Incorporating Alcohol
`Pharmacotherapies
`Into Medical Practice
`
`A Treatment
`Improvement
`Protocol
`TIP
`49
`
`U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
`Substance Abuse and Mental Health Services Administration
`Center for Substance Abuse Treatment
`www.samhsa.gov
`
` PHARMACO­
`
`THERAPIES
`
`ALKERMES EXHIBIT 2008
`Amneal Pharmaceuticals LLC v. Alkermes Pharma Ireland Limited
`IPR2018-00943
`
`Page 1 of 126
`
`

`

`Incorporating Alcohol
`Pharmacotherapies Into
`Medical Practice
`
`Treatment Improvement Protocol (TIP) Series
`
`49
`
`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
`
`
`
`Page 2 of 126
`
`

`

`Acknowledgments
`This publication was produced under
`the Knowledge Application Program,
`contract number 270-04-7049, a Joint
`Venture of The CDM Group, Inc., and
`JBS International, Inc., for the Center
`for Substance Abuse Treatment (CSAT),
`Substance Abuse and Mental Health
`Services Administration (SAMHSA),
`U.S. Department of Health and Human
`Services (HHS). Christina Currier served
`as the CSAT Government Project Officer.
`
`Disclaimer
`The views, opinions, and content
`expressed herein are those of the expert
`panel and do not necessarily reflect the
`views, opinions, or policies of CSAT,
`SAMHSA, or HHS. No official support of
`or endorsement by CSAT, SAMHSA, or
`HHS for these opinions or for particular
`instruments, software, or resources is
`intended or should be inferred.
`
`Public Domain Notice
`All materials appearing in this
`
`volume except those taken directly
`
`from copyrighted sources are in the
`
`public domain and may be reproduced
`or copied without permission from
`SAMHSA/CSAT or the authors. Citation
`of the source is appreciated. However,
`this publication may not be reproduced
`or distributed for a fee without the
`
`
`
`specific, written authorization of the
`Office of Communications, SAMHSA,
`HHS.
`
`
`
`
`
`
`
` Electronic Access and Copies
`
`of Publication
`This publication may be downloaded
`or ordered at http://www.samhsa.gov/
`shin. Or, please call SAMHSA’s Health
`Information Network at 1-877-SAMHSA-7
`(1-877-726-4727) (English and Español).
`
`Recommended Citation
`Center for Substance Abuse Treatment.
`Incorporating Alcohol Pharmacotherapies
`Into Medical Practice. Treatment
`Improvement Protocol (TIP) Series 49.
`HHS Publication No. (SMA) 09-4380.
`Rockville, MD: Substance Abuse and
`Mental Health Services Administration,
`2009.
`
`Originating Office
`Quality Improvement and Workforce
`Development Branch, Division of Services
`Improvement, Center for Substance
`Abuse Treatment, Substance Abuse and
`Mental Health Services Administration,
`1 Choke Cherry Road, Rockville, MD
`20857.
`
`HHS Publication No. (SMA) 09-4380
`Printed 2009
`
`
`
`Page 3 of 126
`
`

`

`Contents
`
`
`
`
` Consensus Panel....................................................................................................................... vii
`
`
`
`
` Expert Advisory Board ........................................................................................................... ix
`
`
`
`
` What Is a TIP? ............................................................................................................................ xi
`
`
`Foreword ...................................................................................................................................xiii
`
`
`
`Chapter 1—Introduction ...........................................................................................................1
`
`
`Alcohol Use Disorders in Medical Settings .............................................................................1
`
`
`Audience for TIP 49 ..................................................................................................................2
`
`
`Recognition of Alcohol Dependence as a Chronic Illness .......................................................3
`
`
`Purpose of TIP 49......................................................................................................................3
`
`
`What TIP 49 Does Not Cover...................................................................................................4
`
`
`
`Specialty Treatment Versus Screening and Brief Intervention ............................................5
`
`
`Why Use Medications To Treat Alcohol Dependence? ...........................................................5
`
`
`Format, Approach, and Organization of TIP 49 .....................................................................7
`
`
`
`Chapter 2—Acamprosate...........................................................................................................9
`
`
`What Is Acamprosate?..............................................................................................................9
`
`
`Why Use Acamprosate?..........................................................................................................10
`
`
`How Is Acamprosate Used?....................................................................................................11
`
`
`Who Is Appropriate for Treatment With Acamprosate? ......................................................13
`
`
`Treatment Duration and Discontinuing Acamprosate.........................................................14
`
`
`Final Clinical Thoughts..........................................................................................................14
`
`
`
`Chapter 3—Disulfiram .............................................................................................................15
`
`
`What Is Disulfiram?................................................................................................................15
`
`Why Use Disulfiram?..............................................................................................................18
`
`
`How Is Disulfiram Used? ......................................................................................................19
`
`
`Who Is Appropriate for Treatment With Disulfiram?..........................................................25
`
`
`Treatment Duration and Discontinuing Disulfiram.............................................................25
`
`
`Final Clinical Thoughts..........................................................................................................26
`
`
`
`iiiiii
`
`Page 4 of 126
`
`

`

`
` Chapter 4—Oral Naltrexone ...................................................................................................27
`
` What Is Oral Naltrexone? ......................................................................................................27
`
`
` Why Use Oral Naltrexone?.....................................................................................................28
`
`
` How Is Oral Naltrexone Used? ..............................................................................................29
`
`
` Who Is Appropriate for Treatment With Oral Naltrexone?.................................................34
`
`
`
`Treatment Duration and Discontinuing Oral Naltrexone ...................................................35
`
`
`Final Clinical Thoughts .........................................................................................................35
`
`
`
`Chapter 5—Extended-Release Injectable Naltrexone......................................................37
`
`
`What Is Extended-Release Injectable Naltrexone? ..............................................................37
`
`
`Why Use Extended-Release Injectable Naltrexone?.............................................................38
`
`
`How Is Extended-Release Injectable Naltrexone Used? ......................................................39
`
`
`Who Is Appropriate for Treatment With Extended-Release Injectable Naltrexone?.........42
`
`Treatment Duration and Discontinuing Extended-Release Injectable Naltrexone............43
`
`
`Final Clinical Thoughts..........................................................................................................43
`
`
`
`Chapter 6—Patient Management ..........................................................................................45
`
`
`Integrating Medication for Alcohol Dependence Into Clinical Practice Settings ...............45
`
`
`Initial Assessment ..................................................................................................................46
`
`
`Choosing a Medication............................................................................................................51
`
`
`Combination Therapy .............................................................................................................51
`
`
`Choosing a Psychosocial Intervention ...................................................................................54
`
`
`Developing a Treatment Plan ................................................................................................56
`
`
`Patient Awareness ..................................................................................................................57
`
`
`Monitoring Patient Progress..................................................................................................57
`
`
`Modifying the Treatment Strategy........................................................................................60
`
`
`Discontinuing Pharmacotherapy ...........................................................................................61
`
`
`Final Clinical Thoughts..........................................................................................................61
`
`
`
`Appendix A—Bibliography .....................................................................................................63
`
`
`Appendix B—NIAAA’s A Pocket Guide for Alcohol Screening and
`
`
`
`Brief Intervention ................................................................................................................71
`
`
`
`
`Appendix C—Excerpts From Quick Guide for Clinicians Based on TIP 45 ...............77
`
`
`
`Appendix D—Excerpts From Quick Guide for Clinicians Based on TIP 24...............87
`
`
`
`Appendix E—Resource Panel.................................................................................................97
`
`
`
`Appendix F—Field Reviewers................................................................................................99
`
`
`
`Appendix G—Acknowledgments..........................................................................................101
`
`
`iv
`
`Contents
`
`Page 5 of 126
`
`

`

`
`
` Index...........................................................................................................................................103
`
`
`Exhibits
`
` 2-1 Acamprosate Side Effects.............................................................................................12
`
`
`
` 2-2 Acamprosate Contraindications...................................................................................12
`
`
`
` 2-3 Acamprosate Cautions..................................................................................................13
`
`
`
` 2-4 Adverse Reactions to Acamprosate and Their Management.....................................13
`
`
`
` 3-1 Brief History of Disulfiram Development ...................................................................16
`
`
`
`
`3-2 Possible Effects of the Disulfiram–Alcohol Reaction..................................................17
`
`
`
`3-3 Disulfiram Dosages.......................................................................................................20
`
`
`3-4 Disulfiram Side Effects.................................................................................................20
`
`
`
`3-5 Symptoms of Disulfiram-Induced Hepatic Impairment.............................................21
`
`
`
`3-6 Disulfiram Contraindications ......................................................................................21
`
`
`
`3-7 Disulfiram Cautions .....................................................................................................22
`
`
`
`3-8 Adverse Reactions to Disulfiram and Their Management.........................................23
`
`
`
`3-9 Drug Interactions With Disulfiram .............................................................................24
`
`
`
`3-10 Laboratory Testing in Disulfiram Therapy.................................................................25
`
`
`4-1 Oral Naltrexone Dosages..............................................................................................30
`
`
`
`4-2 Oral Naltrexone Side Effects .......................................................................................30
`
`
`
`4-3 Naltrexone Contraindications......................................................................................31
`
`
`
`4-4 Naltrexone Cautions.....................................................................................................31
`
`
`
`4-5 Adverse Reactions to Naltrexone and Their Management ........................................32
`
`
`
`4-6 Signs and Symptoms of Liver Disease ........................................................................32
`
`
`
`4-7 Drug Interactions With Oral Naltrexone....................................................................33
`
`
`
`5-1 Extended-Release Injectable Naltrexone Side Effects ...............................................40
`
`
`
`5-2 Extended-Release Injectable Naltrexone Contraindications .....................................40
`
`
`
`5-3 Extended-Release Injectable Naltrexone Cautions ....................................................41
`
`
`
`6-1 Useful Laboratory Tests...............................................................................................47
`
`
`
`6-2 Questions To Assess Quantity and Frequency of Consumption................................50
`
`
`
`6-3 Questions To Assess Patients’ Readiness for Change................................................51
`
`
` 6-4 AUD Medication Decision Grid....................................................................................52
`
`
`
` 6-5 Comparison of Approved Medications for Maintenance
`
`
` of Abstinence From Alcohol..........................................................................................53
`
`
`
` 6-6 Resources for Office-Based Psychosocial Approaches ................................................55
`
`
`
`
` 6-7 Elements of Patient Education....................................................................................57
`
`
`
`
`6-8
`Information Resources for Patients.............................................................................58
`
`
`Contents
`
`v
`
`Page 6 of 126
`
`

`

`Page 7 of 126
`
`Page 7 of 126
`
`

`

`Consensus Panel
`
`
`
`
`Chair
`Eric C. Strain, M.D.
`
`
` Professor
`
`Department of Psychiatry and
`
`
`
` Behavioral Sciences
`
`Johns Hopkins University School
`
`
`
` of Medicine
`
`Baltimore, Maryland
`
`
`
`
`
`
`Consensus Panelists
`
`Adam J. Gordon, M.D., M.P.H.
`Assistant Professor
`Division of General Internal Medicine
`Department of Medicine
`University of Pittsburgh
`Pittsburgh, Pennsylvania
`Bankole A. Johnson, M.D., Ph.D.,
`
`D.Sc.
`Chairman
`Department of Psychiatric Medicine
`University of Virginia Health System
`Charlottesville, Virginia
`
`
`
`
`
`
`
`Mary Elizabeth McCaul, Ph.D.
`Professor
`
`Department of Psychiatry and
`
`
`Behavioral Sciences
`Johns Hopkins School of Medicine
`Baltimore, Maryland
`Andrew Saxon, M.D.
`Professor of Psychiatry
`
`Department of Psychiatry and
`
`
`Behavioral Sciences
`
`University of Washington
`
`Seattle, Washington
`
`Robert Swift, M.D., Ph.D.
`Professor of Psychiatry and Human
`
`Behavior
`Brown University Medical School
`
`Center for Alcohol and Addiction
`
`Studies
`
`Providence, Rhode Island
`
`Allen Zweben, D.S.W.
`
`Professor and Associate Dean
`
`for Research and Sponsored Projects
`School of Social Work
`Columbia University
`New York, New York
`
`
`
`viivii
`
`Page 8 of 126
`
`

`

`Page 9 of 126
`
`Page 9 of 126
`
`

`

`Expert Advisory Board
`
`
`Randall T. Brown, M.D.
`Assistant Professor
`Department of Family Medicine
`
`University of Wisconsin School
`of Medicine and Public Health
`
`
`Madison, Wisconsin
`
`
`Dominic Ciraulo, M.D.
`Professor and Chairman
`Division of Psychiatry
`Boston University School of Medicine
`Boston, Massachusetts
`
`Scott M. Davis, M.D.
`Addiction Medicine Physician
`
`Inpatient Medical Services
`
`Betty Ford Center
`
`Rancho Mirage, California
`
`
`George Kolodner, M.D.
`CEO and Medical Director
`
`Kolmac Clinic
`
`Silver Spring, Maryland
`
`
`Henry Kranzler, M.D.
`Associate Scientific Director
`Alcohol Research Center
`University of Connecticut Health
`
`Center
`
`Farmington, Connecticut
`
`
`
`
`Robert J. Malcolm, Jr., M.D.
`Associate Dean and Attending
`
`Psychiatrist
`Institute of Psychiatry
`Medical University of South Carolina
`Charleston, South Carolina
`
`
`
`Barbara J. Mason, Ph.D.
`Professor
`
`Molecular and Integrative
`
`
`
`Neurosciences Department
`
`Scripps Research Institute
`
`La Jolla, California
`
`
`Richard N. Rosenthal, M.D.
`Chairman
`Department of Psychiatry
`St. Luke’s Roosevelt Hospital Center
`New York, New York
`
`ix
`
`Page 10 of 126
`
`

`

`Page 11 of 126
`
`Page 11 of 126
`
`

`

`What Is a TIP?
`
`Treatment Improvement Protocols (TIPs), developed by the
`Center for Substance Abuse Treatment (CSAT), part of the
`Substance Abuse and Mental Health Services Administration
`(SAMHSA) within the U.S. Department of Health and Human
`Services (HHS), are best-practice guidelines for the treatment
`of substance use disorders. CSAT draws on the experience and
`knowledge of clinical, research, and administrative experts to
`produce TIPs, which are distributed to facilities and individu­
`als across the country. As alcohol and drug use disorders are
`increasingly recognized as a major problem, the audience for
`TIPs is expanding beyond public and private treatment facilities
`
`to include practitioners in mental health, criminal justice,
`primary care, and other healthcare and social service settings.
`
`TIP Development Process
`TIP topics are based on the current needs of substance abuse
`treatment professionals and other healthcare practitioners for
`information and guidance. After selecting a topic, CSAT invites
`staff from Federal agencies and national organizations to be
`members of a resource panel that reviews an initial draft pro­
`spectus and outline and recommends specific areas of focus as
`well as resources that should be considered in developing the
`content for the TIP. These recommendations are communicated
`to a consensus panel composed of experts on the topic who have
`been nominated by their peers. In partnership with Knowledge
`Application Program writers, consensus panel members par­
`ticipate in creating a draft document and then meet to review
`and discuss the draft. The information and recommendations on
`which they reach consensus form the foundation of the TIP. A
`panel chair ensures that the guidelines mirror the results of the
`group’s collaboration.
`A diverse group of experts closely reviews the draft document.
`Once the changes recommended by these field reviewers have
`been incorporated, the TIP is prepared for publication, in print
`
`xi
`
`Page 12 of 126
`
`

`

`and online. TIPs can be accessed via the
`Internet at http://www.kap.samhsa.gov.
`Although each TIP strives to include an evi­
`dence base for the practices it recommends,
`CSAT recognizes that the field of substance
`abuse treatment is evolving, and research
`frequently lags behind the innovations pio­
`neered in the field. A major goal of each TIP
`is to convey “front-line” information quickly
`but responsibly. For this reason, recommen­
`dations proffered in the TIP are based on
`either panelists’ clinical experience or the
`literature.
`
`TIP Format
`CSAT is embarking on a new approach to
`and format for TIPs:
`
` • Most of the fundamental research that
`forms the evidence basis for a particu­
`lar TIP is not provided in the TIP itself.
`Rather, those who wish to review the sup­
`porting research can access an annotated
`bibliography and literature review via the
`Internet at http://www.kap.samhsa.gov.
`These online resources include abstracts
`along with references; the online bibliog­
`raphy and literature review are updated
`every 6 months for 5 years after publication
`of the TIP.
`• TIPs focus on how-to information. Coverage
`
`of topics is limited to what the audience
`needs to understand and use to improve
`treatment outcomes.
`
`• TIPs increasingly use quick-reference tools
`
`such as tables and lists in lieu of extensive
`text discussion, making the information
`more readily accessible and useful for treat­
`ment providers.
`
`How TIP 49 Is Organized
`This TIP, Incorporating Alcohol
`Pharmacotherapies Into Medical Practice,
`revises and expands on TIP 28, Naltrexone
`and Alcoholism Treatment, and includes dis­
`cussion of the other medications currently
`approved for treating alcohol use disorders
`(AUDs). It provides the basic information,
`evidence- and consensus-based guidelines,
`tools, and resources necessary to help health-
`care practitioners treat patients with AUDs.
`Chapter 1 provides an overview of the use
`of medications to treat AUDs. Chapters 2
`through 5 present detailed information about
`each medication:
`
`• Chapter 2—Acamprosate
`
`• Chapter 3—Disulfiram
`
`• Chapter 4—Oral Naltrexone
`
`• Chapter 5—Extended-Release Injectable
`Naltrexone.
`
`Finally, Chapter 6 discusses factors to con­
`sider when treating patients with medica­
`tions for AUDs. The appendices in the TIP
`provide handy resources for practitioners.
`
`xii
`
`What Is a TIP?
`
`Page 13 of 126
`
`

`

`Foreword
`
`The Treatment Improvement Protocol (TIP) series supports
`SAMHSA’s mission of building resilience and facilitating recovery
`for people with or at risk for mental or substance use disorders
`by providing best-practices guidance to clinicians, program
`administrators, and payers to improve the quality and effectiveness
`of service delivery and, thereby, promote recovery. TIPs are the result
`of careful consideration of all relevant clinical and health services
`research findings, demonstration experience, and implementation
`requirements. Clinical researchers, clinicians, and program
`administrators debate and discuss their particular areas of expertise
`until they reach a consensus on best practices. This panel’s work is
`then reviewed and critiqued by field reviewers.
`The talent, dedication, and hard work that TIP panelists and
`reviewers bring to this highly participatory process have helped bridge
`the gap between the promise of research and the needs of practicing
`clinicians and administrators to serve, in the most scientifically sound
`and effective ways, people who abuse substances. We are grateful to
`all who have joined with us to contribute to advances in the substance
`abuse treatment field.
`Eric B. Broderick, D.D.S., M.P.H.
`Acting 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
`
`Page 14 of 126
`
`

`

`Page 15 of 126
`
`Page 15 of 126
`
`

`

` In This
`
`
`
`Chapter . . .
`
`
` Alcohol Use Disorders
`
`
`in Medical Settings
`
`
`Audience for TIP 49
`
`
` Recognition
`
`
` of Alcohol Dependence
`
`
`as a Chronic Illness
`
`
`Purpose of TIP 49
`
`
` What TIP 49
`
`
`
` Does Not Cover
`
`
`Specialty Treatment
`
`Versus Screening and
`
`Brief Intervention
`
`
`Why Use Medications
`
`To Treat Alcohol
`
`Dependence?
`
`
`Format, Approach, and
`
`Organization of TIP 49
`
`
` 1 Introduction
`
`Alcohol Use Disorders in Medical
`Settings
`Many health problems or mental disorders that healthcare prac­
`titioners (particularly those in primary care) encounter in their
`everyday practices derive from or are complicated by alcohol use
`disorders (AUDs). Consequently, healthcare practitioners are in
`key positions to manage the care of large numbers of individuals
`with AUDs. However, only a small percentage of these patients
`are actually treated for AUDs in these settings.
`The U.S. Food and Drug Administration (FDA) has approved
`four medications to treat AUDs. These medications make
`treatment in primary care and other general medical settings
`a viable adjunct or alternative to specialty care, with many
`potential advantages. The consensus panel for this Treatment
`Improvement Protocol (TIP) believes that direct intervention
`by healthcare practitioners to treat AUDs is both possible and
`practical.
`Screening for and providing brief interventions to treat AUDs
`in general medical settings promote healthy life choices and
`increase the likelihood of recovery, especially for patients who
`have not yet progressed to chronic alcohol dependence, those
`with comorbid medical disorders being treated in these settings,
`and those who otherwise would not seek or receive treatment for
`their AUDs. Interventions in primary care provide an opportu­
`nity to educate and motivate patients who are alcohol dependent
`and need long-term care to consider a specialty substance abuse
`treatment program.
`From the patient’s viewpoint, initiating treatment in a health-
`care practitioner’s office may be more acceptable than entering a
`specialty substance abuse treatment program. Perceived or actu­
`al barriers to these programs, such as stigma, cost, employment
`concerns, lack of family or social support, misunderstandings
`
`1
`
`Page 16 of 126
`
`

`

`about the nature of treatment, and lack
`of program availability, discourage many
`patients from seeking specialty treatment
`for AUDs. In fact, the number of persons
`with alcohol or substance use disorders
`who received treatment at a private doc­
`tor’s office increased from 254,000 in
`2005 to 422,000 in 2006 (Office of Applied
`Studies, 2007).
`
`Terms Used in TIP 49
`Abstinence. The point at which a person has
`refrained from any use of alcohol or illicit
`drugs.
`
`
`Alcohol use disorders. As used in the
`Diagnostic and Statistical Manual of Mental
`Disorders IV-TR (American Psychiatric
`Association, 2000), encompasses alcohol abuse
`
` and dependence. This TIP uses the term broadly
`to encompass the range of alcohol use prob­
`lems, from intermittent binge drinking to haz­
`ardous drinking to chronic alcohol abuse and
`dependence.
`
`Brief intervention. A treatment modality in
`which treatment approaches ranging from
`simple suggestions and unstructured counseling
`and feedback to more formal structured meth­
`ods (e.g., motivational enhancement) are used,
`usually in short one-on-one sessions between
`the practitioner and patient.
`
`Healthcare practitioners. Individuals
`
`with prescribing privileges, including
`physicians, physician assistants, and nurse
`practitioners.
`
`
`
`Medical management. The components of brief
`intervention such as patient education, feed­
`back, motivational enhancement, and medi­
`cation monitoring that facilitate medication
`adherence.
`
`Specialty substance abuse treatment or spe­
`
`cialty substance abuse care. The integrated
`group of counseling and complementary ser­
`vices offered in substance abuse treatment
`programs. Services focus on achieving and
`maintaining long-term recovery from AUDs and
`other substance use disorders.
`
`Initiating treatment in a physician’s office
`offers advantages for these patients:
`• Screening, diagnosis, and treatment
`
`of AUDs can increase patient motiva­
`tion and cooperation (versus the effect
`of delays between screening, diagno­
`sis, and treatment when patients are
`referred to specialty programs).
`• Integration of treatment for AUDs with
`
`that for comorbid medical disorders may
`increase the likelihood of adherence to
`treatment and overall patient recovery.
`• Familiarity with the primary care set­
`
`ting and “mainstream” methods (e.g.,
`medical management) to treat AUDs
`reduces the stigma surrounding AUDs.
`
` • The ongoing relationship a patient has
`with a healthcare practitioner may
`make referral to specialty substance
`abuse care more acceptable to a patient.
`Helping patients with AUDs can be grati­
`fying; few interventions in medicine can
`lead to such substantial improvement in
`individual and public health. This TIP
`provides a resource to assist the health-
`care provider in this effort.
`
`Audience for TIP 49
`
`
`
`
`
`The intended audience for this TIP
`includes physicians and other health-
`
`
`
`
`
`care practitioners who can prescribe and
`
`administer medications for AUDs, in
`either specialty substance abuse treat­
`
`
`
`
`ment programs or healthcare settings
`
`such as primary care physicians’ offices.
`Other addiction professionals (e.g., coun­
`
`
`
`
`
`selors) who want to understand how
`
`
`
`
`
`
`these medications work and to review the
`recommended guidelines for medication-
`
`assisted treatment of AUDs also will find
`
`
`the book useful.
`
`2
`
`Chapter 1
`
`Page 17 of 126
`
`

`

`
`
` Recognition of Alcohol
`
`
`
` Dependence as a
`Chronic Illness
`Research has clarified the strong simi­
`larity between substance dependence
`
`
`
`and other chronic illnesses (e.g., asth­
`ma, diabetes, hypertension) for which
`primary care physician-administered
`
`
`pharmacotherapy and medical manage­
`ment are routine practices (reviewed by
`
`
`
`
`
`McLellan, Lewis, O’Brien, & Kleber, 2000,
`
`p. 1693). Genetics, personal choice, and
`
`
`
`
`
`environmental factors contribute to both
`
`
`
`
`
`substance dependence and other illnesses.
`
`
`
`
`Research into the pathophysiologic effects
`
`
`
`
`of alcohol and drugs—including enduring
`
`
`
`and possibly permanent neurophysiologic
`
`
`
`changes—provides further evidence that
`
`
`
`
`
`substance dependence is a chronic illness.
`
`
`
`
`
`By addressing AUDs in their practices,
`
`healthcare practitioners also address the
`
`source of substantial risk for many other
`
`
`
`
`
`health problems in their patients (see
`
`
`
`
`
`Why Use Medications To Treat Alcohol
`
`Dependence? on page 5).
`
`Purpose of TIP 49
`This TIP provides clinical guidelines for
`the proper use of medications in the treat­
`ment of AUDs. The underlying objective
`is to expand access to information about
`the effective use of these medications, not
`only in specialty substance abuse treat­
`ment programs but also in physicians’
`offices and other general medical care set­
`tings. Members of the Clinical Research
`Roundtable of the Institute of Medicine
`have identified failure to disseminate
`information about and implement new
`therapies proven effective in clinical
`trials as a principal roadblock to health-
`care improvement in the United States
`(Crowley et al., 2004). TIP 49 addresses
`this problem for the pharmacotherapy of
`AUDs.
`
`Costs and Prevalence of AUDs
`Annual economic costs of AUDs in the
`United States have been estimated at
`approximately $185 billion (Harwood,
`2000) and include the following:
`• Direct treatment costs
`
`• Lost earnings
`
`• Costs of other medical consequences,
`
`including premature death
`• Costs of accidents and emergencies
`
`• Criminal justice costs.
`
`Approximately 7.9 percent of Americans
`ages 12 and older (about 19.5 million
`people) met standard diagnostic crite­
`ria for alcohol abuse or dependence in
`2006 (Office of Applied Studies, 2007).
`However, only 1.6 million people with an
`AUD received treatment at a specialty
`facility (Office of Applied Studies, 2007).
`Of those who did not receive treatment,
`
`just 3.0 percent thought they needed
`treatment and 40.6 percent tried to get
`treatment but were unable to (Office of
`Applied Studies, 2007).
`
`
`
` Findings on Medication-Assisted
`Treatment for AUDs
`Researchers continue to evaluate the
`efficacy of numerous compounds to treat
`AUDs. To date, FDA has approved four
`medications for treatment of AUDs:
`• Acamprosate (Campral®)
`
`
`• Disulfiram (Antabuse®)
`
`• Oral naltrexone (ReVia®, Depade®)
`
`• Extended-release injectable naltrexone
`(Vivitrol®).
`This TIP provides recommended guide­
`lines for using the four FDA-approved
`
`medications in clinical practice.
`
`Introduction
`
`3
`
`Page 18 of 126
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`

`

`Although the mechanisms of action
`
`of these medications in treating AUDs
`are not fully understood, knowledge about
`them is growing.
`Researchers are evaluating the efficacy
`of combinations of medications and the
`use of individual medications along with
`behavioral approaches to treat AUDs
`(e.g., Mason, 2005b). In 2006, an ambi­
`tious clinical trial—the Combining
`Medications and Behavioral Interventions
`(COMBINE) study, sponsored by the
`National Institute on Alcohol Abuse
`and Alcoholism (NIAAA)—compared
`the relative efficacy of two medications
`(acamprosate and naltrexone) admin­
`istered individually, together, or in
`combinati