and appendix • Be expected to be reasonably compliant H.) It should be assumed that many with such treatment patients are unaware that buprenor- • Understand the risks and benefits of phine is an opioid, thus they should be buprenorphine treatment so informed. The risks and benefits of • Be willing to follow safety precautions for buprenorphine treatment should be buprenorphine treatment presented to potential patients, and • Agree to buprenorphine treatment after a their understanding of these factors review of treatment options evaluated. Physicians must review the safety, efficacy, side effects, potential Patients who request treatment with bup- treatment duration, and other factors renorphine to achieve abstinence from all with each patient.

Patient Assessment 41 5. Can the patient be expected to adhere homicidal? Has he or she recently to the treatment plan? This is a judg- attempted suicide or homicide? Do ment call, based on the patient’s past current emotional, behavioral, or adherence to treatment for addiction or cognitive conditions complicate other medical conditions, comorbid treatment? Patients who have significant psychiatric conditions, psychosocial untreated psychiatric comorbidity are stability, comorbid substance use less-than-ideal candidates for office- disorders, and other factors. based buprenorphine treatment. A full 6. Is the patient willing and able to follow psychiatric assessment is indicated for safety procedures? If a patient is all patients who have significant unwilling or unable to follow safety psychiatric comorbidity. Psychiatric procedures, or is dismissive of them, comorbidity requires appropriate then that patient is not a good candidate management or referral as part of for office-based treatment with treatment. It should be noted that the buprenorphine. buprenorphine clinical trials reported to date have not included patients 7. Does the patient agree to treatment maintained on antipsychotic or mood- after review of the options? Bupre- stabilizing agents (e.g., lithium), and norphine treat- thus there is limited or no information ment is not on the potential interactions with these …a candidate for coercive; the medications. patient must buprenorphine agree to treat- 10. Is the patient pregnant? If a patient is ment before it is pregnant or is likely to become pregnant treatment for opioid initiated. Treat- during the course of treatment, bupre- ment options norphine may not be the best choice. (including no (See “Pregnant Women and Neonates” addiction should treatment, dose- in chapter 5.) Currently, methadone reduction, maintenance, when it is available, is the have an objectively abstinence-based treatment of choice for patients who are treatment, and pregnant and are opioid addicted. ascertained diagnosis the variety of 11. Is the patient currently dependent on medication treat- or abusing alcohol? Patients with of opioid addiction… ments) and their alcohol abuse or dependence, whether associated risks continuous or periodic in pattern, may and benefits be at risk of overdose from the combi- should be nation of alcohol with buprenorphine. reviewed so that Patients with high-risk or harmful patients can make informed decisions drinking patterns are, therefore, less about buprenorphine treatment. likely to be appropriate candidates for 8. Can the needed resources for the office-based buprenorphine treatment. patient be provided (either onsite or 12. Is the patient currently dependent on offsite)? Each patient’s needs should be or abusing benzodiazepines, barbitu- assessed. If the resources that are rates, or other sedative-hypnotics? available onsite or offsite are insuf- Patients who have sedative-hypnotic ficient for a particular patient, he or she abuse or dependence, whether contin- should be referred to an appropriate uous or periodic in pattern, may be at treatment setting or provider. some risk of overdose and death from 9. Is the patient psychiatrically stable? Is the combination of sedative-hypnotics the patient actively suicidal or with buprenorphine.

42 Patient Assessment 13. What is the patient’s risk for continued not a reasonable clinical alternative, the opioid use or continued problems? patient may not be a candidate for Does the patient have a history of buprenorphine treatment. Use of other multiple previous treatments or medications, such as those metabolized relapses, or is the patient at high risk by the cytochrome P450 3A4 system for relapse to opioid use? Is the (e.g., azoles, macrolide antibiotics, patient using other drugs? Several calcium channel blockers, selective factors may increase a patient’s risk for serotonin reuptake inhibitors [SSRIs]) continued use of opioids or continued may need to be closely monitored when problems. A patient who is using other used concurrently with buprenorphine. (nonopioid) drugs or who has a history (See figure 2–3.) of multiple previous treatments or 16. Does the patient have medical prob- relapses may not be an appropriate lems that are contraindications to candidate for office-based buprenor- buprenorphine treatment? Could phine treatment. Physicians should physical illnesses complicate treat- assess the patient’s understanding of ment? A complete history and physical problems and relapse triggers, as well as assessment must address any medical his or her skills in managing cravings problems or physical illnesses, and and controlling impulses to use drugs. physicians must evaluate the impact of Multiple previous attempts at detoxifica- these conditions on buprenorphine tion which were followed by relapse to treatment. opioid use, however, are not a contra- diction to maintenance with buprenor- 17. What kind of recovery environment phine. Rather, such a history is a strong does the patient have? Are the indication for maintenance treatment patient’s psychosocial circumstances with pharmacotherapy. sufficiently stable and supportive? Any threats to the patient’s safety or treat- 14. Has the patient had prior adverse ment engagement should be addressed at reactions to buprenorphine? Cases of the beginning of assessment. Supportive acute and chronic hypersensitivity to relationships and resources will increase Subutex® have been reported both in the likelihood of successful treatment. clinical trials and in the postmarketing experience. The most common signs and 18. What is the patient’s level of motiva- symptoms include rashes, hives, and tion? What stage of change charac- pruritus. Cases of bronchospasm, terizes the patient? Motivation is a angioneurotic edema, and anaphylactic dynamic quality that can be enhanced shock have been reported. A history of by treatment providers. Physicians hypersensitivity to buprenorphine is a may wish to determine each patient’s contraindication to Subutex® and readiness to change using tools such as Suboxone® use. A history of hypersen- the Stages of Change Readiness and sitivity to naloxone is a contraindication Treatment Eagerness Scale to Suboxone® use. (Reckitt Benckiser (SOCRATES) (see appendix G) and to Healthcare [UK] Ltd. et al. 2002). make interventions directed to the patient’s current stage of change. Highly 15. Is the patient taking other medications motivated individuals are more appro- that may interact with buprenorphine? priate candidates for office-based Certain medications (e.g., naltrexone) buprenorphine treatment. may be absolutely contraindicated with buprenorphine treatment (see chapter 2) Figure 3–12 provides a checklist for and must be discontinued or changed ascertaining the appropriateness for before starting buprenorphine. If this is buprenorphine treatment.

Patient Assessment 43 Figure 3–12 Buprenorphine Treatment Checklist

1. Does the patient have a diagnosis of opioid dependence?

2. Are there current signs of intoxication or withdrawal? Is there a risk for severe withdrawal?

3. Is the patient interested in buprenorphine treatment?

4. Does the patient understand the risks and benefits of buprenorphine treatment?

5. Can the patient be expected to adhere to the treatment plan?

6. Is the patient willing and able to follow safety procedures? 7. Does the patient agree to treatment after a review of the options?

8. Can the needed resources for the patient be provided (either on- or offsite)?

9. Is the patient psychiatrically stable? Is the patient actively suicidal or homicidal; has he or she recently attempted suicide or homicide? Does the patient exhibit emotional, behavioral, or cognitive conditions that complicate treatment? 10. Is the patient pregnant?

11. Is the patient currently dependent on or abusing alcohol?

12. Is the patient currently dependent on benzodiazepines, barbiturates, or other sedative-hypnotics?

13. What is the patient’s risk for continued use or continued problems? Does the patient have a history of multiple previous treatments or relapses, or is the patient at high risk for relapse to opioid use? Is the patient using other drugs?

14. Has the patient had prior adverse reactions to buprenorphine?

15. Is the patient taking other medications that may interact with buprenorphine? 16. Does the patient have medical problems that are contraindications to buprenorphine treatment? Are there physical illnesses that complicate treatment? 17. What kind of recovery environment does the patient have? Are the patient’s psychosocial circumstances sufficiently stable and supportive?

18. What is the patient’s level of motivation? What stage of change characterizes this patient?

44 Patient Assessment Patients less likely to be appropriate candi- may be altered. (See figure 2–3.) In addi- dates for office-based treatment are individ- tion, the relative risk of interaction between uals whose circumstances or conditions buprenorphine and sedative-hypnotics (e.g., include or have previously included those phenobarbital, clonazepam) should be kept listed in figure 3–13. in mind. Monitoring for therapeutic plasma levels of seizure medications should be Cautions and considered. Contraindications for HIV Treatment Buprenorphine Treatment Buprenorphine should be used cautiously in Several medical conditions and medications, combination with HIV antiretroviral medi- as well as concurrent abuse of other drugs cations that may inhibit, induce, or be and alcohol, necessitate caution or are metabolized by the cytochrome P450 3A4 relative contraindications to buprenorphine enzyme system. (See figure 2–3.) Protease treatment. inhibitors inhibit cytochrome P450 3A4. Metabolism of buprenorphine and/or the Seizures antiretroviral medications may be altered Buprenorphine should be used cautiously in when they are combined. In some cases, patients who are being treated for seizure therapeutic blood levels may need to be disorders. When buprenorphine is used monitored. Note that this is a caution, not a concurrently with antiseizure medications contraindication; successful treatment of (e.g., phenytoin, carbamazepine, valproic addiction with buprenorphine in HIV- acid, and others), metabolism of buprenor- infected patients has been well demonstrated phine and/or the antiseizure medications (Berson et al. 2001; Carrieri et al. 2000;

Figure 3–13 Conditions and Circumstances That May Preclude a Patient as a Candidate for Office-Based Buprenorphine Treatment

• Comorbid dependence on high doses of benzodiazepines or other central nervous system depressants (including alcohol) • Significant untreated psychiatric comorbidity • Active or chronic suicidal or homicidal ideation or attempts • Multiple previous treatments for drug abuse with frequent relapses (except that multiple previous detoxification episodes with relapse are a strong indication for long-term maintenance treatment) • Poor response to previous well-conducted attempts at buprenorphine treatment • Significant medical complications • Conditions that are outside the area of the treating physician’s expertise

Patient Assessment 45 McCance-Katz et al. 2001; Moatti et al. Use of Other Drugs 2000). Buprenorphine is a treatment for opioid addiction, not for addiction to other classes Hepatitis and Impaired of drugs. Although the use of other drugs Hepatic Function tends to be a predictor of poor adherence, other drug use is not an absolute contra- Pharmacotherapy with buprenorphine is not indication to buprenorphine treatment. (See contraindicated on the basis of mildly below for exceptions.) elevated liver enzymes; however, elevated liver enzymes should be appropriately Patients should be encouraged to abstain evaluated and monitored frequently. Viral from the use of all nonprescribed drugs hepatitis (especially infection with HBV or while receiving buprenorphine treatment. HCV) is common among individuals who However, abuse of or dependence on other abuse opioids and should be evaluated and drugs (e.g., alcohol, cocaine, stimulants, treated appropriately. sedative-hypnotics, hallucinogens, inhalants) is common among individuals who are Pregnancy addicted to opioids, and such abuse or dependence may interfere with overall Buprenorphine is classified by FDA as a treatment adherence. Category C agent. Very few studies exist on the use of bup- Patients who use or abuse more than one renorphine in substance present unique problems and may pregnant women. need referral to resources outside the office Although the use of If a patient is setting for more intensive treatment. pregnant or is Patients should be encouraged to be truthful other drugs tends to likely to become about their use of all drugs. A recent drug pregnant during use history and a toxicology screen for be a predictor of the course of drugs of abuse are guides to help assess use, treatment with abuse, and dependence on opioids and other poor adherence, buprenorphine, drugs. Treatment of patients with more than the physician one addiction problem will depend largely on other drug use is not must consider the physician’s level of comfort in treating whether bupre- addiction, the availability of psychosocial norphine is the an absolute support and counseling, and the availability appropriate of other forms of addiction treatment. (See treatment and “Polysubstance Abuse” in chapter 5.) contraindication to must weigh the risks and benefits buprenorphine of buprenorphine Sedative-Hypnotics treatment against The use of sedative-hypnotics (benzodia- treatment. all the risks zepines, barbiturates, and others) is a associated with relative contraindication to treatment with continued heroin buprenorphine because the combination or other opioid use. In the United States, (especially in overdose) has been reported to methadone is the standard of care for be associated with deaths (Reynaud et al. pregnant women who are addicted to 1998a,b). The combination of buprenor- opioids. (See “Pregnant Women and phine and sedative-hypnotics may increase Neonates” in chapter 5.) depression of the central nervous system. If

46 Patient Assessment treatment with buprenorphine and sedative- or other sedative-hypnotic substances. hypnotics is necessary, the doses of both Benzodiazepines and barbiturates, the most medications may need to be lowered. Physi- commonly used pharmacological treatments cians must assess for use, intoxication, and for seizures caused by alcohol or other withdrawal from sedative-hypnotics. Unfor- sedative-hypnotic withdrawal, should be tunately, the use of certain benzodiazepines used only with caution in combination with and other sedatives may not be detected buprenorphine because of the increased risk on routine drug screens. Physicians must of central nervous system and respiratory determine their laboratory’s specific param- depression from the combination. eters for detection of sedative-hypnotic use.

Alcohol Summary Because alcohol is a sedative-hypnotic drug, Patients who may be good candidates for patients should be advised to abstain from opioid addiction treatment with buprenor- alcohol while taking buprenorphine. Rarely phine are those who have an objective are individuals with active, current alcohol diagnosis of opioid addiction, who have the dependence appropriate candidates for appropriate understanding of and motiva- office-based buprenorphine treatment. (It tion for buprenorphine treatment, and who may be possible to treat such patients do not have medical or psychiatric contra- through initial, intensive services that indications to this form of treatment. This effectively detoxify the patient from alcohol chapter has provided information on the while concurrently starting buprenorphine questions, cautions, and contraindications [e.g., in an inpatient or residential setting].) that should be considered when determining Patients may present with withdrawal whether a patient is an appropriate candi- symptoms from other drugs at the same time date for opioid addiction treatment with they are experiencing opioid withdrawal buprenorphine. Chapter 4 describes the next symptoms. Buprenorphine will not control steps in providing treatment with buprenor- seizures caused by withdrawal from alcohol phine for opioid addiction.

Patient Assessment 47 48 4 Treatment Protocols

Overview In This Office-based treatment of opioid addiction has been unavailable in the Chapter… United States since the early 1900s. Thus, most U.S. physicians today have little or no experience in the management of opioid addiction. As a consequence, physicians often treat substance-related disorders Maintenance Treatment With Buprenorphine (e.g., infectious diseases) without having the resources to treat the concurrent substance-use disorder itself. With the introduction of Opioid Detoxification buprenorphine, office-based physicians now will have the ability to With Buprenorphine treat both the complications of opioid addiction and opioid addiction itself. (For articles on managing opioid-dependent patients in the office Patient Management setting, please see Fiellin et al. 2001, 2002; O’Connor et al. 1996, 1998.)

Physicians who use buprenorphine to treat opioid addiction must consider the entire process of treatment, from induction, through stabilization, and then maintenance. At each stage of the process, many different factors must be considered if the physician is to provide comprehensive and maximally effective opioid addiction care. Physicians should conduct a comprehensive assessment to understand the nature of an individual’s addiction problem, especially with regard to the primary type of opioid abused. Before initiating buprenorphine treatment, physicians should obtain a signed release of information (see Title 42, Part 2 of the Code of Federal Regulations [42 C.F.R. Part 2]) from patients who are currently enrolled in Opioid Treatment Programs (OTPs) or other programs (42 C.F.R. Part 2 2001). (See “Confidentiality and Privacy” in chapter 6.) This chapter provides detailed protocols on the use of buprenorphine for the treatment of opioid addiction. The chapter begins with a discussion of some general issues regarding treatment with buprenorphine.

49 Buprenorphine Monotherapy buprenorphine alone is to be used for extended periods, the number of doses to be and Combination prescribed should be limited, and the use of Buprenorphine/Naloxone the monotherapy formulation should be Treatment justified in the medical record. The consensus panel recommends that the Although controlled trials have not compared buprenorphine/naloxone combination be used buprenorphine monotherapy to the for induction treatment (and for stabilization buprenorphine/naloxone combination for and maintenance) for most patients. However, induction, clinical experience in office-based pregnant women who are determined to be trials conducted by the National Institute on appropriate candidates for buprenorphine Drug Abuse (NIDA) has demonstrated that treatment should be inducted and maintained physicians were comfortable starting patients on buprenorphine monotherapy. In addition, on either the monotherapy formulation or the patients who desire to change from long-acting combination formulation and did not report opioids (e.g., methadone, levo-alpha-acetyl- adverse events when patients began directly methadol [LAAM]) to buprenorphine should on combination treatment. Physicians will be inducted using need to find their own comfort level with the buprenorphine induction protocols, but the consensus panel monotherapy.* If sees no contraindication to the use of the The consensus panel the buprenorphine buprenorphine/naloxone combination in the monotherapy initiation of buprenorphine treatment, except recommends that the formulation is as noted above. elected for induc- buprenorphine/ tion treatment, it is recommended Opioid Withdrawal Syndrome naloxone that patients who With Buprenorphine are not pregnant Induction combination be used be switched to the buprenorphine/ Because buprenorphine (and particularly buprenorphine/naloxone) can precipitate an naloxone combi- for induction opioid withdrawal syndrome if administered nation form as to a patient who is opioid dependent and early in treatment treatment…for whose receptors are currently occupied by as possible to opioids, a patient should no longer be intoxi- minimize the cated or have any residual opioid effect from most patients. possibility of his or her last dose of opioid before receiving a diversion of first dose of buprenorphine. Subutex® to abuse via the injection Due to this required abstinence before route. When the buprenorphine monotherapy initiating buprenorphine treatment, it is likely formulation is used for induction, it is that patients will feel that they are experi- recommended that it be used for no more than encing the early stages of withdrawal when 2 days before switching to the buprenorphine/ they present for buprenorphine induction naloxone combination formulation (for treatment, unless they are on maintenance patients who are not pregnant). If treatment with a long-acting opioid agonist

*Due to a number of factors, including the association of LAAM with cardiac arrhythmias in some patients, as of January 1, 2004, the sole manufacturer has ceased production of the drug.

50 Treatment Protocols (e.g., methadone). If a patient has early symp- addiction: (1) opioid maintenance treatment, toms of withdrawal, then the opioid receptors and (2) medically supervised withdrawal are unlikely to be occupied fully; precipitated (detoxification) with either opioid (e.g., withdrawal from administration of buprenor- methadone) or nonopioid (e.g., clonidine) phine will be avoided, and the efficacy of medications. Because opioid-assisted mainte- buprenorphine in alleviating withdrawal nance and medically supervised withdrawal symptoms can be assessed more easily. treatments have not been available outside the OTP setting, many patients may not be aware Withdrawal symptoms can occur if either too that these forms of treatment are now avail- much or too little buprenorphine is admin- able in new clinical settings. Thus, a discus- istered (i.e., spontaneous withdrawal if too sion with patients of all available treatment little buprenorphine is given, precipitated options is essential. withdrawal if buprenorphine is administered while the opioid receptors are occupied to a For many patients, it may be inappropriate to high degree by an opioid agonist). Therefore, decide arbitrarily on the length of treatment physicians must be careful when timing at initial evaluation. It is more likely that initiation of buprenorphine induction. Each patients will need to be started in treatment patient’s history and concerns must be within a flexible timeframe that responds to considered carefully, and patient counseling the progress and needs of the patient. For about potential side effects from buprenor- example, in one report of rapid-term opioid phine overdosing (especially in combination detoxification using buprenorphine, it was with benzodiazepines) or underdosing (e.g., noted that 25 percent of patients initially a reemergence of opioid craving) must be requesting detoxification subsequently emphasized. Before undertaking bupre- switched to maintenance treatment within the norphine treatment of opioid addiction, 10-day study (Vignau 1998). Thus, as treat- physicians should be familiar with the signs, ment progresses, it may become a more symptoms, and time course of the opioid appropriate time to assess the duration of withdrawal syndrome. (See figure 3–7.) various aspects of treatment, including medications, counseling therapies, and self-help Method of Administration groups. Therefore, it is important to assess initially, and to reassess periodically, a Buprenorphine sublingual tablets should be patient’s motivation for treatment, as well as placed under the tongue until they are dis- his or her willingness to engage in appropriate solved. For doses requiring the use of more counseling and/or a structured rehabilitation than two tablets, patients should either place program. (See “Assessment” in chapter 3.) all the tablets at once or alternatively, if they cannot fit in more than two tablets comfort- ably, place two tablets at a time under the Maintenance tongue. Either way, the tablets should be held under the tongue until they dissolve; swal- Treatment With lowing the tablets reduces the bioavailability Buprenorphine of the drug. To ensure consistency in bioavailability, patients should follow the same The three phases of maintenance treatment manner of dosing with continued use of the with buprenorphine for opioid addiction medication. Dissolution rates vary, but, on are (1) induction, (2) stabilization, and average, the sublingual tablets should dissolve (3) maintenance. The following sections in approximately 5–10 minutes. describe these phases.

Treatment Approach Induction Phase There are two general approaches to the Buprenorphine induction (usual duration medication-assisted treatment of opioid approximately 1 week), the first phase of

Treatment Protocols 51 treatment, involves helping a patient begin the Patients Dependent on process of switching from the opioids of abuse to buprenorphine. The goal of the induction Short-Acting Opioids phase is to find the minimum dose of bupre- Before the initial buprenorphine induction norphine at which the patient discontinues or dose is administered to a patient dependent markedly diminishes use of other opioids and on short-acting opioids, a minimum of experiences no withdrawal symptoms, minimal 12–24 hours should have elapsed since the or no side effects, and no uncontrollable last use of opioids. The patient should pre- cravings for drugs of abuse. The physician ferably be exhibiting early signs of opioid should assess for signs and symptoms of with- withdrawal (e.g., sweating, yawning, rhinor- drawal or inadequate dosing during induction. rhea, lacrimation). (See figure 3–7.) Patients Patients should be advised to avoid driving or who are not in active withdrawal because they operating other machinery until they are have not abstained from using opioids for a familiar with the effects of buprenorphine and sufficient period should receive a careful their dose is stabilized. Induction protocols explanation of the advantages of waiting and differ, depending on the type of opioid to should be urged to wait until they begin to which the patient is addicted (e.g., short- or experience the symptoms of withdrawal. long-acting) and whether or not the patient is in active withdrawal at the time of induction. Patients who are experiencing objective signs of opioid withdrawal and whose last use of The consensus panel recommends that physi- a short-acting opioid was more than cians administer initial induction doses as 12–24 hours prior to the initiation of observed treatment (e.g., in the office); induction can receive a first dose of further doses may be provided via prescrip- 4/1–8/2 mg of the buprenorphine/naloxone tion thereafter. This ensures that the amount combination (buprenorphine monotherapy for of buprenorphine located in the physician’s pregnant women). (See figure 4–1.) If the office is kept to a minimum. Following the initial dose of the buprenorphine/naloxone initial buprenorphine dose, patients should be combination is 4/1 mg and opioid withdrawal observed in the physician’s office for up to symptoms subside but then return (or are still 2 hours. For patients who do not experience present) after 2 hours, a second dose of 4/1 mg excessive opioid agonist symptoms after the can be administered. The total amount of initial dose, induction protocols can be buprenorphine administered in the first day followed as described below. should not exceed 8 mg.

Induction Days 1 and 2: Who Patients Dependent on Is the Patient and What Does Long-Acting Opioids He or She Need? Induction onto buprenorphine from long- It is important to identify the opioid(s) that acting opioids (e.g., methadone, LAAM) may patients have been using, as the response to be complicated and is best managed by buprenorphine treatment in individuals physicians experienced with this procedure. If dependent on long-acting opioids is different this treatment will be conducted in an than that seen with short-acting opioids and, office-based setting, the physician’s office therefore, the appropriate induction protocol must contact the patient’s OTP (after must be chosen. Most patients starting bup- receiving signed consent) to determine the renorphine induction will be physically methadone or LAAM dosage levels and time of dependent on a short-acting opioid (e.g., last dose. Such contact will ensure that the heroin, oxycodone, hydrocodone) and should physician knows the exact quantity and time be in the early stages of withdrawal at the time of the last methadone or LAAM dose, as well they receive their first dose of buprenorphine. as prevent patients from receiving opioid (See figure 4–1 and appendix B.) agonist treatment (OAT) and office-based

52 Treatment Protocols Figure 4–1 Induction Days 1–2

Patient dependent on opioids

Long-acting opioids Short-acting opioids

Methadone: Taper to £30 mg per day Discontinue short-acting opioids LAAM: Taper to £40 mg per 48-hour dose

Methadone: Withdrawal Withdrawal symptoms 24+ hours No No symptoms Reevaluate suitability after last dose? present 12–24 for induction LAAM: Withdrawal hours after last dose symptoms 48+ hours of opioids? after last dose?

Yes Yes

Administer 2 mg Administer 4/1 mg buprenorphine monotherapy. buprenorphine/naloxone. Observe 2+ hours Observe 2+ hours

Yes Yes Withdrawal Day 1 dose established Withdrawal symptoms relieved? (see figure 4–2) symptoms relieved?

No No

Repeat dose up to maximum Repeat dose up to maximum 8 mg per 24 hours 8/2 mg per 24 hours

No Yes Withdrawal symptoms relieved?

Manage withdrawal symptomatically

Return next day for repeat Day 1 dose established induction attempt (see figure 4–2) (see figure 4–2)

Treatment Protocols 53 buprenorphine treatment simultaneously. To proceed in the same manner and at the same allow this exchange of addiction treatment dosage levels as recommended for methadone information per Federal confidentiality patients. regulation 42 C.F.R. Part 2 (see “Confidentiality and Privacy” in chapter 6), Induction Management When the patient must provide signed consent to both the OTP and the buprenorphine-treating Withdrawal Symptoms Are physician. Not Relieved by 8 mg For patients taking methadone, the metha- Buprenorphine in the First done dose should be tapered to 30 mg or less 24 Hours per day for a minimum of 1 week before initiating buprenorphine induction treatment. If withdrawal symptoms are still not relieved Patients should not receive buprenorphine after a total of 8 mg of buprenorphine on until at least 24 hours after the last dose of Day 1, symptomatic relief with nonopioid methadone. The first dose of buprenorphine medications should be provided and the should be 2 mg of the monotherapy formula- patient asked to return the following day for tion. (See figure 4–1.) If a patient develops dose management. (See “Induction Day 2 and signs or symptoms of withdrawal after the first Forward” below.) dose, a second dose of 2 mg should be administered and repeated, if necessary, to a maxi- Patients Not Physically mum of 8 mg buprenorphine on Day 1. Dependent on Opioids It should be noted that not all patients main- Patients who are not physically dependent on tained on methadone may be good candidates opioids but who have a known history of for the switch to buprenorphine treatment opioid addiction, have failed other treatment at a methadone dose of 30 mg/day. As a meth- modalities, and have a demonstrated need to adone taper approaches 30 mg/day many cease the use of opioids, may be candidates for patients become uncomfortable, develop with- buprenorphine treatment. Patients in this drawal symptoms, and are at increased risk category will be the exception rather than the of relapse to opioid abuse. Such patients may rule, however. Other patients in this category request the transfer to buprenorphine at would be those recently released from a higher daily doses of methadone. The deci- controlled environment who have a known sion to transfer a patient to buprenorphine history of opioid addiction and a high at higher daily methadone doses should be potential for relapse. based on clinician judgment, informed by the patient’s subjective and objective findings. Patients who are not physically dependent on While there have been case reports of trans- opioids should receive the lowest possible dose ferring patients to buprenorphine from meth- (2/0.5 mg) of buprenorphine/naloxone for adone doses as high as 80 mg/day, there is induction treatment. insufficient data to formulate recommendations regarding which patients may be able to Induction Day 2 and Forward tolerate a switch at these higher doses or the best way to manage the transfer. If buprenorphine monotherapy was administered on Day 1, switch to buprenorphine/ No clinical experience with inducting patients naloxone on Day 2 (for a patient who is not from LAAM to buprenorphine is documented. pregnant). However, extrapolating from consensus panel members’ experience with such patients, the For patients who do not experience any dif- panel recommends that the dose of LAAM be ficulties with the first day of buprenorphine tapered down to 40 mg or less per 48-hour dosing, and who are not experiencing with- dose, and buprenorphine induction should not drawal symptoms on Day 2, the induction be undertaken until at least 48 hours after the schedule shown in figure 4–2 can be followed. last dose of LAAM. Induction should then The daily buprenorphine/naloxone dose is

54 Treatment Protocols Figure 4–2 Induction Day 2 Forward

Patient returns to office on buprenorphine/naloxone*

Withdrawal No Daily dose established equal to symptoms present total buprenorphine/naloxone since last dose? administered on previous day**

Yes

Administer dose equal to the total amount of buprenorphine/naloxone administered on previous day plus an additional 4/1 mg (maximum 12/3 mg on Day 2). Observe 2+ hours

Withdrawal Yes symptoms relieved?

Administer 4/1 mg buprenorphine/naloxone Daily buprenorphine/naloxone (maximum 16/4 mg total on Day 2) dose established**

Withdrawal Yes symptoms relieved?

Manage withdrawal symptomatically

On subsequent induction days, if the patient returns experiencing withdrawal symptoms, continue dose increases as per the schedule shown above, up to a maximum of 32/8 mg buprenorphine/naloxone per day.

*If buprenorphine monotherapy was administered on Day 1, switch to buprenorphine/naloxone on Day 2 (for a patient who is not pregnant). **Dose may be increased by 2/0.5–4/1 mg increments on subsequent days as needed for symptom relief. Target dose of 12/3–16/4 mg buprenorphine/naloxone per day by the end of the first week.

Treatment Protocols 55 established as equivalent to the total amount Stabilization Phase of buprenorphine/naloxone (or buprenorphine) that was administered on Day 1. Doses The induction phase is completed and the may be subsequently increased in 2/0.5 to stabilization phase (usual duration approximately 1 to 2 months) is begun when the 4/1 mg increments each day, if needed for patient is experiencing no withdrawal symp- symptomatic relief, with a target dose of toms, is experiencing minimal or no side 12/3 to 16/4 mg per day to be achieved within effects, and no longer has uncontrollable the first week, unless side effects occur. If side cravings for opioid agonists. (See figure 4–3.) effects occur, the dose of buprenorphine As with any pharmacotherapy, the goal of should be maintained or lowered until these buprenorphine treatment is to treat with the side effects disappear. minimum dose of medication needed to address target signs, symptoms, desired Patients who return on Day 2 experiencing benefits, and laboratory indices while mini- withdrawal symptoms should receive an initial mizing side effects. Elimination of objective dose of buprenorphine/naloxone equivalent to evidence of opioid use (negative toxicology) the total amount of buprenorphine/naloxone represents the key target sign for which to (or buprenorphine) administered on Day 1 strive. The goal is to reduce self-reported plus an additional 4/1 mg (maximum initial cravings and self-reported use of illicit dose of 12/3 mg). If withdrawal symptoms are opioids. One benefit worth achieving is a self- still present 2 hours after the dose, an reported increase in opioid blockade such that additional 4/1 mg dose can be administered. self-administered illicit opioids induce little or The total dose on Day 2 should not exceed no euphoria. A reduction in opioid-positive 16/4 mg. Continue dose increases on subse- toxicology specimens confirms a successful quent days according to the induction sched- direction in treatment. ule shown in figure 4–2 up to a maximum of Dosage adjustments may be necessary during 32/8 mg per day. early stabilization, and frequent contact with If patients have problems adjusting to bupre- patients increases the likelihood of compli- norphine (e.g., experience withdrawal symp- ance. Until full stabilization is achieved, weekly assessments of patients may be toms or continue to feel compelled to use illicit indicated to make necessary dosage adjust- drugs), the dose may need to be increased ments. With stabilization goals in mind, doses more rapidly, or to a higher maintenance dose of buprenorphine/naloxone may be increased level, and patients may need intensive psycho- in 2/0.5–4/1 mg increments per week until social treatments to help them cease illicit use. stabilization is achieved. Nearly all patients Patients who continue to take illicit opioids will stabilize on daily doses of 16/4–24/6 mg; should be warned strongly of the dangers of some, however, may require up to 32/8 mg continuing to do so. Physicians also should daily. verify that patients are taking the medication correctly and should assess the timing of doses Some patients may prefer or may respond in relation to last opioid use, amount of time better to less-than-daily dosing regimens of the medication is allowed to dissolve under the buprenorphine. It is possible that less-than- daily dosing will most likely be advantageous tongue, and dose taken. If a dose of buprenor- in an OTP or other directly observed dose phine makes a patient feel worse, it is likely setting, where daily visits might otherwise be that the medication is causing precipitated required. A variety of studies have shown the withdrawal. In this situation, the physician efficacy of alternate-day or thrice-weekly should help the patient to decrease the use of buprenorphine administration (Amass et al. the illicit opioid while gradually increasing the 2000; Bickel et al. 1999; Perez de los Cobos dose of buprenorphine. Toxicology testing for et al. 2000; Petry et al. 1999). The typical drugs of abuse may be helpful in determining method of determining the dose for less-than- adequacy of clinical response. daily dosing regimens was to double (for

56 Treatment Protocols Figure 4–3 Stabilization Phase

Patient receiving induction

Induction phase No completed?

Yes

Continued Yes illicit opioid use?

Withdrawal Yes Continue adjusting dose up to symptoms 32/8 mg buprenorphine/ present? naloxone per day

Continued illicit Compulsion Yes opioid use Yes to use, cravings despite present? maximum dose?

No No

Maintain on buprenorphine/naloxone dose. Daily dose of buprenorphine/ Increase intensity of nonpharmacological naloxone established interventions. Consider referral to OTP or other more intense level of treatment

Treatment Protocols 57 alternate-day dosing) or triple (for every- Long-Term Medication third-day dosing) the stable daily dose for the patient. Although all regimens were deter- Management mined to be safe and, in most cases, effective, The design of long-term treatment depends in several authors noted that some subjects were part on the patient’s personal treatment goals more likely to have urine samples positive for and in part on objective signs of treatment opioids on the less-than-daily dosing regimens. success. Maintenance can be relatively short- During induction and early stabilization daily term (e.g., <12 months) or a lifetime process. dosing is recommended. Treatment success depends on the achieve- ment of specific goals that are agreed on by If a patient continues to use illicit opioids both the patient and the physician. Following despite the maximal treatment available in the successful stabilization, decisions to decrease physician’s clinical setting, the physician or discontinue buprenorphine should be should consider referral to a more intensive based on a patient’s desires and commitment therapeutic environment. to becoming medication-free, and on the physician’s confidence that tapering would be successful. Factors to be considered when Maintenance Phase determining suitability for long-term The longest period that a patient is on bupre- medication-free status include stable housing norphine is the period of maintenance. This and income, adequate psychosocial support, period may be indefinite. It is easy for physi- and the absence of legal problems. For cians to lessen their vigilance during this patients who have not achieved these indices period, but significant considerations still of stabilization, a longer period of mainte- must be addressed. Attention must be main- nance, during which they work through any tained to the psychosocial and family issues barriers that exist, may be appropriate. Data suggest that longer duration of medication that have been identified during the course of treatment is associated with less illicit drug use treatment. Other issues that will need con- and fewer complications. tinual monitoring are related to cravings for opioids and to preventing relapse. Some other issues related to opioid abuse that need to be Opioid Detoxification addressed during maintenance treatment include, but are not limited to, the following: With Buprenorphine • Psychiatric comorbidity This section discusses the use of buprenorphine for the medically supervised withdrawal • Somatic consequences of drug use (detoxification) from short-acting opioids and • Family and support issues from OAT with methadone or LAAM. The goal • Structuring of time in prosocial activities of medically supervised withdrawal from opioids is to provide a smooth transition from • Employment and financial issues a physically dependent to a physically nonde- • Legal consequences of drug use pendent state. A patient can then engage in • Other drug and alcohol abuse further rehabilitation with or without the use of opioid antagonist treatment to assist in The frequent presence of some or all of these relapse prevention. Before considering the use problems underscores the importance of pro- of buprenorphine for withdrawal from illicit viding nonpharmacological services to address opioids or to discontinue OAT, a patient’s comprehensively the needs of patients and to appropriateness as a candidate for withdrawal maximize the chances of the best possible or cessation must be determined at the time of outcomes. assessment. Withdrawal treatment must be

58 Treatment Protocols followed by long-term drug-free, or naltrex- stabilization or maintenance should be con- one, treatment in order to minimize the risk of sidered. (See figure 4–4.) relapse to opioid abuse. It should be noted, however, that absent a compelling need for the Dose Reduction Phase complete avoidance of all opioids, long-term maintenance treatment with buprenorphine is Long-Period Reduction. The literature sug- to be preferred in most instances to any form gests that the use of buprenorphine for of detoxification or withdrawal treatment. gradual detoxification over long periods is probably more effective than its use for rapid detoxification over short or moderate periods; Buprenorphine for however, little research has been conducted Detoxification From Short- on this use of buprenorphine. Patients who Acting Opioids are unwilling or unable to engage actively in rehabilitation services without agonist support Detoxification in patients addicted to short- may not be appropriate candidates for short- acting opioids is only a part of the overall term detoxification; however, such patients approach to treatment. The purpose of using may benefit from long-term detoxification (or, buprenorphine for detoxification from short- even more so, from maintenance treatment). acting opioids is to provide a transition from the state of physical dependence on opioids to Moderate-Period Reduction. Patients without an opioid-free state, while minimizing with- a compelling need to undergo short-term drawal symptoms (and avoiding side effects of detoxification, but with a desire to become buprenorphine). opioid free and to engage in rehabilitation aimed at an Induction Phase opioid-free lifestyle, can be The consensus panel recommends that Withdrawal treatment patients dependent on short-acting opioids detoxified over a be inducted directly onto buprenorphine/ 10- to 14-day (or must be followed by naloxone tablets. Before initiating buprenor- longer) period by gradually decreas- phine induction, patients should have discon- long-term drug-free, tinued the use of illicit opioids and should be ing the initial stabilization dose exhibiting the early symptoms of withdrawal. or naltrexone, An initial 4/1 mg dose of buprenorphine/ of buprenorphine naloxone is recommended. This dose can be (usually 8–16 mg followed in 2–4 hours with a second dose of per day) by 2 mg treatment in order to 4/1 mg, if indicated. Over the next 2 days, the every 2–3 days. It dose of buprenorphine/naloxone should be is extremely minimize the risk of increased to 12/3–16/4 mg per day. The objec- important that tives of induction should be to stabilize the patients engage in relapse to opioid patient as rapidly as possible, to minimize rehabilitation pro- any withdrawal symptoms, and to eliminate grams during the abuse. further use of illicit opioids. Only after a detoxification patient has completely discontinued use of period and that illicit opioids should the dose-reduction phase they remain begin. Unless a patient is in a controlled envi- engaged in such programs after the conclusion ronment (e.g., a hospital or residential of the detoxification protocol. setting), cessation of opioid use should be documented with a negative toxicology test for Short-Period Reduction. Patients with a illicit opioids. If a patient is unable to discon- compelling reason to achieve an opioid-free tinue illicit opioid use, as documented by neg- state quickly (e.g., impending incarceration, ative toxicology results, a further period of foreign travel, job requirement) may have

Treatment Protocols 59 Figure 4–4 Detoxification From Short-Acting Opioids

Patient dependent on short-acting opioids

Discontinue short-acting opioids. Administer 4/1 mg buprenorphine/naloxone

No Withdrawal Yes Adjust dose to relieve withdrawal symptoms symptoms (see figure 4–1) emerge?

Stabilize on appropriate dose for at least 2 days

Compelling No reason for rapid Stabilize on buprenorphine/ discontinuation naloxone (1 week or longer) of opioids?

Yes

Taper buprenorphine/naloxone Taper buprenorphine over moderate-period or over 3–6 days long-period (preferred) reduction

No Yes Withdrawal symptoms emerge?

Continue taper Discontinue taper until patient stabilizes, then resume

Discontinue buprenorphine/naloxone

60 Treatment Protocols their buprenorphine dose reduced over 3 days Methadone Discontinuation and then discontinued. When compared to clonidine for the treatment of short-term In general, patients who are clinically stable opioid withdrawal, buprenorphine is better and are being slowly tapered off methadone accepted by patients and more effective in maintenance treatment experience little relieving withdrawal symptoms (Cheskin et al. difficulty until the daily methadone dose reaches 30 mg or less. As the daily dose drops 1994). Relapse rates and long-term outcomes below 30 mg, opioid withdrawal symptoms from such rapid opioid withdrawal using bup- often emerge between methadone doses. renorphine have not been reported, however. Additionally, the euphoria-blocking and Studies of other withdrawal modalities have anticraving effects of methadone are much shown that such brief withdrawal periods are diminished at this low dose level. (1) unlikely to result in long-term abstinence and (2) produce minimal, if any, long-term benefits in the treatment of patients depend- LAAM Discontinuation ent on opioids. Cessation of OAT with LAAM follows a protocol similar to that for methadone cessation. Patients previously stabilized on LAAM may Buprenorphine for be candidates for buprenorphine once the Discontinuation of OAT LAAM dose is tapered to 40 mg or less per 48 hour dose. At this point, buprenorphine The use of buprenorphine (either as bupre- monotherapy can be instituted similarly to norphine monotherapy or as buprenorphine/ procedures for methadone discontinuation, naloxone combination treatment) to taper off although LAAM’s pharmacology must be OAT with methadone or LAAM should be taken into account. (See figure 4–5.) When the considered only for those patients who have patient has been stabilized on buprenorphine evidence of sustained medical and psycho- monotherapy, the physician should employ the social stability. Requests to provide pharma- same decision process described above for cological withdrawal with buprenorphine or methadone discontinuation. If there is a buprenorphine/naloxone should be enter- compelling reason for OAT discontinuation, tained with caution. Only a small proportion short-term discontinuation with buprenor- of patients who have achieved stability with phine monotherapy can be achieved with a OAT are likely to maintain abstinence without 3-day protocol as described above. In the medication. Ideally, this decision would be absence of a compelling reason, the patient made in conjunction, and in coordination, should be switched to buprenorphine/ with a patient’s OTP. The option of continued naloxone combination treatment, which can maintenance with buprenorphine/naloxone if be reduced subsequently and eventually withdrawal proves unsuccessful should be discontinued if the patient remains clinically discussed. stable without evidence of illicit opioid use. Physicians should remember that patients are The guidelines in figure 4–5 describe both most likely to relapse during or after discon- short-period (3-day) and moderate-period tinuation. Therefore, patients should be (2-week) discontinuation of OAT with bupre- monitored closely for relapse to illicit opioid norphine. Short-period discontinuation is not use, and the dose of buprenorphine should be recommended unless there is a compelling increased in response to cravings or need for rapid discontinuation. withdrawal symptoms. Compelling reasons for discontinuing OAT Discontinuation of within a relatively short timeframe might include impending incarceration, foreign Buprenorphine/Naloxone travel, conditions of employment, or other When the decision is made to discontinue circumstances expected to preclude the buprenorphine/naloxone combination patient from continuing OAT. treatment, the daily dose should be decreased

Treatment Protocols 61 Figure 4–5 Discontinuation of OAT Using Buprenorphine

Patient being treated with methadone or LAAM; displays evidence of medical and psychosocial stability

Methadone: Compelling Taper to £30 mg per day reason to discontinue Yes methadone or LAAM? LAAM: Taper to £40 mg per 48-hour dose

Buprenorphine monotherapy Continue current treatment induction (see figure 4–1)

Compelling Switch to No reason for rapid buprenorphine/naloxone discontinuation?

Yes Stabilize on buprenorphine/naloxone Taper buprenorphine monotherapy (1+ weeks) over 3–6 days, then discontinue

Taper buprenorphine/naloxone (2+ weeks)

Yes Withdrawal Split into 2–3 smaller symptoms emerge? doses per day

Discontinue buprenorphine/naloxone

62 Treatment Protocols gradually over a predetermined period or at The ability to provide counseling and educa- a rate negotiated by the patient and the tion within the context of office-based practice physician together. Withdrawal symptoms may vary considerably, depending on the type may emerge as the buprenorphine/naloxone and structure of the practice. Psychiatrists, dose is decreased. In this event, the taper may for example, may include components of be temporarily suspended. cognitive-behavioral therapy or motivational As with the protocols described above, dis- enhancement therapy during psychotherapy continuation of buprenorphine/naloxone sessions. Some medical clinics may offer combination treatment may be performed patient education, which generally is provided over short periods (e.g., 3 days), but this by allied health professionals (e.g., nurses, approach should be used only in the presence nurse practitioners, physician assistants). A of a compelling urgency to discontinue bup- drug abuse treatment program typically renorphine/naloxone in this manner; discon- includes counseling and prevention education tinuation over a longer period is the preferred as an integral part of the clinic program. In a manner. stand-alone general or family practice, the opportunities for education/counseling may be Patient Management more limited. As part of their training in opioid addiction treatment, physicians should obtain, at a minimum, some knowledge of the Psychosocial Treatment basic principles of brief intervention in case of Modalities and Adjuncts relapse. (See appendix E.) Physicians may want to consider providing to office staff some Pharmacotherapy alone is rarely sufficient treatment for drug addiction (McLellan et al. training in brief treatment interventions and 1993). Treatment outcomes demonstrate a motivational interviewing; this information dose-response effect based on the level or could also enhance the effectiveness of amount of psychosocial treatment services treatment for other medical problems. A list that are provided. Therefore, physicians have of trainers may be found at http:// an additional level of responsibility to patients www.motivationalinterview.org. with opioid addiction problems; this responsibility goes beyond prescribing and/or Many physicians already have the capability administering buprenorphine. For most to assess and link substance abuse patients to patients, drug abuse counseling—individual ancillary services for substance abuse. Physi- or group—and participation in self-help cians considering making buprenorphine programs (e.g., Alcoholics Anonymous [AA]; available to their patients should ensure that Narcotics Anonymous [NA]; Methadone they are capable of providing psychosocial Anonymous, a 12-Step group that supports services, either in their own practices or recovery concurrent with OAT; Self Manage- through referrals to reputable behavioral ment and Recovery Training [SMART] health practitioners in their communities. In Recovery; or Moderation Management) are fact, the Drug Addiction Treatment Act of considered necessary. Self-help groups may be 2000 (DATA 2000) stipulates that, when phy- beneficial for some patients and should be considered as one adjunctive form of psycho- sicians submit notification to the Substance social treatment. It should be kept in mind, Abuse and Mental Health Services Admin- however, that the acceptance of patients who istration (SAMHSA) to obtain the required are maintained on medication for opioid waiver to practice opioid addiction therapy treatment is often challenged by many 12-Step outside the OTP setting, they must attest to groups. Furthermore, many patients have their capacity to refer such patients for better treatment outcomes with formal ther- appropriate counseling and other non- apy in either individual or group settings. pharmacological therapies.

Treatment Protocols 63 It is incumbent on practitioners of buprenor- Physicians may find the sample contract (or phine treatment to be aware of the options an adapted version) in appendix H a useful and services that are available in their com- tool in working with patients in an office- munities and to be able to make appropriate based setting. referrals. Physicians should be able to determine the intensity of services needed by indi- After obtaining signed patient consent vidual patients and when those needs exceed (according to 42 C.F.R. Part 2), physicians what the practitioner can offer. Contingency should clarify assessment and treatment goals plans should be established for patients who with family members. Whenever possible, do not follow through with referrals to significant others should be engaged in the psychosocial treatments. Physicians should treatment process, as their involvement is work with qualified behavioral health prac- likely to have a positive effect on outcomes. titioners to determine the intensity of services Conversely, when patients refuse to involve needed beyond the medical services. their significant others, or when the latter refuse to become involved, positive outcomes are less likely. Treatment Monitoring Frequency of Visits Treatment Plan During the stabilization phase, patients Patients and their physicians together need to receiving maintenance treatment should be reach agreement on the goals of treatment seen on at least a weekly basis. Part of the through a treatment plan that is based on purpose of the ongoing assessment is to deter- assessment of the patient. Treatment plans mine whether patients are adhering to the should include both treatment goals and the dosing regimen and handling their medications conditions under which treatment is to be dis- responsibly (e.g., storing it safely, taking it as continued. The prescribed, not losing it). Once a stable initial plan should buprenorphine dose is reached and toxico- Treatment plans contain contingen- logical samples are free of illicit opioids, the cies for treatment physician may determine that less frequent should include both failure, such as visits (biweekly or longer, up to 30 days) are referral to a more acceptable. Visits on a monthly basis are treatment goals and structured treat- considered a reasonable frequency for ment modality patients on stable buprenorphine doses who (e.g., an OTP). the conditions under are making appropriate progress toward For polysubstance treatment objectives and in whom toxicology users, it is also which treatment is to shows no evidence of illicit drugs. However, important for physicians should be sensitive to treatment patients to set a be discontinued. barriers, such as geographical issues, travel goal of abstinence distance to treatment, domestic issues such as from all illicit child care and work obligations, as well as the drugs, provided cost of care. that counseling to address other drug use is also available. (Abstinence from all illegal or Patients’ progress in achieving treatment inappropriate substances of abuse should be goals should be reviewed periodically. Various the goal of all patients, whether single or poly- goal-attainment scales, which can be adminis- substance users.) Treatment contracts are tered by a nurse or case manager, can assist in often employed to make explicit what is monitoring and documenting patients’ prog- expected of patients in terms of their coopera- ress. Measures used to evaluate maintenance tion and involvement in addiction treatment. treatment with buprenorphine are similar to

64 Treatment Protocols those used for other areas of addiction Care: Dispelling the Myths & Designing treatment: Strategies (Gourlay et al. 2002). • No illicit opioid drug use occurs and no Methadone and heroin metabolites are each other ongoing drug use (including prob- detected by commercially available urine- lematic alcohol use) is found that might testing kits. Buprenorphine does not cross- compromise patient safety (e.g., ongoing react with the detection procedures for abuse of alcohol and/or benzodiazepines). methadone or other opioids; therefore, it will • Toxicity is absent. not be detected in a routine urine drug screen. Both physicians and patients should be aware • Medical adverse effects are absent. of this fact. • Behavioral adverse effects are absent. • Patient is handling the medication Buprenorphine and its metabolites are responsibly. excreted in urine. Urine testing for buprenorphine can be performed at a medical • Patient is adhering to all elements of the laboratory, but at the time of this document’s treatment plan (e.g., seeing a psychother- publication, there are no CLIA-waived, apist or attending groups as scheduled, in-office buprenorphine urine test kits participating in recovery-oriented commercially available. activities). There are two primary reasons to consider Unstable Patients testing for buprenorphine: (1) in new patients to confirm that they do not already have Given these evaluations, physicians need to buprenorphine in their system, (2) to assist decide when they cannot appropriately pro- with evaluating adherence in patients on bup- vide further management for particular renorphine treatment. (Refer to chapter 3 patients. For example, if a patient is abusing for additional information on drug-testing other drugs that a physician does not feel methodologies.) As new testing procedures competent to manage, or if toxicology tests are and protocols are recommended for use in still not free of illicit drugs after 8 weeks, then addiction treatment with buprenorphine, the physician may want to assess (1) whether SAMHSA will be making additional infor- to continue to treat that patient without mation available through the Division of additional evidence of ongoing counseling or Pharmacologic Therapies (DPT) Web site at (2) whether to refer the patient to specialists http://www.dpt.samhsa.gov/. or to a more intensive treatment environment. Decisions should be based on the treatment Discontinuation of plan to which the patient previously agreed. Medication Toxicology Testing for Drugs Under ideal conditions, discontinuation of of Abuse medication should occur when a patient has achieved the maximum benefit from treatment During opioid addiction treatment with bup- and no longer requires continued treatment to renorphine, toxicology tests for all relevant maintain a drug-free lifestyle. Once this goal is illicit drugs should be administered at least achieved, buprenorphine should be tapered monthly. Urine screening is the most common slowly and appropriately while psychosocial testing method, although testing can be per- services continue to be provided. Patients formed on a number of other bodily fluids should be assessed for continued stability in and tissues—including blood, saliva, sweat, maintaining their drug-free lifestyle. Patients and hair. A comprehensive discussion of urine should then be followed with psychosocial drug testing in the primary care setting can services and/or the reintroduction of be found in Urine Drug Testing in Primary medication, if needed, for continued progress.

Treatment Protocols 65 Certain situations undoubtedly will arise, this regard. In the event of involuntary ter- however, in which a physician may feel that a mination of treatment, it is necessary for patient is not progressing satisfactorily. For physicians to make appropriate referrals—to example, a patient may not be in compliance OTPs, to other physicians who are willing to with the treatment plan or with office pro- prescribe buprenorphine, or to other appro- cedures (e.g., timely payment). Under some priate treatment facilities. If a patient will not conditions, physicians may consider invol- be receiving OAT in another treatment setting, untary termination of treatment, but must be the physician must manage the appropriate careful to not abandon patients. Physicians withdrawal of buprenorphine so as to mini- can and should take a variety of actions to mize withdrawal discomfort. A patient may or prevent this situation. Physicians should have may not be willing to accept referrals made on written policies in place regarding patient his or her behalf, but physicians must make behavior, office procedures, and adherence to good faith efforts to ensure that their patients treatment. These policies should be discussed have an appropriate level of care available with patients before initiating buprenorphine treatment, and patients should agree to after their own therapeutic involvement is comply with these policies. ended. Physicians should develop practices for deal- For more information about treatment man- ing with minor infractions of rules or policies agement issues, see the forthcoming TIP and with minor nonadherence to treatment Medication-Assisted Treatment for Opioid plans. Clearly defined points should be identi- Addiction (CSAT in development). The fied at which patients will be notified that they treatment management principles addressed are not adhering to treatment plans, and they in that TIP will also be applicable to office- should be given the opportunity to improve in based buprenorphine treatment.

66 Treatment Protocols 5 Special Populations

Overview In This The presence of certain life circumstances or comorbid medical or Chapter… psychosocial conditions warrant special attention during the evaluation and treatment of opioid addiction with buprenorphine. Patients with circumstances or conditions that require special attention include those Patients With Medical with certain medical comorbidities (e.g., AIDS, tuberculosis), concur- Comorbidities rent mental disorders, or concurrent alcohol or other substance abuse disorders, as well as pregnant women, adolescents, geriatric patients, Pregnant Women patients under the jurisdiction of the criminal justice system, and and Neonates healthcare professionals who are addicted. Because of the unique issues presented by these circumstances, addiction treatment for these Adolescents/ patients may require additional training or specialty care and consul- Young Adults tation. Before treating individuals with these circumstances for opioid addiction in an office setting, physicians should consider whether Geriatric Patients patient needs can be met with the resources at hand or if referral to specialized treatment programs or to addiction specialists is indicated. Patients With Significant Psychiatric Comorbidity Patients With Medical Polysubstance Abuse Comorbidities Patients With Pain Patients addicted to opioids who present for treatment often have other comorbid medical problems. These conditions are often a Patients Recently consequence of high-risk behaviors, including injection drug use Discharged From (intravenous, intramuscular, or subcutaneous), or of the direct toxic Controlled Environments effects of the active and inert ingredients in illicit drugs. The prevalence of infectious diseases (e.g., HIV/AIDS, hepatitis B and C, tuber- Healthcare culosis, skin and soft tissue infections, syphilis and other sexually Professionals Who Are transmitted diseases [STDs]) is increased in these patients and should Addicted to Opioids be screened for, as outlined in chapter 3. Other comorbid conditions (e.g., seizure disorders, valvular heart disease secondary to endocarditis, pulmonary hypertension secondary to talc granulomatosis, lymphedema, pseudoaneurysms of the neck and groin secondary to

67 thrombophlebitis, and renal insufficiency effectiveness. Because the interactions of most secondary to heroin-associated nephropathy) medications with buprenorphine have not also are seen in this population and may been systematically studied, physicians should require special attention. Patients with a monitor for any signs or symptoms of opioid history of endocarditis need antibiotic pro- side effects, loss of effectiveness, or phylaxis before certain dental procedures. withdrawal after a patient starts any new Patients with a history of hepatitis C may medications. Buprenorphine dose adjustments require hepatitis A and B vaccinations and may be necessary after starting new may be intolerant of potentially hepatotoxic medications, even for patients who have been medications. One retrospective study found on a stable maintenance dose. that liver function tests were significantly elevated in patients treated with buprenor- Other potential, and as yet unknown, drug phine who also had a history of hepatitis, interactions include the possibility of bupre- suggesting that liver function tests should be norphine increasing or decreasing metabolism monitored in these patients on a regular basis of medications used in treating comorbid during buprenorphine treatment (Petry et al. medical conditions. Informing patients of 2000). A detailed discussion of medical comor- potential drug–drug interactions, especially bidities in addiction is beyond the scope of this sedation or precipitated opioid withdrawal, is chapter and is reviewed extensively elsewhere important to prevent jeopardizing adherence (Cherubin and Sapira 1993; Stein 1990). with medical treatment and/or precipitating relapse to illicit opioid use. Treatment of opioid addiction in patients with comorbid medical conditions is likely to result In summary, it is important to screen for and in better outcomes for the comorbid condi- manage common comorbid medical conditions tions than would be achieved in the absence of in patients being treated with buprenorphine treatment of the substance use disorder. for opioid addiction and to anticipate known Moatti et al. (2000) found that patients on and potential drug interactions. For addi- buprenorphine tended to be more compliant tional information on drug–drug interactions with highly active antiretroviral therapies with buprenorphine, refer to chapter 2. (HAART) than patients who were not treated concurrently for opioid addiction. Pregnant Women and Pharmacological treatments of comorbid Neonates medical disorders may have important drug interactions with buprenorphine due to The continued use of heroin during preg- shared pharmacokinetic properties. Although nancy, with its attendant risks of infection, Carrieri et al. (2000) found no detrimental overdose, and intrauterine withdrawal, is life short-term effect of buprenorphine treatment threatening to both the woman and the fetus. on the effect of HAART on viral load, Research on the safety and efficacy of bup- buprenorphine is metabolized by the hepatic renorphine in pregnant women and neonates cytochrome P450 3A4 enzyme system and will is scarce, however. If a patient is pregnant or likely interact with other medications is likely to become pregnant during the course metabolized by the same system. Certain of opioid addiction treatment, the physician antiretrovirals may occupy the cytochrome must consider whether buprenorphine is an P450 3A4 system and thus inhibit the appropriate option for treatment. Physicians metabolism of buprenorphine. Other drugs should weigh all the risks and benefits of that induce the cytochrome P450 3A4 system treatment with buprenorphine against all the (e.g., certain antituberculosis, anticonvulsant, risks associated with the continued use of and antiretroviral medications) may decrease illicit opioids. Methadone is currently the serum concentrations of buprenorphine, standard of care in the United States for the resulting in opioid withdrawal or decreased treatment of opioid addiction in pregnant

68 Special Populations women. Methadone has been shown to be safe review of the published literature on the use of and effective for both pregnant women and buprenorphine in the treatment of opioid neonates. addiction in pregnant women, see Johnson et al. 2003a. The FDA classifies buprenorphine as a Preg- nancy Category C drug. The FDA Pregnancy Labeling Task Force, whose long-term goal is Infants of Mothers Treated to determine how animal toxicologic infor- With Buprenorphine mation contributes to clinically meaningful information in pregnancy, assigns a human Buprenorphine and its metabolite norbup- prescription drug to Pregnancy Category C renorphine have been found in high concen- (1) if animal reproduction studies have shown trations in the blood, urine, and meconium of an adverse effect on the fetus, (2) if there are the neonates of women maintained on bupre- no adequate and well-controlled studies in norphine (Johnson et al. 2003a; Marquet humans, and (3) if the benefits from the use of et al. 1997). the drug in pregnant women may be accept- The published literature includes information able despite its potential risks. In addition to on at least 309 infants born to women main- considering the FDA warnings pertaining to tained on buprenorphine treatment. Although the use of buprenorphine in pregnant women, not systematically studied, a neonatal absti- physicians also must consider the risks of nence syndrome (NAS) has been reported in infectious diseases and lifestyle issues (e.g., 191 of these 309 infants, with approximately poor nutrition, lack of prenatal care) when one-half of those addressing the needs of these patients. with NAS requiring treat- Methadone is Effects of Buprenorphine in ment. In more than 40 percent of currently the Pregnancy the cases, however, evaluation of Data on the pharmacokinetics of buprenor- standard of care in phine in pregnant women and neonates are the abstinence extremely limited (Johnson et al. 2003a; syndrome was Marquet et al. 1997). Likewise, data are confounded by the United States for limited regarding the clinical use of bupre- other drug use by norphine for the maintenance treatment of the mothers. the treatment of opioid addiction in pregnant women. The Overall, although no randomized literature in this area generally consists of opioid addiction in controlled trials case reports and a small number of prospec- have been tive studies; there have been no controlled pregnant women. reported, the NAS clinical trials. In case reports from European associated with and Australian sources on the use of bupre- buprenorphine norphine in opioid-addicted pregnant women, has been reported to be less intense than that doses have ranged from 0.4 to 24 mg per day. observed with methadone. In these limited reports, pregnancies have generally progressed normally, with low rates One prospective open-label study (Fischer of prematurity or other problems. Maternal et al. 2000) found signs of NAS in 7 of clinical laboratory data in these reports 15 neonates exposed to buprenorphine in generally have been within normal limits; or utero. Of these 15 neonates, 3 had moderate were deemed either clinically nonsignificant signs of NAS that required treatment, 4 had at levels expected during pregnancy, when mild signs of NAS that required no treatment, outside normal limits, or were due to factors and 8 had no signs of NAS. A second prospec- other than the medication. For a complete tive open-label study (Johnson et al. 2003a)

Special Populations 69 reported NAS in 3 of 3 neonates; however, medications, it is the consensus of the panel none required treatment with medications. that any effects of these medications on the breastfed infant would be minimal and that NAS from buprenorphine generally appears breastfeeding is not contraindicated. How- within the first 2 days of life, peaks within ever, given the limited literature in this 3 or 4 days, and lasts for 5 to 7 days. Few subject area, physicians are advised to use infants were reported to have had a with- their professional judgment in their drawal syndrome for 6 to 10 weeks. recommendations. Similar to the treatment of NAS following exposure to methadone, several different The Buprenorphine/Naloxone medications (including chlorpromazine, phenobarbital, benzodiazepine, paregoric Combination in Pregnancy elixir, and morphine drops) have been used The panel notes that there is a question successfully to treat the NAS associated with whether the buprenorphine/naloxone combi- buprenorphine. The American Academy of nation is or is not recommended for use in Pediatrics recommends tincture of opium as pregnancy. Naloxone is labeled by FDA as a the medication of choice for treatment of Pregnancy Category B drug. The FDA Preg- neonatal opioid withdrawal symptoms nancy Labeling Task Force assigns a human (American Academy of Pediatrics Committee prescription drug to Pregnancy Category B on Drugs 1998). (1) if animal reproduction studies have failed to demonstrate a risk to the fetus and (2) if there are no adequate and well-controlled Breast Feeding While on studies in pregnant women. Despite the fact Buprenorphine Treatment that naloxone is classified as a Pregnancy The limited human pharmacokinetic data Category B drug, it should be used with show that buprenorphine passes into the caution in pregnant women who are addicted breast milk of lactating women at a plasma- to opioids. Because both mother and fetus will to-milk ratio of approximately 1. As a result, be dependent on the opioids used by the and because of the poor oral bioavailability mother, administration of naloxone could of buprenorphine, the nursing infant will be precipitate withdrawal in both. exposed to only 1/5–1/10 of the total amount If it is determined that buprenorphine is the of buprenorphine available. only acceptable option for the treatment of a The literature includes reports on approxi- pregnant woman, and she understands the mately 40 to 50 women who were maintained issues and risks, then she should be treated on buprenorphine and who breastfed after with buprenorphine monotherapy so as not to delivery (Johnson et al. 2003a; Lejeune et al. risk fetal exposure to naloxone. It should be 2001; Loustauneau et al. 2002; Marquet et al. noted that use of buprenorphine mono- 1997). These reports indicate that buprenor- therapy, because of its greater potential for phine present in breast milk does not appear abuse, necessitates more frequent monitoring to suppress NAS. Additionally, NAS has not of patients and of their medication supplies. been observed after the cessation of breast- To prevent abuse and diversion of the feeding by women who were maintained on buprenorphine monotherapy formulation, buprenorphine (Loustauneau et al. 2002). quantities of take-home supplies and quantities provided via prescription should be Although the Subutex® and Suboxone® smaller compared to treatment with the package inserts state that breastfeeding is buprenorphine/naloxone combination not advised in mothers treated with these formulation.

70 Special Populations Summary multiple relapses but who are not currently dependent on opioids. Buprenorphine may be Buprenorphine is classified by FDA as a preferred to methadone for the treatment of Pregnancy Category C drug. Data from opioid addiction in adolescents because of the controlled studies on the use of buprenor- relative ease of phine in pregnant women are needed. The withdrawal from available evidence does not show any causal buprenorphine Buprenorphine adverse effects on pregnancy or neonatal treatment. outcomes from buprenorphine treatment, but Because adoles- this evidence is from case series not from cents often present can be a useful controlled studies. Methadone is currently the with short standard of care in the United States for the histories of drug option for the treatment of heroin addiction in pregnant use, detoxification women. Pregnant women presenting for with buprenor- treatment of treatment of opioid addiction should be phine, followed referred to specialized services in methadone by drug-free or adolescents who have maintenance treatment programs. If such naltrexone treat- specialized services are refused by a patient ment, should be opioid addiction or are unavailable in the community, mainte- attempted first nance treatment with the buprenorphine before proceeding problems. monotherapy formulation may be considered to opioid mainte- as an alternative. In such circumstances, it nance. Naltrexone should be clearly documented in the medical may be a valuable record that the patient has refused methadone therapeutic adjunct after detoxification. maintenance treatment, or that such services Naltrexone has no abuse potential and may were unavailable; that she was informed of the help to prevent relapse by blocking the effects risks of using buprenorphine, a medication of opioids if the patient relapses to opioid use. that has not been thoroughly studied in Naltrexone has been a valuable therapeutic pregnancy; and that she understands those adjunct in some opioid-abusing populations, risks. particularly youth and other opioid users early in the course of addiction. Naltrexone is most likely to be effective for patients with Adolescents/Young strong support systems that include one or Adults more individuals willing to observe, supervise, or administer the naltrexone on a daily basis. The use of buprenorphine for the treatment of In those adolescent patients in whom detoxifi- opioid addiction in adolescents has not been cation is followed by relapse, buprenorphine systematically studied. It is known, however, maintenance may then be the appropriate that patients younger than 18 years of age, alternative. Refer to chapter 4 for bupre- with relatively short addiction histories, are norphine maintenance and detoxification at particularly high risk for serious compli- procedures. cations of addiction (e.g., overdose deaths, suicide, HIV, other infectious diseases). Many The treatment of patients younger than experts in the field of opioid addiction treat- 18 years of age can be complicated due to ment believe that buprenorphine should be psychosocial considerations, the involvement the treatment of choice for adolescent patients of family members, and State laws concerning with short addiction histories. Additionally, consent and reporting requirements for buprenorphine may be an appropriate treat- minors. Ancillary counseling and social serv- ment option for adolescent patients who have ices are important to support cooperation and histories of opioid abuse and addiction and follow through with the treatment regimen.

Special Populations 71 Parental Consent abuse treatment information to any third parties, including parents, without patient Parental consent is a critical issue for physi- consent. The sole exception allows a “program cians who treat adolescents addicted to director” (i.e., treating physician) to commun- opioids. In general, adult patients with icate “facts relevant to reducing a threat to “decisional capacity” have the unquestioned the life or physical well-being of the applicant right to decide which treatments they will or any other individual to the minor’s parent, accept or refuse, even if refusal might result in guardian, or other person authorized under death. The situation for adolescents is some- State law to act in the minor’s behalf,” when what different, however. Adolescents do not the program director believes that the adoles- have the legal status of adults unless they are cent, because of extreme youth or mental or legally “emancipated minors.” Adolescents’ physical condition, lacks the capacity to rights to consent to or to refuse medical decide rationally whether to consent to the treatment differ from those of adults. Rules notification of his or her parent or guardian differ from State to State regarding whether (42 C.F.R. Part 2, Subpart B, Section 2.14d an adolescent may obtain substance use 2001). The program director must believe the disorder treatment without parental consent. disclosure to a parent or guardian is necessary Some State statutes governing consent and to cope with a substantial threat to the life or parental notification specify consideration of a physical well-being of the adolescent applicant number of fact-based variables, including the or someone else. In some cases, communica- adolescent’s age and stage of cognitive, tion with State child protection agencies or emotional, and social development, as well as judicial authorities may be an acceptable issues concerning payment for treatment and alternative, or the required course of action, rules for emancipated minors. if the physician believes neglect or abuse has More than one-half of the States permit already occurred. individuals younger than 18 years of age to consent to substance use disorder treatment Treatment Setting without parental consent. In States that do require parental consent, providers may The more intensive a proposed treatment is, admit adolescents to treatment when parental the more risk a program assumes in admitting consent is obtained. In States requiring adolescents without parental consent. Out- parental notification, treatment may be patient programs may have a better justifi- provided to an adolescent when the adolescent cation for admitting adolescents without is willing to have the program communicate parental consent than do intensive outpatient with a parent. Histories of neglect or abuse or residential programs. may be revealed during the care of adolescent patients, and physicians must be aware of Summary reporting requirements in their State. Manda- tory child abuse reporting takes precedence Buprenorphine can be a useful option for the over Federal addiction treatment confiden- treatment of adolescents who have opioid tiality regulations, according to Title 42, addiction problems. The treatment of addic- Part 2 of the Code of Federal Relations tion in adolescents is complicated by a number (42 C.F.R. Part 2). of medical, legal, and ethical considerations, however. Physicians intending to treat addic- Additional difficulties may arise when adoles- tion in adolescents should be thoroughly cents requesting treatment refuse to permit familiar with the laws in their State regarding notification of a parent or guardian. With one parental consent. Physicians who do not very limited exception, the Federal confiden- specialize in the treatment of opioid addiction tiality regulations prohibit physicians (or their or adolescent medicine should strongly con- designees) from communicating substance sider consulting with, or referring adolescent

72 Special Populations addiction patients to, such specialists. Addi- psychiatric disorder (including personality tionally, State child protection agencies can be disorders) in their lifetimes, and 70.3 percent a valuable resource when determining the met criteria for a current psychiatric disorder. proper disposition for adolescent patients. It should be noted, however, that, although the rates of major depressive disorder, alcoholism, antisocial personality, minor mood disorders, Geriatric Patients and anxiety disorders in this group exceeded Literature on the use of buprenorphine in those found in the general population, the geriatric patients is extremely limited. Because rates of schizophrenia and mania did not. of potential differences in rates of metabolism Although the etiological significance of psy- and absorption compared to the nonelderly, chiatric disorders in the genesis of opioid care should be exercised in the use of bupre- addiction is not established, it is known that norphine in elderly individuals. Particular treatment for both care should be exercised during buprenor- conditions is phine induction both because of differences necessary for in body composition and because of the substance abuse Assessment is critical possibility of medication interactions. treatment to be effective. There- to determine whether Patients With fore, the presence and severity of psychiatric Significant Psychiatric comorbid psychiatric conditions symptoms represent Comorbidity must be assessed The association of psychopathology and opioid in patients who primary psychiatric addiction is well established. Psychiatric are opioid symptoms and disorders may be drug- addicted before, induced, independent, or interrelated. or while, initiating disorders or Substance use and addiction can mimic, buprenorphine exacerbate, or precipitate psychiatric symp- treatment, and a substance-induced toms and disorders. Most substances of abuse determination produce moderate-to-severe psychiatric must be made conditions. symptoms, and there is a complex association whether referral between substance use and psychiatric status. to specialized A study of rates of psychiatric disorders behavioral health among 716 patients addicted to opioids seek- services is indicated. ing treatment with methadone (Brooner et al. Untreated or inadequately treated psychiatric 1997), found a lifetime rate of 47 percent, and disorders can interfere with the effective a current rate of 39 percent. Of note, patients treatment of addiction. Polysubstance use in this study were stabilized in treatment for and psychiatric problems are both associated 1 month before the psychiatric evaluation. with negative treatment outcomes unless they Other, earlier studies have reported higher are identified and treated appropriately. For rates of depression, antisocial personality characteristics, schizophrenia or schizotypal example, patients with major depression or features, manic symptomatology, and alcohol- dysthymia are more likely to use illicit drugs ism in opioid-addicted patients. For example, during treatment than patients who do not in a study of 533 opioid-addicted patients in suffer from depression. Assessment is critical treatment for their drug problems, to determine whether psychiatric symptoms Rounsaville and colleagues (1982) found that represent primary psychiatric disorders or 86.9 percent met diagnostic criteria for some substance-induced conditions. Primary

Special Populations 73 psychiatric disorders may improve but do not the maintenance phase of buprenorphine dissipate with abstinence or maintenance treatment require continued assessment and therapies, and these disorders may require should be treated appropriately. additional treatment. The psychiatric disorders most commonly encountered in patients who are opioid addicted are other Polysubstance Abuse substance abuse disorders, depressive dis- The abuse of multiple drugs (polysubstance orders, posttraumatic stress disorder, abuse) among individuals addicted to opioids substance-induced psychiatric disorders, is common. Although polysubstance abuse or and antisocial and borderline personality dependence may be identified during assess- disorders. ment, physicians should remain alert to their presence throughout the course of addiction The presence of comorbid psychiatric dis- treatment. orders should not exclude patients from admission to opioid addiction treatment. Pharmacotherapy with buprenorphine for Diagnosis of psychiatric disorders is critical to opioid addiction will not necessarily have a matching patients to appropriate treatment beneficial effect on an individual’s use of other services. In first encounters with patients, it drugs. It is essential that patients be referred is essential to evaluate for the presence of for treatment of addiction to other types of suicidal or homicidal ideations, signs or drugs when indicated. In addition, care must symptoms of acute psychosis, and other acute be exercised in the prescribing of buprenor- or chronic psychiatric problems that may phine for patients who abuse alcohol and for render patients unstable. Initiation of anti- those who abuse sedative/hypnotic drugs depressant therapy, in conjunction with (especially benzodiazapines) because of the treatment for opioid addiction, may be con- documented potential for fatal interactions. sidered in patients presenting with signs or (See chapter 2 for further information.) symptoms of depression. If manic behavior is present, attempts should be made to determine whether it is substance induced or Patients With Pain whether the etiology is a primary mood disorder. Patients Being Treated for When psychiatric symptoms are severe or Pain Who Become Dependent unstable, hospitalization for protection and on Opioids containment may be appropriate to ensure the safety of the patient and others. Patients who Patients who need treatment for pain but not for addiction should be treated within the are considered actively suicidal should not context of their regular medical or surgical receive buprenorphine on an outpatient, setting. They should not be transferred to an prescription basis. Rather, they should be opioid maintenance treatment program simply referred immediately for appropriate treat- because they are being prescribed opioids and ment, which may include psychiatric hospital- have become physically dependent on the ization. Those who are not currently suicidal opioids in the course of their medical but who have a history of suicidal ideation or treatment. attempts should be monitored closely in terms of medication supply and followup. It can be difficult to distinguish between the legitimate desire to use opioids for pain relief Psychiatrically stable patients can be readily and the desire to procure them for purposes accepted into treatment and stabilized on of obtaining a high. This may be especially buprenorphine; subsequently they may true in patients who have become physically receive additional psychiatric assessment to dependent on opioids in the course of the identify conditions requiring treatment. treatment of a pain condition when that pain Patients who present with depression during has been undertreated and inadequately

74 Special Populations relieved. Figure 5–1 presents some distin- abusers may place prescribing physicians at guishing features in the use of opioids by risk for prosecution unless the medical record patients who are not addicted and who are clearly distinguishes between treatment of the using opioids for pain relief versus their use addiction and treatment of the pain condition. by patients who are addicted. Treatment Approach. Little clinical experience is documented regarding the treatment of Patients Who Are Addicted to pain in patients receiving buprenorphine. Opioids and Who Require Pain in patients receiving buprenorphine treatment initially should be treated with Treatment for Pain nonopioid analgesics when appropriate. Behaviors associated with drug abuse fre- Although buprenorphine itself has powerful quently result in the development of acute and analgesic properties, the once-daily adminis- chronic pain conditions. These conditions may tration of buprenorphine, as used for the be caused by the toxic effects of the drug treatment of opioid addiction, often does not itself, as well as by trauma and infection. provide sufficiently sustained relief of pain. Patients receiving addiction treatment also Additionally, the onset of action of analgesia may experience pain due to illness or injury with buprenorphine may not be adequate for unrelated to drug use. Physicians must the treatment of acute pain. In a study of the manage this pain efficiently and appropri- use of buprenorphine for acute analgesia ately. Opioids are among the most effective (Nikoda et al. 1998), the high analgesic available options for managing pain, but they activity of buprenorphine was comparable to are often not prescribed to patients receiving that of morphine, but the onset of action was treatment for addiction out of fear of “feeding found to be inadequate for urgent care. the addiction” or of triggering relapse in currently abstinent patients. State laws governing Patients maintained on buprenorphine whose the prescription of opioids to known substance acute pain is not relieved by nonopioid

Figure 5–1

Clinical Features Distinguishing Opioid Use in Patients With Pain Versus Patients Who Are Addicted to Opioids

Patients Patients Who Are Clinical Features With Pain Addicted to Opioids Compulsive drug use Rare Common Crave drug (when not in pain) Rare Common Obtain or purchase drugs from nonmedical sources Rare Common Procure drugs through illegal activities Absent Common Escalate opioid dose without medical instruction Rare Common Supplement with other opioid drugs Unusual Frequent Demand specific opioid agent Rare Common Can stop use when effective alternate treatments Usually Usually not are available Prefer specific routes of administration No Yes Can regulate use according to supply Yes No

Special Populations 75 medications should receive the usual aggres- buprenorphine and require end-of-life opioid sive pain management, which may include the analgesia, buprenorphine administration use of short-acting opioid pain relievers. should be discontinued, unless the While patients are taking opioid pain medica- buprenorphine provides adequate analgesia tions, the administration of buprenorphine or the patient prefers buprenorphine for some generally should be discontinued. Note that, other reason. until buprenorphine clears the body, it may be difficult to achieve analgesia with short-acting In patients who are opioid addicted and who opioids in patients have severe chronic pain, methadone several who have been times per day or other “round the clock” …it may be difficult maintained on (rather than as required) long-acting, full- buprenorphine, agonist medications may be the best alterna- to achieve analgesia and higher doses tive for treatment. This form of treatment is of short-acting often best undertaken in conjunction with an Opioid Treatment Program (OTP). However, with short-acting opioids may be required. Non- if the physician is (1) otherwise qualified to treat the condition causing the pain and opioids in patients combination opioid analgesics (2) careful to document that the primary are generally purpose of the opioid pharmacotherapy is the who have been preferred to avoid management of that pain condition, then it the risk of aceta- may be acceptable to treat that patient in the maintained on minophen or office setting without further referral. As long salycilate toxicity as this type of patient remains compliant and buprenorphine… when combination is not abusing the pain medication or other products are used drugs, there is no legal need for the patient to at the doses that be treated in an OTP or with buprenorphine are likely to be for the preexisting or concurrent addictive required for pain control in patients who have disorder. However, the Drug Enforcement been maintained on buprenorphine. Analgesic Administration (DEA) frowns on the use of dose requirements should be expected to this as a rationale to treat the “pain of with- decrease as buprenorphine clears the body. drawal” or spurious and ill-defined pain conditions to justify unsanctioned opioid When restarting buprenorphine administra- maintenance. Patients who are on chronic tion, physicians should refer to chapter 4 for opioids for pain management and who have a induction procedures. To prevent the precipi- history of drug abuse or addiction can be tation of withdrawal, buprenorphine should referred to a 12-Step program or other not be restarted until an appropriate period self-help group to help them maintain their after the last dose of the opioid analgesic, level of recovery. Random drug screening also depending on the half-life of the opioid can reassure the physician that both physician analgesic used. and patient are staying within lawful bounds.

Patients who are receiving opioids for chronic Because all pharmacological treatment with severe pain may not be good candidates for opioids is highly regulated, physicians who buprenorphine treatment because of the desire to use opioids to treat chronic pain in ceiling effect on buprenorphine’s analgesic patients who are at risk for opioid addiction properties. This rationale also would be or relapse are advised to consult with a col- applicable to terminally ill patients. In league knowledgeable in opioid maintenance patients who are maintained on pharmacology.

76 Special Populations Patients Recently because they are typically reincarcerated after failing parole or drug-testing Discharged From requirements. Controlled Environments Assessment of Patients Who Are Opioid Addicted This section focuses on the assessment and treatment of patients with opioid addiction and Who Are Recently who are recently released from controlled Released From Controlled environments (e.g., prison) and who would be Environments presumed to have involuntarily detoxified from opioids while incarcerated. Other Physicians should consider the following situations that may warrant special consider- factors when assessing for addiction in ation include (1) patients discharged from patients recently released from controlled extended hospital or rehabilitation center environments: length of incarceration; stays, (2) patients returning from extended postrelease addiction patterns and cycles; overseas travel/expatriate duty in countries addiction treatment history (drug-free, without easy access to licit or illicit opioids, outpatient, recovery, or therapeutic com- and (3) other conceivable situations that may munity); self-help involvement (before, have caused an involuntary break in active during, and since incarceration); and use of and addiction to opioids. reported triggers of illegal drug use and addiction upon release. Physicians should The findings on patient assessment will help to evaluate for the presence of comorbid mental clarify the diagnosis of opioid dependence/ health issues or history of other drug or addiction and whether a patient is at serious alcohol use that could complicate buprenor- risk for resumption of an addiction lifestyle if phine treatment. (See chapter 3 for further not treated with a buprenorphine mainte- information.) If office-based buprenorphine nance regimen. Other considerations for providers include possible psychosocial needs treatment is being considered, physicians and issues, as well as collateral contacts that should carefully assess the patient’s level of may be required when treating patients who commitment to treatment and the likelihood of may have continuing involvement with the self control. criminal justice system. Assessing Psychosocial Issues Opioid Addiction in Patients Attention to psychosocial issues is important Under the Jurisdictions of in patients who are coming out of controlled Criminal Justice Systems environments. Issues that often affect the success of addiction treatment include It is well documented that the crimes committed by most of the more than 1 million • Number and/or length of incarcerations individuals incarcerated in the United States • Types of crimes committed (e.g., violent are related to the abuse of or addiction to offenses, drug-related) drugs. Opioids are the preferred contraband • Gang affiliations drugs of choice in prisons and can be relatively easy to obtain in some institutions. • Type and length of parole or probation Prison environments and inmate culture (e.g., whether the patient will be given reinforce the addiction cycle and addiction regular or random drug testing) lifestyle. Recidivism rates are higher in • The patient’s collateral contacts and patients with a history of opioid addiction reporting requirements

Special Populations 77 • Prior and current involvement of the system, employers, and others. Physicians patient’s social support system (e.g., the should consider potential issues associated presence of opioid addiction problems or with detoxification in jail if a patient is current use in family members) reincarcerated. The cost of treatment needs to • Recent changes in familial or marital be considered, as well as whether the costs are relationships covered by a patient’s health insurance. Additionally, potential risk issues need to be • Whether permission from the criminal considered (e.g., diversion, overdose, criminal justice system is required for treatment with activity while in a limited, professional care buprenorphine setting, mixing with other patients). Physicians should ask the patient whether he or she has a reasonable plan for a stable lifestyle (e.g., involvement in job, school, family) Healthcare and whether the plan includes total abstinence Professionals Who Are from drug and alcohol use. If there is no plan, the physician should ask why not and offer to Addicted to Opioids help the patient create one. A substantial problem of addiction to prescription opioids exists among physicians Final determination of a patient’s appropri- and other health professionals, especially ateness for buprenorphine treatment will within certain specialties (e.g., anesthesiology) involve analysis of the subjective assessment (Talbott et al. 1987). Prescription opioid and disclosed information, as well as a review addiction in health professionals should be of medical records to determine treatment viewed as an occupational hazard of the compliance and cooperation. Physicians practice of medicine. Health professionals who should assess a patient’s psychosocial needs have substance abuse disorders often require and the compatibility of the patient with the specialized, extended care. potential limitations of an outpatient, office- based environment. If the addictive drug of choice is present in the workplace, reentry planning after initial treatment should consider relapse by the Determining Appropriateness health professional who is in early recovery. for Buprenorphine Treatment The opioid antagonist naltrexone and other adjunctive medications are often required. A number of issues should be considered in Naltrexone has been a routine adjunct for the determining the most appropriate treatment treatment of anesthesiologists who are modality for patients with addiction who are addicted to opioids. The key to successful recently released from controlled environ- naltrexone use by a highly motivated patient is ments. If a methadone clinic alternative is a strong social support system that includes a available, the physician should determine the significant other, coworker, or health factors that may preclude referral. The professional who directly observes the existing doctor/patient relationship should be naltrexone use on a regular basis. assessed, as well as eligibility for other assistance, and the presence of a solid support Buprenorphine may be an appropriate system. A physician’s limitations with regard treatment option for some health professionals to potentially intensive buprenorphine moni- who are opioid dependent, but the use of a toring activities should be considered, as a partial agonist would need to be part of a treating physician may be called on to comprehensive, monitored recovery plan. If determine, verify, and explain a treatment the professional has already come under regimen (e.g., to parole and probation regulatory scrutiny, such a plan might require officers); to document the patient’s approval by the State authority to which the compliance; and to interact with the legal professional reports.

78 Special Populations 6 Policies and Procedures

Overview In This This chapter discusses policies and procedures relating to the Drug Addiction Treatment Act of 2000 (DATA 2000), to preparations for Chapter… providing opioid addiction treatment in practices that are new to this form of care, to State and Federal laws and regulations that protect the The DATA 2000 Waiver privacy and confidentiality of addiction treatment information, and to the use of buprenorphine in federally regulated Opioid Treatment Preparing for Programs (OTPs). Physicians should become thoroughly familiar with Office-Based Opioid these issues before engaging in the practice of opioid addiction treat- Treatment ment (Brooks 1997). In addition, readers are referred to appendix F, which contains additional information about many of these topics. Confidentiality and Privacy The DATA 2000 Waiver Buprenorphine Use DATA 2000 enables qualifying physicians to receive a waiver from the in OTPs special registration requirements in the Narcotic Addict Treatment Act (NATA) of 1974 (and its enabling regulations, including Title 42, Part 8 of the Code of Federal Regulations, that govern OTPs) for the provision of opioid addiction treatment. This waiver allows qualifying physicians (see “Physician Waiver Qualifications”) to prescribe or dispense Schedule III, IV, and V “narcotic” medications for the treatment of opioid addiction in the office and other clinical settings if (and only if) those medications have been approved by the Food and Drug Admin- istration (FDA) for use in addiction treatment. As of this writing, Subutex® (buprenorphine) and Suboxone® (buprenorphine/naloxone) sublingual tablets are the only Schedule III, IV, or V pharmaceuticals to have received such FDA approval. NATA makes it illegal for narcotics to be used “off label” to treat opioid addiction. This prohibition extends even to other forms of buprenorphine (e.g., Buprenex®) that have not been specifically approved for the treatment of opioid addiction.

79 Notification of Intent Intent to SAMHSA but before receipt of a waiver and identification number. To provide To receive a DATA 2000 waiver to practice this “immediate-type” treatment, a physician opioid addiction treatment with approved must not only submit the usual Notification of Schedule III, IV, and V opioid medications, a Intent to SAMHSA but also must include physician must notify the Substance Abuse notification of intent to begin immediately and Mental Health Services Administration treating an individual patient. SAMHSA’s (SAMHSA) of his or her intent to begin dis- Notification of Intent form includes a check- pensing or prescribing this treatment. This box for indicating this immediate-type intent. Notification of Intent must be submitted to SAMHSA before the initial dispensing or prescribing of opioid treatment. Notification Physician Waiver of Intent forms can be obtained on the Qualifications SAMHSA Buprenorphine Web site at http://www.buprenorphine.samhsa.gov. To qualify for a waiver under DATA 2000, a Forms can be submitted to SAMHSA online or licensed physician (M.D. or D.O.) must meet printed out and then submitted via ground any one or more of the following criteria: mail or fax. • The physician holds a subspecialty board The Notification of Intent must contain certification in addiction psychiatry from information on the physician’s qualifying the American Board of Medical Specialties. credentials (as defined below) and additional • The physician holds an addiction certifica- certifications, including that the physician has tion from the American Society of Addiction the capacity to refer addiction patients for Medicine (ASAM). appropriate counseling and other nonpharm- • The physician holds a subspecialty board acological therapies, and that the physician certification in addiction medicine from the will not have more than 30 patients on such American Osteopathic Association (AOA). addiction treatment at any one time. (Note • The physician has, with respect to the that the 30-patient limit applies both to treatment and management of patients who physicians in solo practice and to entire group are opioid addicted, completed not less than practices, and the limit is not affected by the 8 hours of training (through classroom number of locations of practice of the physi- situations, seminars at professional society cians or groups.) meetings, electronic communications, or Physicians who meet the qualifications defined otherwise) that is provided by ASAM, the American Academy of Addiction Psychiatry, in DATA 2000 are issued a waiver by SAMHSA and a special identification number the American Medical Association, AOA, the American Psychiatric Association, or any by the Drug Enforcement Administration other organization that the Secretary of the (DEA). DEA has issued regulations that U.S. Department of Health and Human require physicians to include this identifi- Services (DHHS) determines is appropriate cation number on all records when dispensing for purposes of this subclause. and on all prescriptions when prescribing approved opioid medications (currently • The physician has participated as an investi- only Subutex® and Suboxone®) for opioid gator in one or more clinical trials leading to addiction. the approval of a narcotic drug in Schedule III, IV, or V for maintenance or detoxification treatment, as demonstrated by a state- Immediate-Type Notifications ment submitted to the DHHS Secretary by Under DATA 2000, a physician may initiate the sponsor of such approved drug. opioid addiction treatment for “an individual • The physician has such other training or patient” after submitting a Notification of experience as the State medical licensing

80 Policies and Procedures board (of the State in which the physician ensure the highest quality experience for will provide maintenance or detoxification patients, providers, and staff. Providers and treatment) considers to demonstrate the practice staff should have an appropriate level ability of the physician to treat and manage of training, experience, and comfort with this patients who are opioid addicted. new form of treatment. Linkages with other • The physician has such other training or medical and mental health professionals experience as the DHHS Secretary considers should be established to ensure the avail- as demonstrating the ability of the physician ability of comprehensive community-based to treat and manage opioid-dependent treatment services. patients. Any criteria of the DHHS Secretary under this subclause shall be Physician Training, established by regulation. Experience, and Comfort Level For More Information Physicians who intend to treat opioid addic- Proper training on the use of buprenorphine tion should seek to establish a level of comfort will be key to the successful introduction of and expertise with this form of care. A physi- this new treatment paradigm, regardless of the cian’s comfort level in providing treatment for clinical setting of buprenorphine treatment. addiction will vary Thus, SAMHSA and the consensus panel according to the strongly encourage all physicians who plan to physician and his Proper training on practice opioid addiction treatment with or her practice buprenorphine to participate in a DATA 2000- situation. For qualifying 8-hour training program on bup- the use of example, a renorphine. SAMHSA maintains a list of physician might upcoming DATA 2000-qualifying bupre- buprenorphine will be choose to refer a norphine training sessions on the SAMHSA Buprenorphine Web site at http:// patient with addic- key to the successful tion and depres- www.buprenorphine.samhsa.gov. These sion, depending on sessions include Web-based courses accessible introduction of this from the physician’s own computer. Detailed the severity of depression, information about the DATA 2000 paradigm new treatment and the physician waiver process also can be whether a psych- found on the SAMHSA Buprenorphine Web ologist or psychia- site. Additionally, information can be trist is available paradigm… obtained by contacting the SAMHSA Bup- in the area, and renorphine Information Center by phone at whether the 866-BUP-CSAT (866-287-2728) or by e-mail at patient can afford specialized mental health [email protected]. care, among other factors. Expertise in treating opioid addiction includes Preparing for knowledge of applicable practice standards or guidelines, familiarity with the evidence Office-Based Opioid supporting the recommended treatments, Treatment protocols for primary treatment or referral of patients with certain complicating conditions Prior to embarking on the provision of office- (e.g., severe depression), and knowledge of based addiction treatment services, medi- any applicable regulations or laws. Physicians cal practices that will be new to this type of must become knowledgeable about the most care should undertake certain preparations to up-to-date treatments for opioid addiction,

Policies and Procedures 81 including pharmacotherapy, psychosocial behavioral characteristics of addiction, and interventions, self-help and mutual-help the medical approach to addiction treatment. groups, and other appropriate treatments. Common behaviors and defense mechanisms Physicians who treat opioid-addicted patients of addicted patients should be anticipated. with buprenorphine should participate in Medication must be stored in a secure loca- addiction medicine training and professional tion, and the possibility of diversion must be activities and should learn from other pro- minimized. Office items (e.g., prescription fessionals in addiction treatment. Basic and pads, syringes, needles) and staff possessions ongoing training in addiction treatment will should be secured to minimize theft. greatly enhance a physician’s effectiveness in treating opioid addiction. Establishing Treatment Each patient presents with different and usually complex needs. Physicians who treat Linkages patients with opioid addiction in the office- Establishing linkages with other medical based setting must consider and plan for the professionals is essential. Because patients full range of their patients’ needs before addicted to opioids commonly have coexisting initiating treatment. Candidates for buprenor- medical and psychiatric conditions, most phine treatment of opioid addiction should be physicians will need to establish linkages with assessed for a broad array of biopsychosocial other medical and mental health specialists, needs in addition to opioid use and addiction, particularly those specializing in the evalua- and should be treated and/or referred for help tion and treatment of common comorbid in meeting those needs. conditions (e.g., hepatitis B and C, HIV, tuberculosis, mood disorders, anxiety disorders, personality disorders, risk of suicide Establishing Office and homicide). Physical examinations and Procedures laboratory evaluations will need to be completed either onsite or offsite from the office Before undertaking the provision of office- of the physician who provides office-based based buprenorphine treatment, physicians buprenorphine treatment. should make arrangements to provide comprehensive care and contingency plans for An up-to-date listing of community referral resources (e.g., therapy groups, support patients who may not be appropriate can- groups, residential therapeutic communities, didates for this treatment. In addition, physi- sober-living options) should be given to cians should arrange for other physicians with patients. Referral resource lists are available DATA 2000 waivers to be available to provide from the substance abuse agencies of some care to the treating physician’s opioid addic- local and State governments. To maximize tion patients in the treating physician’s followthrough with referrals, it is most helpful absence (e.g., while on vacation). if the physician has firsthand knowledge of these groups and programs. When referrals Office policies and procedures for opioid are made, compliance will increase if staff call addiction treatment should be established, to make appointments in the presence of written, and clearly communicated to staff patients. When making referrals to support members and patients. Staff members groups, it is helpful to have an individual in should be trained and educated about opioid the group who is willing to accompany the addiction, addiction treatment, patient patient to his or her first meeting. Referrals to confidentiality (see “Confidentiality and social workers and case managers are often Privacy” section below), medication treat- beneficial in helping patients address legal, ments, nonpharmacological treatments, employment, and family issues.

82 Policies and Procedures Summary protected by SAMHSA confidentiality regulation Title 42, Part 2 of the Code of Federal Figure 6–1 summarizes the policies, proced- Regulations (42 C.F.R. Part 2). This regu- ures, and items that should be established or lation mandates that addiction treatment arranged for in a medical practice prior to initiating office-based opioid addiction information in the possession of substance treatment. abuse treatment providers be handled with a greater degree of confidentiality than general medical information. Confidentiality and Occasionally, physicians will need to com- Privacy municate with pharmacists and other healthcare providers about the addiction Prior to initiating office-based opioid addic- treatment of a particular patient (e.g., to tion treatment, practice policies and proced- verify a Suboxone® or Subutex® pre- ures should be established that will guarantee scription). Regulation 42 C.F.R. Part 2 the privacy and confidentiality of addiction requires physicians providing opioid treatment patients. Providers must comply addiction treatment to obtain signed patient with all applicable laws and regulations regarding the privacy and confidentiality of consent before disclosing individually identifiable addiction treatment information to medical records in general, and of information pertaining to addiction treatment services in any third party. A sample consent form with particular. all the elements required by 42 C.F.R. Part 2 is included as appendix D. It is The privacy and confidentiality of individ- recommended that physicians have each new ually identifiable information relating to buprenorphine patient sign a copy of this patients receiving drug or alcohol treatment is form to prevent confidentiality problems at

Figure 6–1 Policies, Procedures, and Items for Medical Practices To Establish Prior to Initiating Office-Based Opioid Addiction Treatment

• Office policies and procedures for • A referral network of psychologists and buprenorphine treatment psychiatrists with expertise in addictions, affective disorders, and chronic pain • Staff education and training • Linkages with addiction and psychiatric • Backup coverage for the practice treatment programs • Assurance of the privacy and confidentiality • Listing of community referral resources, of addiction treatment information including specific self-help groups who would • Linkages with qualified colleagues who will welcome buprenorphine patients (e.g., Self accept new referrals for buprenorphine Management and Recovery Training [SMART] treatment Recovery, Moderation Management) • A referral network of medical specialists • Online/Internet listings of self-help groups • Timely physical examinations (e.g., SMART Recovery, Moderation • Linkages with medical treatment facilities, Management) that are accepting of individuals including opioid treatment programs in recovery who are using medications as a part of that recovery

Policies and Procedures 83 pharmacies when patients present with Between the Confidentiality of Alcohol and buprenorphine prescriptions. It is partic- Substance Abuse Patient Records (42 C.F.R. ularly important to obtain patient consent Part 2) and the Health Insurance Portability when telephoning or faxing prescriptions to and Accountability Act 1996. This document pharmacies, as this information constitutes and a number of other HIPAA technical disclosure of the patient’s addiction treat- assistance tools are available on the SAMHSA ment. When physicians directly transmit HIPAA Web pages at http:// prescriptions to pharmacies, further redis- www.hipaa.samhsa.gov/. See also the closure of patient-identifying information by SAMHSA Treatment Assistance Publication (TAP) 13 Confidentiality of Patient Records the pharmacy is prohibited, unless signed for Alcohol and Other Drug Treatment patient consent is obtained by the pharmacy. (Lopez 1994), available on the SAMHSA Regulation 42 C.F.R. Part 2 does not apply to Treatment Improvement Exchange Web site at pharmacies, however, when the patient http://www.treatment.org/taps/index.html. delivers a buprenorphine prescription with- Additionally, the Subutex® and Suboxone® out telephone confirmation or other direct package labels (available on the FDA Web site communication from a physician to the at http://www.fda.gov/cder/drug/infopage/ pharmacist. subutex_suboxone/default.htm) also contain information on Federal confidentiality rules The Health Insurance Portability and and regulations. Physicians should also Accountability Act (HIPAA) of 1996, Public consult with their State medical authorities Law 104-191 (see http://aspe.hhs.gov/ concerning privacy and confidentiality rules admnsimp/pl104191.htm), which amends the in their locales. Figure 6–2 lists some of the Internal Revenue Service Code of 1986, privacy and confidentiality issues that can mandates standardization of exchange formats arise in the course of addiction treatment. for patient health, administrative, and financial data; requires development of unique identifiers for individuals, employers, health Buprenorphine Use in plans, and healthcare providers; and estab- OTPs lishes security standards for protecting the confidentiality and integrity of individually On May 22, 2003, SAMHSA announced an identifiable health information. SAMHSA has interim final rule permitting OTPs serving prepared a document titled Comparison individuals addicted to opioids to offer

Figure 6–2 Privacy and Confidentiality Issues in Addiction Treatment

• Information covered by the doctor/patient privilege • Circumstances in which confidential information is protected from disclosure • Exceptions to State laws protecting medical information • Duty to report • Communications with third parties (e.g., families, employers, allied healthcare providers, third-party payers, law-enforcement officers, responses to subpoenas)

84 Policies and Procedures buprenorphine treatment along with OTPs providing Subutex® and Suboxone® for methadone and levo-alpha-acetyl-methadol opioid maintenance or detoxification (LAAM). The rule enables OTPs that are treatment must conform to the Federal certified by SAMHSA to provide Subutex® opioid treatment standards set forth under and Suboxone® for opioid maintenance or 42 C.F.R. § 8.12. These regulations require detoxification treatment. that OTPs provide medical, counseling, drug abuse testing, and other services to patients The provision of opioid addiction treatment ® ® ® admitted to treatment. To offer Subutex with Subutex and Suboxone in SAMHSA- ® certified OTPs does not require a DATA and Suboxone , OTPs need to modify their 2000 waiver. Additionally, such treatment is registration with the DEA to add Schedule III not subject to the 30-patient limit that narcotics to their registration certificates. applies to individual physicians and group OTPs can initiate this streamlined process by practices providing opioid addiction fax or letter. The letter should include the treatment outside the OTP system under OTP’s DEA registration number and request the authority of a DATA 2000 waiver. The that the registration be amended to list provision of opioid addiction treatment with Schedule III narcotic drugs. The letter must Subutex® or Suboxone® in treatment settings be signed by the program sponsor (program other than OTPs, even by physicians who director) or medical director. Further infor- are licensed to work in OTPs, does require a mation about this process can be found on the DATA 2000 waiver and is subject to the DEA Drug Registration Web site at http:// 30-patient limit for individual physicians and www.deadiversion.usdoj.gov/drugreg/ group practices. change_requests/sched_change.htm.

Policies and Procedures 85 86 Appendix A Bibliography

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Amass, L.; Bickel, W.K.; Higgins, S.T.; and Badger, G.J. Alternate- day dosing during buprenorphine treatment of opioid dependence. Life Sciences 54(17):1215–1228, 1994a.

Amass, L.; Bickel, W.K.; Higgins, S.T.; and Hughes, J.R. A preliminary investigation of outcome following gradual or rapid buprenorphine detoxification. Journal of Addictive Diseases 13(3):33–45, 1994b.

Amass, L.; Kamien, J.B.; and Mikulich, S.K. Efficacy of daily and alternate-day dosing regimens with the combination buprenorphine-naloxone tablet. Drug and Alcohol Dependence 58(1–2):143–152, 2000.

Amass, L.; Kamien, J.B.; and Mikulich, S.K. Thrice-weekly supervised dosing with the combination buprenorphine-naloxone tablet is preferred to daily supervised dosing by opioid-dependent humans. Drug and Alcohol Dependence 61(2):173–181, 2001. American Academy of Pediatrics Committee on Drugs. Neonatal drug withdrawal. Pediatrics. 1998 Jun;101(6):1079–1088. Erratum in: Pediatrics 102(3 Pt 1):660; 1998. http://www.aap.org/policy/ re9746.html [Accessed June 9, 2004].

American Psychiatric Association (APA). Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision (DSM-IV-TR). Washington, DC, American Psychiatric Association, 2000.

Angres, D.H.; Talbott, G.D.; and Bettinardi-Angres, K. Healing the Healer: The Addicted Physician. Madison, CT: Psychosocial Press, 1998.

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Bibliography 99 100 Appendix B Assessment and Screening Instruments

Several of the following drug and alcohol assessment and screening instruments are available online at: http://www.niaaa.nih.gov/ publications/publications.htm.

General • Addiction Severity Index (ASI) (McLellan et al. 1980) (http:// www.tresearch.org and http://www.niaaa.nih.gov/publications/ asi.htm) • Substance Use Disorders Diagnostic Schedule (SUDDS-IV) (Hoffmann and Harrison 2002) (http://www.evinceassessment.com/ product_sudds.html) Readiness to Change See appendix G.

Screening Instruments

Drug Abuse Screening Test (DAST-10), Drug Use Questionnaire The following questions concern information about your possible involvement with drugs not including alcoholic beverages during the past 12 months. Carefully read each statement and decide if your answer is “Yes” or “No.” Then circle the appropriate response beside the question.

101 In the following statements “drug abuse” (e.g., Valium), barbiturates, cocaine, refers to stimulants (e.g., speed), hallucinogens (e.g., lysergic acid diethylamide [LSD]), or • The use of prescribed or over-the-counter narcotics (e.g., heroin). Remember that the drugs in excess of the directions, and questions do not include alcoholic • Any nonmedical use of drugs. beverages. • The various classes of drugs may include Please answer every question. If you have cannabis (e.g., marijuana, hashish), difficulty with a question, then choose the solvents (e.g., paint thinner), tranquilizers response that is mostly right.

These Questions Refer to the Past 12 Months

1. Have you used drugs other than those required for medical reasons? Yes No 2. Do you abuse more than one drug at a time? Yes No 3. Are you always able to stop using drugs when you want to? Yes No 4. Have you ever had blackouts or flashbacks as a result of drug use? Yes No 5. Do you ever feel bad or guilty about your drug use? Yes No 6. Does your spouse (or parents) ever complain about your involvement Yes No with drugs? 7. Have you neglected your family because of your use of drugs? Yes No 8. Have you engaged in illegal activities in order to obtain drugs? Yes No 9. Have you ever experienced withdrawal symptoms (felt sick) when you Yes No stopped taking drugs? 10. Have you had medical problems as a result of your drug use (e.g., Yes No memory loss, hepatitis, convulsions, bleeding)?

Interpretation (Each “Yes” response = 1)

Degree of Problems Score 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

Source: Adapted from Addictive Behaviors, 7(4), Skinner, H.A. The drug abuse screening test, 363–371, copyright 1982, with permission from Elsevier. Available online at http://www.drugabuse.gov/Diagnosis-Treatment/DAST10.html.

102 Assessment and Screening Instruments Skinner Trauma History

Since your 18th birthday, have you

Had any fractures or dislocations to your bones or joints? Been injured in a road traffic accident? Injured your head? Been injured in an assault or fight (excluding injuries during sports)? Been injured after drinking?

A score of two or more positive responses to the five questions has been shown to indicate a high probability of excessive drinking or alcohol abuse.

Source: Skinner et al. 1984, reprinted with permission from American College of Physicians–American Society of Internal Medicine (ACP–ASIM).

CAGE Questionnaire

Have you ever felt you ought to Cut down on your drinking? Have people Annoyed you by criticizing your drinking? Have you ever felt bad or Guilty about your drinking? Have you ever had a drink first thing in the morning to steady your nerves or get rid of a hangover (Eye-opener)?

One or more “yes” responses constitute a positive screening test. Note, however, that due to language barriers, individual interpretation of the questions, or other con- founding factors, individuals answering “no” to all CAGE questions may still be at risk due to elevated drinking levels.

Source: Maisto et al. 2003.

CAGE-AID: The CAGE Questions Adapted To Include Drugs

Have you felt you ought to Cut down on your drinking or drug use? Have people Annoyed you by criticizing your drinking or drug use? Have you felt bad or Guilty about your drinking or drug use? Have you ever had a drink or used drugs first thing in the morning to steady your nerves or to get rid of a hangover (Eye-opener)?

One or more “yes” responses constitute a positive screening test. Note, however, that due to language barriers, individual interpretation of the questions, or other con- founding factors, individuals answering “no” to all CAGE-AID questions may still be at risk due to elevated drinking or drug use levels.

Source: Brown and Rounds 1995.

Assessment and Screening Instruments 103 The TWEAK Questionnaire

Tolerance: (a) How many drinks can you hold, or (b) How many drinks does it take before you begin to feel the first effects of the alcohol?

Worried: Have close friends or relatives worried or complained about your drinking in the past year?

Eye openers: Do you sometimes take a drink in the morning when you first get up?

Amnesia: Has a friend or family member ever told you about things you said or did while you were drinking that you could not remember?

Kut down: Do you sometimes feel the need to cut down on your drinking?

The TWEAK questionnaire was originally developed to screen for risk drinking during pregnancy (Russell et al. 1991). It can also be used to screen for harmful drinking in the general population (Chan et al. 1993).

Scoring: A 7-point scale is used to score the test. The Tolerance question scores 2 points if (a) the patient reports he or she can hold more than five drinks without falling asleep or passing out, or (b) if it is reported that three or more drinks are needed to feel high. A positive response to the Worry question scores 2 points. A positive response to the last three questions scores 1 point each.

A total score of 3 or 4 usually indicates harmful drinking. In an obstetric patient, a total score of 2 or more indicates the likelihood of harmful drinking.

Source: The National Institute on Alcohol Abuse and Addiction Web site at http://www.niaaa.nih.gov/publications/tweak.htm

104 Assessment and Screening Instruments The Alcohol Use Disorders Identification Test (AUDIT): Interview Version

1. How often do you have a drink* containing alcohol? [ ] Never (0) [Skip to Questions 9–10] [ ] Monthly or less (1) [ ] 2 to 4 times a month (2) [ ] 2 to 3 times a week (3) [ ] 4 or more times a week (4)

2. How many drinks containing alcohol do you have on a typical day when you are drinking? [ ] 1 or 2 (0) [ ] 3 or 4 (1) [ ] 5 or 6 (2) [ ] 7, 8, or 9 (3) [ ] 10 or more (4)

3. How often do you have six or more drinks on one occasion? [ ] Never (0) [ ] Less than monthly (1) [ ] Monthly (2) [ ] Weekly (3) [ ] Daily or almost daily (4)

[Skip to Questions 9 and 10 if Total Score for Questions 2 and 3 = 0]

4. How often during the last year have you found that you were unable to stop drinking once you had started? [ ] Never (0) [ ] Less than monthly (1) [ ] Monthly (2) [ ] Weekly (3) [ ] Daily or almost daily (4) 5. How often during the last year have you failed to do what was normally expected of you because of drinking? [ ] Never (0) [ ] Less than monthly (1) [ ] Monthly (2) [ ] Weekly (3) [ ] Daily or almost daily (4)

6. How often during the last year have you needed a first drink in the morning to get yourself going after a heavy drinking session? [ ] Never (0) [ ] Less than monthly (1) [ ] Monthly (2) [ ] Weekly (3) [ ] Daily or almost daily (4)

Assessment and Screening Instruments 105 7. How often during the last year have you had a feeling of guilt or remorse after drinking? [ ] Never (0) [ ] Less than monthly (1) [ ] Monthly (2) [ ] Weekly (3) [ ] Daily or almost daily (4)

8. How often during the last year have you been unable to remember what happened the night before because you had been drinking? [ ] Never (0) [ ] Less than monthly (1) [ ] Monthly (2) [ ] Weekly (3) [ ] Daily or almost daily (4)

9. Have you or someone else been injured as the result of your drinking? [ ] No (0) [ ] Yes, but not in the last year (1) [ ] Yes, during the last year (2)

10. Has a relative, friend, or a doctor or other health worker been concerned about your drinking or suggested you cut down? [ ] No (0) [ ] Yes, but not in the last year (1) [ ] Yes, in the last year (2)

Record the total of the specific items. [ ]

*In determining the response categories it has been assumed that one drink contains 10 g alcohol. In countries where the alcohol content of a standard drink differs by more than 25 percent from 10 g, the response category should be modified accordingly.

Source: Babor et al. 2001. Available at http://whqlibdoc.who.int/hq/2001/ WHO_MSD_MSB_01.6a.pdf

A self-report version of the AUDIT is also available in Babor et al. 2001. Scoring and Interpretation of the AUDIT

The minimum score (for nondrinkers) is 0 and the maximum possible score is 40. A score of 8 is indicative of hazardous and harmful alcohol use, and possibly of alcohol dependence. Scores of 8–15 indicate a medium level and scores of 16 and above a high level of alcohol problems. Babor et al. (2001) recommend a cutoff score of 7 for women and individuals over 65 years of age; Bradley et al. (1998) recommended an even lower cutoff score of 4 points for women. For patients who are resistant, uncooperative, or noncommunicative, a clinical screening procedure (described by Babor et al. 2001) may be necessary.

106 Assessment and Screening Instruments Michigan Alcoholism Screening Test (MAST)

0. Do you enjoy a drink now and then? YES NO (2) 1. *Do you feel you are a normal drinker? (By normal we mean you drink YES NO less than or as much as most other people) (2) 2. Have you ever awakened the morning after some drinking the night before YES NO and found that you could not remember a part of the evening? (1) 3. Does your wife, husband, a parent, or other near relative ever worry or YES NO complain about your drinking? (2) 4. *Can you stop drinking without a struggle after one or two drinks? YES NO (1) 5. Do you ever feel guilty about your drinking? YES NO (2) 6. *Do friends or relatives think you are a normal drinker? YES NO (2) 7. *Are you able to stop drinking when you want to? YES NO (5) 8. Have you ever attended a meeting of Alcoholics Anonymous (AA)? YES NO (1) 9. Have you gotten into physical fights when drinking? YES NO (2) 10. Has your drinking ever created problems between you and your wife, YES NO husband, a parent, or other relative? (2) 11. Has your wife, husband (or other family member) ever gone to anyone for YES NO help about your drinking? (2) 12. Have you ever lost friends because of your drinking? YES NO (2) 13. Have you ever gotten into trouble at work or school because of drinking? YES NO (2) 14. Have you ever lost a job because of drinking? YES NO (2) 15. Have you ever neglected your obligations, your family, or your work for YES NO two or more days in a row because you were drinking? (1) 16. Do you drink before noon fairly often? YES NO (2) 17. Have you ever been told you have liver trouble? Cirrhosis? YES NO (2) 18. **After heavy drinking have you ever had delirium tremens (DTs) or YES NO severe shaking or heard voices or seen things that really weren’t there? (5) 19. Have you ever gone to anyone for help about your drinking? YES NO (5) 20. Have you ever been in a hospital because of drinking? YES NO (2) 21. Have you ever been a patient in a psychiatric hospital or on a psychiatric YES NO ward of a general hospital where drinking was part of the problem that resulted in hospitalization? (2) 22. Have you ever been seen at a psychiatric or mental health clinic or gone to YES NO any doctor, social worker, or clergyman for help with any emotional problem where drinking was part of the problem? (2) 23. ***Have you ever been arrested for drunk driving, driving while YES NO intoxicated, or driving under the influence of alcoholic beverages? If YES, how many times? ______(2) 24. Have you ever been arrested, or taken into custody, even for a few hours, YES NO because of other drunk behavior? If YES, how many times?______

* Alcoholic response is negative ** 5 points for each DT *** 2 points for each arrest MAST Scoring System

In general, five points or more would place the subject in alcoholic category. Four points would be suggestive of alcoholism, and three points or fewer would indicate the subject is not alcoholic (Selzer 1971).

Source: American Journal of Psychiatry, 127, 1653–1658 (1971). Copyright (1971). The American Psychiatric Association, http://ajp.psychiatryonline.org. Reprinted by permission. See http:// www.niaaa.nih.gov/publications/mast.htm.

Assessment and Screening Instruments 107 Self-Administered Short Michigan Alcoholism Screening Test (SMAST)

Patient Name:

Date of Birth:

Date of Administration:

1. Do you feel you are a normal drinker? (By normal we mean you drink less YES NO than or as much as most other people.) 2. Does your wife, husband, a parent, or other near relative ever worry or YES NO complain about your drinking? 3. Do you ever feel guilty about your drinking? YES NO 4. Do friends or relatives think you are a normal drinker? YES NO 5. Are you able to stop drinking when you want to? YES NO 6. Have you ever attended a meeting of Alcoholics Anonymous? YES NO 7. Has drinking ever created problems between you and your wife, husband, a YES NO parent, or other near relative? 8. Have you ever gotten into trouble at work or school because of drinking? YES NO 9. Have you ever neglected your obligations, your family, or your work for two YES NO or more days in a row because you were drinking? 10. Have you ever gone to anyone for help about your drinking? YES NO 11. Have you ever been in a hospital because of drinking? YES NO 12. Have you ever been arrested for drunken driving, driving while intoxicated, YES NO or driving under the influence of alcoholic beverages? 13. Have you ever been arrested, even for a few hours, because of other YES NO drunken behavior?

Source: Adapted from Selzer et al. 1975. Reprinted with permission from the Journal of Studies on Alcohol. SMAST Scoring System

Each of the 13 items on the Short MAST is scored 1 (one) or 0 (zero), with questions 1, 4, and 5 scored 1 for each “no” answer, and the other items scored 1 for each “yes” answer. A score of 2 indicates possible alcoholism; a score of 3 or greater indicates probable alcoholism.

108 Assessment and Screening Instruments Withdrawal Assessments

Narcotic Withdrawal Scale Fultz and Senay (1975); (Table 1 page 816) used a grading scheme for hospitalized patients undergoing opiate withdrawal to determine initial methadone therapy as follows:

Grade Physical Findings Initial Dose of Methadone

1 Lacrimation and/or rhinorrhea 5 mg Diaphoresis Yawning Restlessness Insomnia

2 Dilated pupils 10 mg Piloerection Muscle twitching and/or myalgia Arthralgias Abdominal pain

3 Tachycardia 15 mg Hypertension Tachypnea Fever Anorexia or nausea Extreme restlessness

4 Diarrhea and/or vomiting 20 mg Dehydration Hyperglycemia Hypotension Curled-up position

Source: Fultz and Senay 1975, reprinted with permission from American College of Physicians–American Society of Internal Medicine (ACP–ASIM).

Assessment and Screening Instruments 109 The Clinical Institute Narcotic Assessment (CINA) Scale for Withdrawal Symptoms The Clinical Institute Narcotic Assessment (CINA) Scale measures 11 signs and symptoms commonly seen in patients during narcotic withdrawal. This can help to gauge the severity of the symptoms and to monitor changes in the clinical status over time.

PARAMETERS FINDINGS POINTS Parameters based on Questions and Observation: (1) abdominal changes: No abdominal complaints; normal bowel sounds 0 Do you have any pains Reports waves of crampy abdominal pain 1 in your abdomen? Crampy abdominal pain; diarrhea; active bowel sounds 2 (2) changes in temperature: None reported 0 Do you feel hot or cold? Reports feeling cold; hands cold and clammy to touch 1 Uncontrolled shivering 2 (3) nausea and vomiting: No nausea or vomiting 0 Do you feel sick in your Mild nausea; no retching or vomiting 2 stomach? Intermittent nausea with dry heaves 4 Have you vomited? Constant nausea; frequent dry heaves and/or vomiting 6 (4) muscle aches: No muscle aching reported; arm and neck muscles soft at rest 0 Do you have any muscle Mild muscle pains 1 cramps? Reports severe muscle pains; muscles in legs arms or neck in 3 constant state of contraction Parameters based on Observation Alone: (5) goose flesh None visible 0 Occasional goose flesh but not elicited by touch; not permanent 1 Prominent goose flesh in waves and elicited by touch 2 Constant goose flesh over face and arms 3 (6) nasal congestion No nasal congestion or sniffling 0 Frequent sniffling 1 Constant sniffling watery discharge 2 (7) restlessness Normal activity 0 Somewhat more than normal activity; moves legs up and down; 1 shifts position occasionally Moderately fidgety and restless; shifting position frequently 2 Gross movement most of the time or constantly thrashes about 3 (8) tremor None 0 Not visible but can be felt fingertip to fingertip 1 Moderate with patient’s arm extended 2 Severe even if arms not extended 3 (9) lacrimation None 0 Eyes watering; tears at corners of eyes 1 Profuse tearing from eyes over face 2 (10) sweating No sweat visible 0 Barely perceptible sweating; palms moist 1 Beads of sweat obvious on forehead 2 Drenching sweats over face and chest 3 (11) yawning None 0 Frequent yawning 1 Constant uncontrolled yawning 2 TOTAL SCORE [Sum of points for all 11 parameters]

Minimum score=0, Maximum score=31. The higher the score, the more severe the withdrawal syndrome. Percent of maximal withdrawal symptoms=((total score)/31) x 100%. Source: Adapted from Peachey, J.E., and Lei, H. Assessment of opioid dependence with naloxone. British Journal of Addiction 83(2):193–201, 1988. Reprinted with permission from Blackwell Publishing, Ltd.

110 Assessment and Screening Instruments Clinical Opiate Withdrawal Scale (COWS) For each item, circle the number that best describes the patient’s signs or symptoms. Rate just on the apparent relationship to opiate withdrawal. For example, if heart rate is increased because the patient was jogging just prior to assessment, the increased pulse rate would not add to the score.

Patient Name: Date: Time: Reason for this assessment: 1. Resting pulse rate: ______beats/minute 7. GI upset: over last half hour Measured after the patient is sitting or lying for one minute. 0 No GI symptoms 0 Pulse rate 80 or below 1 Stomach cramps 1 Pulse rate 81–100 2 Nausea or loose stool 2 Pulse rate 101–120 3 Vomiting or diarrhea 4 Pulse rate greater than 120 5 Multiple episodes of diarrhea or vomiting

2. Sweating: over past half hour not accounted for by 8. Tremor: observation of outstretched room temperature of patient activity hands 0 No reports of chills or flushing 0 No tremor 1 Subjective reports of chills or flushing 1 Tremor can be felt, but not observed 2 Flushed or observable moisture on face 2 Slight tremor observable 3 Beads of sweat on brow or face 4 Gross tremor or muscle twitching 4 Sweat streaming off face

3. Restlessness: observation during assessment 9. Yawning: observation during assessment 0 Able to sit still 0 No yawning 1 Reports difficulty sitting still, but is able to do so 1 Yawning once or twice during assessment 3 Frequent shifting or extraneous movements of legs/arms 2 Yawning three or more times during assessment 5 Unable to sit still for more than a few seconds 4 Yawning several times/minute

4. Pupil size 10. Anxiety or irritability 0 Pupils pinned or normal size for room light 0 None 1 Pupils possibly larger than normal for room light 1 Patient reports increasing irritability or anxiousness 2 Pupils moderately dilated 2 Patient obviously irritable, anxious 5 Pupils so dilated that only the rim of the iris is visible 4 Patient so irritable or anxious that participation in the assessment is difficult

5. Bone or joint aches: if patient was having pain 11. Gooseflesh skin previously, only the additional component attributed to opiate withdrawal is scored. 0 Not present 0 Skin is smooth 1 Mild diffuse discomfort 3 Piloerection of skin can be felt or hairs 2 Patient reports severe diffuse aching of joints/muscles standing up on arms 4 Patient is rubbing joints or muscles and is unable to sit 5 Prominent piloerection still because of discomfort

6. Runny nose or tearing: not accounted for by cold Total Score: symptoms or allergies [The total score is the sum of all 11 items.] 0 Not present Initials of person completing assessment: 1 Nasal stuffiness or unusually moist eyes 2 Nose running or tearing 4 Nose constantly running or tears streaming down cheeks

Score: 5–12=Mild; 13–24=Moderate; 25–36=Moderately severe; >36=Severe withdrawal Source: Adapted from Wesson et al. 1999. Reprinted with permission.

Assessment and Screening Instruments 111 Subjective Opiate Withdrawal Scale (SOWS) Instructions: Answer the following statements as accurately as you can. Circle the answer that best fits the way you feel now. 0=not at all 1=a little 2=moderately 3=quite a bit 4=extremely

Not at all A little Moderately Quite a bit Extremely 1 I feel anxious. 0 1 2 3 4 2 I feel like yawning. 0 1 2 3 4 3 I’m perspiring. 0 1 2 3 4 4 My eyes are tearing. 0 1 2 3 4 5 My nose is running. 0 1 2 3 4 6 I have goose flesh. 0 1 2 3 4 7 I am shaking. 0 1 2 3 4 8 I have hot flashes. 0 1 2 3 4 9 I have cold flashes. 0 1 2 3 4 10 My bones and muscles ache. 0 1 2 3 4 11 I feel restless. 0 1 2 3 4 12 I feel nauseous. 0 1 2 3 4 13 I feel like vomiting. 0 1 2 3 4 14 My muscles twitch. 0 1 2 3 4 15 I have cramps in my stomach. 0 1 2 3 4 16 I feel like shooting up now. 0 1 2 3 4

The Subjective Opiate Withdrawal Scale (SOWS) consist of 16 symptoms rated in intensity by patients on a 5-point scale of intensity as follows: 0=not at all, 1=a little, 2=moderately, 3=quite a bit, 4=extremely. The total score is a sum of item ratings, and ranges from 0 to 64.

Source: Reprinted from Handelsman et al. 1987, p. 296, by courtesy of Marcel Dekker, Inc.

Other Sources: Gossop 1990; Bradley 1987.

112 Assessment and Screening Instruments Addiction Research Foundation Clinical Institute for Withdrawal Assessment (CIWA-Ar)

Patient: Date: Time: (24 hour clock, midnight = 00:00) NAUSEA AND VOMITING—Ask “Do you feel sick to TACTILE DISTURBANCES—Ask “Have you any itching, your stomach? Have you vomited?” pins and needles sensations, any burning, any numbness, or do Observation. you feel bugs crawling on or under your skin?” 0 no nausea and no vomiting Observation. 1 mild nausea with no vomiting 0 none 2 1 mild itching, pins and needles, burning or numbness 3 2 very mild itching, pins and needles, burning or numbness 4 intermittent nausea with dry heaves 3 moderate itching, pins and needles, burning or numbness 5 4 moderately severe hallucinations 6 5 severe hallucinations 7 constant nausea, frequent dry heaves and 6 extremely severe hallucinations vomiting 7 continuous hallucinations TREMOR—Arms extended and fingers spread apart. AUDITORY DISTURBANCES—Ask “Are you more aware of Observation. sounds around you? Are they harsh? Do they frighten you? 0 no tremor Are you hearing anything that is disturbing to you? Are you 1 not visible, but can be felt fingertip to fingertip hearing things you know are not there?” 2 Observation. 3 0 not present 4 moderate, with patient’s arms extended 1 very mild harshness or ability to frighten 5 2 mild harshness or ability to frighten 6 3 moderate harshness or ability to frighten 7 severe, even with arms not extended 4 moderately severe hallucinations 5 severe hallucinations 6 extremely severe hallucinations 7 continuous hallucinations PAROSYSMAL SWEATS—Observation. VISUAL DISTURBANCES—Ask “Does the light appear to be 0 no sweat visible too bright? Is its color different? Does it hurt your eyes? Are 1 barely perceptible sweating, palms moist you seeing anything that is disturbing to you? Are you seeing 2 things you know are not there?” 3 Observation. 4 beads of sweat obvious on forehead 0 not present 5 1 very mild sensitivity 6 2 mild sensitivity 7 drenching sweats 3 moderate sensitivity 4 moderately severe hallucinations 5 severe hallucinations 6 extremely severe hallucinations 7 continuous hallucinations ANXIETY—Ask “Do you feel nervous?” HEADACHE, FULLNESS IN HEAD—Ask “Does your head Observation. feel different? Does it feel like there is a band around your 0 no anxiety, at ease head?” Do not rate for dizziness or lightheadedness. Otherwise, 1 mildly anxious rate severity. 2 0 not present 3 1 very mild 4 moderately anxious, or guarded, so anxiety is 2 mild inferred 3 moderate 5 4 moderately severe 6 5 severe 7 equivalent to acute panic states as seen in severe 6 very severe delirium or acute schizophrenic reactions. 7 extremely severe AGITATION—Observation. ORIENTATION AND CLOUDING OF SENSORIUM—Ask 0 normal activity “What day is this? Where are you? Who am I?” 1 somewhat more than normal activity 0 oriented and can do serial additions 2 1 cannot do serial additions or is uncertain about date 3 2 disoriented for date by no more than 2 calendar days 4 moderately fidgety and restless 3 disoriented for date by more than 2 calendar days 5 4 disoriented for place and/or person 6 7 paces back and forth during most of the interview, or constantly thrashes about Total CIWAr-Score Rater’s Initials Maximum Possible Score 67 This scale is not copyrighted and can be reproduced freely. Source: Sullivan et al. 1989.

Assessment and Screening Instruments 113 114 Appendix C DSM-IV-TR Material

Criteria for Substance Dependence A maladaptive pattern of substance use, leading to clinically significant impairment or distress, as manifested by three (or more) of the following, occurring at any time in the same 12-month period (emphasis ours): (1) Tolerance, as defined by either of the following: a. A need for markedly increased amounts of the substance to achieve intoxication or desired effect or b. Markedly diminished effect with continued use of the same amount of the substance (2) Withdrawal, as manifested by either of the following: a. The characteristic withdrawal syndrome for the substance or b. The same (or a closely related) substance is taken to relieve or avoid withdrawal symptoms (3) The substance is often taken in larger amounts or over a longer period than was intended (4) There is a persistent desire or unsuccessful efforts to cut down or control substance use (5) A great deal of time is spent on activities necessary to obtain the substance (e.g., visiting multiple doctors or driving long distances), use the substance (e.g., chain-smoking), or recover from its effects (6) Important social, occupational, or recreational activities are given up or reduced because of substance use (7) The substance use is continued despite knowledge of having a persistent physical or psychological problem that is likely to have been caused or exacerbated by the substance (e.g., current cocaine use despite recognition of cocaine-induced depression, or continued drinking despite recognition that an ulcer was made worse by alcohol consumption)

115 Specify if: Two additional specifiers have been provided: On Agonist Therapy and In a Controlled With Physiological Dependence: Evidence of Environment. For an individual to qualify for tolerance or withdrawal (i.e., either Item 1 or Early Remission after cessation of agonist 2 is present) therapy or release from a controlled envi- Without Physiological Dependence: No ronment, there must be a 1-month period in evidence of tolerance or withdrawal (i.e., which none of the criteria for Dependence of neither Item 1 nor 2 is present) Abuse are met. The following Remission specifiers can be Substance Dependence applied only after no criteria for Dependence or Abuse have been met for at least 1 month. Course Specifiers Note that these specifiers do no apply if the Six course specifiers are available for Sub- individual is on agonist therapy or in a con- stance Dependence. The four Remission trolled environment (see below). specifiers can be applied only after none of the criteria for Substance Dependence or Sub- Early Full Remission: This specifier is used stance Abuse have been present for at least if, for at least 1 month, but for less than 1 month. The definition of these four types of 12 months, no criteria for Dependence or Remission is based on the interval of time that Abuse have been met. has elapsed since the cessation of Dependence Early Partial Remission: This specifier is (Early versus Sustained Remission) and used if, for at least 1 month, but less than whether there is continued presence of one or 12 months, one or more criteria for Depen- more of the items included in the criteria sets dence or Abuse have been met (but the full for Dependence or Abuse (Partial versus Full criteria for Dependence have not been met). Remission). Because the first 12 months following Dependence is a time of particularly Sustained Full Remission: This specifier is high risk for relapse, this period is designated used if none of the criteria for Dependence or Early Remission. After 12 months of early Abuse have been met at any time during a Remission have passed without relapse to period of 12 months or longer. Dependence, the person enters into Sustained Remission. For both Early Remission and Sustained Partial Remission: This specifier is Sustained Remission, a further designation of used if full criteria for Dependence have not Full is given if no criteria for Dependence or been met for a period of 12 months or longer; Abuse have been met during the period of however, one or more criteria for Dependence remission; a designation of Partial is given if or Abuse have been met. at least one of the criteria for Dependence or On Agonist Therapy: This specifier is used if Abuse has been met, intermittently or con- the individual is on a prescribed agonist tinuously, during the period of remission. The medication, and no criteria for Dependence or differentiation of Sustained Full Remission Abuse have been met for that class of medica- from recovered (no current Substance Abuse tion for at least the past month (except toler- Disorder) requires consideration of the length ance to, or withdrawal from, the agonist). of time since the last period of disturbance, This category also applies to those being the total duration of the disturbance, and the treated for Dependence using a partial agonist need for continued evaluation. If, after a or an agonist/antagonist. period of remission or recovery, the individual again becomes dependent, the application of In a Controlled Environment: This specifier the Early Remission specifier requires that is used if the individual is in an environment there again be at least 1 month in which no where access to alcohol and controlled sub- criteria for Dependence or Abuse are met. stances is restricted, and no criteria for

116 DSM-IV-TR Material Dependence or Abuse have been met for at with spouse about consequence of intoxica- least the past month. Examples of these tion, physical fights) environments are closely supervised and The symptoms have never been met the substance-free jails, therapeutic communities, criteria for Substance Dependence for this or locked hospital units. class of substance.

Criteria for Substance Opioid Dependence Abuse Refer, in addition, to the text and criteria for Substance Dependence. Most individuals with A maladaptive pattern of substance use Opioid Dependence have significant levels of leading to clinically significant impairment or tolerance and will experience withdrawal on distress, as manifested by one (or more) of abrupt discontinuation of opioid substances. the following, occurring within a 12-month Opioid Dependence includes signs and symp- period: toms that reflect compulsive, prolonged self- administration of opioid substances that are • Recurrent substance use resulting in a used for no legitimate medical purpose or, if a failure to fulfil major role obligations at general medical condition is present that work, school, or home (e.g., repeated requires opioid treatment, that are used in absences or poor work performance related doses that are greatly in excess of the amount to substance use; substance-related needed for pain relief. Persons with Opioid absences, suspensions, or expulsions from Dependence tend to develop such regular school; neglect of children or household patterns of compulsive drug use that daily • Recurrent substance use in situations in activities are typically planned around which it is physically hazardous (e.g., obtaining and administering opioids. Opioids driving an automobile or operating a are usually purchased on the illegal market machine when impaired by substance use) but may also be obtained from physicians by • Recurrent substance-related legal problems faking or exaggerating general medical prob- (e.g., arrests for substance-related dis- lems, or by receiving simultaneous prescrip- orderly conduct) tions from several physicians. Health care professionals with Opioid Dependence will • Continued substance use despite having often obtain opioids by writing prescriptions persistent or recurrent social or inter- for themselves or by diverting opioids that personal problems caused or exacerbated by have been prescribed for patients or from the effects of the substance (e.g., arguments pharmacy supplies.

DSM-IV-TR Material 117 Other DSM-IV Substance-Related Disorders ICD-9-CM 292.82 Persisting Dementia 292.83 Persisting Amnestic Disorder 292.11 Psychotic Disorder with Delusions 292.12 Psychotic Disorder with Hallucinations 292.84 Mood Disorder 292.89 Anxiety Disorder 292.89 Sleep Disorder 292.89 Sexual Dysfunction 292.89 Persisting Perception Disorder (Flashbacks) 292.9 Disorder Not Otherwise Specified

Substance Related Disorders 305.01 Alcohol abuse, continuous 305.02 Alcohol abuse, episodic 305.03 Alcohol abuse, remission 305.00 Alcohol abuse, unspec. 303.00 Alcohol intoxication, acute, unspec. 291.81 Alcohol withdrawal 303.91 Alcoholism, chronic, continuous 304.41 Amphetamine dependence, continuous 304.11 Barbiturate dependence, continuous 305.22 Cannabis abuse, episodic 304.31 Cannabis dependence, continuous 305.62 Cocaine abuse, episodic 304.21 Cocaine dependence, continuous 305.90 Drug abuse, unspec. 305.92 Drug abuse, unspec., episodic 304.90 Drug dependence, unspec. 292.11 Drug-induced paranoia 305.52 Opioid abuse, episodic 304.01 Opioid dependence, continuous 305.1 Tobacco abuse

118 DSM-IV-TR Material Appendix D Consent to Release of Information Under Title 42, Part 2, Code of Federal Regulations

The privacy and confidentiality of individually identifiable drug or alcohol treatment information is protected by SAMHSA confidentiality regulation Title 42, Part 2 of the Code of Federal Regulations (42 C.F.R. Part 2). This regulation requires that physicians providing opioid addiction treatment obtain signed patient consent before disclosing individually identifiable addiction treatment information to any third party. On the next page is a sample consent form containing all the data elements required by 42 C.F.R. Part 2.

119 1. I (name of patient)

2. Authorize: Dr.

3. To disclose: (kind and amount of information to be disclosed) Any information needed to confirm the validity of my prescription and for submission for payment for the prescription.

4. To: (name or title of the individual or organization to which disclosure is to be made) The dispensing pharmacy to which I present my prescription or to which my prescription is called/sent/faxed, as well as to third party payors.

5. For (purpose of the disclosure) Assuring the pharmacy of the validity of the prescription, so it can be legally dispensed, and for payment purposes.

6. Date (on which this consent is signed)

7. Signature of patient

8. Signature of parent or guardian (where required)

9. Signature of individual authorized to sign in lieu of the patient (where required)

10. This consent is subject to revocation at any time except to the extent that the program which is to make the disclosure has already taken action in reliance on it. If not previously revoked, this consent will terminate on: (specific date, event, or condition)

Termination of treatment.

(c) Expired, deficient, or false consent. A disclosure may not be made on the basis of a consent which: (1) Has expired; (2) on its face substantially fails to conform to any of the requirements set forth in paragraph (a) of this section; (3) is known to have been revoked; or (4) is known, or through a reasonable effort could be known, by the individual holding the records to be materially false. (Approved by the Office of Management and Budget under control number 0930-0099.)

Notice to accompany disclosure:

Each disclosure made with the patient’s written consent must be accompanied by the following written statement: This information has been disclosed to you from records protected by Federal confidentiality rules (Title 42, Part 2, Code of Federal Regulations [42 C.F.R. Part 2]). The Federal rules prohibit you from making any further disclosure of this information unless further disclosure is expressly permitted by the written consent of the individual to whom it pertains or as otherwise permitted by 42 C.F.R. Part 2. A general authorization for the release of medical or other information is NOT sufficient for this purpose.

120 Consent to Release of Information Appendix E Clinical Toolbox: Chapter 3 Supplemental Information

Motivational Interviewing and Motivational Enhancement Therapy A number of engagement and motivation strategies have been employed successfully in opioid addiction therapy. This section discusses briefly one such approach: motivational interviewing and motivational enhancement therapy (MET).

MET assumes that a patient is responsible for and capable of changing his or her behavior, and the MET therapist focuses on helping a patient mobilize his or her own inner resources. The basic motivational principles utilized in MET are expression of empathy, the development of discrepancy, avoiding argumentation, rolling with resistance, and supporting self-efficacy. Motivation for change is developed by eliciting self-motivational statements, listening with empathy, questioning, presenting personal feedback, affirming the patient, handling resistance, and reframing.

MET is a specific application of motivational interviewing that was developed for use in the treatment of alcohol abuse. In this brief, two- to four-session treatment approach, counselors first guide patients through an examination of the pros and cons of their drug use and of the difference between where they are and where they want to be, in an attempt to lead them to state their desire to change—the first step in recovery. Counselors then strengthen patients’ commitment to change by helping them to identify their goals for recovery and to determine ways to reach these goals. Motivational interviewing can be used as a

121 stand-alone counseling approach, but more about the first use of all drugs: age at first use, often it is used as a first step in the recovery drugs used, description of the experiences and process and is followed by other interventions. the situations, amounts used, feelings, com- It can also be incorporated into subsequent plications, and results. “How old were you treatment sessions to bolster patients’ motiva- when you first tried alcohol or any other tion as needed. drugs? Describe the experience to me.”

Additional information about motivational Ask about all psychoactive substances: interviewing and MET can be found on the alcohol, amphetamines, caffeine, cannabis, Motivational Interviewing Page at http:// cocaine, hallucinogens, inhalants, nicotine, www.motivationalinterview.org and in Center opioids, phencyclidine (PCP), sedatives, for Substance Abuse Treatment (CSAT) TIP hypnotics, anxiolytics, and others. What 35: Enhancing Motivation for Change in substances has the patient ever used? When Substance Use Disorder Treatment (CSAT were each of these first used? What were the 1999b). (See http://www.kap.samhsa.gov/ effects? What has happened over time? Focus products/manuals/index.htm.) on opioid use, progression of problems, and recent symptoms in patients being considered FRAMES for buprenorphine treatment. Brief interventions by physicians or allied health professionals can be effective measures Effects of the Drugs Over in opioid addiction therapy. Effective brief Time interventions should include the following six Explore the pattern of use of each substance. elements: feedback, responsibility, advice, What has been the evolution and progression menu of strategies, empathy, and self-efficacy of use over time? Determine the frequency of (Miller and Sanchez 1994). These elements are use, amount of drugs used, route(s) used, commonly referred to using the acronym progression of symptoms, and social context(s) FRAMES, and are further described in of use. Has the patient attempted to cut down figure E–1. Additional information about brief or control use; taken greater amounts of drugs interventions is found in CSAT TIP 34 Brief or over a longer period than intended; spent Intervention and Brief Therapies for Sub- much time using, obtaining drugs, or recover- stance Abuse (CSAT 1999a). (See http:// ing from use? Has the patient had blackouts, www.kap.samhsa.gov/products/manuals/ shakes, withdrawal symptoms, compulsivity index.htm.) of use, and/or craving? Has he or she injected drugs; reduced or abandoned important Details of Taking a activities as a consequence of use; and/or continued to use despite problems or Comprehensive Patient consequences? If so, give examples.

History in Opioid When did regular opioid use begin? Does the Addiction Assessment patient have to use to feel “normal”? Describe periods of heaviest use. Explore in detail the pattern of use during the weeks prior to History of Drug Use evaluation, including the amount and time of What substances have been used over time? last use. When did he or she last consume Begin with the first psychoactive substance alcohol or ingest or inject drugs? What was used (licit or illicit, prescribed or nonpre- used? How much? What were the effects of the scribed), including nicotine and caffeine. Ask last drugs used?

122 Clinical Toolbox Figure E–1 FRAMES: Elements of Brief Interventions

• FEEDBACK of personal risk or impairment. Most successful brief interventions provide clients with some form of feedback of the results of their assessment of alcohol and other drugs. • Emphasis on personal RESPONSIBILITY for change. Many brief interventions advise patients that drinking is their own responsibility and choice. The implicit or explicit message is that “What you do about your drinking is up to you.” Perceived control has been recognized as an element of motivation for behavior change and maintenance (Miller 1985). • Clear ADVICE to change. Effective brief interventions contain explicit verbal or written advice to reduce or stop drinking. In fact, advice has been described as the essence of the brief intervention (Edwards et al. 1977). • A MENU of alternative change options. Effective brief interventions seldom advise a single approach, but rather a general goal or a range of options. Presumably, this broad approach increases the likelihood that an individual will find an approach appropriate to his or her situation. • Therapeutic EMPATHY as a counseling style. Successful interventions have emphasized a warm, reflective, empathic, and understanding approach. No reports of effective brief counseling contain aggressive, authoritarian, or coercive elements. • Enhancement of client SELF-EFFICACY or optimism. It is common in brief interventions to encourage self-efficacy for change, rather than emphasizing helplessness or powerlessness. Optimism regarding the possibility of change is often embedded in effective motivational counseling. • Ongoing followup. In addition to these six elements, effective use of brief intervention often includes repeated followup visits. At least two studies have found that a reduction in drinking occurs after the first followup visit (Elvy et al. 1988; Heather et al. 1987). However, even without the benefit of repeated followup, studies consistently document the occurrence of marked behavior change immediately following the brief intervention. Source: Adapted from Miller and Sanchez 1994.

Tolerance, Intoxication, and • Has tolerance developed to any drugs of Withdrawal abuse? How has tolerance manifested in this patient? Has any decrease in tolerance For each drug ever used, explore tolerance, occurred? Quantify tolerance by the amount intoxication, and withdrawal syndromes. used and/or the cost of drugs needed to Especially focus on opioid-related syndromes. achieve effects. Tolerance is the need for markedly increased • What is the most of each substance the amounts of the substance to achieve intoxica- patient can consume in a 24-hour period tion or desired effect, or markedly diminished effect with continued use of the same amount now? What is the most ever consumed in a of the substance. 24-hour period?

Clinical Toolbox 123 Intoxication and Overdose What treatment was received for these past complications, and what was the treatment • Explore symptoms of intoxication for each response? drug used. • Intoxication. What was the patient’s age at Relapse or Attempts at first intoxication? What drug(s) were involved in that intoxication? How have Abstinence intoxication episodes progressed over time? • Has the patient had a persistent desire or Describe recent intoxication episodes. made unsuccessful efforts to cut down or • For opioids, has the patient experienced control substance use? How many times has drowsiness (“nodding out”), slurred speech, the patient attempted to become abstinent? impaired memory or attention, respiratory How was the patient able to achieve absti- depression, and/or coma? nence? Quantify the longest time completely • Overdose. Have there been any episodes of abstinent from all psychoactive drugs. What intentional or nonintentional overdose with was going on during the time of abstinence? any drug or drug combinations? What To what does the patient attribute his or her symptoms did the individual have? What abstinence? treatments were received? How did the • What is the patient’s relapse history? What episodes resolve? happened to end any abstinent periods? What triggered or preceded relapses? What Withdrawal drug(s) did the patient use when relapsing? What pattern of use developed after the • Withdrawal is the characteristic withdrawal relapses? How did the patient’s use patterns syndrome for the substance. The same (or a change over time with each relapse? Are closely related) substance may be taken to there any life circumstances that would give relieve or avoid withdrawal symptoms. (The clues to events precipitating either relapse signs and symptoms of opioid withdrawal or abstinence? are shown in figure 3–7.) • Has the patient ever been abstinent from all • Describe withdrawal symptoms or syn- psychoactive drugs for an extended period dromes the patient has ever experienced. of time? When and for how long? What has What is the pattern of withdrawal been the longest time free of opioids in the symptoms? What relieves the symptoms past year, the past 5 years, and lifetime? (e.g., more of the drug and/or a cross- What has been the longest time free of all tolerant drug)? Describe the characteristics psychoactive substances in the past year, the of withdrawal episodes over time. past 5 years, and lifetime? Has the patient • What signs of opioid withdrawal occurred switched from one addicting substance to after discontinuation of use (e.g., another over time? dysphoria, nausea or vomiting, aching muscles, tearing, rhinorrhea, dilated pupils, Treatment History—Addiction piloerection, sweating, diarrhea, yawning, fever, and insomnia)? Treatment History • What treatments for withdrawal or its • What previous diagnoses—addiction, complications have been received in the psychiatric, and medical—have been given past? to this patient? • Withdrawal complications. Is there any • Describe all past attempts at detoxification. history of withdrawal complications (e.g., How many times has detoxification been seizures—from withdrawal with sedative- tried? Was detoxification medically super- hypnotics or intoxication with stimulants or vised? If so, how long were the detoxification opioids, delirium tremens, hallucinations)? treatments? What were the complications of

124 Clinical Toolbox detoxification? What were the outcomes? to describe his or her involvement in those How long after detoxification did the patient programs. How many meetings were start using opioids again? Why? attended? Did he or she ever get a sponsor • If the patient has ever been treated for and work the steps? Does he or she have a addiction: current sponsor? How frequent is meeting attendance now? – How many times has he or she received treatment? How long was each treatment? • Has the patient been involved in support groups other than 12-Step? If so, which – What level(s) of care were received ones? Ask the patient to describe the sup- (detoxification, inpatient, residential, port groups and the level of his or her outpatient, sober-living environment, activities and involvement. opioid maintenance therapy)? What treatments were received (group, individual, or family psychotherapy; relapse Psychiatric History prevention; pharmacotherapy; educa- • Review of symptoms: What psychiatric tion; cognitive-behavioral therapy; symptoms has the patient ever experienced? motivational enhancement therapy; Ask about depression, anxiety, irritability, others)? Was the focus of the treatment agitation, delusions, hallucinations, mood on psychiatric symptoms or addiction swings, suicidal thoughts or attempts, problems, or did the individual receive homicidal thoughts or attempts, sleep integrated addiction and psychiatric disturbance, appetite or energy disturb- treatment services? How long was each ance, memory loss, dissociation, etc. What treatment? Did the patient complete the current psychiatric complaints or symptoms recommended treatments? If not, why does the patient have? Are they related to not? current drug use or inability to stop using? – Has the patient received pharmaco- • Were psychiatric symptoms present before, therapy for addiction? What previous during, and/or after substance use? What treatment was received (e.g., brief effects did abstinence from other drugs and medical detoxification, opioid mainte- alcohol and/or compliance with maintenance nance therapy, disulfiram, naltrexone, or treatment have on psychiatric symptoms? other medication therapy)? Has previous Has the patient ever had a substance- treatment been medical therapy alone or induced psychotic disorder, mood disorder, medical therapy in combination with anxiety disorder, persisting perceptual comprehensive treatment interventions? disorder, persisting amnestic disorder, – Was the patient compliant with previous persisting dementia, or sexual dysfunction? drug and alcohol treatment, including • Has the patient ever had contact with prior opioid treatment programs? Did he psychiatrists or psychologists? What were or she use drugs and alcohol while in previous psychiatric diagnoses? What treatment? How long did she remain medications were provided? completely abstinent from all nonpre- • Has the patient ever been in psychotherapy? scribed psychoactive drugs after each If so, what kind and for how long? Has he or treatment? Which treatment was the most she ever been hospitalized for psychiatric successful? Which one was least suc- treatment? If so, what precipitated cessful? What factors contributed to the hospitalization? success or failure of treatments? • What psychotropic medications have been • Has the patient had contact with Alcoholics prescribed and what was the response to Anonymous (AA), Narcotics Anonymous each? List current psychotropic medica- (NA), Cocaine Anonymous (CA), or other tions, prescribers of each medication, and 12-Step recovery programs? Ask the patient the patient’s clinical response.

Clinical Toolbox 125 • Were other treatments recommended? Was ulcers, pancreatitis, hepatomegaly, hepati- the patient compliant? What has helped the tis, or cirrhosis; pulmonary edema, chronic most? cough, pneumonia, lung abscess, chronic • What stressors and traumas have occurred obstructive pulmonary disease; renal throughout life? Was the patient ever failure, renal calculi; sexual dysfunction; physically, emotionally, and/or sexually anemia, thrombocytopenia, neutropenia, abused, or traumatized in other ways? If so, lymphocytosis, or other blood disorders; lymphadenopathy; aseptic necrosis; at what age and under what circumstances? osteoporosis; cellulitis, septic arthritis, Has the patient ever discussed such trauma osteomyelitis; brain, epidural, or subdural with a treatment provider or received abscess; fungal meningitis; other infections; treatment for these problems? headaches, seizures, stroke, neuropathy, or other neurologic problems; physical trauma, Family History accidents, and hospitalizations; any other • Which biological relatives have a history of medical complications of addiction. See addiction, alcoholism, “drinking problems,” figure 3–11 for a listing of selected medical “drug problems” (including prescription disorders related to drug and alcohol use. drug addiction), cirrhosis or other associ- • For any female patient, is it possible that ated medical problems, depression, anxiety, she is pregnant? When was her last men- sleep problems, attempted or completed strual period? Is she sexually active with suicide or homicide, psychiatric disorders or men? What method of birth control does she problems, overdoses, incarceration, crim- use? Does she desire to become pregnant in inal involvement, etc.? Have any family the near future? members been in recovery from addiction? • Obtain the names and addresses of all other • What other illnesses have affected the physicians currently providing care to the patient’s biological relatives? patient and obtain written consent to contact all treatment providers. Does the Medical History patient have a designated primary care physician? Is he or she being treated by a • Perform a detailed review of systems. What number of physicians? (See chapter 6 for a medical problems or complaints does the discussion of privacy and confidentiality patient have now? Which ones are or could laws and regulations pertaining to substance be related to drug or alcohol use? abuse treatment information.) • Past medical history: Ask about delirium • What medications is the patient taking now, tremens (DTs), withdrawal complications, and for what reason? Who prescribed the or overdoses; tuberculosis or positive current medications? What has been the purified protein derivative (PPD) skin test, response to medication? Ask the patient to HIV infection, viral hepatitis (hepatitis A, list all current medications and comple- B, C, D), syphilis, gonorrhea, pelvic mentary or alternative therapies, such as inflammatory disease, or other sexually vitamins, minerals, herbs, and supplements. transmitted diseases (STDs); menstrual • Explore the use, past and present, of abnormalities, pregnancy or obstetric addicting prescription drugs. What was the complications, spontaneous abortion; pattern of use of prescription drugs? Did the diabetes, thyroid disease, or other patient take the medications as prescribed, endocrine problem; cancer; hypertension, or more than prescribed, or in combination endocarditis, pericarditis, cardiomyopathy, with alcohol or other drugs? Has the patient congestive heart failure, ischemic heart received prescriptions from several physi- disease, arrhythmia, heart murmur, mycotic cians? Has the patient ever “lost” prescrip- aneurysm, thrombophlebitis; gastritis, tions in order to obtain new ones, forged or

126 Clinical Toolbox phoned in prescriptions, stolen prescription educational, occupational, legal, physical pads, split prescriptions with others, or health, and mental health arenas? otherwise misused prescription medications? • Has functioning been affected by drug use? • Does the patient have pain problems? What If so, how? What financial, familial, social, pain treatments have been tried or recom- emotional, occupational, legal, medical, or mended? Have opioid medications been spiritual problems have occurred while the prescribed? What was the response to patient has been using drugs or as a result of various pain treatments? What is the level having used drugs? Has the patient experi- of pain now? enced legal problems, arrests, been charged with driving while intoxicated, had multiple Sexual History divorces, marital discord, bankruptcy, fights, injuries, family violence, or suicidal • Is the patient sexually active? How many thoughts? Describe specific problems and sexual partners does the patient have? How consequences. long has he or she been involved with his • Has there been hazardous or impairing or her current partner(s)? Quantify the substance use? If so, describe specifics. number and gender of sexual partners over the patient’s lifetime. Has the patient had • Has a great deal of time been spent in sex with multiple partners or strangers? Has activities necessary to obtain the substance, the patient had sex with males, females, or use the substance, or recover from its both? effects? Have important social, occupational, or recreational activities been given • What specific sexual activities has the up or reduced because of substance use? patient engaged in? Does he or she ever have sex without a condom or other barrier • Has there been continued use despite protection? Has he or she traded sex for adverse physical and social consequences? money or drugs? Has the substance use continued despite knowledge of having persistent problems • Has the patient or any of his or her partners that are likely to have been caused or ever had or been treated for an STD? If so, worsened by the substance? If so, give which ones (syphilis, gonorrhea, HIV, examples. chlamydia, or others)? How long ago were these treatments? How many times has the patient been treated for an STD? Compulsivity or Craving • Does the patient have any current symptoms • Does the patient report drug craving and/or of an STD, such as genital discharge, pain, urges to use? How does the patient deal with itching, sores, or lumps? them? • Has the patient ever been hurt or abused by • Does the patient obsess about using drugs? a sexual partner? Has he or she ever been Is there a compulsive pattern to the drug sexually abused, molested, raped, or use? assaulted? • Is sex satisfying for the patient? Does he or Control she have any problems with or concerns • Has loss of consistent control over drug use about his or her sexual activities or occurred? Does the patient feel he or she has function? ever lost control over use, even one time? When did this first occur? What was the Cost/Consequences of Drug situation? What happened? Has the patient Use often taken a substance in larger amounts or over a longer period than was intended? • What is the patient’s current level of func- Describe the evidence for loss of consistent tioning in social, family or relationship, control over use.

Clinical Toolbox 127 • If the patient does not think control has ever is he or she to motivational enhancement been lost, do others (family, friends, therapy? employers, physicians, or others) think differently? Why Now? • Why did the patient seek treatment or help Social and Recovery at this time? Environment • Is treatment coerced or voluntary? What • What is the quality of recovery environment are the consequences if the patient does not for this patient (supportive, nonsupportive, seek help or complete treatment? How does or toxic)? What has been the response of the patient feel about these consequences? family, significant others, friends, employer, and others to the patient’s problems? What Detection of Drugs in is the existing problem as the spouse, partner, or significant other sees it? Have Urine and Other any of these individuals suggested that the Samples patient may have an alcohol or drug problem? When did they first suggest this? What Physicians should become familiar with their do others object to about the patient’s laboratory’s collection procedures, sample drinking or drug use? What are their testing methodology, quality control and concerns or complaints? assurance procedures, and adulterant testing methodology. They must understand labora- • Is the patient’s neighborhood, job, or tory report forms and procedures, the drugs profession a factor that does not support screened in a routine panel, other drug tests recovery? performed at the laboratory, sensitivity of • What is or has been the patient’s support tests, and cutoff levels for reporting positive system? Have supportive individuals been or negative test results. A comprehensive involved in Al-Anon, Nar-Anon, or similar discussion of urine drug testing in the primary programs? Are they supportive of the care setting can be found in Urine Testing in patient’s getting help? Who has been Primary Care: Dispelling the Myths & alienated? Designing Strategies (Gourlay et al. 2002). • How many friends, family, or associates are It is advisable that physicians become partners in drinking or using? Are alcohol acquainted with the laboratory director and or other drugs present or used in the house other personnel who can answer questions and where the patient lives? Who is drinking or provide other useful information. using drugs in the patient’s home? What addicting drugs, either prescribed or Initial screening typically utilizes an enzyme nonprescribed, are still at home now? multiplied immunoassay test (EMIT), a radio- immunoassay (RIA), or a florescent polarization immunoassay (FPIA) test; each is based Insight, Motivation, on antigen-antibody interactions and is highly Readiness to Change sensitive for specific drugs. Gas chromato- • What is the patient’s understanding of his graphy with mass spectrometry (GC/MS) is a or her problem? What does the patient highly sensitive and specific test that is labor understand about the disease of addiction? intensive and costly, and is generally used to confirm the results of screening tests. • What Stage of Change is the patient in now: Precontemplation, Contemplation, Prepara- Detection of a drug depends on usage factors tion, Action, Maintenance, Relapse? (See (e.g., dose used, frequency of use, proximity appendix G.) What stages has he or she of last use) and characteristics of the specific passed through in the past? How responsive drug. Most common drugs of abuse (e.g.,

128 Clinical Toolbox cocaine, methamphetamine, heroin, mari- become commercially available; none were juana) or their metabolites are readily available at the time this document was detectable in the urine. Recent alcohol use is prepared. detectable in saliva, breath, blood, and urine samples. Low-potency benzodiazepines (e.g., diazepam and chlordiazepoxide) are readily detected in Morphine (the metabolite of heroin) is routine urine drug screens. However, clonaze- detected by commercially available urine pam, flunitrazepam, alprazolam, and several testing; however, methadone will not be other benzodiazepines may be undetected in detected as an opiate on some drug tests, urine samples. Since the combination of unless a methadone assay is specifically buprenorphine and benzodiazepines can be requested. Oxycodone will cross-react only at high concentrations. Buprenorphine does not lethal (Reynaud et al. 1998a,b; Tracqui et al. cross-react with the detection procedures for 1998), it is essential to screen effectively for methadone or heroin. Although buprenor- the recent use of benzodiazepines. It may be phine and its metabolite are excreted in urine, necessary to specifically request that a sample routine screening for the presence of bupre- be evaluated for benzodiazepines that are not norphine is not feasible until testing kits detected on routine drug screens.

Clinical Toolbox 129 130 Appendix F Federation of State Medical Boards— Model Policy Guidelines for Opioid Addiction Treatment in the Medical Office

SECTION I: PREAMBLE The (name of board) recognizes that the prevalence of addiction to heroin and other opioids has risen sharply in the United States and that the residents of the State of (name of state) should have access to modern, appropriate and effective addiction treatment. The appropriate application of up-to-date knowledge and treatment modalities can successfully treat patients who suffer from opioid addiction and reduce the morbidity, mortality and costs associated with opioid addiction, as well as public health problems such as HIV, HBV, HCV and other infectious diseases. The Board encourages all physicians to assess their patients for a history of substance abuse and potential opioid addiction. The Board has developed these guidelines in an effort to balance the need to expand treatment capacity for opioid addicted patients with the need to prevent the inappropriate, unwise or illegal prescribing of opioids. Until recently, physicians have been prohibited from prescribing and dispensing opioid medications in the treatment of opioid addiction, except within the confines of federally regulated opioid treatment programs. Because of the increasing number of opioid-addicted individuals and the associated public health problems, as well as the limited availability of addiction treatment programs, federal laws now enable qualified physicians to prescribe Schedule III-V medications approved by the Food and Drug Administration for office-based treatment of opioid addiction[1]. Physicians who consider office-based treatment of opioid addiction must be able to recognize the condition of drug or opioid addiction and

131 be knowledgeable about the appropriate use DEA identification number that specifically of opioid agonist, antagonist, and partial authorizes such office-based treatment. agonist medications. Physicians must also demonstrate required qualifications as The waiver to provide addiction treatment defined under and in accordance with the under DATA is granted by the Secretary of “Drug Addiction Treatment Act of 2000” HHS, presumably through SAMHSA, no later (DATA) (Public Law 106-310, Title XXXV, than 45 days after receipt of the physician’s Sections 3501 and 3502) and obtain a waiver written notification. Upon request from from the Substance Abuse and Mental Health SAMHSA, the Attorney General, presumably Services Administration (SAMHSA), as through DEA, will automatically assign the authorized by the Secretary of HHS. In order physician an identification number that will be to qualify for a waiver, physicians must hold a used with the physician’s DEA registration current license in the State of (name of state) number. However, if SAMHSA has not acted and, at a minimum, meet one or more of the on the physician’s request for a waiver by the following conditions to be considered as end of this 45-day period, DEA will qualified to treat opioid addicted patients in automatically assign the physician an an office-based setting in this state: identification number. • Subspecialty board certification in addiction Furthermore, if a physician wishes to pre- psychiatry from the American Board of scribe or dispense narcotic drugs for main- Medical Specialties tenance or detoxification treatment on an • Subspecialty board certification in addiction emergency basis in order to facilitate the medicine from the American Osteopathic treatment of an individual patient before the Association 45-day waiting period has elapsed, the physician musty notify SAMHSA and the DEA of • Addiction certification from the American the physician’s intent to provide such Society of Addiction Medicine treatment. • Completion of not less than 8 hours of training related to the treatment and The Board recognizes that new treatment management of opioid-dependent patients modalities offer an alternative in the treat- provided by the American Society of Addic- ment of opioid addiction. Based on appro- tion Medicine, the American Academy of priate patient assessment and evaluation, it Addiction Psychiatry, the American Medical may be both feasible and desirable to provide Association, the American Osteopathic office-based treatment of opioid addicted Association, the American Psychiatric patients with Schedules III-V opioid medica- Association, or other organization approved tions approved for such use by the FDA and by the board. regulated in such use by Center for Substance • Participation as an investigator in one or Abuse Treatment (CSAT)/SAMHSA. Physi- more clinical trials leading to the approval cians are referred to the Buprenorphine of a narcotic drug in Schedule III, IV, or V Clinical Practice Guidelines, available at the or a combination of such drugs for treat- CSAT/SAMHSA, Division of Pharmacologic ment of opioid addicted patients (must be Therapies, Second Floor, 1 Choke Cherry evidenced by a statement submitted to the Road, Rockville, MD 20857; (301) 443-7614 Secretary of Health and Human Services by or http://www.dpt.samhsa.gov/. the sponsor of such approved drug). The medical recognition and management of • Additional qualification criteria may be opioid addiction should be based upon added through legislative enactment. current knowledge and research and includes In addition to the waiver, physicians must the use of both pharmaceutical and non- have a valid DEA registration number and a pharmaceutical modalities. Prior to initiating

132 FSMB Model Policy Guidelines for Opioid Addiction Treatment treatment, physicians should be knowledge- SECTION II: GUIDELINES able about addiction treatment and all available pharmacologic treatment agents as The Board has adopted the following guide- well as available ancillary services to support lines when evaluating the documentation and both the physician and patient. In order to treatment of opioid addiction under DATA: undertake treatment of opioid addicted patients, in accordance with these guidelines, Compliance With Controlled physicians must demonstrate a capacity to refer patients for appropriate counseling and Substances Laws and other ancillary services. Regulations The (state medical board) is obligated under Generally, to prescribe and dispense the laws of the State of (name of state) to Schedules III-V opioid medications for the protect the public health and safety. The treatment of opioid addiction under DATA, Board recognizes that inappropriate pre- the physician must be licensed in the state, scribing of controlled substances, including have a valid DEA controlled substances opioids, may lead to drug diversion and abuse registration and identification number, by individuals who seek them for other than comply with federal and state regulations legitimate medical use. Physicians must be applicable to controlled substances, and have diligent in preventing the diversion of drugs a current waiver issued by SAMHSA. To for illegitimate and nonmedical uses. obtain this waiver, the physician must submit written notification to the Secretary of HHS Qualified physicians need not fear disciplinary of their intent to provide this treatment action from the Board or other state regula- modality, certifying the physician’s qualifi- tory or enforcement agency for appropriate cations and listing his/her DEA registration prescribing, dispensing or administering number. SAMHSA will then notify DEA approved opioid drugs in Schedules III, IV, or whether a waiver has been granted. If V, or combinations thereof, for a legitimate SAMHSA grants the physician a waiver, DEA medical purpose in the usual course of opioid will issue the qualifying physician an identifi- addiction treatment. The Board will consider cation number. In addition to these require- appropriate prescribing, ordering, adminis- ments, the DATA limits the number of patients tering, or dispensing of these medications for that a physician or a group practice is per- opioid addiction to be for a legitimate medical mitted to treat to 30. This numerical limitation purpose if based on accepted scientific may be changed by regulation in the future. knowledge of the treatment of opioid addiction and in compliance with applicable state and Physicians are specifically prohibited from federal law. delegating prescribing opioids for detoxification and/or maintenance treatment purposes The Board will determine the appropriateness to non-physicians. Physicians are referred to of prescribing based on the physician’s overall DEA regulations (21CFR, Part 1300 to end) treatment of the patient and on available and the DEA Physician’s Manual documentation of treatment plans and out- www.deadiversion.usdoj.gov and (any comes. The goal is to document and treat the relevant documents issued by the state patient’s addiction while effectively addressing medical board) for specific rules governing other aspects of the patient’s functioning, issuance of controlled substances prescrip- including physical, psychological, medical, tions as well as applicable state regulations. social and work-related factors. The following guidelines are not intended to define complete Evaluation of the Patient or best practice, but rather to communicate what the Board considers to be within the A recent, complete medical history and boundaries of accepted professional practice. physical examination must be documented in

FSMB Model Policy Guidelines for Opioid Addiction Treatment 133 the medical record. The medical record • important social, occupational or recrea- should document the nature of the patient’s tional activities are given up or reduced addiction(s), evaluate underlying or coexisting because of substance use diseases or conditions, the effect on physical • the substance use is continued despite and psychological function, and history of knowledge of having a persistent or substance abuse and any treatments therefor. recurrent physical or psychological problem The medical record should also document the that is likely to have been caused or exacer- suitability of the patient for office-based bated by the substance (e.g., current treatment based upon recognized diagnostic cocaine use despite recognition of cocaine- criteria.[2] induced depression, or continued drinking despite recognition that an ulcer was made DSM-IV-TR Substance worse by alcohol consumption) Dependence Criteria [3] Treatment Plan A maladaptive pattern of substance use, The written treatment plan should state leading to clinically significant impairment or objectives that will be used to determine distress, as manifested by three (or more) of treatment success, such as freedom from the following, occurring at any time in the intoxication, improved physical function, same 12-month period: psychosocial function and compliance and • tolerance, as defined by either of the should indicate if any further diagnostic following: evaluations are planned, as well as counseling, psychiatric management or other ancillary – a need for markedly increased amounts services. This plan should be reviewed of the substance to achieve intoxication or desired effect, or periodically. After treatment begins, the physician should adjust drug therapy to the – markedly diminished effect with con- individual medical needs of each patient. tinued use of the same amount of the Treatment goals, other treatment modalities substance or a rehabilitation program should be eval- • withdrawal, as manifested by either of the uated and discussed with the patient. If following: possible, every attempt should be made to – the characteristic withdrawal syndrome involve significant others or immediate family for the substance, or members in the treatment process, with the patient’s consent. The treatment plan should – the same (or closely related) substance is also contain contingencies for treatment taken to relieve or avoid withdrawal failure (i.e., due to failure to comply with the symptoms treatment plan, abuse of other opioids, or • the substance is often taken in larger evidence that the Schedules III-V medications amounts or over longer period than was are not being taken). intended • there is a persistent desire or unsuccessful efforts to cut down or control substance use Informed Consent and • a great deal of time is spent in activities Agreement for Treatment necessary to obtain the substance (e.g., The physician should discuss the risks and visiting multiple doctors or driving long benefits of the use of these approved opioid distances), use the substance (e.g., chain- medications with the patient and, with appro- smoking), or recover from its effects priate consent of the patient, significant

134 FSMB Model Policy Guidelines for Opioid Addiction Treatment other(s), family members, or guardian. The objectives. The physician should pursue a patient should receive opioids from only one team approach to the treatment of opioid physician and/or one pharmacy when addiction, including referral for counseling possible. The physician should employ the use and other ancillary services. Ongoing com- of a written agreement between physician and munication between the physician and con- patient addressing such issues as (1) alterna- sultants is necessary to ensure appropriate tive treatment options; (2) regular toxicologic compliance with the treatment plan. This may testing for drugs of abuse and therapeutic be included in the formal treatment agreement drug levels (if available and indicated); between the physician and patient. Special (3) number and frequency of all prescription attention should be given to those patients refills and (4) reasons for which drug therapy who are at risk for misusing their medications may be discontinued (i.e.; violation of and those whose living or work arrangements agreement). pose a risk for medication misuse or diversion. The management of addiction in patients with comorbid psychiatric disorders requires extra Periodic Patient Evaluation care, monitoring, documentation and con- Patients should be seen at reasonable inter- sultation with or referral to a mental health vals (at least weekly during initial treatment) professional. based upon the individual circumstance of the patient. Periodic assessment is necessary to determine compliance with the dosing regi- Medical Records men, effectiveness of treatment plan, and to The prescribing physician should keep assess how the patient is handling the pre- accurate and complete records to include scribed medication. Once a stable dosage is (1) the medical history and physical examina- achieved and urine (or other toxicologic) tests tion; (2) diagnostic, therapeutic and labora- are free of illicit drugs, less frequent office tory results; (3) evaluations and consultations; visits may be initiated (monthly may be (4) treatment objectives; (5) discussion of risks reasonable for patients on a stable dose of the and benefits; (6) treatments; (7) medications prescribed medication(s) who are making (including date, type, dosage, and quantity progress toward treatment objectives). prescribed and/or dispensed to each patient); Continuation or modification of opioid (8) a physical inventory of all Schedules III, therapy should depend on the physician’s IV, and V controlled substances on hand that evaluation of progress toward stated treat- are dispensed by the physician in the course of ment objectives such as (1) absence of toxicity (2) absence of medical or behavioral adverse maintenance or detoxification treatment of an effects (3) responsible handling of medications individual; (9) instructions and agreements; (4) compliance with all elements of the treat- and (10) periodic reviews. Records should ment plan (including recovery-oriented remain current and be maintained in an activities, psychotherapy and/or other accessible manner and readily available for psychosocial modalities) and (5) abstinence review. The physician must adhere to the from illicit drug use. If reasonable treatment special confidentiality requirements of goals are not being achieved, the physician 42CFR, Part 2, which apply to the treatment should re-evaluate the appropriateness of of drug and alcohol addiction, including the continued treatment. prohibition against release of records or other information, except pursuant to a proper patient consent or court order in full Consultation compliance with 42CFR2, or the Federal or The physician should refer the patient as State officials listed in 42CFR2, or in cases of necessary for additional evaluation and true medical emergency or for the mandatory treatment in order to achieve treatment reporting of child abuse.

FSMB Model Policy Guidelines for Opioid Addiction Treatment 135 SECTION III: with continued use of the same amount of substance; DEFINITIONS • The characteristic withdrawal syndrome for For the purposes of these guidelines, the the substance or the same (or closely following terms are defined as follows: related) substance is taken to relieve or avoid withdrawal symptoms; Addiction: A primary, chronic, neurobiologic • The substance was taken in larger amounts disease, with genetic, psychosocial, and or over a longer period of time than was environmental factors influencing its develop- intended; ment and manifestations. It is characterized by behaviors that include one or more of the • There is a persistent desire or unsuccessful following: impaired control over drug use, efforts to cut down or control substance use; compulsive use, continued use despite harm • Significant time is spent on activities to and craving. obtain the substance, use the substance, or recover from its effects; Agonists: Agonist drugs are substances that • Important social, occupational, or recrea- bind to the receptor and produce a response tional activities are discontinued or reduced that is similar in effect to the natural ligand because of substance use; that would activate it. Full mu opioid agonists activate mu receptors, and increasing doses of • Substance use is continued despite full agonists produce increasing effects. Most knowledge of having a persistent physical or opioids that are abused, such as morphine and psychological problem that is caused or heroin are full mu opioid agonists. exacerbated by the substance. Opioid Drug: Opioid drug means any drug “Approved Schedule III-V Opioids”: Opioids having an addiction-forming or addiction- referred to by the DATA, specifically sustaining liability similar to morphine or approved by the FDA for treatment of opioid being capable of conversion into a drug having dependence or addiction. such addiction-forming or addiction Antagonists: Antagonists bind to but do not sustaining liability. (this is referred to as an activate receptors. They prevent the receptor opiate in the Controlled Substances Act) from being activated by an agonist compound. Opioid Treatment Program (OTP) (some- Examples of opioid antagonists are naltrexone times referred to as a methadone clinic or and naloxone. narcotic treatment program): Opioid treat- Maintenance Treatment: Maintenance treatment program means a licensed program or ment means the dispensing for a period in practitioner engaged in the treatment of excess of 21 days of an opioid medication(s) at opioid addicted patients with approved stable dosage levels in the treatment of an Scheduled II opioids (methadone and/or individual for dependence upon heroin or LAAM). other morphine-like drugs. Partial Agonists: Partial agonists occupy and Opioid Dependence: A maladaptive pattern activate receptors. At low doses, like full of substance use, leading to clinically signifi- agonists, increasing doses of the partial cant impairment or distress, manifested by agonist produce increasing effects. However, 3 or more of the following, occurring at any unlike full agonists, the receptor-activation time in the same 12-month period: produced by a partial agonist reaches a plateau over which increasing doses do not • A need for markedly increased amounts of produce an increasing effect. The plateau may the substance to achieve intoxication or have the effect of limiting the partial agonist’s desired effect or markedly diminished effect therapeutic activity as well as its toxicity.

136 FSMB Model Policy Guidelines for Opioid Addiction Treatment Buprenorphine is an example of a partial Tolerance: A state of adaptation in which agonist. exposure to a drug induces changes that result Physical Dependence: A state of adaptation in diminution of one or more of the drug’s that is manifested by a drug class specific effects over time. withdrawal syndrome that can be produced by abrupt cessation, rapid dose reduction, Waiver: A documented authorization from the decreasing blood level of the drug, and/or Secretary of HHS issued by SAMHSA under administration of an antagonist. the DATA that exempts qualified physicians from the rules applied to OTPs. Implementa- Qualified Physician: A physician, licensed in the State of (name of state) who holds a tion of the waiver includes possession of a current waiver issued by SAMHSA (as auth- valid DEA certificate with applicable suffix. orized by the Secretary of HHS) and meets one or more of the conditions set forth in Footnotes: Section 1. In addition, a physician must have a valid DEA registration and identification [1] Drug Addiction Treatment Act of 2000, number authorizing the physician to conduct Public Law 106-310, Title XXXV, Section 3501 office-based treatment. and 3502.

Substance Abuse: A maladaptive pattern of [2] Buprenorphine Clinical Practice substance use leading to clinically significant Guidelines, Table 3-1. impairment or distress, as manifested by one or more of the following, occurring within a [3] American Psychiatric Association, 12-month period: Diagnostic and Statistical Manual of Mental • Recurrent substance use resulting in a Disorders, 4th ed., Text Revision, failure to fulfill major role obligations at Washington, D.C. work, school, or home; • Recurrent substance use in situations in This document can be found on model policy which it is physically hazardous; guidelines at http://www.fsmb.org, then click • Recurrent substance-related legal problems; on policy documents. The recommendations • Continued substance use despite having contained herein were adopted as policy by persistent or recurrent social or inter- the House of Delegates of the Federation of personal problems caused or exacerbated State Medical Boards of the United States, by the effects of the substance. Inc., April 2002.

FSMB Model Policy Guidelines for Opioid Addiction Treatment 137 138 Appendix G Stages of Change

As an important component of effective treatment planning, physicians may find it helpful to determine which stage of change characterizes the patient. There are six stages of change: precontemplation, contemplation, preparation, action, maintenance, and relapse. Patients can be conceptualized as moving along a continuum marked by these stages, each of which is described below. Readiness to change and stage of change can be evaluated by interview and instruments such as the Stages of Change Readiness and Treatment Eagerness Scale (Miller and Tonigan 1996). Stages of change are clearly linked to a patient’s motivation. It may be possible for a physician to increase motivation (e.g., through motivational enhancement therapy) and thus help a patient move from an early stage of change (e.g., contemplation) to a more active and healthy stage (e.g., action). The discussion of Stages of Changes below is excerpted from Center for Substance Abuse Treat- ment (CSAT) TIP 35, Enhancing Motivation for Change in Substance Abuse Treatment (CSAT 1999b). (See http://www.kap.samhsa.gov/ products/manuals/index.htm.)

Transtheoretical Model of Stages of Change It is important to note that the change process is cyclical, and individuals typically move back and forth between the stages and cycle through the stages at different rates. In one individual, this movement through the stages can vary in relation to different behaviors or objectives. Individuals can move through stages quickly. Sometimes, they move so rapidly that it is difficult to pinpoint where they are because change is a dynamic process. It is not uncommon, however, for individuals to linger in the early stages.

For most substance-using individuals, progress through the stages of change is circular or spiral in nature, not linear. In this model, recurrence is a normal event because many clients cycle through the

139 different stages several times before achieving decisional balance tips in favor of change. stable change. The six stages and the issue of Once instigation to change occurs, an indi- relapse are described below. vidual enters the preparation stage, during which commitment is strengthened. Prep- aration entails more specific planning for Precontemplation change, such as making choices about whether During the precontemplation stage, substance- treatment is needed and, if so, what kind. using individuals are not considering change Preparation also entails an examination of and do not intend to change behaviors in the one’s perceived capabilities—or self- foreseeable future. They may be partly or efficacy—for change. Individuals in the completely unaware that a problem exists, preparation stage are still using substances, that they have to make changes, and that they but typically they intend to stop using very may need help in this endeavor. Alternatively, soon. They may have already attempted to they may be unwilling or too discouraged to reduce or stop use on their own or may be change their behavior. Individuals in this experimenting now with ways to quit or cut stage usually have not experienced adverse back (DiClemente and Prochaska 1998). They consequences or crises because of their begin to set goals for themselves and make substance use and often are not convinced commitments to stop using, even telling close that their pattern of use is problematic or associates or significant others about their even risky. plans.

Contemplation Action As these individuals become aware that a Individuals in the action stage choose a problem exists, they begin to perceive that strategy for change and begin to pursue it. At there may be cause for concern and reasons this stage, clients are actively modifying their to change. Typically, they are ambivalent, habits and environment. They are making simultaneously seeing reasons to change and drastic lifestyle changes and may be faced with reasons not to change. Individuals in this particularly challenging situations and the stage are still using substances, but they are physiological effects of withdrawal. Clients considering the possibility of stopping or may begin to reevaluate their own self-image cutting back in the near future. At this point, as they move from excessive or hazardous use they may seek relevant information, reeval- to nonuse or safe use. For many, the action uate their substance use behavior, or seek stage can last from 3 to 6 months following help to support the possibility of changing termination or reduction of substance use. behavior. They typically weigh the positive For some, it is a honeymoon period before and negative aspects of making a change. It is they face more daunting and longstanding not uncommon for individuals to remain in challenges. this stage for extended periods, often for years, vacillating between wanting and not wanting to change. Maintenance During the maintenance stage, efforts are made to sustain the gains achieved during the Preparation action stage. Maintenance is the stage at which When an individual perceives that the envi- individuals work to sustain sobriety and sioned advantages of change and adverse prevent recurrence (Marlatt and Gordon consequences of substance use outweigh any 1985). Extra precautions may be necessary to positive features of continuing use at the same keep from reverting to problematic behaviors. level and maintaining the status quo, the Individuals learn how to detect and guard

140 Stages of Change against dangerous situations and other DiClemente 1992). These experiences con- triggers that may cause them to use substances tribute information that can facilitate or again. In most cases, individuals attempting hinder subsequent progression through the long-term behavior change do return to use at stages of change. Recurrence, often referred least once and revert to an earlier stage to as relapse, is the event that triggers the (Prochaska and DiClemente 1992). Recur- individual’s return to earlier stages of change rence of symptoms can be viewed as part of and recycling through the process. Individuals the learning process. Knowledge about the may learn that certain goals are unrealistic, personal cues or dangerous situations that certain strategies are ineffective, or certain contribute to recurrence is useful information environments are not conducive to successful for future change attempts. Maintenance change. Most substance users will require requires prolonged behavioral change—by several revolutions through the stages of remaining abstinent or moderating consump- change to achieve successful recovery tion to acceptable, targeted levels—and (DiClemente and Scott 1997). After a return continued vigilance for a minimum of to substance use, clients usually revert to an 6 months to several years, depending on the earlier change stage—not always to mainte- target behavior (Prochaska and DiClemente nance or action, but more often to some level 1992). of contemplation. They may even become precontemplators again, temporarily unwilling or unable to try to change soon. Resuming Relapse substance use and returning to a previous Most individuals do not immediately sustain stage of change should not be considered a the new changes they are attempting to make, failure and need not become a disastrous or and a return to substance use after a period of prolonged recurrence. A recurrence of symp- abstinence is the rule rather than the excep- toms does not necessarily mean that a client tion (Brownell et al. 1986; Prochaska and has abandoned a commitment to change.

Stages of Change 141 Stages of Change Readiness and Treatment Eagerness Scale (SOCRATES 8D)

INSTRUCTIONS: Please read the following statements carefully. Each one describes a way that you might (or might not) feel about your drug use. For each statement, circle one number from 1 to 5 to indicate how much you agree or disagree with it right now. Please circle one and only one number for every statement.

NO! ? YES! Strongly No Undecided Yes Strongly Disagree Disagree or Unsure Agree Agree

1. I really want to make changes in my use of 1 2 3 4 5 drugs. 2. Sometimes I wonder if I am an addict. 1 2 3 4 5 3. If I don’t change my drug use soon, my 1 2 3 4 5 problems are going to get worse. 4. I have already started making some 1 2 3 4 5 changes in my use of drugs. 5. I was using drugs too much at one time, but 1 2 3 4 5 I’ve managed to change that. 6. Sometimes I wonder if my drug use is 1 2 3 4 5 hurting other people. 7. I have a drug problem. 1 2 3 4 5 8. I’m not just thinking about changing my 1 2 3 4 5 drug use, I’m already doing something about it. 9. I have already changed my drug use, and I 1 2 3 4 5 am looking for ways to keep from slipping back to my old pattern. 10. I have serious problems with drugs. 1 2 3 4 5 11. Sometimes I wonder if I am in control of my 1 2 3 4 5 drug use. 12. My drug use is causing a lot of harm. 1 2 3 4 5 13. I am actively doing things now to cut down 1 2 3 4 5 or stop my use of drugs. 14. I want help to keep from going back to the 1 2 3 4 5 drug problems that I had before. 15. I know that I have a drug problem. 1 2 3 4 5 16. There are times when I wonder if I use 1 2 3 4 5 drugs too much. 17. I am a drug addict. 1 2 3 4 5 18. I am working hard to change my drug use. 1 2 3 4 5 19. I have made some changes in my drug use, 1 2 3 4 5 and I want some help to keep from going back to the way I used before.

Source: Miller and Tonigan 1996. SOCRATES 8D and SOCRATES 8D Scoring Sheet. Center on Alcoholism, Substance Abuse, and Addictions (CASAA), Assessment Instruments. Available at http://casaa.unm.edu/inst/inst.html. Reprinted with permission.

142 Stages of Change SOCRATES Scoring Form (19-Item Version 8.0)

Transfer the client’s answers from questionnaire (see note below):

Recognition Ambivalence Taking Steps

1 2

3 4

7 8

10 11

12 13

15 16

17 18

TOTALS Re Am Ts

Possible Range: 7–35 4–20 8–40

Stages of Change 143 SOCRATES Profile Sheet (19-Item Version 8A)

INSTRUCTIONS: From the SOCRATES Scoring Form (19-Item Version) transfer the total scale scores into the empty boxes at the bottom of the Profile Sheet. Then for each scale, CIRCLE the same value above it to determine the decile range.

DECILE SCORES Recognition Ambivalence Taking Steps 90 Very High 19–20 39–40 80 18 37–38 70 High 35 17 36 60 34 16 34–35 50 Medium 32–33 15 33 40 31 14 31–32 30 Low 29–30 12–13 30 20 27–28 9–11 26–29 10 Very Low 7–26 4–8 8–25 RAW SCORES Re= Am= Ts= (from Scoring Sheet)

These interpretive ranges are based on a sample of 1,726 adult men and women presenting for treatment of alcohol problems through Project MATCH. Note that individual scores are therefore being ranked as low, medium, or high relative to people already presenting for alcohol treatment.

144 Stages of Change Guidelines for either because they “know” their drinking is causing problems (high Recognition), or Interpretation of because they “know” that they do not have SOCRATES-8 Scores drinking problems (low Recognition). Thus a low Ambivalence score should be interpreted Using the SOCRATES Profile Sheet, circle the in relation to the Recognition score. client’s raw score within each of the three scale columns. This provides information as to whether the client’s scores are low, average, TAKING STEPS or high relative to individuals already seeking HIGH scorers report that they are already treatment for alcohol problems. The following doing things to make a positive change in their are provided as general guidelines for inter- drinking, and may have experienced some pretation of scores, but it is wise in an indi- success in this regard. Change is underway, vidual case also to examine individual item and they may want help to persist or to responses for additional information. prevent backsliding. A high score on this scale has been found to be predictive of successful RECOGNITION change. HIGH scorers directly acknowledge that they LOW scorers report that they are not cur- are having problems related to their drinking, rently doing things to change their drinking tending to express a desire for change and to and have not made such changes recently. perceive that harm will continue if they do not change. Resources for More LOW scorers deny that alcohol is causing them serious problems, reject diagnostic labels Information such as “problem drinker” and “alcoholic,” • Recovery Attitude and Treatment Evaluator and do not express a desire for change. (RAATE) (Mee-Lee 1988). http:// www.niaaa.nih.gov/publications/raate.htm AMBIVALENCE • University of Rhode Island Change HIGH scorers say that they sometimes wonder Assessment (URICA) (McConnaughy et al. if they are in control of their drinking, are 1983). http://www.uri.edu/research/cprc/ drinking too much, are hurting other individ- Measures/urica.htm uals, and/or are alcoholic. Thus a high score • SOCRATES (Miller and Tonigan 1996) reflects ambivalence or uncertainty. A high http://casaa.unm.edu/inst/forms/ score here reflects some openness to reflec- socratesv8.pdf tion, as might be particularly expected in the • Readiness to Change Questionnaire contemplation stage of change. (Rollnick et al. 1992). LOW scorers say that they do not wonder http://www.niaaa.nih.gov/publications/ whether they drink too much, are in control, rtcq.htm are hurting others, or are alcoholic. Note that http://www.dva.gov.au/health/provider/ an individual may score low on ambivalence care_plans/change.htm

Stages of Change 145 146 Appendix H Sample Treatment Agreement/Contract

Treatment agreements/contracts are often employed in the treatment of addiction to make explicit the expectations regarding patient cooperation and involvement in the treatment process. On the following page is a sample addiction treatment agreement/contract that may be a useful tool in working with patients in an office-based setting.

147 As a participant in the buprenorphine protocol for treatment of opioid abuse and dependence, I freely and voluntarily agree to accept this treatment agreement/contract, as follows:

I agree to keep, and be on time to, all my scheduled appointments with the doctor and his/her assistant.

I agree to conduct myself in a courteous manner in the physician’s office.

I agree not to arrive at the office intoxicated or under the influence of drugs. If I do, the doctor will not see me, and I will not be given any medication until my next scheduled appointment.

I agree not to sell, share, or give any of my medication to another individual. I understand that such mishandling of my medication is a serious violation of this agreement and would result in my treatment being terminated without recourse for appeal.

I agree not to deal, steal, or conduct any other illegal or disruptive activities in the doctor’s office.

I agree that my medication (or prescriptions) can be given to me only at my regular office visits. Any missed office visits will result in my not being able to get medication until the next scheduled visit.

I agree that the medication I receive is my responsibility and that I will keep it in a safe, secure place. I agree that lost medication will not be replaced regardless of the reasons for such loss.

I agree not to obtain medications from any physicians, pharmacies, or other sources without informing my treating physician. I understand that mixing buprenorphine with other medications, especially benzodiazepines such as valium and other drugs of abuse, can be dangerous. I also understand that a number of deaths have been reported among individuals mixing buprenorphine with benzodiazepines.

I agree to take my medication as the doctor has instructed and not to alter the way I take my medication without first consulting the doctor.

I understand that medication alone is not sufficient treatment for my disease, and I agree to participate in the patient education and relapse prevention programs, as provided, to assist me in my treatment.

Printed Name Signature Date

148 Sample Treatment Agreement/Contract Appendix I Glossary

21 C.F.R. Part 291 Code of Federal Regulations (C.F.R.) that, among other things, sets standards for narcotic treatment and use of methadone. 42 C.F.R. Part 2 Federal Regulation concerning confidentiality of alcohol and drug abuse patient treatment records. 42 C.F.R. Part 8 Federal Regulation concerning dispensing of drugs through opioid treatment programs.

Addiction A behavioral syndrome characterized by the repeated, compulsive seeking or use of a substance despite adverse social, psychological, and/or physical consequences. Addiction is often (but not always) accompanied by physical dependence, a withdrawal syndrome, and tolerance.

Alcoholism A pattern of compulsive use of alcohol in which individuals devote substantial periods of time to obtaining and consuming alcoholic beverages despite adverse psychological or physical consequences, e.g., depression, blackouts, liver disease, or other consequences. (Adapted from Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision [DSM-IV-TR].) Antagonist Substance that tends to nullify the effect of another (e.g., a drug that binds to a receptor without eliciting a response). AUDIT Alcohol Use Disorders Identification Test. A screening tool for identification of alcohol use disorders.

149 Biopsychosocial improve the health and safety of children Combining biological, psychological, and in child care. Title XXXV of the social concerns or effects. Children’s Health Act is the Drug Addiction Treatment Act of 2000 (DATA ® Buprenex (Generic: buprenorphine) 2000), which authorizes qualifying Injectable formulation of the Schedule III physicians to treat opioid addiction in narcotic (opioid) partial agonist buprenor- clinical settings other than the Opioid phine. Approved for use as an analgesic. Treatment Program (OTP) setting. Not approved for use in the treatment of opioid addiction. CINA Clinical Institute Narcotic Assessment Buprenorphine Scale for Withdrawal. An interview and An opioid partial agonist that is a syn- observation tool for assessing opioid thetic derivative of thebaine. Two sub- withdrawal signs and symptoms. lingual formulations of buprenorphine, the Schedule III pharmaceuticals COWS Subutex® (buprenorphine) and Suboxone® Clinical Opiate Withdrawal Scale. An (buprenorphine/naloxone), received Food interview and observation tool for and Drug Administration (FDA) approval assessing opioid withdrawal signs and in October 2000 for use in the treatment symptoms. ® of opioid addiction. Buprenex , an DAST 10 injectable formulation of buprenorphine, Drug Abuse Screening Test. A question- has previously been available in the naire tool for identification of drug and United States and is approved for use as a alcohol use disorders. parenteral analgesic. DATA 2000 Buprenorphine/naloxone See Drug Addiction Treatment Act of Drug combination; see separate defini- 2000. tions and brand name Suboxone®. Dependence CAGE-AID A condition manifested as a characteristic CAGE Questionnaire Adapted to Include set of withdrawal signs and symptoms Drugs. upon reduction, cessation, or loss of the active compound at cell receptors (a CAGE Questionnaire withdrawal syndrome). A screening tool for identification of alcohol use disorders (questions use words Drug Addiction Treatment Act of 2000 beginning with letters C, A, G, and E Title XXXV of the Children’s Health Act consecutively). of 2000. The Drug Addiction Treatment Act of 2000 (DATA 2000) establishes a Children’s Health Act of 2000 waiver authority for qualifying physicians (P.L. 106-310) to prescribe or dispense specially Legislation (Public Law) that authorizes approved Schedule III, IV, and V narcotic expanded research and services for a medications for the treatment of opioid variety of childhood health problems, addiction in clinical settings other than reauthorizes programs of the Substance the Opioid Treatment Program setting. Abuse and Mental Health Services Administration (SAMHSA), addresses the HIPAA problem of youth substance abuse and the Health Insurance Portability and violence associated with it, and works to Accountability Act.

150 Glossary LAAM and addiction through drug-induced Closely related to methadone, the synthe- activation. When an opioid agonist, or tic compound levo-alpha-acetyl-methadol partial agonist (e.g., buprenorphine), or LAAM (Brand name: ORLAMM®), has binds to a mu opioid receptor, a series of an even longer duration of action (from 48 other proteins associated with the mu to 72 hours) than methadone, permitting a receptor-signalling pathway becomes reduction in frequency of use. In 1994, it activated. Other opioid receptors are the was approved as a Schedule II treatment delta and kappa receptors. drug for narcotic addiction. Both metha- Naloxone done and LAAM have high abuse poten- Brand name: Narcan®. An opioid antag- tial. Their acceptability as narcotic onist, similar to naltrexone, that works by treatment drugs is predicated on their blocking opioid receptors in the brain, ability to substitute for heroin, the long thereby blocking the effects of opioid full duration of action, and their mode of oral agonists (e.g., heroin, morphine) and administration. partial agonists (e.g., buprenorphine). MAST Naltrexone Michigan Alcohol Screening Test. A Naltrexone, a narcotic antagonist, works questionnaire tool for identification of by blocking opioid receptors in the brain alcohol use disorders. and therefore blocking the effects of opioid full agonists (e.g., heroin, mor- MCV phine) and partial agonists (e.g., Mean corpuscular volume. buprenorphine). Methadone NATA A Schedule II synthetic opioid with Narcotic Addict Treatment Act. pharmacologic actions similar to morphine and heroin; almost equally addictive. Needle embolization Approved for use in the treatment of Blood clot caused by use of a needle. If opioid addiction in federally regulated dislodged, the clot may cause death. Opioid Treatment Programs. May be administered orally, intramuscularly, and Nonopioid subcutaneously. Drug or compound not related to natural or synthetic opium and related alkaloids. Monotherapy Therapy using one drug or approach. OAT Opioid Agonist Treatment. Morphine Most active narcotic alkaloid of opium. Opioids Has powerful analgesic action; abuse leads Drugs that are derived naturally from the to dependence. flower of the opium poppy plant (e.g., morphine and heroin) and those that are Mu agonist synthetically produced in the lab (e.g., A drug that has affinity for and stimulates methadone and oxycodone). physiologic activity at mu opioid cell receptors. See also opioid full agonist. Used therapeutically to treat pain, but also produce a sensation of euphoria—the Mu opioid receptor narcotic “high.” Repeated misuse and A receptor on the surface of brain cells abuse of opioids often leads to dependence that mediates opioid analgesia, tolerance, and addiction.

Glossary 151 Opioid full agonist as smoking tobacco, snorting cocaine, Drugs that have affinity for and stimulate inhaling glue fumes). physiologic activity at opioid cell receptors (mu, kappa, and delta) that are normally Psychosocial stimulated by naturally occurring opioids. Combining psychological and social Repeated administration often leads to aspects. dependence and addiction. SMAST Opioid partial agonist Short Michigan Alcohol Screening Test. Drugs that can both activate and block Shortened, self-administered version of opioid receptors, depending on the clinical the MAST alcohol use disorder screening situation. Partial agonists have properties tool. of both agonists and antagonists. The mu SOWS agonist properties of partial agonists Subjective Opioid Withdrawal Scale. Self- reach a maximum at a certain dose and do administered scale for grading opioid not continue to increase with increasing withdrawal symptoms. doses of the partial agonist. This is termed the ceiling effect. The ceiling effect limits Sublingual the abuse potential and untoward side Under the tongue. effects of opioid partial agonists. The Schedule III medication buprenorphine is Suboxone® an opioid partial agonist. Brand name for the Schedule III sublingual formulation of buprenorphine Parenteral combined with naloxone. Received FDA Not through the gastrointestinal route; for approval in October 2000 for use in the instance, given via intramuscular or treatment of opioid addiction. Naloxone is intravenous injection. added to the formulation to decrease the likelihood of abuse of the combination via Pharmacodynamics the parenteral route. Study of the biochemical and physiological effects of drugs and the mechanisms of Subutex® their actions, including correlation of Brand name for the Schedule III sub- these actions and effects with the drugs’ lingual formulation of buprenorphine. chemical structure. Received FDA approval in October 2000 for use in the treatment of opioid Pharmacokinetics Study of the action of drugs in the body addiction. over a period of time, including the Talc granulomatosis processes of absorption, distribution, Formation of granulomas (small nodules) localization in tissues, biotransformation, as a chronic inflammatory response, in the and excretion. lungs or other organs, in this case to talc or other fine powder. Talc granulomatosis Pharmacotherapy Treatment of disease by using medicines. may occur in drug users because many injected drugs have been adulterated with Polysubstance abuse an inert substance (such as talcum Concurrent use or abuse of multiple powder) to cut or dilute the amount of substances (e.g., drinking alcohol as well drug.

152 Glossary Appendix J Field Reviewers

Emizie Abbott, CCDC III Judith A. Arroyo, Ph.D. Executive Director Coordinator Cleveland Treatment Center, Inc. Project COMBINE Cleveland, Ohio Center on Alcoholism, Substance Abuse and Addictions Patrick Abbott, M.D. University of New Mexico Center on Alcoholism, Substance Abuse Albuquerque, New Mexico and Addiction Albuquerque, New Mexico Candace L. Baker, MAC, ACSW Director, Clinical Issues Cynthia E. Aiken, M.S., LPA The National Association of Alcoholism Executive Director and Drug Abuse Counselors Narcotic Drug Treatment Center, Inc. Arlington, Virginia Anchorage, Alaska

Doug Allen, M.S.W. Doug Baker Administrator Head, Adult Services Branch Planning Policy and Legislative Relations Substance Abuse Services Section Division of Alcohol and Substance Abuse Division of Mental Health, Developmental Department of Social & Health Services Disabilities and Substance Abuse Services State of Washington State of North Carolina Olympia, Washington Raleigh, North Carolina

Leslie Amass, Ph.D. Roxanne Baker Principal Investigator Director of Nor-Cal NAMA Friends Research Institute, Inc. Northern California National Alliance of Los Angeles, California Methadone Advocates Santa Cruz, California Robert E. Anderson Director, Research and Program Applications Steve Batki, M.D. National Association of State Alcohol and Professor and Director of Research Drug Abuse Directors Department of Psychiatry Washington, District of Columbia Upstate Medical University Syracuse, New York Gerard Armstrong Deputy Director Managed Care/Health and Revenue Services Ann Belk Office of Alcoholism and Substance Abuse Program Analyst Services Office of Diversion Control State of New York Drug Enforcement Administration New York, New York Washington, District of Columbia

153 Mark Beresky Michael F. Brooks, D.O. Secretary/Treasurer Medical Director The Vermont Harm Reduction Coalition Saline Community Hospital Co-Director, The New England Chapter of the Greenbrook Recovery Center National Alliance of Methadone Advocates Saline, Michigan Putney, Vermont Lawrence Brown, M.D., M.P.H. Bruce J. Berg, M.D. Senior Vice President Vice President Medical Services Division of Medical Services Evaluation Magellan Behavioral Health and Research Bryn Mawr, Pennsylvania Addiction Research Corporation Robert Bick, M.A., SAC Brooklyn, New York Director Champlain Drug and Alcohol Services Andrew Byrne, M.D., B.S. Howard Center for Human Services Dependency Specialist, Medical Practitioner Burlington, Vermont Redfern, New South Wales Australia George Bigelow, Ph.D. Professor Jim Callahan, Ph.D. College on Problems of Drug Dependence Executive Vice President/Chief Executive Behavioral Pharmacology Research Unit Officer Behavioral Biology Research Center American Society of Addiction Medicine Johns Hopkins Bayview Campus Chevy Chase, Maryland Baltimore, Maryland James C. Carleton, M.S. Anton C. Bizzell, M.D. Director, Narcotic Treatment Programs Medical Officer CODAC Treatment Center, Inc. Division of Pharmacologic Therapies Providence, Rhode Island Center for Substance Abuse Treatment Substance Abuse and Mental Health Services Administration Louis Cataldie, M.D. Rockville, Maryland Medical Director Office for Addictive Disorders Jack Blaine, M.D. Department of Health and Hospitals Chief of Medications Research Grants Unit State of Louisiana National Institute on Drug Abuse Baton Rouge, Louisiana National Institutes of Health Bethesda, Maryland Susanne Caviness, Ph.D. Captain, U.S. Public Health Service Linda Brady, Ph.D. Division of State and Community Assistance Acting Chief of Molecular and Cellular Center for Substance Abuse Treatment Neuroscience Research Branch Substance Abuse and Mental Health Services National Institute of Mental Health Administration National Institutes of Health Rockville, Maryland Bethesda, Maryland Richard Christensen, P.A., CAS Judy Braslow Deputy Director for Policy Vice President and Director of Medical Substance Abuse and Mental Health Services Services Administration Community Medical Services Rockville, Maryland Phoenix, Arizona

154 Field Review Panel Darrell Christian, Ph.D. Joy Davidoff Clinical Psychologist Coordinator of Addiction Medicine New Leaf Treatment Center Office of Alcoholism and Substance Abuse Concord, California Services State of New York Barbara Cimaglio Albany, New York Administrator Office of Alcohol and Drug Abuse Programs Department of Human Services Peter A. DeMaria, Jr., M.D., FASAM State of Oregon Associate Professor of Psychiatry and Salem, Oregon Human Behavior Jefferson Medical College H. Westley Clark, M.D., J.D., M.P.H., Thomas Jefferson University CAS, FASAM Philadelphia, Pennsylvania Director Center for Substance Abuse Treatment Doug DeShong Substance Abuse and Mental Health Services Senior Product Manager, Suboxone Administration Schering Rockville, Maryland Kenilworth, Texas Denise Clayborn, Ph.D. Pamela Detrick, Ph.D., ARNPC Human Services Adult and Opioid Assistant Professor Replacement Consultant Office of Substance Abuse Services School of Nursing Department of Mental Health, Mental University of Miami Retardation and Substance Abuse Services Miami, Florida Commonwealth of Virginia Richmond, Virginia Herman I. Diesenhaus, Ph.D. Buprenorphine Workgroup Coordinator Edward J. Cone, Ph.D. Office of Evaluation, Scientific Analysis Chief Executive Officer and Synthesis Conechem Research Center for Substance Abuse Treatment Severna Park, Maryland Substance Abuse and Mental Health Services Administration Michael Couty, M.A. Rockville, Maryland Director Division of Alcohol and Drug Abuse Department of Mental Health Alice Diorio State of Missouri President Jefferson City, Missouri The Vermont Harm Reduction Coalition Co-Director, The New England Chapter of the Michael J. Crookston, M.D. National Alliance of Methadone Advocates Psychiatrist, Chemical Dependency Services Putney, Vermont LDS Hospital Salt Lake City, Utah Martin C. Doot, M.D. Chief Denise Curry Division of Addiction Medicine Chief of Liaison Unit Addiction Medicine/Family Practice Office of Diversion Control Drug Enforcement Administration Lutheran General Hospital Advocate Washington, District of Columbia Des Plaines, Illinois

Field Review Panel 155 Alfonzo Dorsey Michael Fingerhood, M.D. Director of Quality Control Associate Professor of Medicine Substance Abuse Treatment and Recovery Center for Chemical Dependence Department of Social and Rehabilitative Johns Hopkins Bayview Medical Center Services Baltimore, Maryland State of Kansas Topeka, Kansas Gary Fisher, Ph.D. Director and Professor Karen Downey, Ph.D. Center for the Application of Substance Abuse Assistant Professor Technologies Research Division on Substance Abuse University of Nevada, Reno Reno, Nevada Department of Psychiatry and Behavioral Neurosciences Luceille Fleming Wayne State University Director Detroit, Michigan Department of Alcohol and Drug Addiction Services Michael Duffy, R.N., CD State of Ohio Acting Assistant Secretary Columbus, Ohio Office of Alcohol and Drug Abuse Department of Health and Hospitals Paul Fudala, Ph.D. State of Louisiana Clinical Toxicologist Baton Rouge, Louisiana Philadelphia VA Medical Center Philadelphia, Pennsylvania Joel Egerston Special Assistant to the Director Robert Fuller, M.D. National Institute on Drug Abuse Director National Institutes of Health Division of Clinical & Preventative Research Bethesda, Maryland National Institute on Alcohol Abuse and Alcoholism John P. Epling, M.D. National Institutes of Health 2303 Line Avenue Rockville, Maryland Shreveport, Louisiana George R. Gilbert, J.D. Director, Office of Policy Coordination Virginia H. Ervin, B.S.N., CARN, COHN and Planning Utilization Review Case Manager Center for Substance Abuse Treatment Department of Alcohol and Other Drug Abuse Substance Abuse and Mental Health Services Services Administration State of South Carolina Rockville, Maryland Columbia, South Carolina Daniel J. Glatt, M.D., M.P.H. Garland S. Ferguson Fellow, Substance Abuse Director, Division of Treatment Services San Francisco VA Medical Center Bureau of Alcohol and Drug Abuse San Francisco, California Prevention Department of Health William Glatt, M.D. State of Arkansas Primary Care Physician Freeway Medical Center Internal Medicine and Addiction Medicine Little Rock, Arkansas South San Francisco, California

156 Field Review Panel Angel A. González, M.D. Reva Harris, M.B.A., B.S. Senior Surgeon, U.S. Public Health Service Fellow Division of Pharmacologic Therapies Office of Congressman Charles Rangel Center for Substance Abuse Treatment Washington, District of Columbia Substance Abuse and Mental Health Services Administration John Harsany, Jr., M.D. Rockville, Maryland Medical Director Riverside County Substance Abuse Program Marc Gourevitch, M.D. Hemet, California Medical Director Division of Substance Abuse Dory Hector Albert Einstein College of Medicine State Methadone Authority Yeshiva University Division of Substance Abuse Services Bronx, New York Department of Mental Health and Mental Retardation Prakash L. Grover, Ph.D., M.P.H. State of Alabama Senior Science Advisor Montgomery, Alabama Center for Substance Abuse Treatment Substance Abuse and Mental Health Services Renata J. Henry Administration Director Rockville, Maryland Division of Alcoholism, Drug Abuse, and Mental Health Jack Gustafson Department of Health and Social Services Executive Director State of Delaware National Association of State Alcohol and New Castle, Delaware Drug Abuse Directors Washington, District of Columbia James Herrera, M.A., NCC, LPCC Senior Counselor Susan W. Haikalis, LCSW Center on Alcoholism, Substance Abuse, Director and Addictions University of New Mexico HIV Services and Treatment Support Albuquerque, New Mexico San Francisco AIDS Foundation San Francisco, California Edward J. Higgins, M.A. Executive Director William F. Haning III, M.D., FASAM Jersey Shore Addiction Services, Inc. Associate Dean Asbury Park, New Jersey John A. Burns School of Medicine University of Hawaii John Hopper, M.D. Honolulu, Hawaii Medical Director UPC Opiate Dependence Treatment Michael Harle Detroit, Michigan President/Executive Director Gaudenzia, Inc. Elizabeth F. Howell, M.D. Norristown, Pennsylvania Senior Medical Editor Atlanta, Georgia Dana Harlow, LISW, CCDC III-E Manager Ronald J. Hunsicker, D.Min., FACATA Department of Alcohol and Drug Addiction President/Chief Executive Officer Services National Association of Addiction Treatment State of Ohio Providers Columbus, Ohio Lititz, Pennsylvania

Field Review Panel 157 Ray Hylton, M.S.N., R.N. Janice F. Kauffman, M.P.H., R.N., CAS Division of Pharmacologic Therapies Director, Substance Abuse Treatment Services Center for Substance Abuse Treatment North Charles, Inc. Substance Abuse and Mental Health Services Director, Addiction Psychiatry Service Administration Brigham and Women’s Hospital Rockville, Maryland Assistant Professor of Psychiatry Harvard Medical School Jerome Jaffe, M.D. Somerville, Massachusetts Clinical Professor of Psychiatry University of Maryland Chris Kelly Towson, Maryland President, DC-Chapter Advocates for Recovery Through Medicine Donald R. Jasinski, M.D. Washington, District of Columbia Chief Center for Chemical Dependence Maureen Kerrigan, J.D. Johns Hopkins Bayview Medical Center Policy and Legislative Analyst Baltimore, Maryland Center for Substance Abuse Treatment Substance Abuse and Mental Health Services Kimberly Johnson Administration Director Amesbury, Massachusetts Office of Substance Abuse State of Maine Steven Kipnis, M.D., FACP Augusta, Maine Medical Director Blaisdell Addiction Treatment Center Rolley E. Johnson, Pharm.D. Orangeburg, New York Associate Professor Department of Psychiatry and Behavioral Monika Koch, M.D. Sciences Addiction Psychiatrist Behavioral Pharmacology Research Unit Friends Research Associates Johns Hopkins University School of Medicine Berkeley, California Baltimore, Maryland Thomas R. Kosten, M.D. Linda R. Wolf Jones, D.S.W. Professor Executive Director Department of Psychiatry Therapeutic Communities of America Yale University Washington, District of Columbia American Academy of Addiction Psychiatry VA Connecticut Healthcare System Herman Joseph, Ph.D. Research Scientist West Haven, Connecticut Office of Alcoholism and Substance Abuse Services Ottis L. Layne, M.D. State of New York Medical Director New York, New York Emergency Department Hill County Memorial Hospital George Kanuck Fredericksburg, Texas Public Health Analyst Center for Substance Abuse Treatment Ira Lubell, M.D., M.P.M. Substance Abuse and Mental Health Services Medical Director Administration Santa Clara Valley Medical Center Rockville, Maryland San Jose, California

158 Field Review Panel Robert Lubran, M.S., M.P.A. John J. McGovern, CSW Director Director Division of Pharmacologic Therapies Clinical Services Center for Substance Abuse Treatment HELP/Project Samaritan, Inc. Substance Abuse and Mental Health Services Bronx, New York Administration Rockville, Maryland Kathleen McGowan, J.D. Legislative Assistant James W. Luckey, Ph.D. Office of Senator Moynihan Associate Director Washington, District of Columbia Substance Abuse Research Group Westat Paul McLaughlin Rockville, Maryland Executive Director Hartford Dispensary Stephen Magura, Ph.D., CSW Hartford, Connecticut Director Institute for Treatment and Services Research John Mendelson, M.D. National Development and Research Institutes Associate Clinical Professor Psychiatry and New York, New York Medicine Drug Dependence Research Center University of California at San Francisco Kathleen Masis, M.D. San Francisco, California Medical Officer for Chemical Dependency Office of Health Care Robert Miller, M.A. Billings Area Indian Health Service Operations Manager U.S. Department of Health and Office of Alcohol and Drug Abuse Programs Human Services Department of Human Services Billings, Montana State of Oregon Salem, Oregon Stephen S. Mason Director Sharon Morello, R.N., B.S.N. Office of Behavioral Health Services Nursing Care Evaluator Division of Alcoholism and Drug Abuse Division of Substance Abuse Department of Health and Human Resources Department of Mental Health, Retardation State of West Virginia and Hospitals Charleston, West Virginia State of Rhode Island Cranston, Rhode Island Mary Mayhew Congressional Division Don Myers National Institute on Drug Abuse Treatment Field Manager/State Methadone National Institutes of Health Authority Bethesda, Maryland Alcohol and Drug Abuse Division Department of Human Services Philip S. McCullough State of Colorado Director Denver, Colorado Bureau of Substance Abuse Services Division of Supportive Living David K. Nace, M.D. Department of Health and Family Services Senior Vice President State of Wisconsin United Behavioral Health Madison, Wisconsin Philadelphia, Pennsylvania

Field Review Panel 159 Madeline A. Naegle, Ph.D., R.N., C.S., J. Thomas Payte, M.D. FAAN Medical Director Associate Professor Drug Dependence Associates Division of Nursing San Antonio, Texas School of Education New York University Lillian Pickup New York, New York Administrator Department of Alcoholism and Substance Susan F. Neshin, M.D. Abuse Medical Director State of Illinois Jersey Shore Addiction Service, Inc. Chicago, Illinois Asbury Park, New Jersey Deborah Powers Thomas Nicholson, Ph.D., M.P.H., M.A.Ed. State Methadone Authority Professor Bureau of Substance Abuse Services Department of Public Health State of Wisconsin Western Kentucky University Madison, Wisconsin Bowling Green, Kentucky Sandi Record Edward V. Nunes, M.D. Director Research Psychiatrist and Assistant Professor Treatment, Prevention and Program of Clinical Psychiatry Department New York State Psychiatric Institute Office for Addiction Disorder, Alcohol and New York, New York Drug Abuse State of Louisiana David Ockert, D.S.W. Baton Rouge, Louisiana Executive Director Parallax Center Nicholas Reuter, M.P.H. New York, New York Division of Pharmacologic Therapies Center for Substance Abuse Treatment Kerry O’Neil Substance Abuse and Mental Health Services Chief of Treatment Services Administration Division of Substance Abuse Rockville, Maryland Department of Mental Health, Retardation and Hospitals State of Rhode Island Michael Rizzi Cranston, Rhode Island Deputy Director CODAC Treatment Centers Patricia Isbell Ordorica, M.D. Cranston, Rhode Island James A. Haley Veterans’ Hospital Tampa, Florida Diedre Roach, M.D. Administrator Mark Parrino, M.P.A. Alcohol Prevention and Recovery President Administration American Methadone Treatment Association District of Columbia Department of Health New York City, New York Washington, District of Columbia

David Pating, M.D. Barbara T. Roberts, Ph.D. Medical Director Policy Analyst Chemical Dependency Recovery Program White House Office of National Drug Kaiser San Francisco Control Policy San Francisco, California Washington, District of Columbia

160 Field Review Panel June Ross, B.S., ICADC Larry Siegel, M.D. Executive Director Senior Deputy Director 12 12, Inc. Administrator Tulsa, Oklahoma Addiction Prevention and Recovery Administration Pedro Ruiz, M.D. District of Columbia Department of Health Mental Sciences Institute Washington, District of Columbia University of Texas Cynthia L. Spencer, D.O. Houston, Texas Medical Director Substance Abuse Services Richard Saitz, M.D., M.P.H. Lansing, Michigan Associate Professor of Medicine Clinical Addiction Research and Education George Stavros, M.D. (CARE) Unit Medical Director Section of General Internal Medicine Community Medical Services Boston Medical Center and Boston University Phoenix, Arizona School of Medicine Boston, Massachusetts Richard T. Suchinsky, M.D. Associate Chief for Addictive Disorders Jeff Samet, M.D., M.A., M.P.H. Mental Health and Behavioral Sciences Associate Professor Service Boston University School of Medicine U.S. Department of Veteran Affairs Boston, Massachusetts Washington, District of Columbia Kenneth Sunamoto, M.D. Sidney Schnoll, M.D., Ph.D. Medical Director Professor and Chairman Drug Addiction Services of Hawaii, Inc. Addiction Medicine Honolulu, Hawaii Medical College of Virginia Virginia Commonwealth University Karen Tannert, R.Ph. Richmond, Virginia Chief Pharmacist Drugs and Medical Devices Division Mary Schumacher Department of Health Director State of Texas Behavioral Health Services Division Austin, Texas Department of Health State of New Mexico Tony Tommasello, Ph.D. Santa Fe, New Mexico Department of Pharmacy Practice and Science University of Maryland School of Pharmacy Ian A. Shaffer, M.D. Baltimore, Maryland Principal Ian A. Shaffer & Associates, L.L.C. Alan Trachtenberg, M.D. Reston, Virginia Medical Director Division of Pharmacologic Therapies Steve Shoptow, Ph.D. Center for Substance Abuse Treatment Integrated Substance Abuse Programs Substance Abuse and Mental Health Services University of California at Los Angeles Administration Los Angeles, California Rockville, Maryland

Field Review Panel 161 Donald Weinbaum William Wood, M.D. Coordinator Chief Medical Officer Criminal Justice and Block Grant ValueOptions Planning Unit Falls Church, Virginia Division of Addiction Services Department of Health State of New Jersey George E. Woody, M.D. Trenton, New Jersey Professor Department of Psychiatry Richard Weisskopf Treatment Research Institute Manager Philadelphia, Pennsylvania Methadone Treatment Services Office of Alcoholism and Substance Abuse Richard Yoast, Ph.D. Department of Human Services State of Illinois Director Chicago, Illinois Office of Alcohol American Medical Association Donald R. Wesson, M.D. Chicago, Illinois Consultant, CNS Medications Development Oakland, California Leah Young Public Affairs Specialist Charles L. Whitfield, M.D. Office of Communication and External Liaison Private Practice of Addiction Medicine Atlanta, Georgia Center for Substance Abuse Treatment Substance Abuse and Mental Health Services Cheryl Williams Administration Director Rockville, Maryland Division of Drug and Alcohol Program Licensure Edward Zborower Department of Health Program Representative/State Methadone State of Pennsylvania Authority Harrisburg, Pennsylvania Bureau of Substance Abuse and General Jaslene Williams Mental Health Assistant Director Department of Health Services Division of Mental Health State of Arizona U.S. Virgin Islands Phoenix, Arizona Christiansted, Virgin Islands Steve Zukin Janet Wood Division of Treatment Research Director Alcohol and Drug Abuse Division and Development Department of Human Services National Institute on Drug Abuse State of Colorado National Institutes of Health Denver, Colorado Bethesda, Maryland

162 Field Review Panel Index

Abbot Laboratories ...... 8f abstinence-based treatment ...... 5 abuse of buprenorphine ...... 16–18, 23–24 actions towards change ...... 140 activation of receptors (see also mu receptors) ...... 14 addiction (see also opioid addiction) ...... 3 definition of ...... 136, 149 symptoms of ...... 30f adolescents ...... 71–73 adverse reactions to buprenorphine (see also contraindications to buprenorphine usage) ...... 43 affinity for receptors ...... 14, 15 agonists (see also full agonists; partial agonists) ...... 5, 11–12 alpha-adrenergic ...... 6 buprenorphine having properties of ...... 7 buprenorphine used with ...... 20 definition of ...... 136 opioid agonist treatment (OAT) ...... 58, 61, 62f tolerance development towards ...... 12 alcohol ...... 19 definition of alcoholism ...... 149 evaluating levels in blood ...... 33 interactions with buprenorphine ...... 47 patient assessment ...... 42 screening instruments for abuse of ...... 26 Alcohol Use Disorders Identification Test (AUDIT) ... 26, 105–106, 149 alpha-adrenergic agonists ...... 6 ambivalence towards drug addiction ...... 145 American Society of Addiction Medicine (ASAM) ...... 80 American Society of Addiction Medicine Patient Placement Criteria (ASAM PPC)...... 27 analgesia (see also pain management) ...... 75

163 antagonists ...... 11 Children’s Health Act (2000) ...... 2, 150 blocking receptors ...... 12 CINA (Clinical Institute Narcotic buprenorphine working as ...... 7 Assessment Scale for Withdrawal) .. 26, 110 combination with buprenorphine assessment of withdrawal ...... 31 warned against ...... 19–20 definition of ...... 150 conceptual representation of CIWA-Ar (Clinical Institute for opioid effect ...... 13f Withdrawal Assessment) ...... 113 definition of ...... 136, 149 Clinical Laboratory Improvement precipitating withdrawal ...... 13–14 Amendments (CLIA) (1988) ...... 35 as treatment modality ...... 5–6 clonidine ...... 6 antisocial personality disorder ...... 74 comorbid medical conditions (see also approved Schedule III–V opioids ...... 136 contraindications to buprenorphine assessment of patients (see also patient usage) ...... 37, 38f–40f, 67–68 assessment) ...... 25–47 comorbid psychiatric disorders ...... 73–74 AUDIT (Alcohol Use Disorders complications using buprenorphine. Identification Test) ...... 26, 105–106, 149 (See contraindications to buprenorphine usage.) baseline laboratory evaluation ...... 34f confidentiality of physicians ...... 83–84 benzodiazepines ...... 19, 42 consent to release of information form .....119 detection tests for ...... 129 contemplation of change ...... 140 interactions with buprenorphine .. 46–47 contracts for treatment ...... 64, 147 bioavailability for buprenorphine ...... 15–16 contraindications to buprenorphine biopsychosocial ...... 150 usage (See also comorbid medical blood alcohol levels ...... 33 conditions) ...... 45–47 breast feeding ...... 70 elevation in liver enzymes ...... 18–19 Buprenex® ...... 7 hypersensitivity ...... 43 definition of ...... 150 pregnancy (see also pregnancy) ....68–71 dosage for ...... 8f controlled environments, patients not approved by Food and Drug released from ...... 77–78 Administration (FDA) ...... 79 counseling ...... 63 buprenorphine COWS (Clinical Opiate Withdrawal definition of ...... 150 Scale) ...... 26, 111 detection tests for ...... 129 assessment of withdrawal ...... 31 dosage forms ...... 8f definition of ...... 150 naloxone combination (see also criminal justice system ...... 77–78 naloxone) ...... 150 cytochrome P450 3A4 enzyme ...... 19 drug interactions with CAGE-AID (CAGE Adapted to buprenorphine ...... 20, 68 Include Drugs) ...... 26, 103, 150 medications metabolized by ...... 21f CAGE Questionnaire ...... 26, 103, 150 metabolizing buprenorphine ...... 18 cancer, associated with opioid addiction....38f protease inhibitors ...... 45 cardiovascular disease ...... 12, 38f ceiling effect ...... 12, 15 DAST-10 (Drug Abuse Screening Center for Substance Abuse Test) ...... 26, 101–102, 150 Treatment (CSAT) ...... 122, 132, 139 DATA (2000). (See Drug Addiction Centers for Disease Control and Treatment Act [2000].) Prevention (CDC) ...... 33–34 DATOS. (See Drug Abuse Treatment central nervous system (CNS) ...... 19 Outcome Studies [DATOS].) change readiness ...... 128, 139–145 DAWN. (See Drug Abuse Warning child abuse ...... 72 Network [DAWN].)

164 Index delta receptors ...... 151 drug interactions ...... 19–20, 43 Department of Health and Human buprenorphine with sedative- Services (DHHS) ...... 80 hypnotics ...... 46–47 dependence, definition of (see also cytochrome P450 3A4 enzyme ...... 68 physical dependence) ...... 150 drug testing ...... 34–36, 65, 128–129 depression ...... 73, 74 DSM. (See Diagnostic and detoxification (see also medically Statistical Manual of Mental supervised withdrawal) ...... 6 Disorders [American Psychiatric Diagnostic and Statistical Manual of Association].) Mental Disorders (American Psychiatric dysthymia ...... 73 Association) ...... 36–37, 115–118, 134 dissociation from receptors ...... 14, 15 education for prevention ...... 63 dosage/dosage forms ...... 14 elderly persons ...... 73 adjustments made during emergency departments at hospitals ...... 4 stabilization phase ...... 56 endocrine disorders ...... 38f buprenorphine ...... 8f, 17 England ...... 16 drug interactions affecting ...... 68 enzyme multiplied immunoassay increases in ...... 15 test (EMIT) ...... 128 in induction phase of buprenorphine family history ...... 126 treatment ...... 52, 53f, 55f, 56 FDA. (See Food and Drug with opioid agonist treatment (OAT)...62f Administration [FDA].) overdosing with buprenorphine ...... 18 florescent polarization immunoassay parenteral dosage ...... 23 (FPIA) test ...... 128 reduction phase of treatment ...... 59, 61 flunitrazepam ...... 19 Drug Abuse Screening Test Food and Drug Administration (FDA) (DAST-10) ...... 26, 101–102, 150 approval of levo-alpha-acetyl- Drug Abuse Treatment Outcome methadol (LAAM) drug ...... 2 Studies (DATOS) ...... 5 buprenorphine classified as Drug Abuse Warning Network (DAWN) ...... 4 Pregnancy Category C drug ...... 69 Drug Addiction Treatment Act Clinical Laboratory Improvement (2000) ...... 2, 79–85 Amendments (CLIA) (1988) ...... 35 buprenorphine usage ...... 84–85 Suboxone® and Subutex® confidentiality and privacy ...... 83–84 approved by ...... 79 definition of ...... 150 42 C.F.R. Part 2 and 8 ...... 149 establishing treatment linkages ...... 82 FRAMES ...... 122, 123f policies and procedures for France ...... 7–8, 16 opioid addiction treatment ...... 83f full agonists (see also agonists; qualifications for waiver of partial agonists) ...... 7, 11–12 physicians ...... 132, 133 conceptual representation of training and experience for opioid effect ...... 13f physicians ...... 81–82 definition of ...... 152 waiver for practicing opioid addiction therapy ...... 63, 79–81 gas chromatography with mass drug administration (see also dosage/ spectrometry (GC/MS) ...... 128 dosage forms) ...... 14 gastrointestinal bioavailability for Drug Enforcement Administration buprenorphine (see also (DEA) ...... 76, 80 bioavailability for buprenorphine) ...... 15 Drug Registration Web site ...... 85 gastrointestinal disorders ...... 39f physicians having a registration genetic heritage ...... 3–4 number ...... 132 geriatric patients ...... 73

Index 165 HAART. (See highly active injection drug use ...... 4 antiretroviral therapies.) abuse of buprenorphine ...... 23 health care professionals as addicts ...... 78 human immunodeficiency Health Insurance Portability virus (HIV) ...... 37 Accountability Act (HIPAA)...... 150 increasing likelihood of infectious hematologic disorders ...... 38f disease ...... 67 hepatic effects ...... 18–19, 38f, 46 instruments for screening hepatitis C ...... 33–34, 68 patients ...... 26, 101–108 heroin interventions with FRAMES...... 122, 123f number of individuals addicted to ...... 4 interviews of patients (see also history taking for patient assessment) ...... 27–29 pregnancy, usage during ...... 68 determining appropriateness of as short-acting opioid ...... 52 buprenorphine usage ...... 41–43 timeline for withdrawal syndrome ..... 13 open-ended questions ...... 28f urine tests detecting ...... 65 quantifiable questions ...... 29f highly active antiretroviral therapies intoxication by opioids ...... 31f, 124 (HAART) ...... 68 intrinsic activity ...... 14 HIPAA (Health Insurance Portability Ireland ...... 16 Accountability Act) ...... 150 history of opioid addiction treatment ...... 1–3 kappa receptors ...... 151 history taking for patient assessment ...... 27–29, 122–128 LAAM. (See levo-alpha-acetyl-methadol drug treatment history ...... 124–125 [LAAM].) drug use history ...... 122–124 laboratory tests ...... 33–36, 65, 128–129 family history ...... 126 laws and regulations for opioid addiction function impairment ...... 127–128 treatment ...... 1–3, 149 medical history ...... 126–127 Children’s Health Act (2000) ...... 2, 150 psychiatric history ...... 125–126 Clinical Laboratory Improvement sexual history ...... 127 Amendments (CLIA) (1988) ...... 35 withdrawal symptoms ...... 124 consent to release of information human immunodeficiency virus (HIV) ...... 4 form ...... 119 as contraindication for buprenorphine Drug Addiction Treatment Act usage ...... 45–46 (2000) (see also Drug Addiction injection drug use ...... 37 Treatment Act [2000]) ...... 79–85 testing for ...... 33 Methadone Regulations (1972) ...... 1 hydrocodone ...... 4 for minors ...... 72 as short-acting opioid ...... 52 Narcotic Addict Treatment Act (1974) ...... 1–2, 79 timeline for withdrawal syndrome ..... 13 state medical board policy guidelines ...... 133 incarceration ...... 77–78 levo-alpha-acetyl-methadol (LAAM) India ...... 16 approved by Food and Drug induction phase of treatment (see Administration (FDA) ...... 2 also treatment of opioid buprenorphine used for addiction) ...... 50–51, 51–56, 59–61 discontinuation of ...... 61 infectious diseases ...... 33–34 definition of ...... 151 associated with opioid addiction....37, 39f as long-acting opioid ...... 50, 52, 54 human immunodeficiency virus (HIV) number of individuals (see also human immunodeficiency treated with ...... 5 virus [HIV]) ...... 4 treatment compared to from injection drug use ...... 67 buprenorphine ...... 21 informed consent ...... 134–135 withdrawal from ...... 58

166 Index liver ...... 18–19, 33 motivational enhancement therapy long-acting opioids ...... 52, 54 (MET) ...... 121–122 long-period withdrawal (see also mu agonist ...... 151 withdrawal/withdrawal syndrome) ... 22, 58 multiple substance abuse (see also polysubstance abuse) ...... 74 maintenance phase of treatment (see also mu receptors ...... 6 treatment of opioid addiction) ...... 58, 136 affinity, activation and maintenance towards change ...... 140–141 dissociation ...... 14, 15 manic behavior ...... 74 buprenorphine displacing MAST (Michigan Alcohol Screen other opioids ...... 7 Test) ...... 26, 107, 151 definition of ...... 151 medical boards, State ...... 131–137 opioid interaction with ...... 11 medical history of patient ...... 126–127 musculoskeletal disorders ...... 40f medically supervised withdrawal (see also withdrawal/withdrawal syndrome) ...... 6, 58–63 naloxone effectiveness of buprenorphine as antagonist ...... 12 treatment ...... 20–23 buprenorphine combined for short-acting opioids ...... 59–61 with ...... 8–9, 17, 23 time frame for ...... 22–23 combined with buprenorphine for induction treatment ...... 50 medical records ...... 135 ® metabolism (see also cytochrome as contraindication to Suboxone ...... 43 P450 3A4 enzyme) ...... 18 definition of ...... 151 methadone discontinuation of treatment buprenorphine, treatment with ...... 61, 63 compared to ...... 20–21 pregnant women cautioned buprenorphine displacing at against using ...... 70 mu receptor ...... 6 naltrexone buprenorphine used for adolescents, treatment for ...... 71 discontinuation of ...... 61 as antagonist ...... 5–6, 12 definition of ...... 151 blocking opioid effects ...... 22 detected by urine tests ...... 65, 129 combination with buprenorphine introduction in 1960s ...... 1 warned against ...... 20 as long-acting opioid ...... 50, 52, 54 definition of ...... 151 number of individuals health care professionals using ...... 78 treated with ...... 5 number of individuals treated with ...... 5 for pain management ...... 76 Narcan® ...... 151 pregnant women using ...... 42, 68–69, 71 Narcotic Addict Treatment Act psychiatric disorders, (1974) ...... 1, 2, 79 patients with ...... 73–74 Narcotics Anonymous (NA) ...... 5, 63 timeline for withdrawal syndrome ..... 13 Narcotic Withdrawal Scale ...... 26, 109 withdrawal from ...... 58 NAS (neonatal abstinence syndrome) ...69–70 Methadone Regulations (1972) ...... 1 National Clearinghouse for Alcohol moderate-period withdrawal (see also and Drug Information (NCADI)...... 5 withdrawal/withdrawal syndrome) ...... 22 National Institute on Drug Abuse monotherapy ...... 151 (NIDA) ...... 7, 50 morphine National Institutes of Health (NIH) ...... 34 buprenorphine displacing at mu NCADI. (See National Clearinghouse receptor ...... 6 for Alcohol and Drug Information buprenorphine more potent than ...... 15 [NCADI].) definition of ...... 151 needle embolization ...... 151 detected by urine tests ...... 129 neonatal abstinence syndrome (NAS) ...69–70

Index 167 neonates (see also pregnancy) ...... 68–71 patient assessment ...... 25–47, 121–129 neurologic disorders ...... 39f contraindications to New Zealand ...... 16 buprenorphine usage ...... 45–47 nonopioid drug ...... 151 controlled environments, patients norbuprenorphine ...... 18, 69 released from ...... 77–78 Notification of Intent for physicians ...... 80 determining appropriateness of nutritional disorders ...... 39f buprenorphine usage ...... 41–47 diagnosis of opioid-related OAT (opioid agonist disorders ...... 36–37 treatment) ...... 52, 58, 61, 62f history taking for (see also Office of National Drug Control Policy history taking for patient (ONDCP) ...... 4 assessment) ...... 27–29, 122–128 opioid addiction (see also injection instruments for ...... 101–113 drug use) ...... 3 interviews of patients (see also compared to pain management interviews of patients) ...... 27–29 patients ...... 75f laboratory tests ...... 33–36, 128–129 DSM criteria for ...... 115–118 medical conditions associated opioid addiction treatment. (See with opioid addiction ...... 37, 38f–40f treatment of opioid addiction.) mental status examination .... 31, 32f, 33 opioid agonist treatment motivational enhancement (OAT) ...... 52, 58, 61, 62f therapy ...... 121–122 opioid dependence ...... 136 physical examinations ...... 29, 30f, 31 opioid receptors (see also mu receptors) ... 11 questions for patients ...... 41–43, 44f opioids, definition ...... 136, 151 screening ...... 25–26, 34–36, 101–108 opioid treatment program (OTP) signs of opioid intoxication/ (see also treatment of opioid addiction) ...... 136 overdose ...... 31f state medical board policy ORLAMM® ...... 151 overdosing ...... 18 guidelines ...... 133–134, 135 assessing history of drug use ...... 124 withdrawal/withdrawal syndrome signs of ...... 31f (see also withdrawal/withdrawal oxycodone ...... 3 syndrome) ...... 109–113 deaths related to ...... 4 patient management (see also detection tests for ...... 129 special populations) ...... 63–66 as short-acting opioid ...... 52 adolescents/young adults ...... 71–73 timeline for withdrawal ...... 13 controlled environments, patients released from ...... 77–78 pain management ...... 20, 74–76 privacy issues ...... 83–84 parental consent ...... 72 perinatal effects (see also parenteral dosage ...... 23, 152 pregnancy) ...... 19, 39f partial agonists (see also agonists; full perioperative disorders ...... 39f agonists) ...... 12 personality disorders ...... 74 buprenorphine as ...... 15 pharmacodynamics ...... 152 conceptual representation of pharmacokinetics ...... 152 opioid effect ...... 13f pharmacology ...... 11–24 definition of ...... 136–137, 152 of buprenorphine ...... 14–18 precipitating withdrawal ...... 14 general opioid ...... 11–14

168 Index pharmacotherapy ...... 4, 5–9, 152 preparation for change ...... 140 physical dependence prison, patients released from ...... 77–78 abuse potential of privacy for patients ...... 83–84, 119 buprenorphine ...... 17–18, 23–24 protease inhibitors ...... 45 buprenorphine not producing ...... 7 psychiatric disorders ..... 73–74, 118, 125–126 definition of ...... 3, 137 psychosocial issues ...... 4–5, 152 in DSM definition of substance family history ...... 126 dependence ...... 115 motivational enhancement patients not exhibiting ...... 54 therapy (MET) ...... 121–122 result of repeated opioid usage ...... 12 as part of patient evaluation ....42, 77–78 physical examinations ...... 29, 30f, 31 readiness to change ...... 128 physicians social support as part of addiction treatment providers, attributes treatment ...... 63–64 of effective ...... 28f pulmonary disorders ...... 40f adolescents, treating ...... 71–73 attitude in interviews ...... 27 questions for patients ...... 28, 28f, 29f confidentiality and privacy .... 83–84, 84f DATA 2000 waiver qualifications ...... 2 radio-immunoassay (RIA) test ...... 128 interventions with FRAMES ... 122, 123f readiness to change ...... 128, 139–145 Readiness to Change Questionnaire ...... 145 medical history assessment, receptors (see also mu receptors) ...... 11 included in ...... 126 recidivism ...... 77 network for treatment ...... 82 Reckitt Benckiser company ...... 7, 8f patient management ...... 63–64 recognition of drug addiction ...... 145 patients released from controlled Recovery Attitude and Treatment environments ...... 77–78 Evaluator (RAATE) ...... 145 policies and procedures for opioid recovery environment ...... 128 addiction treatment ...... 83f referrals ...... 135 referrals to other specialists ...... 135 regulations for opioid addiction. state medical board policy (See laws and regulations for guidelines ...... 131–132 opioid addiction.) training and experience for opioid relapses ...... 43, 61, 78 addiction treatment ...... 81–82 assessing history of drug use ...... 124 waiver for practicing opioid addiction in DSM definition of substance therapy (see also waiver for dependence ...... 116 practicing opioid addiction as stage of change ...... 141 therapy) ...... 79–81, 137 remission ...... 116 polysubstance abuse ...... 74, 152 renal disorders ...... 40f posttraumatic stress disorder ...... 74 respiratory depression ...... 18 precipitated withdrawal (see also risk factors for addiction ...... 3–4 withdrawal/withdrawal syndrome) ...... 13–14, 19 safety with buprenorphine ...... 18–19 precontemplation of change ...... 140 SAMHSA. (See Substance Abuse pregnancy ...... 19 and Mental Health Services buprenorphine/naloxone Administration [SAMHSA].) combination warned against...... 23 Schedule III–V opioids ...... 136 as contraindication for Scotland ...... 16 buprenorphine usage ...... 46, 68–71 screening patients (see also patient disorders associated with opioid assessment) ...... 25–26, 34, 101–108 addiction ...... 39f sedative-hypnotic drugs ...... 42, 46–47 methadone usage ...... 43 seizures ...... 45

Index 169 self-help programs Suboxone® assessing history of drug use ...... 125 approved by Food and Drug pain management patients ...... 76 Administration (FDA) ...... 2, 7, 79 12-Step programs ...... 5, 63 breast feeding ...... 70 sexual history ...... 127 contraindication to ...... 43 sexually transmitted diseases (STDs) ... 34, 67 definition of ...... 152 short-acting opioids ...... 52, 59–61 dosage for ...... 8f short-period withdrawal (see also substance abuse ...... 137 withdrawal/withdrawal syndrome) ....22–23 Substance Abuse and Mental Health side effects of buprenorphine ...... 18 Services Administration (SAMHSA) ...... 2 Skinner Trauma History ...... 103 buprenorphine usage ...... 84–85 sleep disorders ...... 40f certified laboratories ...... 36 SMAST (Short Michigan Alcohol Drug Abuse Warning Network Screening Test) ...... 26 (DAWN) (see also Drug Abuse definition of ...... 152 Warning Network [DAWN]) ...... 4 sample form ...... 108 physicians notifying of intent to smoking/snorting heroin ...... 4 treat opioid addiction ...... 80 SOWS (Subjective Opiate Withdrawal physicians obtaining opioid treatment Scale) ...... 26, 31 waiver from ...... 63, 132, 133, 137 definition of ...... 152 testing procedures for opioid usage .... 65 training programs for Drug Addiction sample form ...... 112 Treatment Act (2000) ...... 80 special populations ...... 67–78 Web site ...... 2, 3 adolescents/young adults ...... 71–73 Subutex® comorbid medical conditions, abuse of ...... 50 patients with ...... 37, 38f–40f, 67–68 adverse reactions to ...... 43 controlled environments, patients approved by Food and Drug released from ...... 77–78 Administration (FDA) ...... 2, 7, 79 geriatric patients ...... 73 breast feeding ...... 70 health care professionals who definition of ...... 152 become addicted ...... 78 dosage for ...... 8f patients treated for pain ...... 74–76 suicidal tendencies ...... 74 pregnant women and neonates ...... 68–71 support system ...... 128 psychiatric disorders, patients symptoms of addiction ...... 30f with...... 73–74 symptoms of withdrawal syndrome spontaneous withdrawal (see also (see also withdrawal/withdrawal withdrawal/withdrawal syndrome) ....12–13 syndrome) ...... 12, 32f stabilization phase of treatment ...... 56–58 syphilis ...... 34 Stages of Change Readiness and Treatment Eagerness Scale talc granulomatosis ...... 152 (SOCRATES) ...... 43, 142–145 Temgesic® ...... 7 state medical boards ...... 131–137 Therapeutic Communities of America ...... 5 sublingual dosages ...... 7 tolerance administration of ...... 51 assessing history of drug use ...... 123 available as analgesic ...... 8 definition of ...... 3, 137 bioavailability for buprenorphine in DSM definition of substance from ...... 15–16, 16f dependence ...... 115 definition of ...... 152 result of repeated opioid usage ...... 12

170 Index toxicology screen (see also laboratory TWEAK Questionnaire ...... 104 tests) ...... 35, 65 12-Step programs ...... 5, 63 trauma induced by opioid usage ...... 40f 21 C.F.R. Part 2 ...... 91, 149 treatment of opioid addiction ...... 49–66 assessing history of drug use .....124–125 University of Rhode Island Change attributes of effective providers of Assessment (URICA) ...... 145 (see also physicians) ...... 28f urine tests ...... 35–36, 65, 128–129 buprenorphine used for ...... 6–9 contracts for ...... 64, 147 waiver for practicing opioid addiction current pharmacotherapy therapy ...... 79–81, 137 options for ...... 5–9 Drug Enforcement Administration current state of ...... 4–6 (DEA) registration number ...... 132 determining appropriateness of referrals for psychosocial networks ... 63 buprenorphine usage ...... 41–47 state medical boards ...... 133 discontinuation of treatment ...... 65–66 withdrawal/withdrawal syndrome (see effectiveness with also medically supervised buprenorphine ...... 20–23 withdrawal) ...... 6, 12–14 framework for beginning assessment of patients .... 31, 41, 109–113 dosages ...... 53f, 55f frequency of visits ...... 64–65 in beginning of buprenorphine history of ...... 1–3 treatment ...... 50–51, 54, 56 induction phase of ...... 50–51, 51–56 from buprenorphine ...... 17–18 maintenance phase of treatment ...... 58 consequences of repeated from monitoring ...... 64–65 opioids ...... 12 patient management (see also definition of ...... 3 patient management) ...... 63–66 neonatal abstinence syndrome policy guidelines, state medical (NAS) ...... 70 boards ...... 131–137 patient beginning before treatment .... 52 short-acting opioids ...... 59–61 precipitated ...... 13–14, 19 stabilization phase of treatment ....56–58 spontaneous ...... 12–13 state medical board policy staging/grading symptoms of ...... 32f guidelines ...... 133–135 symptoms of ...... 12 withdrawal at beginning of ...... 50–51 tuberculosis ...... 34, 37 young adults ...... 71–73

Index 171 Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction

This Treatment Improvement Protocol (TIP), Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction, provides consensus- and evidence-based treatment guidance for the use of buprenorphine, a new option for the treatment of opioid addiction. The goal of this TIP is to provide physicians with information they can use to make practical and informed decisions about the use of buprenorphine to treat opioid addiction. These guidelines address the pharmacology and physiology of opioids, opioid addiction, and treatment with buprenorphine; describe patient assessment and the choice of opioid addiction treatment options; provide detailed treatment protocols for opioid withdrawal and maintenance therapy with buprenorphine; and include information on the treatment of special populations, e.g., pregnant women, adolescents, and polysubstance users. This TIP represents another step by the Center for Substance Abuse Treatment (CSAT) toward its goal of bringing national leaders together to improve substance use disorder treatment in the United States.

Collateral Products Based on TIP 40

Quick Guide for Physicians

DHHS Publication No. (SMA) 04-3939 Printed 2004

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Substance Abuse and Mental Health Services Administration Center for Substance Abuse Treatment