PHARMACOTHERAPIES 

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 
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 
 

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 
 

 

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
 

iii 
 

 

 

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
 

How to Screen for Heavy Drinking........................................................................................73
 

How to Assess for Alcohol Use Disorders..............................................................................73
 

How to Conduct a Brief Intervention ....................................................................................74
 

For At-Risk Drinking (no abuse or dependence).............................................................74
 

For Alcohol Use Disorders (abuse or dependence)..........................................................74
 

iv Contents
What’s a Standard Drink?......................................................................................................75
 

Drinking Patterns...................................................................................................................75
 

Prescribing Medications .........................................................................................................76
 

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
 

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
 

Contents v
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
 

vi Contents

 

 

 

 

 

 

 

 

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 

vii 

 

 

 

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 

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 individuals 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 prospectus 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 participate 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 
and online. TIPs can be accessed via the 

Internet at http://www.kap.samhsa.gov. 

Although each TIP strives to include an evidence base for the practices it recommends, 

CSAT recognizes that the field of substance 

abuse treatment is evolving, and research 

frequently lags behind the innovations pioneered in the field. A major goal of each TIP 

is to convey “front-line” information quickly 

but responsibly. For this reason, recommendations 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 particular TIP is not provided in the TIP itself. 

Rather, those who wish to review the supporting 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 bibliography 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 treatment 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 discussion 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 healthcare 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 consider when treating patients with medications for AUDs. The appendices in the TIP 

provide handy resources for practitioners. 

xii What Is a TIP? 
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 

 

1 Introduction 

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
 

Alcohol Use Disorders in Medical 

Settings 

Many health problems or mental disorders that healthcare practitioners (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 opportunity 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 healthcare practitioner’s office may be more acceptable than entering a 

specialty substance abuse treatment program. Perceived or actual barriers to these programs, such as stigma, cost, employment 

concerns, lack of family or social support, misunderstandings 

1 
 

 

 

 

 

 

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 doctor’s office increased from 254,000 in 

2005 to 422,000 in 2006 (Office of Applied 

Studies, 2007). 

Initiating treatment in a physician’s office 

offers advantages for these patients: 

• Screening, diagnosis, and treatment 

of AUDs can increase patient motivation and cooperation (versus the effect 

of delays between screening, diagnosis, 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 setting 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 gratifying; few interventions in medicine can 

lead to such substantial improvement in 

individual and public health. This TIP 

provides a resource to assist the healthcare provider in this effort. 

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 problems, from intermittent binge drinking to hazardous 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 methods (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, feedback, motivational enhancement, and medication monitoring that facilitate medication 

adherence. 

Specialty substance abuse treatment or specialty substance abuse care. The integrated 

group of counseling and complementary services offered in substance abuse treatment 

programs. Services focus on achieving and 

maintaining long-term recovery from AUDs and 

other substance use disorders. 

Audience for TIP 49 

The intended audience for this TIP 

includes physicians and other healthcare practitioners who can prescribe and 

administer medications for AUDs, in 

either specialty substance abuse treatment programs or healthcare settings 

such as primary care physicians’ offices.

Other addiction professionals (e.g., counselors) who want to understand how 

these medications work and to review the 

recommended guidelines for medicationassisted treatment of AUDs also will find 

the book useful. 

2 Chapter 1 
 

 

 

 

 

 

 

 

 

 

 

 

 

Recognition of Alcohol 

Dependence as a 

Chronic Illness 

Research has clarified the strong similarity between substance dependence 

and other chronic illnesses (e.g., asthma, diabetes, hypertension) for which

primary care physician-administered 

pharmacotherapy and medical management 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 treatment of AUDs. The underlying objective 

is to expand access to information about 

the effective use of these medications, not 

only in specialty substance abuse treatment programs but also in physicians’ 

offices and other general medical care settings. 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 healthcare 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 criteria 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 guidelines for using the four FDA-approved 

medications in clinical practice. 

Introduction 3 
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 ambitious 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) administered individually, together, or in 

combination with specialty substance 

abuse treatment or medical management to improve treatment for alcohol 

dependence (Anton et al., 2006). The 

results of this study are noted in this TIP 

when applicable for treatment planning 

and decisionmaking, and a review of the 

research can be accessed in the online 

literature review for this TIP (http://www.

kap.samhsa.gov). 

Access to Medication-Assisted 

Treatment for AUDs 

Although precise numbers are unknown, 

it seems that a small percentage of 

Americans being treated for AUDs 

receive any of the four FDA-approved 

medications for their disorder. Most 

specialty substance abuse care is provided 

outside medical settings by nonmedical 

personnel (e.g., counselors) and is based 

on psychosocial approaches, such as 

cognitive-behavioral therapy and 

motivational enhancement, reinforced 

by participation in community 12-Step 

or mutual-help groups. These programs 

increase rates of abstinence and prevent 

serious relapse for many patients. 

Unfortunately, many people needing 

treatment for AUDs do not get it (Office 

of Applied Studies, 2007). 

Advances in medication development and 

behavioral treatment methods are providing the tools needed to improve long-term 

recovery for patients in specialty treatment settings. These advances increase 

access to and effective use of AUD treatment services in general medical settings. 

The medications discussed in this TIP 

help people maintain abstinence or 

decrease drinking and avoid serious 

setbacks after the initial withdrawal 

period. None of the four FDA-approved 

medications is considered a “magic bullet.” Developing new and more effective 

medications remains a high priority for 

researchers in this field. 

Information Updates in This TIP 

TIP 49 updates the information in TIP 

28, Naltrexone and Alcoholism Treatment 

(Center for Substance Abuse Treatment 

[CSAT], 1998). It also builds on TIP 24, 

A Guide to Substance Abuse Services for 

Primary Care Physicians (CSAT, 1997). 

When TIP 28 was published, FDA had 

approved only two medications for the 

treatment of AUDs: disulfiram and oral 

naltrexone. FDA has since approved 

two more medications: acamprosate and 

extended-release injectable naltrexone. 

These four medications have unique pharmacological actions and profiles of effects, 

and they produce different types of outcomes in individual patients, hence, the 

need for separate guidelines on their use. 

As more information about these medications becomes available, it will be added 

to the online bibliography and literature 

review that supplement this TIP. (See 

Format, Approach, and Organization of 

TIP 49, page 7.) 

What TIP 49 Does Not 

Cover 

This TIP assumes that a patient’s healthcare practitioner is acquainted with 

4 Chapter 1 
screening and diagnostic procedures, 

the patient has a diagnosed AUD, and 

the patient has gone through (or has not 

needed) detoxification. Therefore, the 

following information about treating 

AUDs is not covered in this TIP: 

• Screening and diagnostic assessment 

for AUDs. The reader can refer to 

Helping Patients Who Drink Too Much: 

A Clinician’s Guide (NIAAA, 2006), 

available at http://www.niaaa.nih.gov. 

NIAAA’s A Pocket Guide for Alcohol 

Screening and Brief Intervention is in 

Appendix B of this TIP. 

• Detoxification and methods to deal 

with initial withdrawal symptoms. 

This information is covered in TIP 45, 

Detoxification and Substance Abuse 

Treatment (CSAT, 2006a). Excerpts 

from the Quick Guide based on TIP 45 

are in Appendix C of this TIP. 

• Medical conditions associated with 

excessive alcohol use such as cirrhosis. Treatment for these disorders 

is covered in resources from NIAAA 

(http://www.niaaa.nih.gov/Publications/

AlcoholResearch). 

Specialty Treatment 

Versus Screening and 

Brief Intervention 

Treatment of AUDs can be viewed as 

continuum-of-care options that include 

choices of treatment settings, types and 

levels of treatment services, and medications. Services may range from screening 

and brief intervention to specialty treatment, with numerous levels of care in 

between. Primary care practitioners can 

provide screening, brief interventions, 

and medical management for many 

patients who have AUDs or are at risk 

for alcohol-related disorders but are not 

receiving care. 

Decisions about care level, setting, and 

type of treatment should be based on 

patient assessment and commitment to 

change, as well as treatment availability. For example, the most appropriate 

patients for brief interventions in a physician’s office—and the least appropriate 

for long-term treatment in a substance 

abuse treatment program—are those 

whose drinking exceeds what is recommended, but who are not dependent 

(NIAAA, 2006). 

Why Use Medications 

To Treat Alcohol 

Dependence? 

When implemented according to recommended guidelines, medication-assisted 

treatment combined with brief intervention or more intensive levels of 

nonpharmacologic treatment can do the 

following: 

• Reduce postacute withdrawal symptoms 

that can lead to a return to drinking 

(e.g., acamprosate’s hypothesized mechanisms of action) 

• Lessen craving and urges to drink or 

use drugs (e.g., naltrexone) 

• Decrease impulsive or situational use of 

alcohol (e.g., disulfiram). 

In addition, maintaining a therapeutic 

alliance with a healthcare practitioner 

can achieve the following: 

• Improve patients’ attitudes toward 

change 

• Enhance motivation 

• Facilitate treatment adherence, including participation in specialty substance 

abuse care and support groups. 

The Collaborative Study on the Genetics 

of Alcoholism indicates a genetic link 

between how an individual experiences 

Introduction 5 
alcohol and his or her susceptibility to an 

AUD (reviewed by Edenberg, 2002). Risk 

of chronic AUDs appears higher for people with certain genetic variants. Further 

identification of these genes may lead to 

new medications for treating AUDs that 

can help repair, alter, or disrupt alcohol’s 

negative effects. 

According to a recent review, chronic 

heavy drinking can cause long-lasting 

changes in brain cell receptors and other 

types of neuroadaptations (Oscar-Berman 

& Marinkovic, 2003). These neuroadaptations are linked with cognitive and 

behavioral changes, resulting in the 

need to drink more to ward off craving 

and symptoms of withdrawal. Studies 

reviewed by Hoffman and colleagues 

(2000) found that neuroadaptations 

related to symptoms of withdrawal and 

persistent craving may trigger relapse 

even after prolonged abstinence. 

Pharmacotherapy has revolutionized 

the treatments of brain-based disorders, including mental disorders such 

as depression, and treatments for these 

disorders are increasingly provided by 

healthcare practitioners. Making such 

treatments available in general medical settings can improve continuity and 

accessibility of care. Expansion in treatment settings is underway in opioid 

addiction treatment. Although most 

opioid addiction treatment is provided 

in specialty programs (i.e., methadone 

treatment clinics), the growing use of 

buprenorphine by physicians in officebased settings is increasing access to 

treatments. The widespread use of 

buproprion in primary care settings for 

smoking cessation is another example of 

how the boundaries of addiction treatment have expanded. 

Medication-assisted treatment of AUDs is 

consistent with treatment of other chronic 

disorders such as diabetes or hypertension. Long-term, perhaps indefinite, use 

of medication for patient stabilization is 

reasonable. Medication for AUDs may be 

employed indefinitely or intermittently 

along with interventions aimed at changing lifestyle practices to sustain recovery. 

Research into alcohol dependence and 

treatment has shown that integrating 

brief intervention and counseling and an 

appropriate medication can have a synergistic or additive effect and improve 

treatment outcome. Medication can 

reduce the cravings that disrupt recovery. 

When cravings are decreased, counseling is more likely to strengthen the 

individual’s coping resources, which are 

necessary to promote medication adherence and behavioral change. Summaries 

of research findings have highlighted the 

following beneficial effects of medicationassisted treatment for AUDs (Garbutt, 

West, Carey, Lohr, & Crews, 1999; 

Kranzler & Van Kirk, 2001; O’Malley & 

Kosten, 2006): 

• Lengthens periods of abstinence, which 

in turn can increase individual coping capacities necessary for long-term 

recovery 

• Prevents a lapse from becoming a fullblown relapse 

• Allows brain cells to readapt to a 

normal nonalcoholic state, helping 

patients stabilize, think more clearly, 

have more positive emotional responses, 

strengthen coping mechanisms, enhance 

self-esteem, and increase motivational 

readiness for change 

• Relieves symptoms of protracted withdrawal (a hypothesized mechanism of 

action of acamprosate) 

• Supports the effects of psychosocial 

treatment and sustains the gains of 

intervention. 

The consensus panel for this TIP believes 

that providing brief interventions (including pharmacotherapy) for AUDs in 

physicians’ offices and general medical 

6 Chapter 1 
settings is a reasonable, practical, and 

desirable trend that should be greatly 

expanded. The panel also recommends 

that screening and periodic reassessment 

of all patients for AUDs should become 

regular parts of patient management in 

primary care and general medical practices because the problem has been shown 

to be more widespread than many primary care practitioners have realized. At a 

minimum, patients diagnosed with health 

problems often associated with AUDs 

should receive alcohol disorder screening. 

Format, Approach, and 

Organization of TIP 49 

The format and approach used in this TIP 

differ substantially from those used in 

other TIPs: 

• Most of the evidence base for 

medication-assisted treatment for 

AUDs is not included in this TIP. 

Those who wish to review the research 

base can access the annotated bibliography and literature review via the 

Internet at http://www.kap.samhsa.gov. 

The online bibliography and literature 

review will be updated every 6 months 

for 5 years after publication of TIP 49. 

• TIP 49 focuses on how-to information 

about medication-assisted treatment for 

AUDs. Coverage is limited to what the 

audience needs to understand to use 

these medications to improve treatment 

outcomes. 

• Increased use of quick-reference tools 

such as tables and lists in lieu of extensive text discussion makes the information readily accessible and useful for 

physicians and other practitioners. 

Practical information and guidelines 

for treating patients with acamprosate, disulfiram, oral naltrexone, or 

extended-release injectable naltrexone 

are presented in Chapters 2 through 

5, respectively. Each chapter follows a 

template: general description of the medication, rationale for its use, how to use it, 

which patients are most appropriate for 

the medication, and clinical advice. 

Chapter 6 covers practical information about patient management during 

pharmacotherapy that applies to all four 

FDA-approved medications for AUDs, 

including how to do the following: 

• Integrate pharmacotherapy for AUDs 

into clinical settings 

• Assess appropriateness of medications 

for patients with AUDs 

• Choose AUD medications 

• Choose psychosocial interventions 

• Develop and adjust treatment plans 

• Educate patients about pharmacotherapy for AUDs 

• Monitor patient progress in medication 

treatment 

• Discontinue AUD medications. 

Appendices include the following: 

• Bibliography (Appendix A) 

• NIAAA’s A Pocket Guide for Alcohol 

Screening and Brief Intervention

(Appendix B) 

• Excerpts from the Quick Guide 

for Clinicians Based on TIP 45, 

Detoxification and Substance Abuse 

Treatment (Appendix C)
 

• Excerpts from the Quick Guide for 

Clinicians Based on TIP 24, A Guide to 

Substance Abuse Services for Primary 

Care Clinicians (Appendix D) 

• Lists of the TIP’s resource panelists and 

field reviewers (Appendices E and F, 

respectively). 

Introduction 7 

2 Acamprosate
 

Acamprosate At a Glance 

Chemical name: Calcium acetyl homotaurinate. 

Trade name: Campral® Delayed-Release Tablets. 

U.S. distributor: Forest Pharmaceuticals (subsidiary of Forest Laboratories, Inc.), St. Louis, MO. 

U.S. Food and Drug Administration approval to treat alcohol dependence: July 2004. 

Dosage/How taken: Two 333 mg delayed-release tablets by mouth three times per day, with or 

without food (a lower dose may be effective with some patients and must be used with those with 

impaired renal function). Pills are swallowed whole, not crushed or broken. 

How supplied: Opaque bottles or Dose Paks of 180 enteric-coated 333 mg tablets. 

Storage: Keep out of reach of children; keep tightly closed in original container; store at room 

temperature, away from excess heat and moisture (not in the bathroom or near a sink); discard when 

outdated or no longer needed. 

What Is Acamprosate? 

Acamprosate was the third medication, after disulfiram and 

naltrexone, to receive U.S. Food and Drug Administration (FDA) 

approval for postwithdrawal maintenance of alcohol abstinence. 

Acamprosate’s mechanism of action has not been clearly established, but it is thought that acamprosate helps modulate and 

normalize alcohol-related changes in brain activity, thereby 

reducing symptoms of postacute (protracted) withdrawal, such 

as disturbances in sleep and mood, that may trigger a relapse 

to drinking. 

Brief History of Development 

The French pharmaceutical company Laboratoires Meram 

began clinical development and testing of acamprosate in 1982. 

From 1982 to 1988, acamprosate was tested for safety and for 

efficacy as a treatment for alcohol dependence. Based on these 

studies, in 1989 Laboratories Meram was granted marketing 

authorization for acamprosate in France under the trade name 

9 
 

Aotal®. Since then, acamprosate has been 

extensively used and studied throughout 

Europe and, subsequently, in the United 

States. 

Although acamprosate has been used in 

Europe for more than 20 years, it was 

not approved by FDA until July 2004. 

Acamprosate became available for use 

in the United States in January 2005, 

under the trade name Campral® 

Delayed-Release Tablets (Merck Santé, 

a subsidiary of Merck KGaA, Darmstadt, 

Germany). Campral is currently marketed in the United States by Forest 

Pharmaceuticals. 

Pharmacology 

Acamprosate’s action in maintenance 

of alcohol abstinence is not completely 

understood, but evidence indicates that 

acamprosate interacts with the glutamate 

neurotransmitter system, reducing and 

normalizing the pathologic glutamatergic hyperactivity that occurs during 

protracted withdrawal from alcohol. It 

is hypothesized that this normalization 

leads to a reduction of common symptoms 

of protracted, or postacute, withdrawal 

such as insomnia, anxiety, and restlessness—symptoms that may contribute to a 

patient’s return to alcohol use (reviewed 

by Litten, Fertig, Mattson, & Egli, 

2005; Myrick & Anton, 2004; Thomson 

Healthcare, Inc., 2006). Chick, Lehert, 

and Landron (2003) have proposed that 

patients who returned to drinking while 

taking acamprosate drank less, and less 

frequently, than those taking placebo. 

The bioavailability of acamprosate after 

oral administration is approximately 

11 percent, and stable plasma concentrations are reached within 5 days of taking 

the medication. Acamprosate is not 

metabolized and is excreted primarily 

by the kidneys as acamprosate. 

Why Use Acamprosate? 

Efficacy 

Considerable evidence supports the 

efficacy of acamprosate in the treatment of alcohol use disorders (AUDs). 

Numerous European trials have found 

acamprosate significantly more effective than placebo in reducing drinking 

days, increasing complete abstinence, and 

lengthening time to relapse. Evidence 

from U.S. studies has been mixed. The 

Combining Medications and Behavioral 

Interventions (COMBINE) study did 

not find acamprosate to be more effective than placebo (Anton et al., 2006). 

However, some analyses and reviews 

have concluded otherwise (although these 

analyses did not include data from the 

COMBINE study). A meta-analysis (an 

analysis of the outcome data of multiple 

individual studies) of European studies 

concluded that acamprosate is moderately effective in achieving and maintaining 

abstinence (Bouza, Magro, Muñoz, & 

Amate, 2004). This analysis of 12 studies found that acamprosate increased the 

continuous abstinence rate and doubled 

continuous abstinence duration compared 

with placebo. Similarly, a review of clinical trials by Mann (2004) concluded that 

acamprosate is more effective than placebo in the short and long term. Mason and 

colleagues (2006) found acamprosate to 

be superior to placebo only when controlling for patient characteristics associated 

with treatment efficacy. They also found 

acamprosate superior to placebo for a 

subgroup of patients motivated to achieve 

total abstinence. 

Methodological differences between U.S. 

and European studies may account for 

differing results. These differences have 

included the following: 

• Duration of pretreatment abstinence 

required 

10 Chapter 2 
 

• Duration of treatment (European 

studies tended to be longer than U.S. 

studies) 

• Concomitant medications allowed 

(European studies tended to be more 

flexible in allowing medications than 

U.S. studies) 

• Nature and intensity of psychosocial 

treatment (U.S. studies tended to have 

more standardized and intensive psychosocial treatments) 

• Outcome measures used 

• Severity of participants’ AUDs. 

A thorough discussion of acamprosate 

efficacy studies is in this TIP’s online literature review. 

Safety 

Acamprosate has a good safety profile: 

• Patients maintained on acamprosate 

have not developed tolerance for or 

dependence on it, and it appears to have 

no potential for abuse. 

• It carries virtually no overdose risk; 

even at overdoses up to 56 grams (a 

normal daily dose is 2 grams), acamprosate was generally well tolerated by 

patients (Thomson Healthcare, Inc., 

2006). 

• Most side effects are mild and transient, 

lessening or disappearing within the 

first few weeks of treatment (diarrhea 

tends to persist). 

• Although there is a pharmacokinetic 

interaction by which acamprosate can 

increase naltrexone blood levels, there 

are no other clinically significant interactions between acamprosate and other 

medications (Johnson et al., 2003). 

Acamprosate also has advantages over 

other medications for treating AUDs in 

some patients: 

• Because acamprosate is not metabolized 

by the liver, it can be used safely even 

by patients with severe liver disease, 

unlike oral or injectable naltrexone or 

disulfiram. 

• Because it does not affect endogenous or 

exogenous opioids, it can be used with 

patients receiving opioid maintenance 

therapy (reviewed by Myrick & Anton, 

2004) or undergoing treatment with 

opioids for acute or chronic pain, unlike 

oral or injectable naltrexone. 

• Because acamprosate does not interact 

with benzodiazepines or other medications used in medical detoxification, 

it can be continued safely if a patient 

returns to drinking and subsequently 

requires detoxification. 

How Is Acamprosate 

Used? 

Initiating Treatment With 

Acamprosate 

Acamprosate is typically initiated 5 days 

following drinking cessation. However, 

acamprosate can be used safely with 

alcohol (and with benzodiazepines), and 

it can be started during medically supervised withdrawal. Acamprosate therapy 

should be maintained if a patient relapses 

to alcohol use. Acamprosate reaches full 

effectiveness in 5 to 8 days. 

Before initiating treatment, healthcare 

practitioners should do the following: 

• Conduct or refer patients for a thorough medical exam and assessment 

(as described in Chapter 6—Patient 

Management). 

• Perform renal function tests (a standard 

panel for urea, electrolytes, and serum 

creatinine) to rule out severe renal 

impairment. 

Acamprosate 11 
 

 

Side Effects, Contraindications, 	

and Cautions 

Exhibit 2-1 lists acamprosate’s side 

effects. The most common side effect of 

acamprosate is diarrhea. This and other 

side effects are usually mild and resolve 

quickly. In some patients, diarrhea is 

severe and persistent. Patients should 

be instructed not to discontinue acamprosate if they experience side effects and 

to inform their prescribing professional. 

Exhibit 2-2 lists acamprosate contraindications, and Exhibit 2-3 lists cautions. 

Patient Management 

Ways for managing adverse reactions to 

acamprosate are listed in Exhibit 2-4. 

There is no evidence that acamprosate impairs renal function. Followup 

laboratory work is not necessary unless 

evidence of renal impairment exists at 

treatment initiation. 

Patient Education 

In addition to giving patients the general 

patient education guidelines discussed in 

Chapter 6, healthcare providers should 

ensure that patients taking acamprosate 

know the following: 

• The benefits and limitations of 

acamprosate 

• What to expect— 

– Possible side effects 

– Full effectiveness in 5–8 days 

• For women of childbearing age, the 

importance of using an effective birth 

control method 

• To continue taking acamprosate if a slip 

or relapse occurs and to inform their 

prescribing professional immediately 

• To notify the prescribing professional 

immediately if they begin to have 

suicidal thoughts, if they begin to feel 

depressed, or if an existing depression 

worsens 

• That tablets should not be crushed 

• Not to take extra medication if a dose 

is missed and it is time to take the next 

dose. 

Exhibit 2-1 

Acamprosate Side Effects 

Most Common Side Effect Less Common Side Effects 

Diarrhea Suicidal ideation 

(less common, but serious) 

Intestinal cramps 

Headache 

Flatulence 

Increased or decreased libido 

Insomnia 

Anxiety 

Muscle weakness 

Nausea 

Itchiness 

Dizziness 

Exhibit 2-2 

Acamprosate Contraindications 

Patient Condition or Circumstance Treatment Recommendation 

Previous hypersensitivity to acamprosate or its components Do not prescribe acamprosate 

Severe renal impairment (creatinine clearance 

≤30 mL/min) 

Do not prescribe acamprosate 

12 Chapter 2 
Exhibit 2-3 

Acamprosate Cautions 

Patient Condition or Circumstance Treatment Recommendation 

Moderate renal impairment (creatinine 

clearance 30–50 mL/min) 

Reduce dosage to one 333 mg tablet daily 

Pregnant or nursing women Avoid using acamprosate unless potential benefits outweigh risks (Acamprosate is FDA pregnancy category C; it is 

unknown whether acamprosate is excreted in human milk.) 

Age 65 or older Because of a higher risk of diminished renal function in 

persons 65 or older, perform baseline and frequent renal 

function tests; acamprosate has not been evaluated for 

safety or efficacy in geriatric populations 

Children or adolescents Prescribe with caution; acamprosate has not been evaluated 

for safety or efficacy in pediatric or adolescent populations 

Exhibit 2-4 

Adverse Reactions to Acamprosate and Their Management 

Adverse Reaction Management 

Suicidal ideation, suicide attempts 

(very uncommon, but serious)* 

Inform patients to contact the prescribing professional immediately 

Monitor patients for onset or worsening of depression 

Obtain a psychiatric consult and/or prescribe antidepressant 

medication as necessary 

Discontinue acamprosate 

Severe and/or persistent diarrhea Treat with Imodium® or Pepto-Bismol® 

Recommend appropriate dietary changes 

Reduce acamprosate dosage or discontinue use if diarrhea remains 

intolerable after treatment 

*Suicidal ideation is closely linked with substance use disorders, with or without acamprosate use. More information about managing the risk can be found at the National Suicide Prevention Center’s Web site (http://www.sprc. 

org) and at the Suicide Prevention for Physicians Web site (http://suicideandmentalhealthassociationinternational. 

org/preventionphy.html). 

Who Is Appropriate 

for Treatment With 

Acamprosate? 

Research on patient-specific characteristics as predictors of acamprosate efficacy 

has not identified any particular characteristics (e.g., level of physiological 

dependence on alcohol, age of onset, gender) that predict acamprosate treatment 

outcomes (Verheul, Lehert, Geerlings, 

Koeter, & Van Den Brink, 2005). 

However, evidence exists that acamprosate is most effective for patients who, at 

treatment onset, are motivated for complete abstinence rather than decreased 

drinking (Mason et al., 2006). 

As noted earlier, acamprosate does not 

affect endogenous or exogenous opioids, 

so it may be particularly appropriate for 

patients who are receiving opioid maintenance therapy (reviewed by Myrick & 

Acamprosate 13 
 

 

 

 

 

 

 

 

 

 

 

 

Anton, 2004), at risk of relapsing to opioid 

use, or undergoing treatment with opioids 

for pain. Because there are no clinically 

significant drug interactions with acamprosate, it can be a safe medication for 

patients who are coping with multiple 

medical issues and are taking many other 

medications. 

Acamprosate must be taken three times 

per day. Extra support will be needed for 

patients with cognitive deficits or who 

otherwise might have trouble remembering and adhering to a schedule. Seven-day 

dosing pillboxes or blistercard packages 

that indicate the time of day for each dose 

may be useful. 

Treatment Duration 

and Discontinuing 

Acamprosate 

The effectiveness and safety of acamprosate have been evaluated for up to 1 year. 

The length of time a particular patient 

takes acamprosate will be determined, 

ideally, with input from the prescribing 

professional, the specialty treatment 

provider, and the patient. Discontinuation 

of acamprosate may be considered once 

a patient has achieved stable abstinence 

from alcohol, reports diminished craving, 

and has established a sound plan and support for ongoing recovery. Acamprosate 

therapy also may be discontinued if a 

patient is not adhering to the medication 

regimen. Acamprosate should not be discontinued just because a patient returns 

to alcohol use. 

There is no withdrawal syndrome associated with discontinuing acamprosate, and 

it is not necessary to taper the dose. 

Final Clinical Thoughts 

Evidence from European studies and 

clinical experience suggest acamprosate

can be an effective medication for the 

treatment of AUDs. Acamprosate has 

several attractive features, including its 

minimal side effects, lack of negative liver 

effects, and drug interaction profiles. For

many patients, these features make it a

worthwhile agent to try despite its small

therapeutic effect. Hence, the clinician 

using medications to treat patients with 

alcohol dependence should be familiar with 

acamprosate and its use and may find it

a useful medication for certain patients 

(e.g., those treated with opioid analgesics) 

or under certain circumstances (e.g., for a

patient who is taking several other medications). The healthcare provider may also 

find it useful when combined with other 

alcohol treatment medications and with 

psychosocial support. 

Because acamprosate must be taken three 

times per day, providers must pay particular attention to patient adherence. 

Providers can help patients adhere to the 

regimen by helping them develop ways to 

remember, such as wearing a “reminder” 

bracelet, setting a watch alarm, implementing a recovery-oriented ritual around 

taking the medication, or providing them 

with a special pillbox or blistercard pack. 

14 Chapter 2 
3 Disulfiram
 

Disulfiram At a Glance 

Chemical name: Bis(diethylthiocarbamoyl) disulfide. 

Trade name: Antabuse®. 

U.S. distributor: Odyssey Pharmaceuticals, Inc., East Hanover, NJ. 

U.S. Food and Drug Administration approval to treat alcohol dependence: 1951. 

Dosage/How taken: Tablet by mouth once daily (also may be crushed and mixed with water, coffee, 

tea, milk, soft drink, or fruit juice). 

How supplied: Bottles of 100 or 1,000 250 mg tablets or bottles of 50, 100, or 500 500 mg tablets. 

Storage: Keep out of reach of children; keep tightly closed in original container; store at room 

temperature, away from excess heat and moisture (not in the bathroom or near a sink); discard when 

outdated or no longer needed. 

What Is Disulfiram? 

Disulfiram was the first medication approved by the U.S. Food 

and Drug Administration (FDA) to treat chronic alcohol dependence. In its pure state, disulfiram is a white to off-white, 

odorless, almost tasteless powder, which is soluble in water and 

alcohol. Disulfiram, an alcohol-aversive or alcohol-sensitizing 

agent, causes an acutely toxic physical reaction when mixed 

with alcohol. Continuing research and clinical findings have 

clarified disulfiram’s mode of action and established its safe and 

effective use in the treatment of alcohol use disorders (AUDs) in 

some patient groups. 

Brief History of Development 

Exhibit 3-1 summarizes disulfiram’s development history. 

15 
Exhibit 3-1 

Brief History of Disulfiram Development 

Dates Events 

1930s Disulfiram’s alcohol-aversive effects are first observed when workers in the vulcanized 

rubber industry, exposed to tetraethylthiuram disulfide, become ill after drinking 

alcohol. 

1947 In Copenhagen, researchers studying compounds to treat parasitic stomach infections 

take a small dose of disulfiram to check its side effects. Later they become ill after an 

alcoholic drink. They conclude that an interaction of disulfiram and alcohol is responsible and conduct a study to confirm their findings (Hald & Jacobsen, 1948). 

Late 1940s, 

early 1950s 

The Danish group performs additional studies of disulfiram treatment for alcohol 

dependence. Basing its initial paradigm on aversion conditioning, it administers high 

disulfiram doses (e.g., 1,000 to 3,000 mg daily) to maximize patient reactions. 

FDA approves disulfiram to treat alcohol dependence in the United States. 

Wyeth-Ayerst Laboratories begins manufacturing Antabuse® tablets (now manufactured by PLIVA and distributed in the United States by Odyssey Pharmaceuticals). 

Ruth Fox, M.D., the founding president of the American Society of Addiction 

Medicine, is the first American to use disulfiram to treat alcohol dependence, starting 

in 1949. When her patients report serious side effects, Fox reduces the dosage and 

counsels them on the severe reactions that could result from drinking alcohol. She 

concludes that disulfiram is effective in deterring drinking in patients with alcohol 

dependence and treats about 2,500 patients with disulfiram. 

Late 1950s to 

the present 

After reports of severe reactions, including some deaths, therapeutic emphasis shifts 

from using disulfiram for aversion conditioning to using it to support abstinence. This 

entails using lower dosages to control disulfiram toxicity, excluding patients with 

myocardial infarction or cirrhosis of the liver, and combining the medication with 

other types of support. 

Pharmacology 

Aversive treatment 

Unlike other medications approved to 

treat alcohol dependence, disulfiram does 

not affect brain opiate, g-aminobutyric

acid, or glutamate receptors directly. 

However, it does have some central 

nervous system effects, inhibiting enzyme 

dopamine β-hydroxylase and affecting 

serotonergic function. Whether disulfiram 

directly decreases the urge to drink 

remains uncertain. However, disulfiram 

definitely disrupts the metabolism 

of alcohol, causing a severe reaction 

when patients mix disulfiram and 

alcohol. Patient knowledge of a possible 

severe reaction to alcohol consumption 

is thought to increase the patient’s 

motivation to remain abstinent. Some 

experts (e.g., Schuckit, 2006) question 

disulfiram’s effectiveness because the 

time between alcohol ingestion and the 

reaction can be as long as 30 minutes 

and the intensity of the reaction is 

unpredictable. 

Effect on oxidation of alcohol 

Normally, the enzyme alcohol dehydrogenase in the liver and brain transforms 

alcohol into acetaldehyde. The enzyme 

aldehyde dehydrogenase (ALDH), also 

in the liver and brain, oxidizes the acetaldehyde byproduct into acetic acid. 

Disulfiram blocks this oxidation by 

inhibiting ALDH, causing a rapid rise 

16 Chapter 3 
of acetaldehyde in the blood when alcohol is consumed. The result is called a 

disulfiram–alcohol reaction, and it may 

increase the acetaldehyde concentration 

in blood to 5 to 10 times that occurring 

without disulfiram. Disulfiram does not 

appear to affect the rate of alcohol elimination from the body. 

The disulfiram–alcohol reaction 

The disulfiram–alcohol reaction usually 

begins about 10 to 30 minutes after 

alcohol is ingested. Its adverse effects 

range from moderate to severe (Exhibit 

3-2). Intensity varies with individual 

patient characteristics. The reaction is 

generally proportional to the amounts 

of disulfiram and alcohol ingested. 

Mild effects may occur at blood alcohol 

concentrations of 5 to 10 mg/100 mL. 

At 50 mg/100 mL, effects usually are 

fully developed. When the concentration 

reaches 125 to 150 mg/100 mL, unconsciousness may occur. Although 

Exhibit 3-2 

Possible Effects of the Disulfiram–Alcohol Reaction 

Body Part Affected Moderate Severe 

Body skin Sweating 

Warmth and flushing, particularly 

on upper chest and face 

None 

Respiratory system Hyperventilation 

Respiratory difficulty/dyspnea 

Respiratory depression 

Head, neck, throat Acetaldehyde breath odor 

Blurred vision 

Head and neck throbbing 

Thirst 

None 

Stomach, 

digestive system 

Nausea/vomiting None 

Chest, heart, circulatory 

system 

Chest pain/palpitations 

Hypotension 

Tachycardia 

Cardiovascular collapse 

Arrhythmia 

Myocardial infarction (in individuals with 

preexisting coronary artery disease) 

Acute congestive heart failure (in 

individuals with preexisting myocardial 

dysfunction) 

Brain/nervous system Vertigo 

Syncope 

Marked uneasiness 

Confusion 

Seizures 

Other Weakness Death 

Disulfiram 17 
disulfiram–alcohol reactions can be life 

threatening, as indicated in Exhibit 3-2, 

the reduced dosages and careful patient 

medical screening now in practice have 

made this outcome extremely rare. 

Early researchers believed that patients 

needed to experience at least one supervised disulfiram–alcohol reaction to 

understand its effects. The practice of 

deliberately inducing a reaction by giving 

large doses of disulfiram in conjunction 

with “alcohol challenges” has been abandoned. A clear, convincing description of 

the reaction is considered sufficient for 

most patients. 

Disulfiram absorption and elimination 

About 80 to 95 percent of ingested 

disulfiram is absorbed from the gastrointestinal tract and rapidly distributed to 

tissues and organs. It is then metabolized 

to various mixed disulfides. The unabsorbed fraction is excreted. Disulfiram is 

irreversibly bound to ALDH. It can take 

up to 2 weeks for the body to synthesize 

sufficient unbound enzyme to metabolize 

alcohol adequately. This is why alcohol 

ingestion may produce unpleasant symptoms for up to 2 weeks after a patient has 

taken the last dose of disulfiram. 

Why Use Disulfiram? 

Disulfiram may work as an adjunct to 

psychosocial treatment to eliminate alcohol consumption for patients who can 

achieve initial abstinence of at least 12 

hours, are committed to maintaining 

abstinence, agree to take the medication, and do not have contraindications to 

disulfiram. 

Efficacy 

Findings on the efficacy of disulfiram 

treatment are mixed. (To review some 

reports, see the online annotated bibliography and literature review at http://

www.kap.samhsa.gov.) 

Positive findings 

Studies concluding that disulfiram is 

effective in treating AUDs frequently 

emphasize the circumstances in which it 

is administered to patients. In particular, the level and quality of supervision a 

patient receives while taking disulfiram 

are believed to be important elements 

in its success (e.g., Brewer, Meyers, & 

Johnsen, 2000; Kristenson, 1995). Some 

studies have found that court-ordered 

disulfiram therapy promotes efficacy 

by increasing adherence to the disulfiram regimen (Martin, Clapp, Alfers, 

& Beresford, 2004; Martin, Mangum, & 

Beresford, 2005). Use of incentives, contracting with the patient and a significant 

other to ensure adherence, providing regular reminders to the patient, and patient 

behavioral training and social support 

also may enhance disulfiram efficacy by 

increasing treatment adherence. 

Most experts (e.g., Schuckit, 2006) agree 

that an optimum disulfiram response 

requires its use in a specialty substance 

abuse treatment program. One study 

suggests that disulfiram might be more 

effective in promoting short-term abstinence and treatment retention after 

detoxification than in preventing longterm relapse (e.g., Chandrasekaran, 

Sivaprakash, & Chitraleka, 2001). 

Nevertheless, the most rigorous study of 

disulfiram therapy (Fuller et al., 1986) 

showed unequivocally that disulfiram 

(250 mg/day), compared with placebo (1 

mg/day) or a vitamin, reduced the proportion of days of alcohol consumption 

for the duration of the study (1 year) in 

male veterans who reported some drinking. However, there were no differences 

between treatment groups in the percentage of veterans sustaining abstinence 

throughout the study period. 

Negative findings 

Some experts dismiss disulfiram as a 

viable treatment option, particularly in 

primary care settings. This conclusion 

18 Chapter 3 
 

is based on mixed results with disulfiram in clinical trials and the severe 

adverse effects that may result from the 

disulfiram–alcohol reaction, as well as 

concerns about other potentially serious 

side effects and “problems with compliance” (Williams, 2005, pp. 1776–1777). 

The capacity to arrange ongoing supervision of disulfiram ingestion may be limited in a primary care setting. 

Appropriate patients 

The consensus panel concludes that 

disulfiram is most effective for patients 

who have undergone detoxification or 

are in the initiation stage of abstinence, 

especially when they are committed to 

abstinence and receive adequate, ongoing 

supervision. Disulfiram may not reduce 

the urge to drink alcohol. However, it 

may assist in motivating the patient 

not to drink. As with other medications, 

general efficacy also increases when disulfiram is administered in conjunction 

with intensive behavioral interventions. 

Patients with severely impaired judgment or who are highly impulsive from a 

severe mental illness or cognitive impairment may be inappropriate candidates for 

treatment with disulfiram. 

Safety 

Disulfiram has been used to treat AUDs 

for almost 60 years. Deaths from the 

disulfiram–alcohol reaction have become 

rare because lower dosages are used 

and patients with severe cardiac disease 

are excluded from disulfiram treatment 

(Chick, 1999). Its hepatotoxicity in some 

patients remains a concern (see Side 

Effects, Contraindications, and Cautions 

on page 20). 

Side effects of disulfiram are usually 

minor (see Exhibit 3-4, page 20). Severe

adverse reactions are uncommon (see 

Exhibit 3-8, page 23). However, patients 

receiving disulfiram should be monitored 

for hepatotoxicity (see Timing of 

Laboratory Work, page 21). Disulfiram 

may cause hepatitis, but the risk is low. 

Estimates of disulfiram-induced hepatitis 

are between 1 in 25,000 (Wright, Vafier, 

& Lake, 1988) and 1 in 30,000 (Chick, 

1999, p. 427) patients treated per year. A 

disproportionate number of these cases 

may be associated with use of disulfiram 

to treat nickel allergy (an unusual but 

known indication for use of disulfiram). 

A black-box warning about treatment 

with disulfiram is included in the 

Antabuse package insert. Before administering disulfiram, the clinician should 

inform patients and their families about 

the disulfiram–alcohol reaction, including that this reaction may occur for up to 

14 days between the last ingested dose of 

disulfiram and alcohol consumption. 

Disulfiram Black-Box Warning 

Disulfiram should never be administered to a 

patient who is in a state of alcohol intoxication 

or without the patient’s full knowledge. The 

physician should instruct relatives accordingly. 

How Is Disulfiram Used? 

Before Initiating Treatment With 

Disulfiram 

Physicians should not administer disulfiram until the following steps have been 

taken: 

• Educate the patient about disulfiram 

and obtain informed consent. 

• Wait until the patient has abstained 

from alcohol at least 12 hours and/or 

breath or blood alcohol level is zero. 

• Perform a physical exam, baseline 

liver and kidney function tests, and a 

pregnancy test for women. Perform an 

electrocardiogram if clinically indicated 

(e.g., history of heart disease). 

Disulfiram 19 
 

• Complete a medical and psychiatric history. Determine allergies to disulfiram 

or other drugs; prescription and nonprescription medications taken, including vitamins; history of cardiovascular 

disease, diabetes, thyroid disease, seizure disorder, central nervous system 

impairment, or kidney or liver disease; 

and for women, reproductive status, 

including current pregnancy or plans to 

become pregnant or to breast-feed. 

Supervised Ingestion 

There is strong evidence that supervised 

ingestion is necessary for disulfiram therapy compliance (e.g., Brewer et al., 2000; 

Kristenson, 1995; reviewed by Fuller & 

Gordis, 2004). Although not absolutely 

essential, supervised administration by 

a pharmacist, healthcare provider, or 

family member is preferred as a key component of the treatment plan. 

Dosage 

Exhibit 3-3 summarizes standard dosage 

information for disulfiram. 

Exhibit 3-3 

Disulfiram Dosages 

Initial dosage 250 mg/day in 1 morning 

or evening dose for 1–2 

weeks 

Average maintenance dosage 250 mg/day 

Dosage range 125–500 mg/day 

Maximum dosage 500 mg/day 

Additional dosage information includes 

the following: 

• Instruct patients who experience 

sedation with disulfiram to take it at 

bedtime. If daytime sedation persists, 

adjust the dosage downward. 

• If a patient can drink alcohol without 

problems when compliant with the 

routine starting dose (which is rare), 

increase the dosage (dosage may be 

increased up to 500 mg/day with careful 

monitoring). Never exceed 500 mg/day. 

• Instruct patients who miss a dose to 

take it as soon as they remember. 

However, if it is almost time for the 

next dose, they should skip the missed 

dose. 

• Tell patients never to take a double dose 

of disulfiram. 

Side Effects, Contraindications, 

and Cautions 

Disulfiram can cause minor side effects 

(Exhibit 3-4). The common side effects 

typically occur during the first 2 weeks of 

therapy and wane either spontaneously or 

after a decrease in the disulfiram dosage. 

Exhibit 3-4 

Disulfiram Side Effects 

Skin/acneiform eruptions* Headache 

Allergic dermatitis* Impotence 

Mild drowsiness Metallic or garlic-

 like aftertaste Fatigue 

*Dermatologic side effects often can be managed 

with concomitant antihistamines. 

Hepatic toxicity including hepatic failure 

resulting in transplantation or death has 

been reported. Severe and sometimes 

fatal hepatitis associated with disulfiram 

therapy may develop even after many 

months of therapy. Hepatic toxicity has 

occurred in patients with or without a 

history of abnormal liver function. 

Patients should be instructed to call their 

physician immediately if they develop 

symptoms of possible hepatic impairment 

(Exhibit 3-5). 

Exhibit 3-6 summarizes contraindications 

for disulfiram therapy, and Exhibit 3-7 

summarizes cautions. 

20 Chapter 3 
Exhibit 3-5 

Symptoms of Disulfiram-Induced 

Hepatic Impairment 

Excessive tiredness Vomiting 

Weakness Yellowness of the skin/eyes 

Lack of energy Dark urine 

Loss of appetite Fever 

Upset stomach Light-colored stools 

Exhibit 3-6 

Disulfiram Contraindications 

Patient Condition or Circumstance Treatment Recommendation 

Known hypersensitivity to disulfiram 

or other thiuram derivatives used in 

pesticides and rubber vulcanization; 

sulfur or nickel allergy 

Do not administer disulfiram. 

Psychosis Disulfiram is relatively contraindicated in patients with 

decompensated psychoses but can be used with caution in 

treated, stable patients with schizophrenia or other psychotic 

disorders. 

Severe myocardial disease and/or 

coronary occlusion 

Disulfiram is relatively contraindicated in patients with severe 

myocardial disease or coronary occlusion, with clinical risk of 

disulfiram therapy balanced against clinical risk of ongoing 

alcohol abuse. Perform an electrocardiogram before and during 

disulfiram therapy and follow closely. 

Pregnant or nursing women Although disulfiram is not absolutely contraindicated, it should 

be avoided because risk to the fetus is unknown. (Pregnant 

patients should receive behavioral treatment, on an inpatient 

basis if necessary.) Do not give disulfiram to nursing mothers. 

Patients should discontinue nursing before taking disulfiram. 

Patient Management 

Exhibit 3-8 lists severe adverse reactions 

that may occur with disulfiram and ways 

to manage them. These reactions are 

uncommon. 

Drug interactions with disulfiram and 

their management 

Exhibit 3-9 describes the most common 

drug interactions with disulfiram and 

their clinical management. 

Timing of laboratory work 

Exhibit 3-10 summarizes the recommended laboratory testing regimen for 

disulfiram therapy. In general, liver 

function requires ongoing monitoring 

because of disulfiram’s occasional 

association with hepatic injury. In 

contrast to liver injury caused by 

alcohol, which typically shows a high 

aspartate aminotransferase-to-alanine 

aminotransferase ratio, disulfiram liver 

injury usually shows equivalent and 

very high elevations of both enzymes 

(Bjornsson, Nordlinder, & Olsson, 2006). 

Pregnant women should discontinue 

taking disulfiram immediately. Urine 

toxicology screening is not an ideal 

method of detecting alcohol use, although 

it sometimes can detect use that occurred 

within a few hours of test administration. 

Disulfiram overdose and its 

management 

Severe cases of disulfiram poisoning have 

been reported, mainly in children who 

Disulfiram 21 
have ingested large amounts because of 

patients’ negligent handling or storage of 

their medication. Symptoms of overdose 

include drowsiness followed by coma or 

persistent nausea, vomiting, aggressive 

or psychotic behavior, and ascending flaccid paralysis that can reach the cranial 

nerves. Treatment consists of administration of oxygen therapy, glucose (5 percent 

intravenously), and sodium ascorbate (1 

gram intravenously). The patient should 

be kept in bed and as quiet as possible 

with appropriate symptomatic treatment. 

Exhibit 3-7 

Disulfiram Cautions 

Patient Condition or Circumstance Treatment Recommendation 

History of cardiac disease, diabetes mellitus, 

hypothyroidism, epilepsy, cerebral damage, 

chronic or acute nephritis, hepatic cirrhosis, 

or hepatic insufficiency 

Use with caution. No evidence exists that patients with 

preexisting liver disease are more likely to suffer severe 

hepatotoxicity from disulfiram therapy. 

Patients with hepatitis C According to current available evidence, if baseline 

transaminase levels are normal or only moderately 

elevated (less than five times the upper limit of 

normal), use with careful monitoring of liver function. 

Children and adolescents Safety and efficacy for children has not been 

determined. One study indicates that disulfiram can be 

safe and effective with adolescents (Niederhofer 

& Staffen, 2003). Administer with caution. 

Patients receiving or who have recently 

received metronidazole, paraldehyde, 

alcohol, or alcohol-containing preparations 

(e.g., cough syrups, tonics); also patients 

exposed to ethylene dibromide or its vapors 

(e.g., in paint, paint thinner, varnish, shellac) 

Do not use disulfiram until substances are out of the 

patient’s system. 

Patients using products that contain alcohol 

in disguised forms (e.g., vinegars, sauces, 

aftershave lotions, liniments) 

Instruct patients to test any alcohol-containing product 

before using it by applying some to a small area of the 

skin for 1 to 2 hours. If there is no redness, itching, or 

unwanted effects, the product may be used safely. 

Age 61 or older Dosages may need to be decreased. 

Addressing reported drinking 

Patients seemingly on an adequate maintenance dosage of disulfiram who report 

that they can drink with impunity could 

be disposing of their tablets without taking them. Physicians should not 

conclude that disulfiram is ineffective 

until patients are proved to have been 

taking their daily tablets. Once patient 

adherence is confirmed, the physician 

should consider increasing the disulfiram dosage (see Exhibit 3-3, page 

20) or changing the patient to another 

medication. 

Genetic factors may influence sensitivity 

to disulfiram in some patients (reviewed 

by Kenna, McGeary, & Swift, 2004a, 

2004b). Wide individual differences 

exist in the activity of the target enzyme 

ALDH. Individuals with low intrinsic 

ALDH activity are more likely to exhibit 

high sensitivity to disulfiram, and those 

with high intrinsic ALDH are more 

likely to show little or no sensitivity to 

disulfiram. 

22 Chapter 3 
Managing a disulfiram–alcohol 

reaction 

The duration of the disulfiram–alcohol 

reaction varies from 30 to 60 minutes in 

mild cases to several hours or until the 

alcohol is metabolized in more severe 

cases. When effects are severe, supportive 

measures may be needed to restore blood 

pressure and treat shock. Administration 

of oxygen or carbogen (95 percent oxygen, 

5 percent carbon dioxide), large intravenous doses of vitamin C (1 g), ephedrine 

sulfate, or intravenous antihistamines 

may be indicated. Potassium levels should 

be monitored particularly in patients on 

digitalis because hypokalemia has been 

reported. 

Exhibit 3-8 

Adverse Reactions to Disulfiram and Their Management 

Adverse Reaction Management 

Optic neuritis Usually diagnosed after patient complains of visual disturbance. 

Discontinue disulfiram and conduct an ophthalmologic examination. 

Peripheral neuritis, polyneuritis, peripheral neuropathy Usually diagnosed after patient complains of paresthesias (numbness or 

tingling). Discontinue disulfiram and observe patient or arrange for neurological evaluation. 

Hepatitis, including cholestatic and fulminant 

hepatitis, as well as hepatic 

failure* 

When symptoms of hepatic dysfunction are reported or observed (see 

Exhibit 3-5), perform a medical history and physical examination and 

obtain followup liver function tests. When clinical or laboratory evidence 

of hepatic dysfunction is found, discontinue disulfiram immediately. 

Maintain clinical monitoring of symptoms and liver function. Follow 

findings to resolution. 

Psychosis Psychotic reactions to disulfiram have been noted, usually attributable 

to high disulfiram dosage associated with toxicity to other drugs (e.g., 

metronidazole, isoniazid) or the unmasking of underlying psychoses in 

patients stressed by alcohol withdrawal. When psychosis is diagnosed 

and other interacting drugs are present, reduce or discontinue disulfiram 

and treat underlying psychoses as indicated. 

*Serious disulfiram-induced hepatic injury occurs rarely, and the precise etiology is unknown. 

Patient Education 

Patients should receive thorough education about disulfiram. Use of disulfiram 

should include ongoing monitoring, 

medical management, and counseling. 

Used without proper patient education, 

motivation, and supportive intervention, 

disulfiram is unlikely to have more than 

a brief effect on drinking patterns, particularly in patients with poor medication 

compliance, more severe forms of alcohol 

dependence, or both. 

In addition to giving patients the general 

patient education discussed in Chapter 

6, healthcare providers should educate 

patients about the following key points 

regarding disulfiram therapy: 

• Benefits and limitations of disulfiram 

• What to expect from disulfiram and 

normal time to full effect 

• Complete information about the 

disulfiram–alcohol reaction 

• Strong cautions about surreptitious 

drinking while on disulfiram 

• Warnings about using alcohol in 

disguised forms, such as in sauces, 

vinegars, cough mixtures, aftershave 

lotions, or liniments 

Disulfiram 23 
 

 

 

• Importance of continued counseling and 

12-Step or mutual-help group participation during disulfiram therapy 

• Importance of informing the counselor 

and prescribing professional if a slip or 

relapse occurs 

• Importance of telling physicians or 

dentists that the patient is taking disulfiram when he or she is scheduled for 

surgery, including dental surgery 

• Importance of carrying a safety identification card indicating that the patient 

is taking disulfiram, symptoms of possible disulfiram–alcohol reactions, and 

the physician or institution to contact in 

an emergency 

• Symptoms of potential neurologic injury 

to report immediately to the physician 

• Symptoms of potential liver injury to 

report immediately to the physician. 

Exhibit 3-9 

Drug Interactions With Disulfiram 

Drug Effect With Disulfiram Recommended Action 

Benzodiazepines 

Chlordiazepoxide 

(Librium®) 

Diazepam (Valium®) 

Decreases plasma clearance of 

chlordiazepoxide or diazepam 

Substitute oxazepam (Serax®) or 

lorazepam (Ativan®) 

Isoniazid May cause unsteady gait, changes 

in mental state 

Discontinue disulfiram if either effect 

is noted 

Rifampin (Rifidin® , 

Rimactane®) 

If used with isoniazid to treat 

tuberculosis, see isoniazid effects 

above 

Adjust dosages as needed 

Metronidazole (Flagyl®) Leads to a greater likelihood of 

confusion or psychosis 

Do not prescribe disulfiram and 

metronidazole concomitantly 

Oral anticoagulant (e.g., 

warfarin [Coumadin®]) 

Inhibits warfarin metabolism Adjust dosages as needed 

Oral hypoglycemic Produces disulfiram-like reactions 

with alcohol 

Monitor carefully if prescribing 

oral hypoglycemics and disulfiram 

concomitantly 

Phenytoin (Dilantin®) Increases serum levels through 

CYP 450 2C9 inhibition 

Obtain baseline phenytoin serum 

level before disulfiram therapy; 

reevaluate level during therapy; 

adjust dosage if phenytoin level 

increases 

Theophylline Increases serum levels through 

CYP 450 1A2 inhibition 

Obtain baseline theophylline serum 

level before disulfiram therapy; 

reevaluate level during therapy; 

adjust dosage if theophylline serum 

level increases 

Tricyclic antidepressants, 

amitriptyline (Elavil®) 

May cause delirium with 

concurrent administration 

Adjust dosages, discontinue 

disulfiram, or switch to another 

class of antidepressant medication 

Desipramine 

(Norpramin®), 

imipramine (Tofranil®) 

Decreases total body clearance and 

increases elimination half-life and 

peak plasma levels of desipramine 

or imipramine 

Monitor closely; adjust dosages if 

needed 

24 Chapter 3 
Clinicians are advised to document that a 

patient has received and understands the 

information described above and to obtain 

the patient’s informed written consent to 

treatment before prescribing disulfiram. 

Exhibit 3-10 

Laboratory Testing in Disulfiram Therapy 

Interval/Period Type of Test 

Before starting disulfiram therapy to 

confirm abstinence and determine 

baselines after stabilization 

Breath or blood alcohol tests (if clinically indicated to confirm 

abstinence) 

Liver function tests: Alanine aminotransferase, aspartate 

aminotransferase, gamma glutamyltransferase, alkaline 

phosphatase, lactate dehydrogenase, bilirubin, total protein, 

albumin, prothrombin time 

Complete blood count, routine chemistries (if clinically 

indicated) 

Kidney function tests: Routine blood urea nitrogen (BUN), 

creatinine 

Pregnancy test (women of childbearing age) 

10–14 days after initiation of therapy 

and then monthly (or more frequently) 

for first 6 months of therapy; every 

3 months thereafter 

Liver function tests: Alanine aminotransferase, aspartate 

aminotransferase, gamma glutamyltransferase, bilirubin 

Monthly during therapy Pregnancy test (women of childbearing age) 

As clinically indicated during therapy Kidney function tests: BUN, creatinine 

Urine toxicology screen: Perform only when concern exists 

about unreported alcohol or drug use 

Who Is Appropriate 

for Treatment With 

Disulfiram? 

• Patients motivated for treatment and 

committed to total abstinence 

• Patients capable of understanding the 

consequences of drinking alcohol while 

taking disulfiram 

• Medically appropriate patients 

• Patients who can receive supervised 

dosing 

• Patients who are abstinent from alcohol 

• Patients who maintain abstinence during treatment 

• Patients who are codependent on or also 

abuse cocaine. 

Treatment Duration and 

Discontinuing Disulfiram 

Prolonged disulfiram administration does 

not produce tolerance. Daily, uninterrupted dosing may be continued until the 

patient has established stable, long-term 

alcohol abstinence. Depending on the 

patient, disulfiram therapy may continue 

for months or years. A 9-year study of 180 

patients with chronic alcohol dependence 

(Krampe et al., 2006) concluded that 

the beneficial action of long-term (12- to 

20-month) supervised disulfiram therapy 

was psychological, not pharmacological, 

because placebo worked as well as disulfiram. Nevertheless, the study found 

Disulfiram 25 
that the likelihood that a patient would 

remain continuously abstinent years after 

termination of medication therapy was 

directly related to the length of time the 

patient continued supervised therapy 

with either disulfiram or placebo. 

For some patients who have completed 

successful treatment with disulfiram 

and who are facing anticipated highrisk relapse situations such as social 

events or travel, it may be appropriate to 

restart disulfiram along with behavioral 

interventions to help them cope with the 

high-risk situation and avoid relapse. 

No withdrawal syndrome is associated with discontinuing disulfiram, but 

patients must be warned that disulfiram–

alcohol reactions may occur within 2 

weeks of discontinuing the medication. 

Final Clinical Thoughts 

Disulfiram appears to have modest 

clinical efficacy in maintaining alcohol abstinence in patients with AUDs, 

particularly when administered under 

supervision. Patients who are motivated 

for treatment, commit to abstinence, 

have supervised dose administration, 

and understand and participate in their 

treatment appear to derive the greatest benefits from disulfiram therapy. 

However, disulfiram does not appear to 

produce overall higher abstinence rates 

than placebo. Disulfiram therapy also has 

rare but serious risks of neurologic and 

hepatic toxicity. Patients require careful 

clinical and laboratory monitoring during disulfiram therapy. Disulfiram can be 

considered for any patient who is alcohol 

dependent, does not display contraindications, has a goal of total abstinence, and 

can comply with appropriate monitoring. 

Clinical visits in which the practitioner 

and patient discuss the risks and benefits 

of disulfiram therapy can motivate the 

patient to commit to alcohol abstinence. 

In addition to the pharmacologic actions 

of the medication, the patient’s simply 

deciding to take the medication can 

enhance motivation for abstinence. The 

risks associated with disulfiram are well 

known and serious. However, patients 

can benefit from disulfiram as long as 

they receive careful clinical and laboratory monitoring to manage the risks 

associated with this therapy. 

26 Chapter 3 
4 Oral Naltrexone
 

Oral Naltrexone At a Glance 

Chemical name: Naltrexone hydrochloride (morphinan-6-one, 17-[cyclopropylmethyl]-4,5-epoxy-3, 

14-dihydroxy-[5α]). 

Trade names: ReVia®; Depade®. 

U.S. distributor: Barr Pharmaceuticals, Inc., Pomona, NY; Mallinckrodt, Inc., St. Louis, MO. 

U.S. Food and Drug Administration approval to treat alcohol dependence: 1994. 

Dosage/How taken: Tablet by mouth once daily. 

How supplied: Bottles of 30 or 100 50 mg tablets (ReVia); bottles of 30 or 100 25, 50, and 100 mg 

tablets (Depade). 

Storage: Keep out of reach of children; keep tightly closed in original container; store in a cool, 

dry place, away from excess heat and moisture (not in the bathroom or near a sink); discard when 

outdated or no longer needed. 

What Is Oral Naltrexone? 

Naltrexone hydrochloride is a relatively pure and long-lasting 

opioid antagonist. Oral naltrexone has been used to treat opioid 

dependence for many years and has been approved to treat alcohol use disorders (AUDs) since 1994. Naltrexone reduces both 

the rewarding effects of alcohol and craving for it. 

Brief History of Development 

Naltrexone was first synthesized in 1963 by Endo Laboratories, 

which was acquired by DuPont in 1969. Naltrexone was initially 

developed to treat addiction to opioids and was approved by the 

U.S. Food and Drug Administration (FDA) for the treatment of 

addiction to drugs such as heroin, morphine, and oxycodone in 

1984. DuPont branded naltrexone as Trexan® and promoted it 

for the treatment of opioid addiction. 

27 
Animal studies conducted in the 1980s 

established that naltrexone decreased 

alcohol consumption through its action 

at the opiate receptors. Human clinical trials followed that confirmed that 

naltrexone, when used in combination 

with psychosocial therapy, could reduce 

cravings for alcohol and decrease relapse 

rates to alcohol use (O’Malley et al., 

1992; Volpicelli, Alterman, Hayashida, & 

O’Brien, 1992; Volpicelli, Watson, King, 

Sherman, & O’Brien, 1995). 

With FDA approval of naltrexone to treat 

AUDs in 1994, DuPont renamed the drug 

ReVia®. ReVia and a generic version of 

naltrexone are now manufactured by 

Barr Pharmaceuticals. Mallinckrodt also 

manufactures naltrexone under the brand 

name Depade®. 

Pharmacology 

Drinking alcohol enhances endogenous 

opioid activity. Several researchers who 

conducted animal studies observed that, 

under certain conditions, administration 

of small doses of morphine (an opioid 

agonist) increased consumption of alcohol 

in rats (Czirr, Hubbell, Milano, Frank, 

& Reid, 1987; Reid, Czirr, Bensinger, 

Hubbel, & Volanth, 1987; Reid, Delconte, 

Nichols, Bilsky, & Hubbell, 1991). Some 

researchers also reported that administration of opioid antagonists, including 

naloxone (which is similar to naltrexone), decreased alcohol consumption 

(Hubbell et al., 1986; Reid et al., 1991). 

It can be concluded that the rewarding effects of alcohol are mediated at 

least partly through the opiate system. 

Two teams of researchers, Woodson and 

Holman and Benjamin and colleagues 

(as cited in Spanagel & Zieglgansberger, 

1997), reported that these rewarding 

effects are reduced when opioid antagonists block opiate receptor occupancy, 

thereby decreasing the amount of the 

neurotransmitter dopamine released 

from the nucleus accumbens. According 

to Spanagel and colleagues (as cited in 

Spanagel & Zieglgansberger, 1997), the 

mesolimbic dopamine reward system is 

important in initiating and maintaining the use of many substances of abuse, 

including alcohol, and may mediate both 

the positive effects of alcohol and the 

development of craving. 

Oral naltrexone is rapidly and nearly 

totally absorbed in the gastrointestinal 

tract and is metabolized almost exclusively by the liver to the primary active 

metabolite, 6-β-naltrexol. Peak naltrexone 

plasma concentrations are reached within 

1 hour of dosing. The long-acting properties of naltrexone are due primarily to 

6-β-naltrexol, which has an elimination 

half-life of 13 hours. Naltrexone achieves 

therapeutic effectiveness rapidly following the initiation of oral dosing. 

Why Use Oral 

Naltrexone? 

Naltrexone appears to be effective for 

attenuating craving in people who are 

alcohol dependent (Monti et al., 1999, 

2001). By blocking craving, naltrexone 

may enhance the ability of patients to 

abstain from drinking. By blocking the 

pleasure from alcohol, naltrexone also 

may reduce the amount of heavy drinking 

in those who do drink. 

Efficacy 

A meta-analysis (Bouza, Magro, Muñoz, 

& Amate, 2004) of 19 controlled clinical 

trials of naltrexone for treatment of 

AUDs (most of which were randomized 

and single or double blind) found that, 

compared with using placebo, shortterm treatment (less than or equal to 

12 weeks) with naltrexone significantly 

improved relapse rates during active 

treatment and a medication-free followup 

period. Short-term naltrexone treatment 

was also linked with a lower percentage 

28 Chapter 4 
 

of drinking days, fewer drinks per 

drinking day, longer times to relapse, 

more days of abstinence, and lower total 

alcohol consumption during treatment. 

Naltrexone may afford people with AUDs 

a measure of control that can prevent a 

slip from becoming a full-blown relapse. 

A European meta-analysis (Roozen et al., 

2006) corroborated the positive findings 

of the Bouza and other studies. 

A more thorough discussion of oral naltrexone efficacy studies is in the TIP’s 

online literature review (http://www.kap.

samhsa.gov). 

Safety 

Naltrexone has a low incidence of common adverse events. Naltrexone’s 

FDA-approved label includes a blackbox warning regarding hepatotoxicity, 

although these reversible effects tend to 

be associated with much higher doses 

than those used in routine clinical practice (e.g., 300 mg/day or more) and tend to 

occur only after a patient is on these high 

doses for extended periods. 

As an opioid antagonist, naltrexone competitively displaces opioid medications 

from their binding sites, precipitating 

withdrawal. Healthcare providers must 

ensure that patients have been fully 

withdrawn from all opioids before considering therapy with naltrexone. 

Oral Naltrexone Black-Box Warning 

Naltrexone has the capacity to cause hepatocellular injury when given in excessive doses. 

Naltrexone is contraindicated in acute hepatitis 

or liver failure, and its use in patients with active 

liver disease must be carefully considered in light 

of its hepatotoxic effects. 

The margin of separation between the apparently safe dose of naltrexone and the dose causing 

hepatic injury appears to be only fivefold or less. 

Naltrexone does not appear to be a hepatotoxin 

at the recommended doses. 

Patients should be warned of the risk of hepatic 

injury and advised to stop the use of naltrexone 

and seek medical attention if they experience 

symptoms of acute hepatitis. 

How Is Oral Naltrexone 

Used? 

Initiating Treatment With Oral 

Naltrexone 

FDA labeling recommends that treatment 

with naltrexone not begin until signs and 

symptoms of acute alcohol withdrawal 

have subsided. At least 3 days of abstinence are usually recommended, with as 

many as 7 days if possible. Patients may 

experience fewer medication side effects 

(particularly nausea) if they are abstinent 

from alcohol when they begin treatment 

with naltrexone. However, it is safe for 

patients to begin taking naltrexone during medically supervised withdrawal or if 

they are actively drinking. 

Before initiating treatment with naltrexone, healthcare practitioners should do 

the following: 

• Conduct a medical evaluation that 

includes a physical exam, psychosocial 

assessment, and laboratory testing, 

including toxicological screening and 

liver function testing to establish suitability for medication and to establish a 

baseline for comparison 

• Discuss the risks of naltrexone use during pregnancy and advise women of 

childbearing age to use birth control 

while taking naltrexone 

• Ensure that patients are not regular 

users of opioids (illicit drugs, opioid 

maintenance medications, or opioid 

pain medications) to avoid precipitating 

withdrawal 

• Strongly caution patients of the 

unpleasant physical effects of opioid 

Oral Naltrexone 29 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

withdrawal that will result if patients 

are not completely detoxified from 

opioids. 

Dosage 

Exhibit 4-1 summarizes dosage information for oral naltrexone. Naltrexone’s 

duration of action (which is greater 

than 24 hours) allows a variety of 

flexible dosing schedules. Although 50 

mg of naltrexone is currently the FDA 

recommended daily dose for treating 

AUDs, evidence from an open-label, 

small-scale trial suggested that higher 

doses (up to 150 mg/day) may be effective 

in reducing alcohol consumption in 

patients with complicated conditions 

(Oslin et al., 1999). Recent results 

from the large, multisite Combining 

Medications and Behavioral Interventions 

(COMBINE) study suggest that 100 mg 

naltrexone in combination with a brief 

medical management intervention is 

efficacious and well tolerated in patients 

dependent on alcohol (Anton et al., 2006). 

Mean adherence (the ratio of pills taken 

from returned blistercard pack counts to 

those prescribed throughout 16 weeks 

of treatment) for this higher naltrexone 

dose was more than 85 percent, and only 

12 percent of patients required a dose 

reduction. 

Exhibit 4-1 

Oral Naltrexone Dosages 

Initial dosage for 

most patients 

50 mg/day in a single 

tablet 

Initial dosage for 

patients at risk of 

adverse events (e.g., 

women, younger 

patients, those with 

shorter abstinence) 

12.5 mg/day (quarter tablet) or 25 mg/ 

day (half tablet) for 1 

week, taken with food 

(2 weeks, if necessary); 

gradually increase to 

50 mg/day 

Average maintenance dosage 50 mg/day 

Side Effects, Contraindications, 

and Cautions 

An attractive feature of naltrexone 

for treating patients who are alcohol

dependent is that, like disulfiram and 

acamprosate, the medication has

virtually no abuse potential and patients

do not develop tolerance for its efficacy. Side effects are generally mild and

often diminish over time (Exhibit 4-2), 

although less common reactions and some 

potentially serious reactions have been 

reported (Exhibit 4-3). Nausea is one of 

the most frequently reported side effects. 

One study (O’Malley, Krishnan-Sarin, 

Farren, & O’Connor, 2000) suggests that 

women may be particularly susceptible to 

this side effect, which the authors argue

supports the use of risk-minimizing strategies, such as gradual dosing starting 

with a lower dose, requiring abstinence 

for a specific amount of time before starting naltrexone, and providing support and

supervision to help patients cope with 

nausea until it subsides. However, in clinical studies side effects were rarely cited 

by patients as reasons for discontinuing 

treatment with naltrexone. 

Exhibit 4-2 

Oral Naltrexone Side Effects 

Most 

Common 

Less 

Common 

Nausea 

Vomiting 

Headache 

Dizziness 

Fatigue 

Nervousness 

Anxiety 

Somnolence 

Diarrhea, constipation, stomach 

pains, cramps 

Chest pain, joint/muscle pain 

Rash 

Difficulty sleeping 

Excessive thirst, loss of appetite 

Sweating 

Increased tears 

Mild depression 

Delayed ejaculation 

Data on safety and effectiveness with 

adolescents are limited. The results of a 

recent small, open-label pilot study 

30 Chapter 4 
suggest that naltrexone is well tolerated 

in adolescents seeking treatment and 

may reduce alcohol consumption and 

craving (Deas, May, Randall, Johnson, & 

Anton, 2005). However, additional work is 

needed before widespread naltrexone use 

in this population can be recommended. 

Exhibit 4-3 

Naltrexone Contraindications 

Patient Condition or Circumstance Treatment Recommendation 

Current illicit opioid use (as indicated by self-report or 

a positive urine screen) or buprenorphine (Suboxone® 

or Subutex®) or methadone maintenance therapy for 

the treatment of opioid dependence; currently undergoing opioid withdrawal 

Do not prescribe oral naltrexone; consider an 

alternative medication 

Acute hepatitis or liver failure Do not prescribe oral naltrexone 

Anticipated need for opioid analgesics within the next 

7 days 

Do not prescribe oral naltrexone 

History of sensitivity to naltrexone, to structurally 

similar compounds (e.g., naloxone or nalmefene), or to 

any inactive ingredients in the tablet 

Do not prescribe oral naltrexone 

Exhibit 4-4 lists situations in which use 

of naltrexone may require careful consideration or monitoring. Naltrexone 

is considered FDA pregnancy category 

C, meaning its effects on the fetus are 

unknown. Women of childbearing age 

should be informed of this and counseled 

to use effective birth control when sexually active. Some clinicians may choose 

to obtain a pregnancy test before starting 

naltrexone and whenever pregnancy is 

suspected. If a patient becomes pregnant 

while using naltrexone, the clinician and 

patient should decide whether to continue 

the medication, given the potential risks 

and benefits. 

Exhibit 4-4 

Naltrexone Cautions 

Patient Condition or Circumstance Treatment Recommendation 

Active liver disease Monitor liver function frequently 

Moderate to severe renal impairment Use with careful monitoring (naltrexone is eliminated through 

the kidneys) 

Pregnant and nursing women Do not prescribe during pregnancy and nursing unless 

potential benefits outweigh risks (oral naltrexone is FDA 

pregnancy category C; it is unknown whether oral naltrexone 

is excreted in human milk) 

Women of childbearing age Caution patients that effects on fetus are unknown and 

encourage use of an effective birth control method 

Serum aminotransferase levels greater 

than 5 times the upper limit of normal 

Generally avoid, unless potential benefits outweigh risks 

Chronic pain syndromes; acute or 

recurring need for opioid analgesics 

Have patients abstain from naltrexone for at least 3 days 

(conservatively, 7 days) before initiating opioid analgesics 

Oral Naltrexone 31 
Exhibit 4-5 

Adverse Reactions to Naltrexone and Their Management 

Adverse Reaction Management 

Nausea Suggest that the patient take naltrexone with complex carbohydrates 

(e.g., bread) rather than on an empty stomach 

Suggest that the patient take naltrexone with a tablespoon of simethicone 

(e.g., Gas-X® and Mylicon®) or bismuth subsalicylate (e.g., Pepto-Bismol®) 

Reduce dose or cease for 3 or 4 days and reinitiate at lower dose 

Liver toxicity Discontinue naltrexone 

Precipitated opioid 

withdrawal 

Discontinue further doses of naltrexone 

Provide supportive treatments (i.e., hydration and antispasmodic and 

antidiarrheal medications) until opioid withdrawal symptoms resolve 

Provide α-2-agonists such as clonidine to mitigate some withdrawal 

symptoms; watch for enhanced side effects of clonidine, including 

dizziness, hypotension, fatigue, and headache 

Naltrexone overdose Treat symptomatically under close supervision 

Contact poison control for most recent information 

Patient Management 

Exhibit 4-5 lists adverse reactions and 

their management. Patients should 

call their physician if they experience 

any signs or symptoms of liver disease. 

Exhibit 4-6 lists symptoms of liver 

disease. 

Exhibit 4-7 lists interactions between naltrexone and other drugs. 

The consensus panel recommends that 

liver function tests (i.e., ALT, AST, 

gamma glutamyltransferase, bilirubin) 

be performed before naltrexone treatment begins and at intervals thereafter. 

In healthy patients without liver disease, typical intervals can be 1, 3, and 

6 months, then yearly thereafter. Liver 

function tests should be performed more 

frequently if baseline liver function test 

results are high, there is a history of 

hepatic disease, a potential hepatotoxic 

medication is also prescribed, or the 

patient is taking doses higher than 

50 mg/day. Naltrexone should be used 

cautiously in patients whose serum 

aminotransferase results are greater than 

five times the upper limit of normal. 

A careful drug use history and urine 

toxicological screening should be used to 

confirm abstinence from opioids, including prescribed pain medications, and a 

lack of opioid dependence before initiating 

treatment. A comprehensive urine test 

should be used to measure methadone 

and other opioids. However, urine testing can be subject to error because typical 

urine screening tests may not cover all 

opioids and samples can be tampered 

with to affect the results. 

Exhibit 4-6 

Signs and Symptoms 

of Liver Disease 

Abdominal pains that last more Fatigue 

 than a few days Fever 

Light-colored bowel movements Nausea 

Dark, tea-colored urine Weakness 

Yellowing of the eyes or skin 

32 Chapter 4 
Exhibit 4-7 

Drug Interactions With Oral Naltrexone 

Drug Effect With Oral Naltrexone 

Cough/cold medications May decrease benefit if medication contains an opioid 

Antidiarrheal medications May block benefit if medication contains an opioid 

Opioid analgesics May require greater amount of analgesic than usual and may result in 

deeper and more prolonged respiratory depression than if the patient 

were not taking naltrexone 

Thioridazine May result in lethargy and somnolence 

Yohimbine May result in anxiety and increased pulse and blood pressure 

Nonsteroidal antiinflammatory drugs 

(NSAIDs) 

May result in liver enzyme elevations (i.e., aspartate aminotransferase 

[AST] and alanine aminotransferase [ALT]) in combination with regular use 

of very high doses of naltrexone (200–250 mg/day) (Kim, Grant, Adson, 

& Remmel, 2001); this effect has not been observed in the recommended 

therapeutic dose range of naltrexone (50–100 mg) 

Patient Education 

In addition to the general patient education guidelines discussed in Chapter 6, 

education about naltrexone should precede its use. Patients should be informed 

of the following: 

• The effects of naltrexone on the fetus 

are unknown, so women who are 

pregnant or think they may be pregnant should inform their physician. 

• The symptoms of protracted alcohol 

withdrawal (e.g., sleep disturbance) 

may overlap with side effects of 

naltrexone; patients should be 

reassured that symptoms typically 

improve with time. 

• Naltrexone blocks the effects of 

opioids in prescription drugs such as 

pain relievers (e.g., morphine, oxycodone) and antidiarrheal and antitussive medications. Physicians should 

inform patients about other options for 

pain relief. 

• Administering opioids to overcome 

naltrexone’s blockade of the opiate 

receptors increases the risk of overdose, 

respiratory arrest, coma, and death. 

• After taking naltrexone for some time 

and then stopping it, patients may be 

more sensitive to lower doses of opioids 

and thus risk overdose if they take 

opioids. 

• Patients should continue to take 

naltrexone if they slip and return to 

drinking because it may help limit the 

severity of relapse. 

• Participation in psychosocial interventions (e.g., cognitive-behavioral or other 

specialized treatment) and 12-Step or 

other mutual-help groups can increase 

the effectiveness of therapy with 

naltrexone. 

• Patients should carry a medical alert 

card that indicates they are taking 

naltrexone and lists the physician or 

institution to contact in an emergency. 

Oral Naltrexone 33 
 

 

Who Is Appropriate for 

Treatment With Oral 

Naltrexone? 

Patients Who Are Motivated 

or Monitored 

A study by Volpicelli and colleagues 

(1997) concluded that patient compliance with naltrexone dosing is associated 

with treatment retention and positive 

treatment outcomes. As a result, it is 

important that either the patient be 

highly motivated for treatment or a 

medication monitoring plan be used to 

encourage naltrexone use if the patient 

is not highly motivated. To maximize 

compliance, physicians should observe 

dosing or encourage a family member or 

significant other to monitor medication 

use, especially at the beginning of treatment with naltrexone. Strategies such as 

incentives and feedback on medication 

compliance have been incorporated into 

treatment planning to enhance compliance. After the patient’s motivation has 

increased and he or she feels better and 

stronger, medication monitoring may no 

longer be needed. 

Patients Who Are Abstinent 

From Opioids 

Naltrexone is an opioid antagonist; 

patients who are using opioids, being 

maintained on opioid replacement 

therapy, or anticipating surgery or dental 

work that will require opioid analgesics 

are not good candidates for treatment 

with naltrexone. Naltrexone’s opioid 

antagonist properties may make it a 

particularly good treatment option for 

individuals with a history of opioid abuse/

dependence who are seeking treatment 

for AUDs because naltrexone will reduce 

the reinforcing effects of and curb 

cravings for both opioids and alcohol. 

Pain Management 

As an opioid antagonist, naltrexone blocks the 

effect of opioid analgesics. Typical doses of 

narcotic analgesics (e.g., codeine, morphine, 

oxycodone, hydrocodone) may not be effective. 

Fortunately, many nonopioid analgesic medications (e.g., aspirin, NSAIDs) and procedures (e.g., 

regional nerve block) can still be used for 

analgesia. 

When opioids must be used, it is possible to 

reverse the naltrexone blockade using higher 

than usual doses of opioids. However, because 

of the potential for opioid-induced respiratory 

depression, reversal of naltrexone blockade 

should be done only in medical settings with 

the provision for respiratory support. 

Naltrexone does not block aspirin, acetaminophen, or NSAIDs, including ibuprofen and 

naproxen sodium. It does not block the effects 

of local anesthetics such as lidocaine or general 

(nonopioid) anesthetics. (If patients taking naltrexone require opioid pain medication, a rapidly acting opioid analgesic is recommended to 

minimize the duration of respiratory depression. 

Patients should be monitored closely.) 

Patients With Intense Alcohol 

Craving 

Patients with intense alcohol cravings 

during treatment may experience greater 

medication benefit than patients with 

low levels of alcohol craving (Monterosso 

et al., 2001). Also, patients with more 

somatic complaints may have better 

outcomes when treated with naltrexone 

compared with patients with less physical 

distress. Both human laboratory studies 

and clinical trials have suggested that 

patients with a family history of alcohol 

dependence may benefit more from naltrexone treatment than patients without 

a family history of alcohol dependence 

(Monterosso et al., 2001; Rubio et al., 

2005). 

34 Chapter 4 
Treatment Duration 

and Discontinuing Oral 

Naltrexone 

The FDA label states that naltrexone 

should be taken for up to 3 months to 

treat AUDs. Healthcare providers should 

tailor the length of treatment to individual patients. Naltrexone has been 

administered to patients who are alcohol 

dependent for 6 months to 1 year with no 

additional safety concerns (Balldin et al., 

2003; O’Malley et al., 2003). 

One controlled study (Hernandez-Avila et 

al., 2006; Kranzler et al., 2003) addressed 

targeted use of naltrexone during periods 

of risk for problem alcohol use. The 

findings and clinical experience support 

periodic or targeted dosing. Because 

of naltrexone’s efficacy in reducing the 

rewarding effects of alcohol consumption 

(McCaul, Wand, Eissenberg, Rohde, & 

Cheskin, 2000) and reducing cravings for 

alcohol (O’Malley et al., 1992), patients 

who achieve abstinence may benefit 

from taking naltrexone at times when 

they are at higher risk of relapse, such 

as on vacations, on holidays, or during a 

personal tragedy. 

Discontinuation of oral naltrexone is not 

associated with a withdrawal syndrome, 

and it is not necessary to taper the dose. 

Providers should remind patients that 

they should not take opioid medications 

for at least 3 days and that they may 

be more sensitive to the effects of opioid 

drugs (see Patient Education, page 33). 

Final Clinical Thoughts 

Controlled clinical trials have demonstrated that naltrexone can be an 

effective medication for the treatment 

of patients who are alcohol dependent. 

Clinicians indicate that some patients 

report that naltrexone helps, and some 

report no difference with its use. These 

anecdotal reports provide intriguing suggestions that particular patient types or 

subgroups may be more likely than other 

groups to respond to naltrexone. A recent 

finding has suggested that a variant in 

a gene encoding for the m opiate receptor 

(OPRM1) in the opiate neurotransmitter 

system may predict response to naltrexone treatment in people dependent 

on alcohol (Anton et al., 2008). When 

treated with naltrexone and a medical 

management intervention, 87.1 percent 

of persons carrying the less prevalent 

Asp40 variant had a good clinical outcome, compared with only 54.8 percent 

of individuals with the more common 

Asn40/Asn40 genotype (odds ratio, 5.75; 

confidence interval, 1.88–17.54); no difference between groups was observed in 

placebo treatment outcomes. This finding 

suggests that OPRM1 genotyping may 

be a useful procedure for improving identification of those patients most likely 

to benefit from naltrexone treatment for 

alcohol dependence. It also suggests that 

clinicians should not become discouraged if the first patients they prescribe 

naltrexone for do not find it beneficial. 

Naltrexone’s efficacy is modest, but it is 

significantly better than placebo in most 

studies, and some patients benefit from 

naltrexone therapy. 

Although attention is frequently drawn 

to the risks of hepatotoxicity with naltrexone, this rarely occurs, is typically 

reversible, and is more likely with very 

high doses used over a sustained period. 

It is unfortunate that such effects have 

become so closely associated with naltrexone, but the clinician would be prudent to 

monitor liver function. 

Naltrexone—and all the medications 

described in this TIP—does not “cure” 

AUDs the way an antibiotic cures 

bacterial pneumonia. However, as a 

part of comprehensive treatment, it 

may increase the likelihood of sustained 

remission from problem alcohol use. 

Oral Naltrexone 35 

 

 

 

 

 

 

5 Extended-Release 

Injectable Naltrexone 

Extended-Release Injectable Naltrexone At a Glance 

Chemical name: Naltrexone for extended-release injectable suspension. 

Trade name: Vivitrol®. 

U.S. distributor: Alkermes, Inc., Cambridge, MA (manufacturer); Cephalon, Inc., Frazer, PA (distributor). 

U.S. Food and Drug Administration approval to treat alcohol dependence: 2006. 

Dosage/How taken: 380 mg intramuscular injection once every 4 weeks. 

How supplied: Single-use cartons, containing one 380 mg vial of Vivitrol microspheres, one vial 

containing 4 mL (to deliver 3.4 mL) diluent for the suspension of Vivitrol, one 5 mL prepackaged 

syringe, one 20-gauge 1⁄2-inch needle, and two 20-gauge 11⁄2-inch needles. 

Storage: Store entire dose pack in refrigerator (2–8° C, 36–46° F); store unrefrigerated Vivitrol at 

temperatures not exceeding 25° C (77° F) for no more than 7 days before administration; do not 

freeze. 

What Is Extended-Release Injectable 

Naltrexone? 

Extended-release injectable naltrexone is a microsphere formulation of the opioid antagonist (blocker) medication naltrexone. 

It is administered by intramuscular (IM) gluteal injection once 

a month. The extended-release injectable form helps address 

patient noncompliance, which can limit the effectiveness of oral 

naltrexone (Volpicelli et al., 1997). 

Brief History of Development 

Interest existed in developing an injectable, long-acting naltrexone formulation for many years. Various long-acting naltrexone 

formulations were studied, but there was particular interest in

the polylactide (Nuwayser, DeRoo, Balskovich, & Tsuk, 1990) 

and polylactide glycolide (PLG) polymer (Sharon & Wise, 1981). 

These polymers are prepared from naturally occurring sugar 

37 
 

 

 

 

 

acids (lactic acid and glycolic acid), are 

known to be safe, and are used widely

in human and veterinary medicine (e.g., 

in absorbable sutures and biodegradable 

orthopedic screws). The U.S. Food and

Drug Administration (FDA) approved

Alkermes’ PLG polymer formulation of 

extended-release injectable naltrexone for 

treating alcohol dependence in April 2006. 

Pharmacology 

Some behavioral effects of alcohol are 

caused by alcohol acting to release endogenous opioid neurotransmitters (e.g., 

endorphins, enkephalins, dynorphins) 

that bind to opiate receptors in the brain. 

Opioid antagonists, such as naltrexone, 

bind to opiate receptors and block the 

action of both opioid medications and opiate neurotransmitters. 

The injectable naltrexone plasma concentration peaks approximately 2 hours 

after IM injection followed by a second 

peak approximately 2 to 3 days later. 

Beginning approximately 7 days after 

dosing, plasma concentrations slowly 

decline, maintaining a therapeutic naltrexone blood level over 4 weeks and 

avoiding daily peaks and troughs that 

occur with oral naltrexone. Steady state 

is reached at the end of the dosing interval following the first injection. 

Unlike oral naltrexone, injectable naltrexone does not undergo first-pass 

metabolism in the liver. As a consequence, the total monthly dose of 

naltrexone administered is considerably 

less for extended-released (380 mg) compared with oral naltrexone (1,500 mg). 

Therefore, the peak concentration of 

the drug to which the liver is exposed is 

substantially less for injectable naltrexone than for oral naltrexone. Because 

naltrexone-induced hepatotoxicity is dose 

dependent, injectable naltrexone would 

be expected to show less hepatotoxicity than the oral form; however, a direct 

comparison of relative hepatotoxicity of 

the two medications has not yet been 

performed. 

Why Use ExtendedRelease Injectable 

Naltrexone? 

Efficacy 

Findings on the efficacy of naltrexone 

in general to treat alcohol use disorders 

(AUDs) are briefly discussed in Chapter 

4, page 28. More detailed information is 

included in the TIP’s online annotated 

bibliography and literature review at 

http://www.kap.samhsa.gov. Garbutt and 

colleagues (2005) conducted a 6-month, 

randomized clinical trial of injectable 

naltrexone to assess its tolerability and 

efficacy. A group of patients receiving IM 

injection of 380 mg of injectable naltrexone (along with psychosocial support) had 

a 25-percent decrease in the event rate of 

heavy drinking days compared with those 

receiving placebo. Patients receiving a 

lower dose (190 mg) of injectable naltrexone also had a significant decrease (17 

percent) in the event rate of heavy drinking days compared with those receiving 

placebo. 

The FDA Center for Drug Evaluation 

and Research (CDER) analysis of the 

study data concluded that injectable 

naltrexone is effective only in those who 

were abstinent at baseline. CDER’s 

analysis emphasized the proportion of 

patients who did not relapse to heavy 

drinking (FDA CDER, personal communication, 2008). O’Malley and colleagues 

(2007) conducted a secondary analysis 

of outcomes from the Garbutt study to 

determine whether patients with leadin abstinence of 4 or more days also 

experienced particularly good treatment 

outcomes—a practical issue in U.S. detoxification settings, where detoxification 

commonly takes 4 days. They found that 

injectable naltrexone prolongs abstinence 

38 Chapter 5 
and reduces both the number of drinking 

days and the number of heavy drinking 

days in patients who are abstinent for as 

few as 4 days before starting treatment. 

The online literature review provides 

more detailed information on these and 

other efficacy studies. 

Enhanced Medication Compliance 

A major benefit of using an extended-release formulation in the treatment of AUDs is decreased 

concern about compliance with daily administration, thus ensuring efficacy of naltrexone delivery 

and therapeutic effect. In a randomized, doubleblind, clinical trial, there were no differences in 

drinking outcomes in 175 patients with alcohol 

dependence assigned to minimal psychosocial 

treatment and treated with either oral naltrexone or placebo (Chick et al., 2000). However, 

when only those subjects demonstrating greater 

than 80-percent medication compliance were 

included in the analysis, oral naltrexone was 

found to be effective. 

The importance of medication compliance is further supported by a clinical trial that compared 

oral naltrexone with placebo in 97 individuals 

with alcohol dependence receiving weekly oneon-one counseling. Among individuals who were 

treatment compliant, those receiving oral naltrexone reported fewer episodes of heavy drinking (14 percent vs. 52 percent) and had fewer 

drinking days (2.8 percent vs. 11 percent) than 

those receiving placebo, whereas the drinking 

outcomes in the noncompliant individuals did 

not differ from individuals who received placebo 

(Volpicelli et al., 1997). 

Safety 

Injectable naltrexone appears to be well 

tolerated, with a side effects profile 

similar to that of oral naltrexone (with 

the exception of injection-site reactions). 

Like oral naltrexone, the injectable formulation carries a black-box warning 

regarding liver toxicity (see Chapter 4, 

page 29). However, because of its lack 

of first-pass metabolism, injectable 

naltrexone significantly reduces liver 

exposure to the drug, reducing the risk of 

potential liver toxicity. 

How Is Extended-Release 

Injectable Naltrexone 

Used? 

Treatment with injectable naltrexone 

should be part of a management program 

that provides patient education, addresses the psychological and social problems 

of patients, and encourages attendance at 

12-Step or mutual-help meetings or other 

community support. 

Before initiating treatment with injectable naltrexone, healthcare practitioners 

should do the following: 

• Conduct a physical examination 

• Determine liver function (alanine aminotransferase [ALT], aspartate aminotransferase [AST], gamma glutamyltransferase [GGT], and bilirubin) 

• Obtain toxicological screening tests. 

Naltrexone is an opioid antagonist, so 

individuals who are opioid dependent 

may experience opioid withdrawal. 

Treatment with injectable naltrexone 

should not be initiated unless the patient 

is opioid free for 7 to 10 days (or at least 

14 days for patients who have been 

taking methadone for more than 3 to 4 

weeks), as determined by medical history 

or toxicological screening. 

Patients being maintained on 

buprenorphine (Suboxone® or Subutex®)

or methadone for the treatment of opioid 

dependence cannot undergo treatment 

with naltrexone. Before administering 

injectable naltrexone, physicians should 

advise patients of the unpleasant physical 

effects of opioid withdrawal that will 

result if patients are not completely 

detoxified from opioids. Injectable 

naltrexone is available through specialty 

pharmacies. 

Extended-Release Injectable Naltrexone 39 
 

 

 

How To Administer 

Injectable naltrexone should be administered only by a medical professional (e.g., 

physician, nurse, physician assistant) 

who can administer IM (gluteal) injections. Injectable naltrexone comes in a 

kit that contains a vial of naltrexone as 

a dry powder that must be reconstituted 

with a liquid diluent immediately before 

use. The kits must be refrigerated during 

storage but should be brought to room 

temperature 30 to 60 minutes before the 

injection. The reconstituted microspheres 

in solution must be mixed vigorously to 

prevent clumping, which can clog a needle during injection. A syringe and two 

needles are provided—one for mixing the 

microspheres with the diluent and one for 

injecting the suspension into the upper 

outer quadrant of the gluteal muscle. 

The medication is administered every 

4 weeks. If a dose is delayed or missed, 

the next injection should be administered 

as soon as possible. However, it is not 

recommended that medication be readministered earlier than 4 weeks or at a 

higher dose than 380 mg. 

Proper IM injection technique is 

essential. Serious injection site reactions, 

sometimes requiring extensive surgical debridement, have been observed 

with Vivitrol. CDER reports that these 

severe reactions may be more common 

if the product is inadvertently administered subcutaneously, rather than 

intramuscularly (FDA CDER, personal 

communication, 2008). 

Side Effects, Contraindications, 

and Cautions 

Exhibit 5-1 lists the most common side 

effects experienced by patients treated 

with injectable naltrexone. As when using 

oral naltrexone, patients should contact 

their physician if they experience signs or 

symptoms of liver disease (see Exhibit 4-6 

on page 32). 

Exhibit 5-1 

Extended-Release Injectable 

Naltrexone Side Effects 

Injection site reactions Fatigue 


(sometimes severe)
 Back pain
 

Nausea
 Upper abdominal 

Vomiting pain 

Headache Decreased appetite 

Dizziness 

Injectable naltrexone carries the same 

contraindications as oral naltrexone (see 

Exhibit 4-3 on page 31) plus those listed 

in Exhibit 5-2. There are no data on use 

of naltrexone in children or adolescents; 

treatment of these populations with naltrexone is not recommended. 

Exhibit 5-2 

Extended-Release Injectable 

Naltrexone Contraindications 

Patient Condition 

or Circumstance 

Treatment 

Recommendation 

History of sensitivity 

to PLG, carboxymethylcellulose, or any 

components of the 

diluent 

Do not administer 

injectable naltrexone 

Anticipated need 

for opioid analgesics 

within the next 30 

days 

Do not administer 

injectable naltrexone 

Patient obesity Do not administer 

injectable naltrexone 

if patient’s body mass 

precludes IM injection 

with the provided 1.5­

inch needle 

Inadvertent subcutaneous injection may cause 

a severe injection-site 

reaction 

Injectable naltrexone should be used with 

many of the cautions applicable to oral 

40 Chapter 5 
 

 

 

 

 

 

 

 

 

 

naltrexone (see Exhibit 4-4 on page 31) 

plus the cautions listed in Exhibit 5-3. 

Injectable naltrexone should be used 

cautiously with individuals with current 

or recent opioid dependence for two reasons. First, these individuals are at risk 

for overdose of opioids if they use large 

amounts of opioids to overcome naltrexone’s opioid blockade (to feel the effects of 

the drugs). Second, naltrexone blockade 

can decrease tolerance for opioids, making 

a person more sensitive to their effects. 

If a person stops taking naltrexone, then 

takes what used to be a “normal” dose of 

opioids, overdose with respiratory depression can result. 

Exhibit 5-3 

Extended-Release Injectable 

Naltrexone Cautions 

Patient Condition 

or Circumstance 

Treatment 

Recommendation 

Thrombocytopenia 

or coagulation 

disorders 

Monitor carefully for 24 

hours after injection 

Recent opioid Explain to the patient the 

dependence risk of precipitated withdrawal if the patient has 

used opioids recently 

Explain to the patient 

that the opioid-blocking 

effects last for at least 

30 days and that the 

risks associated with a 

return to opioid use are 

significant 

Patient Management 

Possible adverse reactions are the same 

as those for oral naltrexone (see Exhibit 

4-5 on page 32). In addition, injection-site 

reactions are common adverse reactions 

to administration of injectable naltrexone. 

Some pain and tenderness at the injection 

site are common and are similar to those 

occurring after any IM injection. Usually, 

this pain resolves within several days. A 

small lump at the injection site frequently 

occurs and resolves over 2 to 4 weeks. 

However, patients should be instructed to 

seek immediate medical attention if skin 

at the injection site becomes painful, red, 

and swollen and does not improve within 

1 week after the injection. As noted 

above, severe injection-site reactions are 

possible. 

Patients taking injectable naltrexone also 

should be monitored for depression. The 

package label states: 

In controlled clinical trials of Vivitrol, 

adverse events of a suicidal nature 

(suicidal ideation, suicide attempts,

completed suicides) were infrequent 

overall, but were more common in 

patients treated with Vivitrol than in 

patients treated with placebo (1% vs.

0). In some cases, the suicidal thoughts 

or behavior occurred after study discontinuation, but were in the context of an 

episode of depression which began while 

the patient was on study drug. In the

24-week, placebo-controlled pivotal trial, 

adverse events involving depressed

mood were reported by 10% of patients

treated with Vivitrol 380 mg, as compared to 5% of patients treated with 

placebo injections. 

Patients who take injectable naltrexone 

should undergo the same tests as those 

required for patients taking oral naltrexone (see page 32). 

Overdose should not be a concern for 

patients receiving injectable naltrexone 

because it is unlikely that patients will 

receive more than one IM injection per 

month. 

Patient Education 

In addition to the general patient education guidelines discussed in Chapter 6, 

patient education specific to injectable 

naltrexone should precede use. 

Extended-Release Injectable Naltrexone 41 
Healthcare providers should ensure that 

patients understand the following: 

• Once naltrexone is injected, it is 

impossible to remove it from the body; 

if problems occur, the effects can last 

up to 30 days. 

• The onset of naltrexone’s effects will 

probably occur within several hours 

although full effectiveness may not 

occur for 2 to 3 days following first 

injection. The duration of the effects 

appears to be 30 days. 

• Injectable naltrexone blocks the effects 

of opioids and opioidlike drugs (e.g., 

heroin, opioid analgesics, opioid-based 

antidiarrheals, and antitussives) for up 

to 30 days, which may complicate the 

treatment of pain if it occurs during this 

period. Patients should be assured that 

other options for analgesia exist. 

• Injectable naltrexone blocks low to moderate doses of opioids, but large doses of 

heroin or other opioids may lead to serious injury, coma, or death. For patients 

with a history of opioid use, the use of 

injectable naltrexone may lower tolerance for opioids, resulting in a greater 

sensitivity to lower doses of opioids 

after injectable naltrexone treatment is 

discontinued; this increased sensitivity 

could result in overdose and respiratory 

depression. 

• Injectable naltrexone is more likely to 

reduce drinking if it is used in conjunction with psychosocial interventions, 

such as specialized substance abuse 

treatment and community supports 

(e.g., counseling, 12-Step, or other 

mutual-help groups). 

• Patients should carry a safety ID card 

that indicates they are taking injectable 

naltrexone. 

Pain Management 

As an opioid antagonist, injectable naltrexone blocks the effects of opioid analgesics. Pain management for patients taking naltrexone is discussed in Chapter 4, page 34. Pain management for patients 

using injectable naltrexone can be even more complicated because the medication is long acting. The 

package insert offers the following advice: 

In an emergency situation in patients receiving Vivitrol, a suggested plan for pain management is regional analgesia, conscious sedation with a benzodiazepine, and use of non-opioid 


analgesics or general anesthesia.
 

In a situation requiring opioid analgesia, the amount of opioid required may be greater 

than usual, and the resulting respiratory depression may be deeper and more prolonged.
 

A rapidly acting opioid analgesic which minimizes the duration of respiratory depression 


is preferred. The amount of analgesic administered should be titrated to the needs of the 


patient. Non-receptor mediated actions may occur and should be expected (e.g., facial swelling, itching, generalized erythema, or bronchoconstriction), presumably due to histamine 


release.
 

Irrespective of the drug chosen to reverse Vivitrol blockade, the patient should be monitored 


closely by appropriately trained personnel in a setting equipped and staffed for cardiopulmonary resuscitation.
 

Who Is Appropriate 

for Treatment With 

Extended-Release 

Injectable Naltrexone? 

This medication should be considered for 

individuals with alcohol dependence who 

have not responded to other pharmacological and behavioral treatments, in 

particular those who have problems with 

treatment adherence. The medication 

42 Chapter 5 
could be considered a first-line therapy 

for any patient who is alcohol dependent, interested in treatment, and not 

subject to the contraindications listed in 

Exhibit 4-3 and Exhibit 5-2. However, the 

monthly cost of injectable naltrexone is 

significantly higher than that of oral naltrexone and may not be a viable choice for 

many patients. 

For optimal results with injectable naltrexone, candidates for treatment should 

meet several criteria: 

• They must be medically appropriate to 

receive naltrexone. 

• They should not be using opioids currently or have evidence of recent use. 

• They should not be anticipating surgery 

or have a condition, such as chronic 

pain, for which opioid analgesics may be 

required in the future. 

• They should not have severe liver or 

kidney disease, although naltrexone can 

be used cautiously in persons with mild 

to moderate hepatic impairment or mild 

renal insufficiency. 

• They should not have a condition, such 

as a bleeding disorder or obesity, that 

prevents them from receiving a deep IM 

injection. 

• They should have been abstinent for at 

least 4 days. 

• They should be motivated to maintain 

abstinence or to reduce their drinking. 

• They should be willing to participate in 

psychosocial substance abuse treatment 

such as counseling and support groups. 

The consensus panel believes that the 

opioid antagonist properties of injectable 

naltrexone may make it a good treatment 

option for individuals who are seeking 

treatment for alcohol dependence and 

who are in recovery from co-occurring opioid use. However, no evidence for efficacy 

in this population is available, and injectable naltrexone has not been approved for 

the treatment of opioid dependence. 

Treatment Duration and 

Discontinuing ExtendedRelease Injectable 

Naltrexone 

Research has not yet clearly defined 

the optimal duration of treatment 

with injectable naltrexone. Healthcare 

providers may consider discontinuing 

injectable naltrexone once a patient 

has achieved stable abstinence from 

alcohol and has established a sound 

plan and support for ongoing recovery 

or if a patient is not compliant with the 

medication regimen. Like oral naltrexone, 

injectable naltrexone may be useful for 

short periods when a patient in stable 

recovery is at particular risk for relapse 

to problem alcohol use. 

Patients discontinuing injectable naltrexone should be reminded that they should 

not take any opioid medications for at 

least 30 days from the date of their last 

injection. Patients also should be warned 

that after discontinuing treatment they 

may be more sensitive to the effects of 

opioid drugs (see Patient Education on 

page 41). 

Final Clinical Thoughts 

Physicians may be concerned that the 

decreased frequency of required medical 

visits that comes with monthly medication will result in decreased use of 

medical and psychosocial services, 

making patients less likely to attend 

counseling, 12-Step, or mutual-help group 

meetings. Treatment with injectable naltrexone is new, but the experience of the 

consensus panel suggests that patients 

who return monthly for their injectable 

Extended-Release Injectable Naltrexone 43 
naltrexone continue to participate in 

treatment and to attend these groups. 

Possible target patients include those 

who are unable to maintain medication 

adherence for some reason (e.g., poor 

memory) and those who would prefer not 

to have the burden of remembering to 

take medication daily. 

Because injectable naltrexone is 

the newest form of a medication for 

the treatment of AUDs, the optimal 

situations for its use remain to be 

defined. However, it combines two 

attractive features: a medication for 

which there is substantial evidence 

for efficacy and a delivery system that 

eliminates daily medication compliance. 

As such, it represents an important 

addition to the list of medications for the 

treatment of alcohol dependence. 

44 Chapter 5 
 

6 Patient Management 

In This 


Chapter . . .
 

Integrating Medication 


for Alcohol Dependence 


Into Clinical Practice 


Settings
 

Initial Assessment
 

Choosing a Medication
 

Combination Therapy
 

Choosing a Psychosocial 


Intervention
 

Developing a Treatment 


Plan
 

Patient Awareness
 

Monitoring Patient 


Progress
 

Modifying the Treatment 


Strategy
 

Discontinuing 


Pharmacotherapy
 

Final Clinical Thoughts
 

Integrating Medication for Alcohol 

Dependence Into Clinical Practice 

Settings 

Pharmacotherapy for alcohol use disorders (AUDs) is underused 

both in specialized substance abuse treatment programs and in 

office-based medical practice. The consensus panel acknowledges 

that much resistance to pharmacotherapy exists—from thirdparty payers, some clinicians, some individuals participating in 

self-help groups who view medications as substituting a pill for 

self-empowerment and self-responsibility, and some patients and 

their families. The diagnoses of alcohol dependence and abuse, 

as well as hazardous alcohol use, continue to carry significant 

social stigma that affects both the person who is alcohol dependent and healthcare providers. This stigma continues to exist, 

in part, because of a lack of understanding of alcohol dependence 

as a treatable medical disorder. In addition, providers often 

worry that persons who are alcohol dependent have complicated 

conditions that take too much time to treat. 

Healthcare providers are, however, in ideal practice settings 

to identify and treat AUDs among users of healthcare services. 

AUDs are associated with many medical (e.g., hypertension, 

gastritis) and behavioral (e.g., major depressive disorder, 

psychoses) health conditions. Screening, identifying, and treating 

patients with AUDs have the potential to improve the health 

of many primary care patients, decrease healthcare costs, and 

prevent the serious sequelae of alcohol misuse. A full discussion 

of reimbursement issues is outside the scope of TIP 49; however, 

healthcare practitioners can find useful information in SBI 

Reimbursement Guide: How to Use Existing Codes to Bill for 

Alcohol Screening and Brief Intervention/Counseling, prepared 

by Ensuring Solutions for Alcohol Problems at the George 

Washington University Medical Center. The guide is available 

at http://www.ensuringsolutions.org/resources/resources_show.

htm?doc_id=385233. 

45 
 

Patients with AUDs may be more likely 

to see a healthcare provider than to seek 

treatment at a specialty addiction treatment program; these patients represent 

an untapped reservoir of individuals 

who are not receiving needed treatment. 

Medications can be a potent means of 

enhancing treatment for many persons 

who are alcohol dependent; medications 

present healthcare providers a unique 

way to contribute to treatment. Some 

aspects of using maintenance medications 

(e.g., the need for concurrent psychosocial 

treatment and for monitoring drinking 

behavior) may seem different from usual 

medical practice. However, integrating 

maintenance medications into practice 

should not present any more difficulty 

than, for example, beginning to prescribe 

antidepressant or antihypertensive 

medications. Monitoring a patient’s maintenance medication regimen is typically 

less complicated than medication regimens for other chronic conditions, such as 

diabetes or coronary disease. 

Healthcare providers may find that using 

maintenance medication provides them 

with an opportunity to have a significant 

effect on patients’ overall health status, 

social functioning, and family relationships. This chapter describes information 

needed for choosing maintenance medications for patients, making effective 

referrals, and monitoring patients’ 

progress. 

Initial Assessment 

Persons with AUDs often have physical and social sequelae from excessive 

alcohol consumption. AUDs influence the 

incidence, course, and treatment of many 

medical and behavioral health conditions. 

Identifying, assessing, and treating AUDs 

can occur concurrently with assessment 

and treatment of other medical problems. 

As noted in Chapter 1, a thorough discussion of screening and assessment for 

AUDs is outside the scope of this TIP. 

The reader can refer to Helping Patients 

Who Drink Too Much: A Clinician’s Guide 

(National Institute on Alcohol Abuse and 

Alcoholism [NIAAA], 2006), available 

at http://www.niaaa.nih.gov. An online 

course (worth one continuing medical 

education unit) based on the guide is also 

available at http://www.niaaa.nih.gov/

Publications/EducationTrainingMaterials/

VideoCases.htm. NIAAA’s A Pocket 

Guide for Alcohol Screening and Brief 

Intervention is in Appendix B of this TIP. 

Once an AUD diagnosis has been made, 

thorough assessments for substance 

use and social, medical, and psychiatric 

histories are essential in evaluating the 

consequences of dependence and identifying problems that can be addressed 

concurrently with treatment. Evaluation 

can identify or rule out contraindications 

to therapy with specific medications. 

At the very least, a clinician considering a patient’s pharmacologic treatment 

for alcohol dependence should perform a physical exam; order laboratory 

tests; assess psychiatric status; obtain 

substance use, treatment, and social histories; and assess motivation for change. 

Physical Exam and Laboratory 

Testing 

Because alcohol dependence can harm 

many organ systems and certain conditions may preclude pharmacotherapy 

with a particular maintenance medication, a physical exam and laboratory 

testing should be performed before any 

treatment is initiated. 

Medical complications of excessive alcohol 

consumption are common and numerous, and TIP 49 cannot discuss them all. 

However, common medical conditions 

such as hypertension and gastritis and 

common psychiatric conditions such as 

depression can be incited or exacerbated 

by AUDs. Various patient complaints 

can be related to alcohol consumption, 

46 Chapter 6 
 

 

 

including dyspepsia, sleep problems, 

sexual difficulties, depressed mood, and 

irritability. AUDs also contribute to 

progression of morbidity for many 

diseases. For instance, according 

to a recent review of the literature 

(Conigliaro, Justice, Gordon, & Bryant, 

2006), excessive alcohol consumption 

increases the morbidity associated with 

HIV and viral hepatidies and can 

complicate medical treatment for these 

conditions. In addition, existing conditions, such as hepatic or renal disease 

or pain syndromes, either acute or chronic, may contraindicate treatment with 

particular maintenance medications. 

Physical exam 

Although physical exam findings may 

not be specific to alcohol consumption 

or alcohol disorders, a thorough physical exam can often corroborate clinician 

suspicions of an AUD and may help with 

disease monitoring. Patients with AUDs 

may have no specific abnormal exam findings. However, when present, abnormal 

exam findings provide evidence of the 

severity of a patient’s AUD. Longstanding 

alcohol consumption may present with 

many “classic” physical exam features, 

including physical manifestations of cirrhosis, encephalopathy, and vitamin 

deficiencies. Alcohol consumption can 

incur tachycardia (including supraventricular tachycardias), tremor (hand or 

tongue), elevated blood pressure, hepatosplenomegaly, a tender liver edge, 

peripheral neuropathy, spider angiomata, 

conjunctival injection, and unexplained 

trauma (Conigliaro, Delos Reyes, Parran, 

& Schulz, 2003). 

Because AUDs often co-occur with drug 

use, the physical exam may help the clinician identify comorbid substance use 

problems. For example, smoking cigarettes frequently co-occurs with excessive 

alcohol use; smoking, along with alcohol 

use, may increase heart rate and promote 

tachyarrhythmias. Needle marks, hard 

blackened veins, and abscesses in the 

arms, hips, buttocks, thighs, or calves 

may indicate concomitant injection drug 

use. Inhaled drugs, such as crack cocaine, 

often cause a brown tongue, nasal septum 

abnormalities, or diffuse wheezes. 

Laboratory testing 

In addition to helping healthcare practitioners assess a patient’s overall health 

status, initial laboratory testing can identify the presence of AUDs, alcohol-related 

damage, and contraindications for use of 

particular medications. Initial and followup laboratory testing may motivate 

patients and reinforce their progress in 

treatment. Exhibit 6-1 provides a list 

of useful laboratory tests that can identify patients with significant alcohol 

consumption. 

Exhibit 6-1 

Useful Laboratory Tests 

Breath or blood alcohol tests 

Urine toxicology 

Gamma glutamyltransferase (GGT) 

Liver function tests, including serum aspartate 

aminotransferase (AST) 

Complete blood count 

Testing for vitamin deficiencies 

Renal function tests: Standard panel for urea 

(blood urea nitrogen), electrolytes, and serum 

creatinine 

Pregnancy test (women of childbearing age) 

Identifying AUDs and illicit drug 

use. Laboratory tests are more specific 

than sensitive for detecting alcohol problems, and there is no single laboratory 

test that is sensitive or specific for AUD 

diagnoses. Detection of AUDs is improved 

when laboratory tests are combined with 

other screening strategies (Escobar, Espi, 

& Canteras, 1995; Gordon et al., 2001). 

However, certain tests help healthcare 

Patient Management 47 
 

 

 

 

providers identify AUDs and possible 

alcohol-related abnormalities. 

Blood/breath/urine alcohol and toxicological screening. Blood alcohol levels and 

urine/breath tests for alcohol are useful

measures of recent alcohol consumption. 

They determine acute physical or legal 

incapacity to do specific tasks. Initial 

laboratory work also should include a

urine toxicology screen to assess for other 

substances. 

Biomarkers for AUDs. Alcohol biomarkers are physiological indicators of alcohol 

exposure or ingestion and may reflect the 

presence of an AUD. Although tests such 

as serum carbohydrate-deficient transferin (CDT) levels are not often used in 

primary care practice, some evidence suggests that they might be used to screen 

for chronic alcohol consumption and to 

monitor consumption during treatment 

under certain conditions (Bell, Tallaksen, 

Try, & Haug, 1994). For example, an 

increase in CDT over time may suggest an increase in alcohol consumption 

(Sorvajarvi, Blake, Israel, & Niemela, 

1996). 

In addition to assessing impairment in 

liver functioning, AST and GGT can be 

used as biomarkers because they are 

often elevated in persons who recently 

consumed significant amounts of alcohol (Aithal, Thornes, Dwarakanath, & 

Tanner, 1998; Bell et al., 1994; Yersin 

et al., 1995). Some studies suggest that 

biomarkers such as AST, GGT, and 

CDT are most useful for screening when 

used in combination (Aithal et al., 1998; 

Sillanaukee, Aalto, & Seppa, 1998). 

Testing for another biomarker, ethyl 

glucuronide (EtG), is becoming widely 

available in the United States and is 

increasingly being used for screening. This marker is highly sensitive for 

alcohol. This sensitivity is a potential 

drawback as well as a strength, as exposure to even small amounts (such as 

those found in some foods and cosmetic 

items) can trigger a positive test result. 

More detailed information about the use 

(and misuse) of biomarkers for identifying AUDs and other substance use 

disorders can be found in the Substance 

Abuse Treatment Advisory, The Role of 

Biomarkers in the Treatment of Alcohol 

Use Disorders (Center for Substance 

Abuse Treatment [CSAT], 2006b). 

Identifying alcohol-related damage 

and medication contraindications. 

Several laboratory tests help healthcare 

practitioners establish a patient’s overall 

health status as well as identify alcoholrelated damage and contraindications for 

using certain medications. 

Complete blood count. Alcohol overuse 

causes anemia and has direct toxic effects 

on bone marrow. An assessment of hematologic laboratory indices is essential 

when considering pharmacologic treatment of AUDs. Many persons who are 

alcohol dependent have macrocytosis, and 

the mean corpuscular volume is often 

elevated. 

Testing for vitamin deficiencies. People

with AUDs may not eat well, and several 

vitamin deficiencies can occur that lead 

to abnormal cellular functions. Thiamine, 

folic acid, and pyridoxine deficits are common in people with chronic AUDs, and 

these deficiencies contribute to abnormal 

cell growth. Vitamin deficiencies may 

lead to Wernicke-Korsakoff’s/amnestic 

syndrome in patients with severely excessive alcohol consumption. 

Hepatic and renal testing. Consideration 

of treatment of AUDs with pharmacotherapy requires the clinician to 

consider evaluating organ systems that 

are involved in the metabolism and excretion of these medications. For example, 

naltrexone and disulfiram should be used 

with caution in patients with liver disease, and naltrexone and acamprosate 

48 Chapter 6 
should be used with caution in patients 

with renal impairment. Therefore, hepatic and renal system testing should be 

done before initiating use of these medications. Finally, all four medications used 

to treat AUDs are U.S. Food and Drug 

Administration (FDA) pregnancy category 

C; women of childbearing age should 

receive a pregnancy test before pharmacotherapy is initiated. 

Motivating patients for treatment 

and reinforcing progress. Providing

feedback about patients’ initial test 

results, compared with norms, and 

the health risks associated with these 

results can be a powerful way to increase 

patients’ motivation and adherence 

to treatment. Laboratory tests help 

healthcare providers objectively monitor 

patients’ progress in treatment and provide patients with objective reinforcement 

by demonstrating biologic evidence of 

their improving health status. 

Psychiatric Assessment 

Psychiatric conditions (such as major 

depression, generalized anxiety disorder, 

posttraumatic stress disorder, schizophrenia, and personality disorders) frequently 

co-occur with excessive alcohol consumption (Kranzler & Rosenthal, 2003). Some 

psychiatric symptoms resolve with abstinence, and others lessen. Nonetheless, 

the prescribing professional should assess 

the patient for these disorders and for 

suicidal ideation or intent (or refer the 

patient for assessment). Untreated psychiatric conditions can seriously interfere 

with a patient’s ability to comply with 

pharmacotherapy and psychosocial treatment for alcohol dependence and can 

cause the patient preventable suffering. 

More information on co-occurring psychiatric disorders can be found in TIP 42, 

Substance Abuse Treatment for Persons 

With Co-Occurring Disorders (CSAT,

2005). 

Substance Use Assessment 

After healthcare providers have ascertained that a patient has an AUD, they 

should obtain an adequate history of 

the patient’s substance use and of prior 

treatments for AUDs. Providers should 

determine whether the patient has experienced alcohol withdrawal syndrome 

because this syndrome can indicate a 

need for more specialized care than 

primary care providers can typically 

provide. More information about alcohol 

withdrawal and detoxification is in TIP 

45, Detoxification and Substance Abuse 

Treatment (CSAT, 2006a). Excerpts of the 

Quick Guide for Clinicians based on TIP 

45 are in Appendix C. 

During the assessment, providers should 

assess the quantity and frequency of 

alcohol consumption, patterns of alcohol 

consumption (e.g., persistent, occasional, 

binge use), episodes of use, duration of 

use, and consequences of alcohol consumption. The NIAAA clinician’s guide 

suggests a stepwise approach that consists of assessment of any use, quantity/

frequency of use, and harm associated 

with alcohol consumption (NIAAA, 2006). 

NIAAA’s A Pocket Guide for Alcohol 

Screening and Brief Intervention, a condensed version of the clinician’s guide, 

is in Appendix B. Exhibit 6-2 lists key 

questions to quickly assess quantity and 

frequency of alcohol use, based on a “standard drink” in the United States that 

contains 14 grams of pure alcohol (about 

0.6 fluid ounces or 1.2 tablespoons). More 

detailed information about what constitutes a standard drink is in Appendix B. 

The history also should include use of 

substances other than alcohol, especially 

opioids, as well as the patient’s history 

of use, misuse, or abuse of prescription 

medications. Misuse of opioid medications 

may complicate or contraindicate 

Patient Management 49 
 

 

 

 

treatment with naltrexone. Abuse 

of sedatives and tranquilizers may complicate detoxification and treatment. 

A complete assessment includes a 

patient’s current involvement in or 

history of professional treatment or 

mutual-help group involvement, including the following: 

• Detoxification episodes 

• Pharmacotherapy interventions 

• Specialty substance abuse treatment 

episodes (including when, where, 

modality, duration, and outcome) 

• Individual therapy 

• 12-Step (e.g., Alcoholics Anonymous) 

or other mutual- or self-help program 

involvement. 

This information can assist the provider 

in treatment planning and advocating 

for psychosocial treatment as an adjunct 

to pharmacologic treatment for alcohol 

dependence. 

Exhibit 6-2 

Questions To Assess Quantity and 

Frequency of Consumption
 

How often do you have a drink containing 

alcohol? 

How many drinks containing alcohol do you 

have on a typical day when you are 

drinking? 

How often do you have five or more drinks 

on one occasion? 

Source: Babor, Higgins-Biddle, Saunders, & 

Monteiro, 2001. 

Social History 

Understanding a patient’s social situation 

identifies problems that may interfere 

with treatment and that necessitate 

referral for ancillary services. Asking a 

patient basic questions about his or her 

work, legal, living, and family situations 

can yield information that is critical to 

treatment planning: 

• What is the patient’s family situation? 

Who should be included in treatment 

planning? Who can monitor a patient’s 

medication compliance? 

• Is the patient on probation at work? 

Could this be a means of motivating 

medication compliance? 

• What is the patient’s living situation? 

Are extra measures required to ensure 

medication compliance? Are psychosocial treatment modalities (residential 

vs. outpatient) recommended? 

Assessing Motivation for Change 

Before offering treatment for alcohol 

dependence, providers should assess 

patients’ readiness to change drinking behavior. Through this assessment, 

patients and providers develop mutually 

agreeable intervention and treatment 

plans. Exhibit 6-3 provides questions that 

determine patients’ readiness for change. 

Regardless of patients’ readiness to 

change, they should, at a minimum, be 

willing to be in a supportive relationship with their healthcare provider. If 

the relationship is strained by dishonesty or mistrust, initial willingness to 

take medication and ongoing compliance 

with a medication regimen may suffer. 

In addition, patients should be willing 

to consider adjunctive options including 

specialty treatment, other independent 

psychosocial treatment providers, or 

forms of community support. A review 

of the literature suggests that although 

psychosocial interventions increase rates 

of abstinence and decrease alcohol consumption, a significant proportion of 

patients relapse to drinking within 1 year 

(Mason, 2005a). Healthcare providers, 

however, can play a significant role in 

motivational enhancement and relapse 

prevention. More information about 

50 Chapter 6 
 

 

 

 

 

 

stages of change and motivational 

enhancement is in TIP 35, Enhancing 

Motivation for Change in Substance 

Abuse Treatment (CSAT, 1999b). 

Exhibit 6-3 

Questions To Assess Patients’ 

Readiness for Change 

In what ways are you concerned about your 

drinking? 

How much does this concern you? 

What are the reasons you see for making a 

change? 

How do you feel about changing your 

drinking? 

How ready are you to change your drinking? 

What do you think will happen if you don’t 

make a change? 

What do you think you want to do about your 

drinking? 

What do you think would work for you, if you 

needed to change? 

Choosing a Medication 

Scant research exists to guide clinicians 

in choosing the best medication for a 

particular patient. This lack of guidance 

results in part from the inconsistent findings of pharmacotherapy efficacy trials 

among subsets of patient populations. 

These inconsistent results may be related 

to the multiple factors associated with 

the effectiveness of these medications. 

Further research with larger patient 

samples is necessary before the proposed 

relationships can have a definitive influence in the individual decisionmaking 

process. 

Each chapter in this TIP that discusses 

a particular medication for treating AUDs 

summarizes the evidence that is available regarding the type of patient most 

appropriate for the medication; a more 

detailed discussion of patient–medication 

matching is found in the TIP’s online literature review (http://www.kap.samhsa.

gov). In addition to considering the characteristics that research has indicated 

may be relevant to choosing a medication, 

providers need to consider the patient’s: 

• Past experience with particular maintenance medications 

• Opinion about which medication may be 

most helpful 

• Level of motivation for abstinence 

• Medical status and contraindications for 

each medication 

• History of medication compliance. 

Exhibit 6-4 provides a decision grid to 

help providers make decisions about 

pharmacotherapy. This grid is based 

on existing evidence regarding patient–

medication matching, medication 

contraindications, and the clinical experiences of consensus panelists. Exhibit 6-5 

provides a quick-reference guide for comparing maintenance medications. 

Combination Therapy 

A number of studies have found that 

treatment outcomes improve when naltrexone is combined with acamprosate or 

disulfiram, particularly for patients who 

responded poorly to therapy with any 

of these medications alone (reviewed by 

Kiefer et al., 2003; Kiefer & Wiedemann, 

2004). Besson and colleagues (1998) 

reported that co-administration of 

disulfiram improved the action of acamprosate. One study reports that combining 

acamprosate with naltrexone boosted 

plasma levels of acamprosate, which may 

have clinical benefits not achieved by 

monotherapy with either drug (Mason, 

2005a). The Combining Medications and 

Behavioral Interventions (COMBINE) 

study (Anton et al., 2006) did not support 

the efficacy of combination therapy with 

acamprosate and naltrexone, although 

Patient Management 51 
 

 

this combination has been used in 

Europe and Australia with some reported 

success (Feeney, Connor, Young, Tucker, 

& McPherson, 2006; Kiefer et al., 2003; 

Kiefer & Wiedemann, 2004). More information is needed about the efficacy of this 

strategy, although it may be worth trying with patients who have not benefited 

from single-drug therapy. 

Exhibit 6-4 

AUD Medication Decision Grid 

A = Appropriate to use C = Use with caution 

X = Contraindicated + = Particularly appropriate 

Pretreatment Indicators Acamprosate 

(Campral®) 

Disulfiram 

(Antabuse®) 

Oral Naltrexone 

(ReVia®, Depade®) 

Injectable 

Naltrexone 

(Vivitrol®) 

Renal failure X A A A 

Significant liver disease A C C C 

Coronary artery disease A C A A 

Chronic pain A A C C 

Current opioid use A A X X 

Psychosis A C A A 

Unwilling or unable to sustain total 

abstinence A X A A 

Risk factors for poor medication adherence C C C A 

Diabetes A C A A 

Obesity that precludes IM injection A A A X 

Family history of AUDs A A + + 

Bleeding/other coagulation disorders A A A C 

High level of craving A A + + 

Opioid dependence in remission A A + + 

History of postacute withdrawal syndrome + A A A 

Cognitive impairment A X A A 

One placebo-controlled but not randomized trial of acamprosate also prescribed 

disulfiram to patients who requested 

it (Besson et al., 1998). Patients who 

received the disulfiram–acamprosate 

combination had significantly more 

abstinent days than those who received 

acamprosate only. However, those who 

requested disulfiram may have been 

more motivated. Because patients were 

not assigned randomly to the disulfiram–

acamprosate regimen, it is unclear 

whether the combination of disulfiram 

and acamprosate or motivation was 

responsible for the results. Another study 

(Petrakis et al., 2005) found no advantage 

for the combination of naltrexone and 

disulfiram in a randomized, placebocontrolled study of patients with a 

co-occurring Axis I mental disorder and 

alcohol dependence, but it did find that 

active medication with either drug produced greater benefit than placebo in this 

population. 

Although no absolute contraindications 

exist for using disulfiram with either 

naltrexone or acamprosate, no clear 

52 Chapter 6 
Exhibit 6-5 

Comparison of Approved Medications 

for Maintenance of Abstinence From Alcohol* 

Acamprosate Disulfiram Oral Naltrexone 

ExtendedRelease Injectable 

Naltrexone 

Mechanism 

of action 

Not clearly understood; 

appears to restore to 

normal the altered 

balance of neuronal 

excitation and inhibition induced by chronic 

alcohol exposure, possibly through interaction 

with the glutamate 

neurotransmitter 

system 

Inhibits aldehyde dehydrogenase, causing a 

reaction of flushing, 

sweating, nausea, and 

tachycardia when alcohol is ingested 

Not clearly understood; 

opioid antagonist; 

blocks the effects of 

endogenous opioid 

peptides; appears to 

attenuate euphoria 

associated with alcohol 

use; may make alcohol 

use less rewarding; may 

reduce craving 

Same as oral 

naltrexone 

Examples 

of drug 

interactions 

No clinically relevant 

interactions 

Metronidazole; medications containing 

alcohol; anticoagulants such as warfarin; 

amytripyline; isoniazid; 

diazepam 

Opioid medications; 

cough/cold medications; 

antidiarrheal medications; thioridazine; 

yohimbine 

Presumed same as 

oral naltrexone; clinical drug interaction 

studies have not been 

performed 

Common 

side effects 

Diarrhea and 

somnolence 

Transient mild drowsiness; metallic taste; 

dermatitis; headache; 

impotence 

Nausea; vomiting; 

anxiety; headache; 

dizziness; fatigue; 

somnolence 

Same as oral naltrexone, plus injection site 

reactions; joint pain; 

muscle aches or cramps 

Contraindications Severe renal impairment (creatinine 

clearance ≤ 30 mL/min) 

Hypersensitivity to 

rubber derivatives; significant liver disease; 

alcohol still in system; 

coronary artery disease 

Currently using opioids or in acute opioid 

withdrawal; anticipated 

need for opioid analgesics; acute hepatitis or 

liver failure 

Same as oral naltrexone, plus inadequate 

muscle mass for deep 

intramuscular injection; body mass that 

precludes deep intramuscular injection; 

rash or infection at 

injection site 

Cautions Dosage may be modified for moderate renal 

impairment (creatinine 

clearance 30–50 mL/ 

min); pregnancy category C† 

Hepatic cirrhosis or 

insufficiency; cerebrovascular disease; 

psychoses; diabetes 

mellitus; epilepsy; renal 

impairment; pregnancy 

category C† 

Renal impairment; 

chronic pain; pregnancy 

category C† 

Same as oral naltrexone, plus 

hemophilia or other 

bleeding problems 

Serious 

adverse 

reactions 

Rare events include 

suicidal ideation; severe 

persistent diarrhea 

Disulfiram–alcohol 

reaction; hepatotoxicity; peripheral 

neuropathy; psychotic 

reactions; optic neuritis 

Precipitates opioid 

withdrawal if the 

patient is dependent on 

opioids; hepatotoxicity 

(although it does not 

appear to be a hepatotoxin at recommended 

doses) 

Same as oral naltrexone plus inadvertent 

subcutaneous injection 

may cause a severe 

injection-site reaction; depression; rare 

events including allergic pneumonia and 

suicidal ideation and 

behavior 

*Based on information in the FDA-approved product labeling or published medical literature. 

†

FDA pregnancy category C: Animal studies have indicated potential fetal risk OR have not been conducted and no or insufficient 

human studies have been done. The drug should be used with pregnant or lactating women only when potential benefits justify 

potential risk to the fetus or infant. 

Patient Management 53 
 

 

 

 

 

 

 

 

 

 

 

 

current evidence indicates that one combination is more efficacious than any of 

the three agents alone. There is some 

concern about concurrent use of naltrexone with disulfiram because of the 

possibility of additive liver toxicity. In 

addition, disulfiram should not be used 

unless the patient’s goal is complete 

abstinence, a goal not necessary when 

treating with naltrexone or acamprosate. 

Finally, the literature is not clear that 

combining disulfiram with either naltrexone or acamprosate improves patient 

outcomes. Therefore, at this time the consensus panel does not recommend using 

disulfiram in combination with either naltrexone or acamprosate. 

Choosing a Psychosocial 

Intervention 

Any pharmacologic treatment for alcohol 

dependence should be used as an adjunct 

to, not a replacement for, psychosocial 

treatment. The literature suggests that 

the medication–psychosocial therapy 

combination is more effective than either 

alone. For example, Anton and colleagues 

(2005, 2006) reported the benefits of 

combining naltrexone and behavioral 

interventions for alcohol dependence, 

including longer time to relapse and 

increased time between relapse episodes. 

Psychosocial treatments are likely to 

enhance compliance with pharmacotherapy; likewise, pharmacotherapies, 

to the extent that they reduce craving 

and help maintain abstinence, may make 

the patient more open to psychosocial 

interventions. 

Types of Psychosocial Therapies 

As with pharmacotherapy, there is no 

psychosocial “magic bullet.” However, 

a number of modalities of psychosocial 

therapy have been studied and validated 

for treatment of alcohol use disorders 

(reviewed by McCaul & Petry, 2003). 

Medical management (MM) is often 

practiced by primary care physicians in 

patients with diabetes and hypertension 

treatment. NIAAA developed an MM 

treatment as part of its COMBINE study 

(NIAAA, 2004). MM was designed specifically to accompany pharmacotherapy 

for AUDs and be delivered by medically 

trained clinicians in a medical setting. 

MM provides the structure and materials 

to enable clinicians to do the following: 

• Provide patients with strategies for 

taking their medications and staying 

in treatment 

• Provide educational materials 

about alcohol dependence and 

pharmacotherapy 

• Support patients’ efforts to change 

drinking habits 

• Make direct recommendations for 

changing drinking behaviors. 

An MM manual is available through 

NIAAA at http://www.niaaa.nih.gov. 

Providers in psychiatric practice may 

provide psychosocial therapies on site. In 

the context of the primary care setting, 

however, delivering particular psychosocial therapies (e.g., group therapy) may 

be difficult because of time constraints, 

patient population, and lack of training. 

Brief interventions, motivational enhancement therapy, and MM treatment are 

more conducive to primary care settings 

(Anton et al., 2005, 2006). Sources of

information about these interventions are 

listed in Exhibit 6-6. If these types of inoffice interventions are not effective with 

a patient, or if the provider does not have 

the resources to offer them, providers

may need to refer the patient for more

intensive or specialized services. 

54 Chapter 6 
 

 

 

 

 

 

 

 

 

 

 

 

 

Exhibit 6-6 

Resources for Office-Based 

Psychosocial Approaches 

TIP 34, Brief Interventions and Brief Therapies 

for Substance Abuse (CSAT, 1999a) 

KAP Keys for Clinicians Based on TIP 34 (CSAT, 

2001a) 

Quick Guide for Clinicians Based on TIP 34 

(CSAT, 2001c) 

TIP 35, Enhancing Motivation for Change in 

Substance Abuse Treatment (CSAT, 1999b) 

KAP Keys for Clinicians Based on TIP 35 (CSAT, 

2001b) 

Quick Guide for Clinicians Based on TIP 35 

(CSAT, 2001d) 

Helping Patients Who Drink Too Much: A 

Clinician’s Guide (NIAAA, 2006) 

NIAAA’s A Pocket Guide for Alcohol Screening 

and Brief Intervention (see Appendix B) 

Medical Management Treatment Manual: A 

Clinical Research Guide for Medically Trained 

Clinicians Providing Pharmacotherapy as Part 

of the Treatment for Alcohol Dependence 

(NIAAA, 2004) 

Referring Patients for Specialty 

Treatment 

Primary care practitioners may need to 

refer patients for psychosocial therapies, 

including to specialty substance abuse 

treatment programs. Many specialty substance abuse treatment programs provide 

comprehensive treatment services, either 

directly or through referrals, that address 

multiple factors affecting recovery. Such 

programs address not only immediate 

withdrawal and craving but management of long-term abstinence through the 

following: 

• Pharmacotherapy 

• Case monitoring 

• Individual, group, and family/couples 

counseling and therapy 

• Other psychosocial services (e.g., 

vocational counseling) 

• Referral to mutual-help groups. 

The underlying basis for a specialty 

program is that optimal outcomes are 

achieved through a range of complementary services and that, as abstinence 

lengthens, other issues related to alcohol 

use become clearer and more amenable 

to treatment. 

A practitioner who is planning to treat 

patients with alcohol dependence should 

become familiar with a range of local 

treatment resources. Developing relationships with treatment staff will facilitate 

smooth referrals and followup. In addition, understanding something about a 

program’s treatment duration, modality, 

philosophy, and continuing-care options 

helps the practitioner better match a 

patient to appropriate treatment; practitioners can prepare the patient for what 

to expect, enhancing compliance with the 

referral. Practitioners can find programs 

in their areas or throughout the United 

States by using the interactive Substance 

Abuse Treatment Facility Locator on 

the Substance Abuse and Mental Health 

Services Administration (SAMHSA) Web 

site at http://dasis3.samhsa.gov. 

Mutual- or Self-Help Programs 

Mutual- or self-help group support can be 

critical to long-term recovery. The oldest, 

best-known, and most accessible mutualhelp program is Alcoholics Anonymous 

(AA) (http://www.aa.org). Patients may 

resist attending AA meetings and may 

fear that disclosure of medication use 

may be unwelcome. Although some AA 

members may have negative attitudes 

toward medications, the organization 

itself supports appropriate medication 

use (AA, 1984). Providers should 

encourage patients to try different 

group meetings if they meet with 

negativity. Lists of local meetings can 

be obtained from http://www.aa.org 

and given to patients. Dual Recovery 

Anonymous (http://www.draonline.org) 

Patient Management 55 
 

is a 12-Step program for patients with 

co-occurring psychiatric disorders. Other 

mutual- or self-help groups include Self 

Management and Recovery Training 

(http://www.smartrecovery.org) and 

Women for Sobriety, Inc. (http://www.

womenforsobriety.org). Although groups 

other than AA are not available in every 

community, they do offer a number of 

online resources. For patients’ family 

members, there are Al-Anon and Alateen 

meetings (http://www.al-anon.alateen.

org). 

Providers should have a working 

knowledge of the most common groups 

so that they can suggest these groups 

to their patients and discuss patients’ 

participation. 

Developing a Treatment 

Plan 

Setting Goals: Abstinence or 

Reduction? 

Each patient–provider interaction should 

assess and clarify outcome goals for the 

patient. A patient initially may seek to 

reduce alcohol consumption. Another 

patient may be motivated for total abstinence. Investigations into prescribing of 

pharmacotherapy employ both alcohol 

use reduction outcomes and abstinence 

outcomes to assess the efficacy of medications to treat alcohol dependence. Clinical 

outcomes to assess progress include the 

length of time to first drink, time to 

heavy drinking, cumulative abstinence 

days, and drinks per drinking episode. 

Each provider and patient should set an 

initial goal and be willing to refine that 

goal as treatment progresses. 

If a patient with an AUD is unwilling to 

be completely abstinent, he or she may 

be willing to cut down on alcohol use. 

Practitioners can work with this while 

noting that abstinence is the safer strategy and has a greater chance of long-term 

success. 

Certain conditions warrant advising 

a patient to abstain from rather than 

reduce drinking. As noted in the NIAAA 

(2006) clinician’s guide, these conditions 

include when drinkers: 

• Are or may become pregnant 

• Are taking a contraindicated medication 

• Have a medical or psychiatric disorder 

caused or exacerbated by drinking 

• Have an AUD. 

For those who drink heavily and who do 

not have an AUD, the practitioner should 

use professional judgment to determine 

whether cutting down or abstaining is 

more appropriate, based on factors such 

as (NIAAA, 2006): 

• A family history of alcohol problems 

• Advanced age 

• Injuries related to drinking. 

Elements of a Treatment Plan 

A comprehensive pharmacotherapy treatment plan for a patient with an AUD 

should include the following: 

• The medication to be used and a rationale for its use 

• Initial and maintenance dosages 

• A schedule for followup office visits and 

laboratory testing for monitoring health 

status and progress 

• Criteria for discontinuing the 

medication 

• A referral and followup plan for 

concurrent specialty substance abuse 

treatment, psychiatric treatment, and/

or family therapy 

56 Chapter 6 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

• A plan for mutual- or self-help group 

attendance 

• Clarification of family or significant 

other involvement in treatment 

• A plan for treating alcohol-related or 

other concurrent conditions. 

Special attention must be paid to developing a medication compliance plan with 

the patient. This plan may include the 

following: 

• Specific strategies for remembering to 

take medications 

• Using blistercard packs or pill boxes 

• Monitoring medication compliance 

on an appropriate schedule given the 

patient’s history of compliance with 

maintenance and other medication 

regimens 

• Involving the patient’s family members 

in monitoring compliance. 

Patient Awareness 

Patient awareness is critical to successful 

pharmacotherapy. When starting any new 

medication, the patient should understand how the medication works and what 

to expect while taking it. Particularly 

when prescribing maintenance medications, treatment providers need to 

offer that information and guidance to 

patients. Patients also need to understand 

that alcohol dependence is a chronic medical disorder. They need to know that they

may experience protracted effects from 

their alcohol use, including postacute 

withdrawal symptoms (e.g., sleep difficulties). When patients do not feel good, it

is a challenge to keep them in treatment.

Providers should educate patients to 

manage their concerns and anxieties. 

Exhibit 6-7 contains elements of effective 

patient education, and Exhibit 6-8 is a 

brief list of information resources 

providers can give patients. 

Exhibit 6-7 

Elements of Patient Education 

Information about alcohol dependence as a 

chronic medical disorder 

Description of what to expect in recovery, 

including symptoms of postacute withdrawal 

List of the possible benefits of a particular 

medication 

Information about the medication itself: 

• How and when to take it and the importance of complying with the regimen 

• When the medication will become fully 

effective 

• Possible common side effects and their 

expected duration 

• Under what conditions the patient should 

immediately call the provider 

• Any cautions regarding daily activities 

• Medication interactions 

Explanation of the importance for women 

of childbearing age to use an effective birth 

control method 

Information about what to do if the patient 

starts drinking after a period of abstinence 

Description of the importance of concurrent 

psychosocial treatment and mutual- or selfhelp programs 

Followup plans 

Specific patient education unique to each medication is in the medication chapters. 

Monitoring Patient 

Progress 

As it is with any chronic illness, monitoring of AUDs and pharmacologic 

treatment is important. Providers should 

monitor patients’ ongoing treatment compliance, abstinence or reduced drinking, 

Patient Management 57 
 

 

levels of craving, health status, social 

functioning, and use of other substances 

so that necessary adjustments in treatment plans can be made. 

Exhibit 6-8 

Information Resources for Patients 

Al-Anon/Alateen 

http://www.al-anon.alateen.org 

1 (888) 425-2666 

General information about how to find local 

meetings 

Alcoholics Anonymous 

http://www.aa.org 

(212) 870-3400 (U.S. General Service Office) 

General information, publications, and how to find 

local meetings 

Dual Recovery Anonymous 

http://www.draonline.org 

General information, publications, and how to find 

local meetings 

National Council on Alcoholism and Drug 

Dependence 

http://www.ncadd.org 

(212) 269-7797 

Publications about AUDs and information about 

advocacy 

NIAAA 

http://www.niaaa.nih.gov
 

Information about AUDs, information for families, 


and publications 

SMART Recovery 

http://www.smartrecovery.org 

1 (866) 951-5357 

Information about recovery, online recovery tools, 

online meetings/chat groups/message boards, how 

to find face-to-face meetings, and publications 

SAMHSA 

http://www.samhsa.gov
 

1 (800) 662-HELP (Substance Abuse Treatment 


Facility Locator)
 

1 (800) 273-TALK (8255); 1 (800) 799-4889 (TTY) 


(National Suicide Prevention Lifeline)
 

Information about substance abuse and self-tests
 

FDA 

http://www.fda.gov 

1 (888) INFO-FDA 

Patient information about medications to treat 

AUDs 

Women for Sobriety, Inc. 

http://www.womenforsobriety.org 

(215) 536-8026 

Online recovery tools, online chat groups, how to 

find face-to-face meetings, and publications 

Monitoring Adherence 

Several means exist for a provider to 

monitor patients’ compliance with treatment plans, including the following: 

• Tracking patients’ record of keeping 

(or not keeping) appointments for 

medication monitoring 

• Monitoring prescription refills 

• Noting whether patients are keeping agreements about payment for 

treatment 

• Requesting periodic status reports from 

specialty substance abuse treatment 

programs, psychiatric referrals, and 

other psychosocial therapy or support. 

Monitoring Abstinence 

or Reduction in Alcohol 

Consumption 

The ways in which providers can monitor 

patients’ drinking behavior include the 

following: 

• Patient self-reports can be useful indicators of treatment success. The provider should discuss with the patient 

the quantity and frequency of drinking, especially during stressful periods 

(e.g., holidays, celebrations, major life 

changes). 

58 Chapter 6 
 

 

• Laboratory tests may include AST, GGT, 

CDT, EtG, and urine drug screening. 

In addition, providers can use periodic 

BreathalyzerTM tests (although these 

detect only for a short period following 

ingestion) to monitor alcohol intake and 

provide positive feedback to patients who 

are successful in maintaining abstinence. 

Monitoring Craving 

Greatly diminished craving to drink alcohol is an optimum outcome of treatment. 

To assess craving, a physician can rely 

largely on the patient’s subjective reports, 

although measures such as the Alcohol 

Urge Questionnaire (Bohn, Krahn, & 

Staehler, 1995) may prove useful. 

More important than the method of monitoring is consistency in how the patient is 

asked about craving patterns and trends. 

Patients should be asked about current 

craving as well as how they felt over the 

past week (e.g., as a rating between 1 

and 10, with 1 being no craving and 10 

the most intense craving the patient has 

ever experienced). Patients may be asked 

whether any episodes have caused particular problems for them. 

The patterns of craving over time can be 

useful. Both the provider and the patient 

can see that the patient’s patterns of 

craving may fluctuate throughout the 

day and over longer periods; these patterns can assess the appropriateness to 

continue, adjust, supplement, enhance, or 

terminate pharmacologic treatment. 

Providers should educate the patient 

about the role of craving in relapse. 

Learning from and responding optimistically to relapse may increase the patient’s 

motivation to reduce or eliminate alcohol 

consumption. 

Monitoring Health Status and 

Social Functioning 

Ultimately, the goal of treatment is 

improved quality of life. It is important 

to monitor patients’ progress over time in 

the following areas: 

• Health 

– Normalization of previously elevated 

blood pressure 

– Improvement of liver function 

– Stabilization of related medical 

problems that the patient was 

experiencing before treatment (e.g., 

control of blood glucose, stabilization 

of asthma, cardiomyopathy, encephalopathy, gastritis, ascites and edema) 

– Signs of increased concern about 

health care, such as seeing a 

physician for the first time in years 

and/or increased compliance with 

prescribed medication regimens 

not related to AUD treatment (e.g., 

asthma or blood pressure medications) 

• Family/social activities 

– Spending more positive time with 

children and/or spouse 

– Greater involvement/participation 

with family members 

– Improved intimate relationships 

– Reduced family conflict 

– Engagement in nondrinking leisure 

and recreational activities 

• Work/vocational status 

– Obtaining employment if previously 

unemployed 

– Improved attendance at work 

– Fewer job-related and financial problems 

– Improved job performance 

Patient Management 59 
• Legal status 

– No parole or probation violations (in a 

patient with legal problems) 

– No new driving-under-the-influence 

charges 

• Mental status 

– Decreased irritability and anxiety 

– Improved mood 

– Improved sleep 

– Getting appropriate treatment for 

anxiety disorders, suicidal ideation, 

depression, or schizophrenia rather 

than self-medicating with alcohol. 

Monitoring Other Substances 

of Abuse 

It is important to address other substances of abuse that pose the same level 

of concern and possible adverse consequences. The abuse of other substances 

can be evaluated by random urinalysis 

collection and testing and self-reports 

from the patient. Use of illicit substances, 

tobacco use, and abuse of prescription 

and nonprescription medications should 

be addressed. The patient’s agreement or 

resistance to continuing treatment may 

indicate his or her willingness to consider 

other substance use a problem. 

Modifying the Treatment 

Strategy 

An AUD is a chronic illness that, despite 

treatment, may wax and wane in intensity over time. Some patients may respond 

to psychosocial interventions, others to 

pharmacotherapy. Because a patient may 

respond to one medication and not to 

another, the provider should be flexible 

in modifying the medical regimen based 

on the patient’s needs. Furthermore, 

a patient may choose to be treated for 

AUDs to reduce, eliminate, or discourage further escalation of consumption. 

A patient’s goals may change over time, 

and providers should adapt to these new 

objectives. 

As with patients who receive treatment 

for other chronic diseases, patients receiving treatment for AUDs may relapse. If 

this occurs, the provider should consider 

several options: 

• Increase monitoring of medication 

adherence 

• Increase the dose of the medication 

• Change the medication 

• Increase or change the intensity of psychosocial treatment to include referring 

the patient to specialty care 

• Examine social, medical, or behavioral factors that contribute to alcohol 

consumption. 

Even after patients and providers have 

examined the reasons for relapse and 

have intensified or modified psychosocial 

treatment or pharmacotherapy, some 

patients may continue to resist reducing 

alcohol consumption. A small proportion of patients with AUDs may simply 

be resistant to treatment. For example, 

chronic relapsing patients are generally defined as patients who persistently 

consume alcohol despite regular and 

intensive social and medical interventions. These patients frequently use 

emergency services (Thornquist, Biros, 

Olander, & Sterner, 2002). They may 

resist or cannot effectively use pharmacological and psychosocial interventions 

because of poor social or environmental 

situations or other personal factors. These 

patients, often labeled as “difficult,” contribute to the perception of providers that 

treating AUDs is unlikely to be successful. Dealing with any chronic condition 

and changing harmful behavior are 

difficult. Understanding and accepting 

these difficulties can help providers keep 

patients moving forward, even if the pace 

60 Chapter 6 
is slow. Because treatment of chronic 

relapsing patients is difficult, it should 

be undertaken by addiction professionals 

in specialty treatment settings that use 

a multifaceted approach incorporating 

social, environmental, medical, behavioral, and motivational interventions. 

Discontinuing 

Pharmacotherapy 

Because an AUD is a chronic disorder, 

patients may need long-term use of 

medication or more than one episode 

of pharmacotherapy. In addition, some 

patients may benefit from using a medication over short periods to help them 

through a particularly stressful period 

or a situation that has typically elicited 

cravings for alcohol (e.g., a patient may 

want to take disulfiram or naltrexone 

while visiting family members who drink 

excessively). 

Ideally, the patient and provider will 

decide together to discontinue pharmacotherapy. A patient may simply stop 

taking the medication. A patient also 

may express a desire to discontinue a 

medication because of side effects or 

for other reasons, or a patient will need 

to discontinue medication because of 

significant negative changes in laboratory findings or physical health status. 

Otherwise, the patient and provider may 

consider discontinuing medication under 

the following conditions: 

• The patient reports substantially 

diminished craving. 

• The patient has maintained stable 

abstinence over a sustained period. 

• The patient feels ready to discontinue 

the medication. 

• The patient is engaged in ongoing 

recovery, including community supports 

(such as attendance at mutual-help 

group meetings). 

None of the medications discussed in this 

TIP are associated with a withdrawal 

syndrome, and they do not need to be 

tapered. 

Final Clinical Thoughts 

Management of the patient with an AUD 

may be seen as a series of stages: 

• Assessing the patient’s suitability for 

treatment with a medication 

• Determining which medication should 

be used 

• Providing and/or referring the patient 

for psychosocial services 

• Assessing the patient’s response to 

medication, including both efficacy (Is 

it working?) and side effects (Are there 

problems?). 

This process is similar to becoming familiar with any new treatment regimen. 

AUDs may differ from other common 

chronic disorders mainly in that healthcare providers may perceive that they 

have few patients with AUDs. However, 

the pervasiveness of alcohol use and the 

substantial rates of AUDs in the United 

States make it extremely unlikely that 

the clinician is not seeing patients with 

AUDs. The provider simply may not recognize patients with problem alcohol use. 

The availability of effective medications 

that can decrease rates of problem alcohol 

use or help patients maintain abstinence 

is an extremely important step forward in 

the treatment of AUDs. Physicians should 

become familiar with these medications, 

with the features of this patient population, and with the services that, combined 

with medication, can improve treatment 

outcome. AUDs are treatable medical conditions, and treatment can improve the 

patient’s health and quality of life. 

Patient Management 61 

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70 Appendix A 
Appendix B— 

NIAAA’s A Pocket Guide 

for Alcohol Screening 

and Brief Intervention 

Included with permission from the National Institute on Alcohol 

Abuse and Alcoholism 

71 

Updated

A POCKET GUIDE FOR 

Alcohol Screening and 


Brief Intervention


Updated 2005 Edition 

This pocket guide is condensed 

from the 34-page NIAAA guide, 

Helping Patients Who Drink Too Much: 


A Clinician’s Guide.


Visit www.niaaa.nih.gov/guide for related 


professional support resources, including:


• patient education handouts 

• preformatted progress notes 

• animated slide show for training 

• materials in Spanish 

Or contact: 

NIAAA Publications Distribution Center 

P.O. Box 10686, Rockville, MD 20849-0686 

(301) 443–3860 

www.niaaa.nih.gov 

HOW TO SCREEN FOR HEAVY DRINKING 

STEP 1 Ask About Alcohol Use 

Ask: Do you sometimes drink beer, wine, 

or other alcoholic beverages? 

NO 

Screening complete. 

YES 

Ask the screening question about 

heavy drinking days: 

How many times in the past year 

have you had . . . 

5 or more 

drinks in a day? 

(for men) 

4 or more 

drinks in a day? 

(for women) 

One standard drink is equivalent to 

12 ounces of beer, 5 ounces of wine, 

or 1.5 ounces of 80-proof spirits. 

Is the answer 1 or more times? 

NO 

Advise staying within these 

limits: 

Maximum Drinking Limits 

For healthy men up to age 65— 

• no more than 4 drinks 

in a day AND 

• no more than 14 drinks 

in a week 

For healthy women (and 

healthy men over age 65)— 

• no more than 3 drinks 

in a day AND 

• no more than 7 drinks 

in a week 

Recommend lower limits or 

abstinence as indicated: for 

example, for patients who take 

medications that interact 

with alcohol, have a health 

condition exacerbated by 

alcohol, or are pregnant 

(advise abstinence) 

Rescreen annually 

YES 

Your patient is an at-risk 

drinker. For a more complete 

picture of the drinking 

pattern, determine the 

weekly average: 

• On average, how 

many days a week 

do you have an 

alcoholic drink? 

• On a typical 

drinking day, how 

many drinks do 

you have? 

Weekly average 

X

Record heavy drinking days 

in past year and weekly 

average in chart. 

GO TO 

STEP 2 

HOW TO ASSESS FOR ALCOHOL USE DISORDERS 

STEP 2 Assess For Alcohol Use Disorders 

Next, determine if there is a maladaptive pattern of alcohol 

use, causing clinically significant impairment or distress. 

Determine whether, in the past 12 months, your patient’s drinking 

has repeatedly caused or contributed to 

risk of bodily harm (drinking and driving, operating 

machinery, swimming) 

relationship trouble (family or friends) 

role failure (interference with home, work, or school 

obligations) 

run-ins with the law (arrests or other legal problems) 

If yes to one or more your patient has alcohol abuse. 

In either case, proceed to assess for dependence symptoms. 

Determine whether, in the past 12 months, your patient has 

not been able to cut down or stop (repeated failed 

attempts) 

not been able to stick to drinking limits (repeatedly 

gone over them) 

shown tolerance (needed to drink a lot more to get 

the same effect) 

shown signs of withdrawal (tremors, sweating, nausea, 

or insomnia when trying to quit or cut down) 

kept drinking despite problems (recurrent physical 

or psychological problems) 

spent a lot of time drinking (or anticipating or 

recovering from drinking) 

spent less time on other matters (activities that had 

been important or pleasurable) 

If yes to three or more your patient has alcohol 

dependence. 

Does patient meet criteria for abuse or dependence? 

NO 

GO TO 

STEPS 3 & 4 

for 

AT-RISK 

DRINKING 

YES 

GO TO 

STEPS 3 & 4 

for 

ALCOHOL USE 

DISORDERS 

HOW TO CONDUCT A BRIEF INTERVENTION 

FOR AT-RISK DRINKING (no abuse or dependence) 

STEP 3 Advise and Assist 

State your conclusion and recommendation clearly and 

relate them to medical concerns or findings. 

Gauge readiness to change drinking habits. 

Is patient ready to commit to change? 

NO

Restate your concern. 

Encourage reflection. 

Address barriers to change.

Reaffirm your willingness 

to help. 

YES 

Help set a goal. 

Agree on a plan. 

Provide educational 

materials. (See www.niaaa.

nih.gov/guide.) 

STEP 4 At Followup: Continue Support 

REMINDER: Document alcohol use and review goals at each visit. 

Was patient able to meet and sustain drinking goal?

NO 

Acknowledge that 

change is difficult. 

Support positive change 

and address barriers. 

Renegotiate goal and 

plan; consider a trial of 

abstinence. 

Consider engaging 

significant others. 

Reassess diagnosis if 

patient is unable to either 

cut down or abstain. 

YES 

Reinforce and support 

continued adherence 

to recommendations. 

Renegotiate drinking 

goals as indicated (e.g., 

if the medical condition 

changes or if an abstaining patient wishes to 

resume drinking). 

Encourage to return 

if unable to maintain 

adherence. 

Rescreen at least annually. 

FOR ALCOHOL USE DISORDERS (abuse or dependence) 

STEP 3 Advise and Assist 

State your conclusion and recommendation clearly and 

relate them to medical concerns or findings. 

Negotiate a drinking goal. 

Consider evaluation by an addiction specialist. 

Consider recommending a mutual help group. 

For patients who have dependence, consider 

• the need for medically managed withdrawal (detoxification) 

and treat accordingly. 

• prescribing a medication for alcohol dependence for patients 

who endorse abstinence as a goal. 

Arrange followup appointments, including medication 

management support if needed. 

STEP 4 At Followup: Continue Support 

REMINDER: Document alcohol use and review goals at each visit. 

Was patient able to meet and sustain drinking goal?

NO 

Acknowledge that change 

is difficult. 

Support efforts to cut down 

or abstain. 

Relate drinking to ongoing 

problems as appropriate. 

Consider (if not yet done): 

• consulting with an 

addiction specialist. 

• recommending a mutual 

help group. 

• engaging significant 

others. 

• prescribing a medication 

for alcohol-dependent 

patients who endorse 

abstinence as a goal. 

Address coexisting 

disorders—medical and 

psychiatric—as needed. 

YES 

Reinforce and support 

continued adherence. 

Coordinate care with 

specialists as appropriate. 

Maintain medications 

for alcohol dependence 

for at least 3 months 

and as clinically indicated 

thereafter. 

Treat coexisting nicotine 

dependence. 

Address coexisting 

disorders—medical and 

psychiatric—as needed. 
~

WHAT’S A STANDARD DRINK? 

A standard drink in the United States is any drink that 

contains about 14 grams of pure alcohol (about 0.6 fluid 

ounces or 1.2 tablespoons). Below are U.S. standard drink 

equivalents as well as the number of standard drinks in 

different container sizes for each beverage. These are approximate, since different brands and types of beverages vary in 

their actual alcohol content. 

STANDARD 

DRINK 

EQUIVALENTS 

APPROXIMATE 

NUMBER OF 

STANDARD DRINKS IN: 

BEER or COOLER 

12 oz. 

~5% alcohol 

• 12 oz. = 1 

• 16 oz. = 1.3 

• 22 oz. = 2 

• 40 oz. = 3.3 

MALT LIQUOR 

8–9 oz. 

~7% alcohol 

• 12 oz. = 1.5 

• 16 oz. = 2 

• 22 oz. = 2.5 

• 40 oz. = 4.5 

TABLE WINE 

5 oz. 

~12% alcohol

• a 750-mL (25-oz.) bottle = 5 

80-proof SPIRITS (hard liquor) 

1.5 oz. 

40% alcohol 

• a mixed drink = 1 or more* 

• a pint (16 oz.) = 11 

• a fifth (25 oz.) = 17 

• 1.75 L (59 oz.) = 39 

*Note: Depending on factors such as the type of spirits and 

the recipe, one mixed drink can contain from one to three or 

more standard drinks. 

DRINKING PATTERNS 

WHAT‘S YOUR 

DRINKING 

PATTERN? 

HOW 

COMMON 

IS THIS 

PATTERN? 

HOW COMMON 

ARE ALCOHOL 

DISORDERS IN 

DRINKERS WITH 

THIS PATTERN? 

Based on the following 

limits—number of drinks: 

On any DAY—Never more 

than 4 (men) or 3 (women) 

– and – 

In a typical WEEK—No more 

than 14 (men) or 7 (women) 

Percentage 

of 

U.S. adults 

aged 18 

or older* 

Combined 

prevalence 

of 

alcohol abuse 

and dependence 

Never exceed the daily or 

weekly limits 

(2 out of 3 people in this group 

abstain or drink fewer than 

12 drinks a year) 72% 

fewer than 

1 in 100 

Exceed only the daily limit 

(More than 8 out of 10 in this 

group exceed the daily limit 

less than once a week) 16% 

1 in 5 

Exceed both daily and 

weekly limits 

(8 out of 10 in this group 

exceed the daily limit 

once a week or more) 10% 

almost 

1 in 2 

*Not included in the chart, for simplicity, are the 2 percent of U.S. adults who 

exceed only the weekly limits. The combined prevalence of alcohol use disorders 

in this group is 8 percent. 

Source: 2001–2002 National Epidemiologic Survey on Alcohol and Related 

Conditions (NESARC), a nationwide NIAAA survey of 43,093 U.S. adults 

aged 18 or older. 

PRESCRIBING MEDICATIONS 

The chart below contains excerpts from page 16 of NIAAA’s Helping Patients Who Drink Too Much: A Clinician’s Guide. It does not provide complete information and is not meant to be a 

substitute for the patient package inserts or other drug references used by clinicians. For patient information, visit http://medlineplus.gov. 

Naltrexone 

(Depade®, ReVia®) 

Extended-Release Injectable 

Naltrexone (Vivitrol®) 

Acamprosate 

(Campral®) 

Disulfiram 

(Antabuse®) 

Action Blocks opioid receptors, resulting in reduced craving and 

reduced reward in response to drinking. 

Same as oral naltrexone; 30-day duration. Affects glutamate and GABA neurotransmitter systems, but 

its alcohol-related action is unclear. 

Inhibits intermediate metabolism of alcohol, causing a 

buildup of acetaldehyde and a reaction of flushing, 

sweating, nausea, and tachycardia if a patient drinks 

alcohol. 

Contraindications Currently using opioids or in acute opioid withdrawal; 

anticipated need for opioid analgesics; acute hepatitis or 

liver failure. 

Same as oral naltrexone, plus inadequate muscle mass for 

deep intramuscular injection; rash or infection at the 

injection site. 

Severe renal impairment (CrCl ≤ 30 mL/min). Concomitant use of alcohol or alcohol-containing 

preparations or metronidazole; coronary artery disease; 

severe myocardial disease; hypersensitivity to rubber 

(thiuram) derivatives. 

Precautions Other hepatic disease; renal impairment; history of suicide 

attempts or depression. If opioid analgesia is needed, 

larger doses may be required, and respiratory depression 

may be deeper and more prolonged. Pregnancy Category 

C. Advise patients to carry a wallet card to alert medical 

personnel in the event of an emergency. For wallet card 

information, see www.niaaa.nih.gov/guide. 

Same as oral naltrexone, plus hemophilia or other 

bleeding problems. 

Moderate renal impairment (dose adjustment for CrCl 

between 30 and 50 mL/min); depression or suicidal 

ideation and behavior. Pregnancy Category C. 

Hepatic cirrhosis or insufficiency; cerebrovascular disease 

or cerebral damage; psychoses (current or history); 

diabetes mellitus; epilepsy; hypothyroidism; renal 

impairment. Pregnancy Category C. Advise patients to 

carry a wallet card to alert medical personnel in the event 

of an emergency. For wallet card information, see 

www.niaaa.nih.gov/guide. 

Serious adverse 

reactions 

Will precipitate severe withdrawal if the patient is 

dependent on opioids; hepatotoxicity (although does not 

appear to be a hepatotoxin at the recommended doses). 

Same as oral naltrexone, plus infection at the injection 

site; depression; and rare events including allergic 

pneumonia and suicidal ideation and behavior. 

Rare events include suicidal ideation 

and behavior. 

Disulfiram-alcohol reaction, hepatotoxicity, optic neuritis, 

peripheral neuropathy, psychotic reactions. 

Common side effects Nausea; vomiting; decreased appetite; headache; 

dizziness; fatigue; somnolence; anxiety. 

Same as oral naltrexone, plus a reaction at the injection 

site; joint pain; muscle aches or cramps. 

Diarrhea; somnolence. Metallic after-taste; dermatitis; transient mild drowsiness. 

Examples of drug 

interactions 

Opioid medications (blocks action). Same as oral naltrexone. No clinically relevant interactions known. Anticoagulants such as warfarin; isoniazid; metronidazole; 

phenytoin; any nonprescription drug containing alcohol. 

Usual adult dosage Oral dose: 50 mg daily. 

Before prescribing: Patients must be opioid-free for a 

minimum of 7 to 10 days before starting. If you feel that 

there’s a risk of precipitating an opioid withdrawal 

reaction, a naloxone challenge test should be employed. 

Evaluate liver function. 

Laboratory followup: Monitor liver function. 

IM dose: 380 mg given as a deep intramuscular gluteal 

injection, once monthly. 

Before prescribing: Same as oral naltrexone, plus examine 

the injection site for adequate muscle mass and skin 

condition. 

Laboratory followup: Monitor liver function. 

Oral dose: 666 mg (two 333-mg tablets) three times 

daily; or for patients with moderate renal impairment (CrCl 

30 to 50 mL/min), reduce to 333 mg (one tablet) three 

times daily. 

Before prescribing: Evaluate renal function. Establish 

abstinence. 

Oral dose: 250 mg daily (range 125 mg to 500 mg). 

Before prescribing: Evaluate liver function. Warn the 

patient (1) not to take disulfiram for at least 12 hours 

after drinking and that a disulfiram-alcohol reaction can 

occur up to 2 weeks after the last dose and (2) to avoid 

alcohol in the diet (e.g., sauces and vinegars), over-thecounter medications (e.g., cough syrups), and toiletries 

(e.g., cologne, mouthwash). 

Laboratory followup: Monitor liver function. 

Note: Whether or not a medication should be prescribed and in what amount is a matter between individuals and their health care providers. The prescribing information provided here is not a substitute for a provider’s judgment in an 

individual circumstance and the NIH accepts no liability or responsibility for use of the information with regard to particular patients. 

January 2007 
Appendix C— 

Excerpts From Quick 

Guide for Clinicians 

Based on TIP 45* 

Introduction 

The “medical model” of detoxification is characterized by the use 

of physicians and nursing staff and the administration of medication to assist people through withdrawal safely. The “social 

model” relies more on a supportive non-hospital environment 

than on medication to ease the passage through withdrawal. 

Definitions 

Detoxification is a series of interventions aimed at managing 

acute intoxication and withdrawal. It denotes a clearing of toxins from the body of the patient who is acutely intoxicated and/

or dependent on substances of abuse. Detoxification seeks to 

minimize the physical harm caused by the abuse of substances. 

Evaluation entails testing for the presence of substances of 

abuse in the bloodstream, measuring their concentration, and 

screening for co-occurring mental and physical conditions. 

Evaluation also includes a comprehensive assessment of the 

patient’s medical, psychological, and social situation. 

Stabilization includes the medical and psychosocial process 

of assisting the patient through acute intoxication and withdrawal to the attainment of a medically stable, fully supported, 

substance-free state. 

Fostering the patient’s entry into treatment involves preparing a 

patient for entry into treatment by stressing the importance of 

following through with a complete continuum of care. 

*TIP 45, Detoxification and Substance Abuse Treatment. 

77 
 

Guiding Principles/Assumptions 

The panel of experts who created TIP 

45 agreed to the following assumptions, 

which served as a basis for their work: 

1.	 Detoxification alone is not sufficient 

treatment for substance dependence 

but is one part of a continuum of care 

for substance-related disorders. 

2.	 The detoxification process consists 

of the following three components: 

• Evaluation 

• Stabilization 

• Fostering patient readiness for and 

entry into treatment 

A detoxification process that does not 

incorporate all three critical components is considered incomplete and 

inadequate by the consensus panel. 

3.	 Detoxification can take place in a wide 

variety of settings and at a number of 

levels of intensity. Placement should 

be appropriate to a patient’s needs. 

4.	 Persons seeking detoxification should 

have access to the components of the 

detoxification process described above, 

no matter what the setting or the 

level of treatment intensity. 

5.	 All persons requiring treatment for 

substance use disorders should receive 

treatment of the same quality and 

appropriate thoroughness and should 

be put into contact with a treatment 

program for substance use disorders 

after detoxification. 

6.	 Ultimately, insurance coverage 

for the full range of detoxification 

services and followup treatment 

services is cost-effective. If reimbursement systems do not provide 

payment for the complete detoxification process, patients may be released 

prematurely, leading to medically or 

socially unattended withdrawal. 

7.	 Patients seeking detoxification services have diverse cultural and 

ethnic backgrounds as well as unique 

health needs and life situations. 

Organizations that provide detoxification services need to ensure that they 

have standard practices in place to 

address cultural diversity. 

8.	 A successful detoxification process 

can be measured, in part, by whether an individual who is substance 

dependent enters, remains in, and is 

compliant with the treatment protocol 

of a substance abuse treatment/rehabilitation program after detoxification. 

Overarching Principles for Care 

During Detoxification Services 

• Detoxification services do not offer a 

“cure” for substance use disorders; they 

are often a first step toward recovery and a “first door” through which 

patients pass to treatment. 

• Substance use disorders are treatable 

and there is hope for recovery. 

• Substance use disorders are brain 

disorders and not evidence of moral 

weakness. 

• Patients should be treated with respect 

and dignity at all times. 

• Patients should be treated in a nonjudgmental and supportive manner. 

• Services planning should be completed 

in partnership with the patient and his 

or her social support network, including 

family, significant others, or employers. 

• All health professionals involved in the 

care of the patient will maximize opportunities to promote rehabilitation and 

maintenance activities and to link the 

patient to appropriate substance abuse 

treatment immediately after the detoxification phase. 

78 Appendix C 
 

 

• Active involvement of the family and 

other support systems, while respecting 

the patient’s right to privacy and confidentiality, is to be encouraged. 

• Patients are treated with due consideration for individual background, 

culture, preferences, sexual orientation, disability, vulnerabilities, and 

strengths. 

Levels of Care and 

Patient Placement 

In addition to the general placement 

criteria for the treatment of substancerelated disorders, the Patient Placement 

Criteria, Second Edition, Revised (PPC2R) of the American Society of Addiction 

Medicine (ASAM) also indicates a second 

set of placement criteria, which are more 

important for the purposes of TIP 45 

and this Quick Guide—the five “Adult 

Detoxification” placement levels of care 

within Dimension 1 (ASAM, 2001). These 

“Adult Detoxification” levels of care are: 

1.	 Level I-D: Ambulatory Detoxification 

Without Extended Onsite Monitoring

(e.g., physician’s office, home health 

care agency). This level of care is an 

organized outpatient service monitored at predetermined intervals. 

2.	 Level II-D: Ambulatory Detoxification 

With Extended Onsite Monitoring

(e.g., day hospital service). This level 

of care is monitored by appropriately 

credentialed and licensed nurses. 

3.	 Level III.2-D: Clinically Managed 

Residential Detoxification (e.g., non21medical or social detoxification 

setting). This level emphasizes peer 

and social support and is intended 

for patients whose intoxication and/

or withdrawal is sufficient to warrant 

24-hour support. 

4.	 Level III.7-D: Medically Monitored 

Inpatient Detoxification (e.g., freestanding detoxification center). Unlike 

Level III.2-D, this level provides 

24-hour medically supervised detoxification services. 

5.	 Level IV-D: Medically Managed 

Intensive Inpatient Detoxification (e.g.,

psychiatric hospital inpatient center). 

This level provides 24-hour care in an 

acute care inpatient setting. 

It is important to note that ASAM PPC2R criteria are only guidelines and 

that there are no uniform protocols for 

determining which patients are placed 

in which level of care. For further information on patient placement, readers 

are advised to consult TIP 13, The Role 

and Current Status of Patient Placement 

Criteria in the Treatment of Substance 

Use Disorders (CSAT 1995). 

Biomedical and 

Psychosocial Issues 

Detoxification presents an opportunity to 

intervene during a period of crisis and to 

encourage a client to make changes in the 

direction of health and recovery. Hence, 

a primary goal of the detoxification staff 

should be to build a therapeutic alliance 

and motivate patients to enter treatment. 

This process should begin as the patient 

is being medically stabilized. 

Symptoms and Signs of 

Conditions That Require 

Immediate Medical Attention 

• Change in mental status 

• Increasing anxiety 

• Hallucinations 

• Temperature greater than 100.4°F 

(these patients should be considered 

potentially infectious) 

Quick Guide for Clinicians Based on TIP 45 79 
• Significant increases and/or decreases 

in blood pressure and heart rate 

• Insomnia 

• Abdominal pain 

• Upper and lower gastrointestinal 

bleeding 

• Changes in responsiveness of pupils 

• Heightened deep tendon reflexes and 

ankle clonus, a reflex beating of the foot 

when pressed rostrally, indicating profound central nervous system irritability and the potential for seizures 

Immediate Mental Health Needs 

The following are mental health issues 

that require immediate attention: 

Suicidality 

• Patients receiving detoxification services should be evaluated for suicide risk. 

• During acute intoxication and withdrawal, it is important to provide an 

environment that minimizes opportunities for suicide attempts. 

• Frequent safety checks should be 

implemented. 

• Patients at risk for suicide should be 

placed in areas monitored by staff. 

Anger and aggression 

• All patients who are intoxicated should 

be considered potentially violent. 

• Symptoms associated with increased 

risk for violence include hallucinations, 

paranoia, anxiety, and depression. 

• Physical restraint should be used as a 

last resort. 

Initial Biomedical and 

Psychosocial Evaluation Domains 

An initial evaluation will help detoxification staff foresee any variables that might 

complicate withdrawal. The following 

is a list of biomedical and psychosocial 

domains that can affect the stabilization 

of the patient. 

Biomedical domains 

• General health history: What is the 

patient’s medical and surgical history? 

Are there any psychiatric or medical conditions? Any known medication 

allergies? A history of seizures? 

• Mental status: Is the patient oriented, 

alert, cooperative? Are thoughts coherent? Are there signs of psychosis or 

destructive thoughts? 

• General physical assessment with neurological exam: This will ascertain the 

patient’s general health and identify 

medical or psychiatric disorders of 

immediate concern. 

• Temperature, pulse, blood pressure 

(should be monitored throughout 

detoxification). 

• Patterns of substance abuse: When 

did the patient last use? What were 

the substances of abuse? How much 

of these substances was used and how 

frequently? 

• Urine and toxicology screen for commonly abused substances. 

• Past substance abuse treatments or 

detoxification. 

Psychosocial domains 

• Demographic features: Gather information on gender, age, ethnicity, culture, 

language, and education level. 

• Living conditions: Is the patient 

homeless or living in a shelter? Are 

80 Appendix C 
significant others in the home (and, if 

so, can they safely supervise)? 

• Violence, suicide risk: Is the patient 

aggressive, depressed, or hopeless? Is 

there a history of violence? 

• Transportation: Does the patient have 

adequate means to get to appointments? 

Do other arrangements need to be 

made? 

• Financial situation: Is the patient able 

to purchase medication and food? Does 

the patient have adequate employment 

and income? 

• Dependent children: Is the patient able 

to care for children, provide adequate 

child care, and ensure the safety of 

children? 

• Legal status: Is the patient a legal resident? Are there pending legal matters? 

Is treatment court ordered? 

• Physical, sensory, or cognitive disabilities: Does the client have disabilities 

that require consideration? 

Considerations for Specific 

Populations 

Adolescents 

• Adolescents are more likely to drink 

large quantities of alcohol in a short 

period of time, making it important that 

staff be alert to escalating blood alcohol 

levels. 

• Adolescents are more likely to use drugs 

they cannot identify, to combine multiple substances with alcohol, to ingest 

unidentified substances, and to be 

unwilling to disclose drug use. 

• Asking open-ended questions and using 

street terminology for drugs can be 

helpful in both establishing rapport and 

obtaining an accurate substance use 

history. 

Parents with dependent children 

• It is of vital importance to ensure that 

the children of someone receiving detoxification services have a safe place to 

stay. 

• Working with patients to identify supportive family or friends may uncover 

temporary childcare resources. 

• A consult or referral to the treatment 

facility’s social services while the 

patient is being detoxified is indicated 

when the care of children is uncertain. 

Alcohol Intoxication and 

Withdrawal 

The following symptoms of alcohol intoxication can vary greatly with the patient’s 

level of tolerance. 

Blood alcohol level is 20–100 mg percent 

• Mood and behavioral changes 

• Reduced coordination 

• Impairment of ability to drive a car or 

operate machinery 

Blood alcohol level is 101–200 mg percent 

• Reduced coordination of most activities 

• Speech impairment 

• Trouble walking 

• General impairment of thinking and 

judgment 

• Somnolence, combative or “psychotic” 

behavior 

• “Normal” mental status 

Blood alcohol level is 201–300 mg percent 

• Marked impairment of thinking, memory, and coordination 

• Marked reduction in level of alertness 

Quick Guide for Clinicians Based on TIP 45 81 
 

 

• Memory blackouts 

• Nausea and vomiting/aspiration 

Blood alcohol level is 301–400 mg percent 

• Worsening of above symptoms with 

reduction of body temperature and blood 

pressure 

• Excessive sleepiness/comatose 

• Amnesia 

• Nausea and vomiting/aspiration 

• Death 

Blood alcohol level is 401–800 mg percent 

• Difficulty waking the patient (coma) 

• Serious decreases in pulse, temperature, 

blood pressure, and rate of breathing 

• Urinary and bowel incontinence 

• Death 

The signs and symptoms of acute alcohol 

withdrawal generally start 6 to 24 hours 

after the patient takes his last drink. 

Acute withdrawal may begin when the 

patient still has significant blood alcohol 

concentrations. The signs and symptoms 

may include the following and are highly 

variable: 

• Restlessness, irritability, anxiety, 

agitation 

• Anorexia, nausea, vomiting 

• Tremor, elevated heart rate, increased 

blood pressure 

• Insomnia, intense dreaming, nightmares 

• Poor concentration, impaired memory 

and judgment 

• Increased sensitivity to sound, light, and 

tactile sensations 

• Hallucinations (auditory, visual, or 

tactile) 

• Delusions, usually of paranoid or persecutory varieties 

• Grand mal seizures 

• Hyperthermia 

• Delirium/disorientation with regard to 

time, place, person, and situation; 

fluctuation in level of consciousness 

Management of Alcohol 

Withdrawal Without Medication 

• Indications for the management of alcohol withdrawal without medication have 

not been established through scientific 

studies or evidence-based methods. 

• The course of alcohol withdrawal is 

unpredictable; it is impossible to tell 

who will or will not experience lifethreatening complications. 

• Positive aspects of the nonmedication 

approach are that it is highly costeffective and provides inexpensive 

access to detoxification for individuals 

seeking aid. 

Social Detoxification 

Social detoxification programs are shortterm, nonmedical treatment service for 

individuals with substance use disorders. 

A social detoxification program offers 

room, board, and interpersonal support to 

intoxicated individuals and individuals in 

substance use withdrawal. Social detoxification programs vary widely in services 

offered, but there should always be medical surveillance, including monitoring of 

vital signs. 

TIP 45 provides several guidelines for 

social detoxification programs: 

• Such programs should follow local governmental regulations regarding licensing and inspection. 

• It is highly desirable that individuals 

entering social detoxification be assessed 

82 Appendix C 
 

 

 

by primary care practitioners with some 

substance abuse treatment experience. 

• An assessment should determine 

whether the patient is currently intoxicated and the degree of intoxication, the 

type of withdrawal syndrome, severity 

of the withdrawal, information regarding past withdrawals, and the presence 

of co-occurring psychiatric, medical, and 

surgical conditions that might require 

specialized care. 

• Particular attention should be paid to 

individuals who have undergone multiple withdrawals in the past and for 

whom each withdrawal appears to be 

worse than previous ones (the so-called 

kindling effect). Patients with a history 

of severe withdrawals are not good candidates for social detoxification. 

• All social detoxification programs 

should have personnel who are familiar 

with the features of substance use withdrawal, have training in basic life support, and have access to an emergency 

medical system that can provide transportation to emergency departments. 

Management of Alcohol 

Withdrawal With Medications 

It is believed that only a minority of 

patients with alcoholism will go into significant alcohol withdrawal requiring 

medication. Identifying that small minority is sometimes problematic, but there 

are signs and symptoms of impending 

problems that can alert the caretaker to 

seek medical attention. 

Deciding whether or not to use medical management for alcohol withdrawal 

requires that patients be separated into 

three groups: 

1.	 Clients who have a history of the most 

extreme forms of withdrawal, that of 

seizures and/or delirium. The medication treatment of this group should 

proceed as quickly as possible. 

2.	 Patients who are already in withdrawal and demonstrating moderate 

symptoms of withdrawal also require 

immediate medication. 

3.	 The third group includes patients 

who may still be intoxicated, or who 

have, at the time of admission, been 

abstinent for only a few hours and 

have not developed signs or symptoms 

of withdrawal. A decision regarding 

medication treatment for this group 

should be based on advancing age, 

number of years with alcohol dependence, and the number of previously 

treated or untreated severe withdrawals. If there is an opportunity to 

observe the patient over the next 6 to 

8 hours, then it is possible to delay 

a decision regarding treatment and 

periodically reevaluate a client of this 

category. 

Benzodiazepine Treatment for 

Alcohol Withdrawal 

These drugs remain the medication 

of choice in treating withdrawal from 

alcohol. The early recognition of alcohol 

withdrawal and prompt administration 

of a suitable benzodiazepine will prevent 

further withdrawal reaction from proceeding to serious consequences. 

• Loading dose of a benzodiazepine. 

Administration of a metabolized benzodiazepine may be carried out every 

1 to 2 hours until significant clinical 

improvement occurs or the patient 

becomes sedated. In general, patients 

with severe withdrawal may receive 20 

mg of diazepam or 100 mg of chlordiazepoxide every 2 to 3 hours until 

improvement or sedation prevails. The 

treatment staff should closely monitor 

blood pressure, pulse, and respiratory 

features. 

Quick Guide for Clinicians Based on TIP 45 83 
 

 

• Symptom-triggered therapy. Using the 

CIWA-Ar or similar alcohol withdrawal 

rating scales, medical personnel can 

be trained to recognize symptoms of 

alcohol withdrawal, make a rating, and 

based on the rating administer benzodiazepines to their patient only when 

signs and symptoms reach a particular 

threshold. A typical routine of administration is as follows: Administer 50 mg 

of chlordiazepoxide for CIWA-Ar >9 and 

reassess in 1 hour. Continue administering 50 mg chlordiazepoxide every 

hour until CIWA-Ar is <10. 

• Gradual, tapering doses. Once the 

patient has been stabilized, oral benzodiazepines can be administered on 

a predetermined dosing schedule for 

several days and gradually tapered over 

time. One example of this regimen is 

that patients might receive 50 mg of 

chlordiazepoxide or 10 mg of diazepam 

every 6 hours during the first day of 

treatment and 25 mg of chlordiazepoxide or 5 mg of diazepam every 6 hours 

on the second and third days. 

• Single daily dosing protocol. According

to studies, this regimen may be attractive in community or social detoxification settings, particularly if patients 

could be monitored between doses. 

Limitations of Benzodiazepines 

in Outpatient Treatment 

The interaction of benzodiazepines with 

alcohol can lead to coma and respiratory 

suppression, motor incoordination, and 

abuse. Abuse is usually in the context of 

the concurrent use of alcohol, opioids, or 

stimulants. There are two other limitations as well: 

• Although benzodiazepines have been 

studied for 30 years and are effective for 

suppressing alcohol withdrawal symptoms, their ability to halt the 

progressive worsening of each successive alcohol withdrawal is in question. 

• Benzodiazepine use to treat outpatients 

in alcohol withdrawal may “prime” 

or reinstate alcohol use during their 

administration. 

Other Medications 

The following is a list of other medications sometimes used in detoxification 

from alcohol: 

• Barbiturates 

• Anticonvulsants 

• Beta blockers/alpha adrenergic agonists 

• Antipsychotics 

• Relapse prevention agents 

Management of Delirium and 

Seizures 

The major goal of medical detoxification 

is to avoid seizures and a special state of 

delirium called delirium tremens (DTs) 

with aggressive use of the primary detoxification drug. Death and disability may 

result from DTs or seizures without medical care. 

For patients with a history of DTs or seizures, early benzodiazepine treatment 

is indicated at the first clinical setting. 

Patients with severe withdrawal symptoms, multiple past detoxifications (more 

than three), and co-occurring unstable 

medical and psychiatric conditions should 

be managed similarly. 

DTs 

• Giving the patient a benzodiazepine 

should not be delayed by waiting for the 

return of laboratory studies, transportation problems, or the availability of a 

hospital bed. 

84 Appendix C 
 

• Once full DTs have developed, they tend 

to run their course despite medication 

management. 

• Patients presenting in severe DTs 

should have emergency medical 

transport to a qualified emergency 

department and generally will require 

hospitalization. 

Seizures 

• Seizures usually occur within the first 

48 hours after cessation or reduction of 

alcohol, with peak incidence around 24 

hours. 

• Someone experiencing a seizure is at 

greater risk for progressing to DTs, 

whereas it is extremely unlikely that 

a patient already in DTs will also then 

experience a seizure. 

• The occurrence of an alcohol withdrawal 

seizure happens quickly, usually without warning to the individual experiencing the seizure or anyone around him. 

• Predicting who will have a seizure 

during alcohol withdrawal cannot be 

accomplished with any great certainty. 

• Patients having a seizure can be treated 

with intravenous (IV) diazepam or 

lorazepam and advanced cardiac life 

support protocol procedures. 

• Patients who have had a single witnessed or suspected alcohol withdrawal 

seizure should be immediately given 

a benzodiazepine, preferably with IV 

administration. 

• Benzodiazepine and/or barbiturate 

intoxication needs to be treated and 

assessed differently, given the potentially life-threatening implications of 

withdrawal from either substance in 

combination with each other and/or 

alcohol. 

Wernicke-Korsakoff’s Syndrome 

• Wernicke-Korsakoff’s Syndrome is 

composed of Wernicke’s encephalopathy 

and Korsakoff’s psychosis. 

• Wernicke’s encephalopathy is an 

acute neurological disorder featuring 

oculomotor dysfunction (bilateral 

abducens nerve palsy-eye muscle 

paralysis), ataxia (loss of muscle coordination), confusion, and weakness. 

• Korsakoff’s psychosis is a chronic neurological condition that includes retrograde and antegrade amnesia (profound 

deficit in new learning and remote 

memory) with confabulation (patients 

make up stories to cover memory gaps). 

• Both syndromes are related to thiamine 

deficiency. 

• Thiamine initially is given parenterally (in a manner other than through 

the digestive tract, as by intravenous 

or intramuscular injection). Afterward, 

oral administration is the treatment 

of choice. 

• Always give thiamine prior to glucose 

administration. 

Quick Guide for Clinicians Based on TIP 45 85 

Appendix D— 

Excerpts From Quick 

Guide for Clinicians 

Based on TIP 24* 

Introduction 

Alcohol-related disorders occur in up to 26 percent of general 

medicine clinic patients, a prevalence rate similar to those for 

such other chronic diseases as hypertension and diabetes. 

Since substance abuse disorders are often chronic conditions 

that progress slowly, primary care clinicians are in an ideal 

position to screen for alcohol and drug problems. Studies have 

shown that primary care clinicians can help patients decrease 

alcohol consumption through office-based interventions that take 

only 10 or 15 minutes. 

General Recommendations for Primary 

Care Clinicians 

Screening 

1.	 Periodically and routinely screen all patients for substance 

use disorders 

2.	 Ask questions about substance abuse in the context of other 

lifestyle questions 

3.	 Use the Alcohol Use Disorder Identification Test (AUDIT) to 

screen for alcohol problems among English-speaking, literate patients, or use the first three quantity/frequency questions from AUDIT, supplemented by the CAGE questionnaire 

*TIP 24, A Guide to Substance Abuse Services for Primary Care Clinicians. 

87 
4.	 Use the CAGE-AID (CAGE Adapted 

to Include Drugs) to screen for drugs 

use among patients 

5.	 Ask “Have you used street drugs 

more than five times in your life?” 

A positive answer suggests further 

screening and possibly assessment are 

needed 

6.	 Ask high-risk patients about alcohol 

and drug use in combination 

7.	 Ask pregnant women “Do you use 

street drugs?” If the answer is yes, 

advise abstinence 

8.	 Use the CAGE, the AUDIT, or the 

Michigan Alcoholism Screening Test–

Geriatric Version (MAST-G) to screen 

patients over 60 

9.	 Screen adolescents for substance 

abuse every time they seek medical 

services 

Brief Intervention 

1.	 Perform a brief intervention with 

patients whose substance abuse problems are less severe 

2.	 Include in the brief intervention 

feedback about screening results and 

risk of use, information about safe 

consumption limits and advice about 

change, assessment of patient’s readiness to change, negotiated goals and 

strategies for change, and arrangements for followup visits 

Assessment and Treatment 

Refer high-risk patients to a specialist, if 

possible, for in-depth assessment 

Warning Signs and Risk 

Factors for Alcohol and 

Illicit Drug Use 

It is important for primary care clinicians to know patients’ drinking levels to 

gauge their potential risk for developing 

problems. 

Physical Signs: General 

• Dental caries 

• Swollen hands or feet 

• Swollen parotid glands 

• Leukoplakia in mouth 

• Gingivitis 

• Perforated septum 

• Needle track marks 

• Skin abscesses, burns on inside of lips 

• Disrupted menstrual cycle 

Physical Signs: Neurological 

• Dilated or constricted pupils 

• Slurred, incoherent, or too rapid speech 

• Inability to focus (both visually and 

mentally) 

• Unsteady gait 

• “Nodding off” 

• Blackouts or other periods of memory 

loss 

• Insomnia or other sleep disturbances 

• Withdrawal symptoms 

• Agitation 

88 Appendix D 
Psychiatric 

• Depression 

• Anxiety 

• Low self-esteem 

• Low tolerance for stress 

• Other mental health disorders 

• Feelings of desperation 

• Feelings of loss of control over one’s life 

• Feelings of resentment 

Behavioral 

• Use of other substances 

• Aggressive behavior in childhood 

• Conduct disorders; antisocial 

personality 

• Impulsiveness and risk taking 

• Alienation and rebelliousness 

• School-based academic or behavioral 

problems 

• Involvement with criminal justice 

system 

• Poor interpersonal relationships 

Social and Sexual History 

• Legal status (minor, in custody) 

• Alcohol or drug use by friends 

• Level of education 

• Occupation/work history 

• Sexual preference 

• Number of sexual relationships 

• Types of sexual activity engaged in 

• Whether the patient practices safe sex 

Family 

• Use of drugs and alcohol by parents, 

siblings 

• Inherited predisposition to alcohol or 

drug dependence 

• Family dysfunction 

• Family trauma 

• Marital/cohabitation status 

• Domestic violence and other abuse 

history 

Demographic 

• Male gender 

• Inner city or rural residence combined 

with low-socioeconomic status 

• Lack of employment opportunities 

Low-Risk and At-Risk 

Low-risk drinkers consume less than an 

average of one to two drinks per day, do 

not drink more than three or four drinks 

per occasion, and do not drink in highrisk situations (while pregnant, driving a 

car, etc.). 

At-risk drinkers occasionally exceed recommended guidelines for use. While they 

are at risk for alcohol-related problems, 

they may never experience negative consequences as a result of their drinking 

and represent a prime target for preventive, educational efforts by primary care 

clinicians. 

Screening Instruments 

Asking potentially sensitive questions 

about substance abuse in the context 

of other behavioral lifestyle questions 

appears to be less threatening to patients. 

Quick for Clinicians Based on TIP 24 89 
CAGE-AID 

Asking the following questions of every 

adult routinely and periodically is a costeffective way of screening for substance 

abuse and detecting possible problems at 

an early stage in their development: 

• Have you ever 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)? 

Scoring: Item responses on the CAGE 

are scored 0 for “no” and 1 for “yes” 

answers. Consider conducting a brief 

intervention (see below) with any patient 

who scores a one or higher. 

The AUDIT Questionnaire 

The AUDIT is designed to be used as a 

brief structured interview or self-report 

survey that can easily be incorporated 

into a general health interview, lifestyle questionnaire, or medical history. 

Patients tend to answer it most accurately when: 

• The interviewer is friendly and 

nonthreatening 

• The purpose of the questions is clearly 

related to a diagnosis of their health 

status 

• The patient is alcohol- and drug-free at 

the time of the screening 

• The information is considered 

confidential 

• The questions are easy to understand 

Health workers should try to establish these conditions before the AUDIT 

is given. Answers should be recorded 

carefully. 

In addition to these general considerations, the following interviewing 

techniques should be used: 

• Try to interview patients under the best 

possible circumstances 

• Look for signs of alcohol or drug intoxication—patients who have alcohol on 

their breath or appear intoxicated may 

be unreliable respondents 

• It is important to read the questions as 

written and in the order indicated 

Circle the number that comes closest to 

the patient’s answer. 

1.	 How often do you have a drink 

containing alcohol? 

(0) Never 

(1) Monthly or less 

(2) Two to four times a month 

(3) Two to three times a week 

(4) Four or more times a week 

2.	 How many drinks containing alcohol 

do you have on a typical day when 

you are drinking? 

[Code number of standard drinks.*] 

(0) 1 or 2 

(1) 3 or 4 

(2) 5 or 6 

(3) 7 to 9 

(4) 10 or more 

*In determining the response categories it has been assumed that one drink contains 10 g of 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. 

90 Appendix D 
3.	 How often do you have six or more 

drinks on one occasion? 

(0) Never 

(1) Less than monthly 

(2) Monthly 

(3) Weekly 

(4) Daily or almost daily 

4.	 How often during the last year have 

you found that you were not able to 

stop drinking once you had started? 

(0) Never 

(1) Less than monthly 

(2) Monthly 

(3) Weekly 

(4) Daily or almost daily 

5.	 How often during the last year 

have you failed to do what was normally expected from you because of 

drinking? 

(0) Never 

(1) Less than monthly 

(2) Monthly 

(3) Weekly 

(4) Daily or almost daily 

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? 

(0) Never 

(1) Less than monthly 

(2) Monthly 

(3) Weekly 

(4) Daily or almost daily 

7.	 How often during the last year have 

you had a feeling of guilt or remorse 

after drinking? 

(0) Never 

(1) Less than monthly 

(2) Monthly 

(3) Weekly 

(4) Daily or almost daily 

8.	 How often during the last year have 

you been unable to remember what 

happened the night before because 

you had been drinking? 

(0) Never 

(1) Less than monthly 

(2) Monthly 

(3) Weekly 

(4) Daily or almost daily 

9.	 Have you or has someone else been 

injured as a result of your drinking? 

(0) No 

(2) Yes, but not in the last year 

(4) Yes, during the last year 

10. Has a relative or friend or a doctor or 

other health worker been concerned 

about your drinking or suggested you 

cut down? 

(0) No 

(2) Yes, but not in the last year 

(4) Yes, during the last year 

Procedures for scoring AUDIT 

Question 1: 

Never = 0 

Monthly or less = 1

Two to four times per month = 2

Two to three times per week = 3

Four or more times per week = 4 

Quick for Clinicians Based on TIP 24 91 
Question 2: 

1 or 2 = 0 

3 or 4 = 1 

5 or 6 = 2 

7 to 9 = 3 

10 or more = 4 

Questions 3–8: 

Never = 0 

Less than monthly = 1

Monthly = 2

Weekly = 3

Daily or almost daily = 4 

Questions 9–10: 

No = 0 

Yes, but not in the last year = 2

Yes, during the last year = 4 

The minimum score (for non-drinkers) is 

0 and the maximum possible score is 40. 

A score of 8 or more indicates a strong 

likelihood of hazardous or harmful alcohol 

consumption. 

TWEAK Test 

Use the TWEAK test to screen pregnant 

women. 

T Tolerance: How many drinks can 

you hold? 

W Have close friends or relatives 

worried or complained about your 

drinking in the past year? 

E Eye-opener: Do you sometimes take 

a drink in the morning when you 

first get up? 

A 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? 

K Do you sometimes feel the need to 

cut down on your drinking? 

Scoring: A 7-point scale is used to score 

the test. The “tolerance” question scores 

2 points if a woman reports she can hold 

more than five drinks without falling 

asleep or passing out. A positive response 

to the “worry” question scores 2 points, 

and a positive response to the last three 

questions scores 1 point each. A total 

score of 2 or more indicates a woman is 

likely to be a risky drinker. 

Screen all adults age 60 or older for alcohol and prescription drug abuse as part of 

their regular physical. 

Michigan Alcoholism Screening 

Test–Geriatric Version (MAST-G) 

The following are yes or no questions: 

1.	 After drinking have you ever noticed 

an increase in your heart rate or beating in your chest? 

2.	 When talking with others, do you ever 

underestimate how much you actually 

drink? 

3.	 Does alcohol make you so sleepy that 

you often fall asleep in your chair? 

4.	 After a few drinks, have you sometimes not eaten or been able to skip a 

meal because you didn’t feel hungry? 

5.	 Does having a few drinks help 

decrease your shakiness or tremors? 

6.	 Does alcohol sometimes make it hard 

for you to remember parts of the day 

or night? 

7.	 Do you have rules for yourself that 

you won’t drink before a certain time 

of the day? 

8.	 Have you lost interest in hobbies or 

activities you used to enjoy? 

9.	 When you wake up in the morning, do 

you ever have trouble remembering 

part of the night before? 

10. Does having a drink help you sleep? 

92 Appendix D 
11. Do you hide your alcohol bottles from 

family members? 

12. After a social gathering, have you ever 

felt embarrassed because you drank 

too much? 

13. Have you ever been concerned that 

drinking might be harmful to your 

health? 

14. Do you like to end an evening with a 

nightcap? 

15. Did you find your drinking increased 

after someone close to you died? 

16. In general, would you prefer to have a 

few drinks at home rather than go out 

to a social event? 

17. Are you drinking more now than in 

the past? 

18. Do you usually take a drink to relax 

or calm your nerves? 

19. Do you drink to take your mind off 

your problems? 

20. Have you ever increased your drinking after experiencing a loss in your 

life? 

21. Do you sometimes drive when you 

have had too much to drink? 

22. Has a doctor or nurse ever said they 

were worried or concerned about your 

drinking? 

23. Have you ever made rules to manage 

your drinking? 

24. When you feel lonely does having a 

drink help? 

Scoring: 5 or more “yes” responses are 

indicative of an alcohol problem. 

Suggestions for Screening 

Risk factors for adolescent drug use 

• Physical or sexual abuse 

• Parental substance abuse 

• Parental incarceration 

• Dysfunctional family relationships 

• Peer involvement with drugs or alcohol 

• Smoking tobacco 

Red flags 

• Marked change in physical health 

• Deteriorating performance in school or 

job 

• Dramatic change in personality, dress, 

or friends 

• Involvement in serious delinquency or 

crimes 

• HIV high-risk activities 

• Serious psychological problems 

Pregnant women and women older than 

60, as well as women who have experienced a major life transition, should be 

queried about their psychoactive prescription drug use and use of over-the-counter 

sleep aids. 

Clinicians will want to use the screening 

instrument that best meets the needs of 

their patient population. 

When treating patient populations at 

high risk for drug abuse, ask questions 

regarding alcohol and drug use at the 

same time. 

Quick for Clinicians Based on TIP 24 93 
Following Up on 

Screening 

• All patients who undergo screening for 

alcohol or drug use should be told the 

results of the screen. 

• Patients with positive results to a 

screen will need some type of followup. 

Assessment questions should cover 

severity of the suspected alcohol or drug 

involvement, the types and frequency of 

problems connected with the patient’s 

use, and other special medical and psychiatric considerations. 

• If a patient’s response to a brief assessment suggests a diagnosis of substance 

abuse or dependence, the clinician 

should initiate a referral for an in-depth 

assessment. 

• The clinician can initiate a brief, officebased therapeutic intervention in these 

situations: 

– Screening reveals only mild to 

moderate substance abuse problems 

– The patient appears to be at risk for 

experiencing negative consequences as 

a result of current patterns 

– Coexisting illness or conditions may 

be worsened by continued drinking or 

other medications 

– Patient refuses referral for further 

assessment or treatment.
 

Brief Intervention 

Brief interventions as secondary prevention tools have the potential to help an 

estimated 15 to 20 million heavy drinkers 

in the U.S. by minimizing serious adverse 

consequences such as costly emergency 

room visits, domestic violence, or road 

accidents. 

Selecting Appropriate Patients 

for Brief Intervention 

In response to screening questionnaires 

patients can be categorized into one of 

three groups: 

1.	 Patients who do not appear to have 

any alcohol- or drug-related problems. 

These patients require no further 

intervention. 

2.	 Patients with positive but low 

scores on any screening tests or who 

occasionally use marijuana. These 

patients may be appropriate candidates for brief intervention. 

3.	 Patients with several positive 

responses to screening questionnaires 

and suspicious drinking or drug use 

histories, symptoms of substance 

dependence, or current use of illicit 

drugs. These patients need further 

assessment. 

Conducting Brief Interventions 

1.	 Give feedback about screening 

results, impairment, and risks 

while clarifying the findings 

• Give prompt feedback to the 

screening.
 

• Present results in a straightforward, 

nonjudgmental manner and in terms 

a patient can readily understand. 

• Concerns about potential or actual 

health effects should be stressed. 

For example, “At this level of consumption, you are at increased risk 

for some health problems as well as 

accidents.” 

• Avoid being adversarial and pay 

attention to semantics. For example, 

the phrase “people for whom substance abuse is creating a problem” 

is less off-putting than the labels 

“alcoholic” or “addict.” 

94 Appendix D 
• Remain tolerant of the range of 

patient reactions, including astonishment, embarrassment, hostility, 

and denial. 

• Try to avoid arguments or discussions about how much others can 

drink without adverse consequences. 

• Be reassuring that alcohol and drug 

problems are not anyone’s “fault” 

and can certainly be addressed during visits. 

2.	 Inform the patient about safe consumption limits and offer advice 

about change 

• Explain what acceptable and safe 

use levels are for the relevant substance. Low-risk drinking is no more 

than two drinks per day for men and 

one drink per day for women. 

• Patients should understand concepts 

of tolerance and metabolism. 

• Clearly state recommendations 

about consumption goals, keeping these in the context of lifestyle 

issues and living habits. For example, “In reviewing your response to 

our screening questionnaire, I notice 

that you are drinking a lot of beer 

on weekends. You don’t seem to 

have any direct problems as a result, 

but I’m concerned that driving while 

intoxicated is not safe and you have 

a young family to consider.” 

• Clinician authority in offering advice 

can be strongly motivating. 

3.	 Assess the patient’s readiness to 

change 

• A patient’s reaction to initial feedback about screening results offers 

strong clues about readiness to 

change. 

• People with substance abuse disorders generally fall into one of five 

stages along a continuum that provides a useful framework for monitoring progress: 

– Precontemplation: Not seeing 

the behavior as a problem or not 

wanting to change the behavior. 

– Contemplation: Beginning to 

understand that the behavior is 

causing difficulties in living or 

taking a toll on their health and 

happiness. 

– Preparation/Determination:

Considering various options for 

change. 

– Action: Taking concrete steps to 

change the behavior in a specific 

way. 

– Maintenance: Avoiding relapse 

into problem behavior. 

• Be prepared for resistance and 

setbacks. 

• Avoid the temptation to regard 

resistance as a challenge to authority or to react in an authoritarian 

way. 

• Have an emphatic and supportive 

attitude and create an atmosphere 

that the patient will be comfortable 

returning to even if goals are not 

successfully achieved. 

4.	 Negotiate goals and strategies for 

change 

• With alcohol, suggest that the client 

reduce consumption to below unsafe 

or potentially hazardous levels. For 

example, “Can we set a specific date 

to reduce your alcohol use? Could 

you cut back, beginning this week?” 

• If a patient who is using illegal 

drugs does not feel ready to 

discontinued use, suggest a tapering 

schedule. 

Quick for Clinicians Based on TIP 24 95 
• The clinician can only remind the 

patient that reducing or stopping 

alcohol use or abstaining from other 

drug use will eliminate the health 

or social problems substance use is 

causing: Ultimately the patient 

must choose the goal. 

• Suggest that patients keep track 

of consumption in a daily diary 

to make them more aware of how 

much they consume. Even patients 

who are not ready to change their 

behavior may be willing to keep a 

diary. 

• Patients will be more motivated to 

change if they are helping to set 

goals and develop strategies for 

change. Some studies have found 

that self-help manuals can be a 

helpful adjunct for planning change. 

• A written contract is a good idea 

since sometimes patients forget 

what they agreed to do. 

5. Arrange for followup treatment 

• Monitor any health problems or 

abnormal physical markers. 

• Express trust in the patient. 

• Confront the patient if he or she 

is not honest about reporting 

substance use. 

• The use of any form of objective 

monitoring beyond self-reports of 

substance abuse must be negotiated between the clinician and the 

patient. 

• Tell patients exactly who will see 

their medical charts and what 

information about screening and 

intervention will be recorded. 

• One researcher found that reduction 

of alcohol consumption correlated 

with the number of practitioner 

intervention sessions that were 

delivered. 

Deciding To Refer for Further 

Assessment or Treatment 

Clinicians should be prepared for the 

brief intervention to fail: The patient may 

not be able to achieve or maintain the 

mutually established goal of reducing 

or stopping use after one try, or even 

several tries. Clinicians cannot force a 

patient to undergo further assessment. 

However, if problem use persists after 

a brief intervention, those discussions 

should serve as a springboard for a 

more in-depth assessment or specialized 

treatment. 

96 Appendix D 
 

 

 

 

 

 

 

 

 

Appendix E—Resource Panel
 

Patricia Allman 

Consultant
 

Cephalon, Inc.

Dillon Allman & Partners, LLC
 

Bethesda, Maryland
 

David R. Anderson 

Communications Director 

Ensuring Solutions to Alcohol Problems

School of Public Health and Health 

Services 

The George Washington University

Washington, D.C. 

Neil A. Capretto, D.O., FASAM 

Representing the National Association 

of Addiction Treatment Providers 

Medical Director
 

Aliquippa, Pennsylvania
 

Heidi L. Coleman, J.D. 

Chief
 

Impaired Driving Division

National Highway Traffic Safety

Administration
 

Washington, D.C. 

Carlo C. DiClemente, Ph.D. 

Representing the Division on Addictions, 

American Psychological Association

Professor
 

University of Maryland, Baltimore 

County

Baltimore, Maryland 

Allyson T. Gage, Ph.D.

Associate Director 

Central Nervous System Therapeutic 

Area
 

Forest Research Institute
 

Jersey City, New Jersey
 

David R. Gastfriend, M.D. 

Vice President, Medical Affairs
 

Alkermes, Inc.
 

Cambridge, Massachusetts
 

Beverley Goggins, RN, Ed.M. 

Representing Therapeutic Communities 

of America 

Lead Nurse
 

Second Genesis, Inc.
 

Silver Spring, Maryland
 

George Kolodner, M.D. 

Representing the American Society 

of Addiction Medicine 

Director
 

KOLMAC Clinic
 

1003 Spring Street

Silver Spring, Maryland
 

Stephen LeBlanc

Public Health Analyst

Consumer Affairs 

Office of the Director 

Center for Substance Abuse Treatment 

Substance Abuse and Mental Health 

Services Administration
 

Rockville, Maryland
 

97 
 

 

 

 

 

 

 

 

 

 

 

 

Cynthia Moreno-Tuohy, NCAC II, 

CCDC III 

Executive Director
 

NAADAC, The Association for
 

Addiction Professionals
 

Alexandria, Virginia
 

Charlotte A. Mullican, M.P.H. 

Senior Advisor for Mental Health 

Research
 

Agency for Healthcare Research 

and Quality

Rockville, Maryland
 

Kevin P. Mulvey, Ph.D.

Branch Chief 

Practice Assessment and Applications 

Branch 

Center for Substance Abuse Prevention 

Substance Abuse and Mental Health 

Services Administration
 

Rockville, Maryland
 

Elyse Sharpe, LCSW-C

Manager

Work-Life Program

Washington, D.C. 

Robert L. Stephenson II, M.P.H.

Director 

Division of Workplace Programs

Center for Substance Abuse Prevention 

Substance Abuse and Mental Health 

Services Administration
 

Rockville, Maryland
 

Richard T. Suchinsky, M.D.

Associate Chief for Addiction Disorders 

Department of Veterans Affairs

Washington, D.C. 

Timothy P. Tunner, Ph.D., M.S.W.

Senior Policy Associate—Behavioral 

Health 

National Association of Social Workers 

Washington, D.C. 

Allan Weber 

General Manager

Odyssey Pharmaceuticals, Inc.

East Hanover, New Jersey 

Wendy J. Wilcox

American Association for Marriage 

and Family Therapy

Bowie, Maryland 

Mark L. Willenbring, M.D.

Director 

Treatment and Recovery Research 

Division 

National Institute on Alcohol Abuse 

and Alcoholism 

National Institutes of Health 

Bethesda, Maryland 

Stephen Wing, M.S.W.

Associate Administrator for Alcohol 

Policy

Division of Policy Coordination

Substance Abuse and Mental Health 

Services Administration
 

Rockville, Maryland
 

Wilbur Woodis, M.A. 

Division of Behavioral Health 

Indian Health Service 

Rockville, Maryland 

98 Appendix E 
 

 

 

 

 

 

 

 

 

 

 

Appendix F—Field Reviewers
 

David D. Atkins, M.S.M., LISW, ACSW 

Alcohol/Substance Abuse Program 

Director 

Indian Health Service, Phoenix 

Area Office 

Phoenix, Arizona 

David A. Fiellin, M.D. 

Associate Professor of Medicine 

Yale University School of Medicine

New Haven, Connecticut 

Sharon Morgillo Freeman, Ph.D., 

APRN-CS, MAC 

President, Center for Brief Therapy, P.C. 

and 

President, NAADAC, The Association 

for Addiction Professionals 

Fort Wayne, Indiana 

Monika A. Koch, M.D. 

Addiction Psychiatrist

Chemical Dependence Recovery

Program

The Permanente Medical Group 

Vallejo, California
 

Sandra C. Lapham, M.D., M.P.H.

Director 

Behavioral Health Research Center 

of the Southwest 

Pacific Institute for Research and 

Evaluation 

Albuquerque, New Mexico 

Peter M. Miller, Ph.D. 

Professor 

Center for Drug and Alcohol Programs

Medical University of South Carolina

Charleston, South Carolina 

Paul Nagy, M.S., LPC, LCAS, CCS

Program Director

Duke Addictions Program

Duke University Medical Center

Durham, North Carolina
 

Charles O’Brien, M.D., Ph.D. 

Professor 

Department of Psychiatry

University of Pennsylvania School 

of Medicine
 

Philadelphia, Pennsylvania
 

Ashwin A. Patkar, M.D., MRC Psych

Medical Director, Duke Addictions 

Program

and 

Associate Professor, Division 

of Biological Psychiatry

Department of Psychiatry and 

Behavioral Sciences
 

Duke University Medical Center

Durham, North Carolina
 

99 
 

 

 

 

 

 

 

 

James Recktenwald, M.S.W., CADC 

Substance Abuse Counselor 

Carl D. Perkins Vocational Training 

Center 

Thelma, Kentucky 

John Scanlon, D.O. 

Assistant Professor of Family Medicine 

and Addiction Medicine 

Pikeville College School of Osteopathic 

Medicine 

Pikeville, Kentucky 

Marvin D. Seppala, M.D.

Medical Director and CEO 

Beyond Addictions

Beaverton, Oregon 

C. Chapman Sledge, M.D., FASAM

Medical Director 

Pine Grove Behavioral Health and 

Addiction Services 

Hattiesburg, Mississippi 

Ruth Robinson Staten, Ph.D., 

ARNP-CS 

Associate Professor
 

University of Kentucky College 

of Nursing

Lexington, Kentucky
 

Scott H. Stewart, M.D. 

Center for Drug and Alcohol Programs

Department of Psychiatry and

Behavioral Sciences 

Medical University of South Carolina

Charleston, South Carolina 

Daniel C. Vinson, M.D., M.S.P.H. 

Professor 

Department of Family and Community 

Medicine 

University of Missouri-Columbia

Columbia, Missouri
 

100 Appendix F 
Appendix G— 

Acknowledgments 

Numerous people contributed to the development of this TIP, 

including the TIP Consensus Panel (see page vii), the Knowledge 

Application Program (KAP) Expert Advisory Panel (see page ix), 

the Resource Panel (see Appendix E), and TIP Field Reviewers 

(see Appendix F). 

This publication was produced under KAP, a Joint Venture of 

The CDM Group, Inc., and JBS International, Inc. (JBS), for the 

Substance Abuse and Mental Health Services Administration, 

Center for Substance Abuse Treatment. 

Lynne MacArthur, M.A., A.M.L.S., served as the JBS KAP 

Executive Project Co-Director, and Barbara Fink, RN, M.P.H., 

served as the JBS KAP Managing Project Co-Director. Other 

JBS KAP personnel included Candace Baker, M.S.W., MAC, 

Deputy Director for Product Development; Dennis Burke, 

M.S., M.A., TIPs, TAPs, and Other Products Manager; Elliott 

Vanskike, Ph.D., Senior Writer; Frances Nebesky, M.A., Quality 

Assurance Editor; and Wendy Caron, Quality Assurance 

Manager. 

101 

Index 

AA. See Alcoholics Anonymous

Abstinence
 

defined, 2
 

goal setting, 56

monitoring, 58–59

Acamprosate

adverse reactions, 12, 13, 53, 76
 

cautions, 12–13, 53, 76
 

contraindications, 12, 52, 53, 76
 

discontinuing treatment, 14

dosage, 9, 13, 76

duration of treatment, 14
 

efficacy, 10–11

history of development, 9–10

initiating treatment, 11

mechanism of action, 53, 76
 

medication comparison, 53, 76

overview, 9
 

patient education, 12

patient management, 12, 13

patient selection, 13–14

pharmacology, 10

safety, 11

side effects, 12, 53, 76
 

storage, 9

treatment decision factors, 52
 

Acetaldehyde, 16–17

Adolescents, 56, 81, 93
 

“Adult Detoxification” levels, 79
 

Adverse reactions
 

acamprosate, 12, 13

comparison, 53, 76

disulfiram, 17–18, 23
 

naltrexone, extended release 

injectable, 41

naltrexone, oral, 32
 

Aggression, 80

Al-Anon, 56
 

Alateen, 56
 

Alcohol challenges, 18

Alcohol cravings, 34, 59

Alcohol dehydrogenase, 16

Alcohol dependence, 3

Alcohol intoxication, 81–85
 

Alcohol Urge Questionnaire, 59

Alcohol Use Disorder Identification Test,
 

87–88, 90–92 

Alcohol use disorders 

access to medication-assisted 

treatment, 4
 

assessment, 73
 

benefits of medication-assisted 

treatment, 5–7
 

costs, 3
 

defined, 2
 

drinking patterns, 75

genetic links, 5–6

identifying, 47–48

integrating medication-assisted 

treatment into clinical practice, 45–46

medication-assisted treatment, 3–4
 

neuroadaptations, 6

patient assessment, 46–50

prevalence of, 3

primary care treatment advantages, 

1–2 

treatment options, 5

Alcohol withdrawal, 82–85
 

Alcoholics Anonymous, 55

Aldehyde dehydrogenase, 16, 18, 22

ALDH. See Aldehyde dehydrogenase

American Society of Addiction Medicine, 79
 

103 
Anger, 80

Antabuse®. See Disulfiram 

ASAM. See American Society of Addiction 

Medicine
 

Aspartate aminotransferase, 47–48

Assessment, 46
 

psychiatric, 49

substance use, 49
 

AST. See Aspartate aminotransferase

At-risk drinkers, 89
 

AUDIT, 87–88, 90–92
 

AUDs. See Alcohol use disorders
 

Benzodiazepine, 83–84

Biomarkers, 48
 

Biomedical issues, 79–81
 

Black-box warning

disulfiram, 19
 

naltrexone, extended release 

injectable, 39

naltrexone, oral, 29
 

Blood alcohol levels, 81–82
 

Blood counts, 48
 

Blood tests, 47–48
 

Breath tests, 47–48
 

BreathalyzerTM tests, 59
 

Brief interventions
 

choosing type of treatment, 5

defined, 2
 

A Guide to Substance Abuse Services 

for Primary Care Clinicians, TIP 24, 

88, 94–96
 

A Pocket Guide for Alcohol Screening 

and Brief Intervention, 49, 74
 

Buprenorphine, 6

Buproprion, 6
 

CAGE Adapted to Include Drugs, 88, 90

CAGE-AID, 88, 90
 

CAGE questionnaire, 87–88

Campral® Delayed-Release Tablets. See
 

Acamprosate

Carbohydrate-deficient transferin, 48

Cautions
 

acamprosate, 12–13

comparison, 53, 76

disulfiram, 20, 22
 

naltrexone, extended-release 

injectable, 41

naltrexone, oral, 30–31
 

CDER. See Center for Drug Evaluation 

and Research 

CDT. See Carbohydrate-deficient

transferin 

Center for Drug Evaluation and 

Research, 38
 

Center for Substance Abuse Treatment, x
 

CIWA-Ar scale, 84
 

COMBINE. See Combining Medications 

and Behavioral Interventions
 

Combining Medications and Behavioral 

Interventions, 4, 51, 54
 

Contraindications
 

acamprosate, 12

comparison, 53, 76

disulfiram, 20–21
 

medication decision grid, 52

naltrexone, extended-release 

injectable, 40

naltrexone, oral, 30–31
 

Cravings, 34, 59

CSAT. See Center for Substance Abuse 

Treatment 

Delirium tremens, 84–85 

Depade®. See Naltrexone, oral 

Detoxification 

defined, 77
 

Detoxification and Substance Abuse 

Treatment, TIP 45
 

alcohol intoxication and withdrawal, 

81–85
 

biomedical issues, 79–81
 

definitions, 77
 

guiding principles and assumptions, 78

levels of care, 79
 

patient placement, 79

principles for care, 78–79

psychosocial issues, 79–81

Disulfiram
 

absorption and elimination, 18

adverse effects of reaction with alcohol, 

17–18, 23, 76
 

adverse reactions, 21, 23, 53
 

black-box warning, 19

cautions, 20, 22, 53, 76
 

contraindications, 20–21, 52, 53, 76
 

discontinuing treatment, 25–26

dosage, 15, 20, 76

drug interactions, 21, 24, 53, 76
 

104 Index 
duration of treatment, 25–26
 

efficacy, 18–19

hepatic toxicity, 21

history of development, 15–16

initiating treatment, 19–20

laboratory testing, 21, 25

mechanism of action, 53, 76
 

medication comparison, 53, 76

overdose, 21–22
 

overview, 15
 

patient education, 23–25

patient management, 21–23

patient selection, 19, 25

pharmacology, 16–18

safety, 19

side effects, 20–21, 53, 76
 

storage, 15

supervised ingestion, 20

treatment decision factors, 52
 

Disulfiram-alcohol reaction, 17–19, 23, 76
 

Drinks, standard, 75
 

Drug interactions

comparison, 53, 76

disulfiram and, 21, 24
 

oral naltrexone and, 33
 

Drug use. See Substance use 

DTs. See Delirium tremens 

Dual Recovery Anonymous, 55–56 

Education. See Patient education
 

EtG. See Ethyl glucuronide

Ethyl glucuronide, 48

Evaluation
 

defined, 77
 

FDA. See U.S. Food and Drug 

Administration 

Gamma glutamyltransferase, 47–48

Genetic variants, 5–6 

Geriatric screening, 88, 92–93

GGT. See Gamma glutamyltransferase 

A Guide to Substance Abuse Services for 

Primary Care Clinicians, TIP 24
 

assessment and treatment, 88
 

brief intervention, 88, 94–96
 

followup, 94

screening, 87–88

screening instruments, 89–93
 

warning signs and risk factors, 88–89, 

93
 

Health status, 59–60 

Healthcare practitioners

defined, 2
 

Hepatic toxicity. See Liver disease
 

Hepatitis, disulfiram-induced, 19

HHS. See U.S. Department of Health and 

Human Services 

Information resources, 58
 

Intoxication, 81–85
 

Kindling effect, 83
 

Laboratory testing

disulfiram therapy and, 21, 25

identifying alcohol-related damage, 

48–49
 

identifying alcohol use disorders, 

47–48
 

monitoring patient progress, 59

useful tests, 47
 

Liver disease
 

disulfiram-induced, 19–21
 

oral naltrexone and, 29, 32
 

Liver function tests, 47–49
 

Low-risk drinkers, 89
 

MAST-G, 88, 92–93
 

Medical detoxification, 77
 

Medical management

benefits of, 54
 

defined, 2
 

Medication-assisted treatment. See also 

specific medications by name

access to, 4
 

benefits of, 5–7
 

choosing a medication, 51–53

combination therapy, 51–52, 54

discontinuing, 61

FDA-approved medications, 3–4

integrating into clinical practice, 

45–46 

medication combinations, 4
 

Mental health issues, 80
 

Michigan Alcoholism Screening TestGeriatric Version, 88, 92–93 

MM. See Medical management 

Appendices Index 105
Mutual-help programs, 55–56 

Naltrexone, extended-release injectable

administering, 40

adverse reactions, 41, 53, 76
 

benefits of, 39
 

black-box warning, 39

cautions, 41, 53, 76
 

compliance, enhanced, 39

contraindications, 40, 52, 53, 76
 

discontinuing treatment, 43

dosage, 37, 76

drug interactions, 53, 76

duration of treatment, 43
 

efficacy, 38–39

history of development, 37–38

initiating treatment, 39

mechanism of action, 53, 76
 

medication comparison, 53, 76

overview, 37
 

pain management and, 42

patient education, 41–42

patient management, 41

patient selection, 42–43, 44

pharmacology, 38

safety, 39

side effects, 40, 53, 76
 

storage, 37

treatment decision factors, 52
 

Naltrexone, oral
 

adverse reactions, 32, 53, 76
 

black-box warning, 29

cautions, 30–31, 53, 76
 

contraindications, 30–31, 52, 53, 76
 

discontinuing treatment, 35

dosage, 27, 30, 76

drug interactions, 33, 53, 76

duration of treatment, 35
 

efficacy, 28–29

history of development, 27–28

initiating treatment, 29–30

liver disease signs and symptoms, 32

mechanism of action, 53, 76
 

medication comparison, 53, 76

overview, 27
 

pain management and, 34

patient education, 33

patient management, 32–33

patient selection, 34

pharmacology, 28
 

safety, 29

side effects, 30, 53, 76
 

storage, 27

treatment decision factors, 52
 

National Institute on Alcohol Abuse and 

Alcoholism, 4, 46, 49, 54, 71–76
 

Neuroadaptations, 6

NIAAA. See National Institute on Alcohol 

Abuse and Alcoholism 

Opioids

addiction treatment, 6
 

oral naltrexone and, 34
 

Overdose, disulfiram, 21–22 

Pain management

extended-release injectable naltrexone 

and, 42
 

oral naltrexone and, 34
 

Parents with dependent children, 81

Patient education
 

acamprosate use, 12

disulfiram use, 23–25
 

elements of, 57
 

information sources, 58
 

naltrexone, extended-release 

injectable, 41–42

naltrexone, oral, 33
 

Patient management

acamprosate use, 12, 13

assessing motivation for change, 50–51

choosing a medication, 51–53

combination therapy, 51–52, 54

developing a treatment plan, 56–57

discontinuing pharmacotherapy, 61

disulfiram use, 21–23
 

fostering patient’s entry into 

treatment, 77
 

information resources for patients, 58

initial assessment, 46
 

integrating medication-assisted 

treatment into clinical practice, 

45–46
 

laboratory testing, 47–49

modifying treatment strategy, 60–61

monitoring progress, 57–60

motivating patients for treatment, 49

naltrexone, extended-release 

injectable, 41

naltrexone, oral, 32–33
 

106 Index 
patient awareness, 57

physical exam, 46–47

psychiatric assessment, 49

psychosocial interventions, 54–56

social history, 50

substance use assessment, 49–50
 

Patient placement, 79

Pharmacology

acamprosate, 10

disulfiram, 16–18
 

naltrexone, extended-release 

injectable, 38

naltrexone, oral, 28
 

Pharmacotherapy. See Medicationassisted treatment
 

Physical exam, 46–47
 

A Pocket Guide for Alcohol Screening and 

Brief Intervention, 49, 71–76
 

Pretreatment indicators, 52
 

Psychiatric assessment, 49

Psychosocial interventions

mutual-help programs, 55–56

referring patients for specialty

treatment, 55
 

resources for office-based approaches, 

55
 

self-help programs, 55–56

types of, 54

Psychosocial issues, 79–81 

Reimbursement guide, 45

Renal function tests, 47–49
 

ReVia®. See Naltrexone, oral
 

SAMHSA. See Substance Abuse and 

Mental Health Services Administration 

Screening

choosing type of treatment, 5

heavy drinking, 73
 

A Guide to Substance Abuse Services 

for Primary Care Clinicians, TIP 24, 

88
 

A Pocket Guide for Alcohol Screening 

and Brief Intervention, 49, 71–76 

Seizures, 84–85 

Self-help programs, 55–56

Self Management and Recovery Training, 

56
 

Self-reports, 58
 

Side effects
 

acamprosate, 12

common, 53, 76
 

comparison, 53, 76

disulfiram, 20–21
 

naltrexone, extended-release 

injectable, 40

naltrexone, oral, 30
 

Smoking cessation treatment, 6

Social detoxification, 77, 82–83
 

Social functioning, 59–60

Social history, 50

Specialty substance abuse treatment/care

choosing type of treatment, 5

defined, 2
 

referring patients, 55

Stabilization 

defined, 77
 

Standard drinks, 75
 

Substance Abuse and Mental Health 

Services Administration, xiii
 

Substance use
 

adolescent risk factors, 93
 

assessment, 49–50
 

monitoring, 60

Suicidality, 80
 

TIP. See Treatment Improvement 

Protocol
 

Tolerance, 92
 

Toxicological screening, 48

Treatment Improvement Protocol
 

Detoxification and Substance Abuse 

Treatment, TIP 45, 77–85 

A Guide to Substance Abuse Services 

for Primary Care Clinicians, TIP 24, 

87–96
 

Treatment plan, 56

Trexan®. See Naltrexone, oral
 

TWEAK test, 92
 

Urine tests, 47–48 

U.S. Department of Health and Human 

Services, ix
 

U.S. Food and Drug Administration

approval of alcohol use disorder 

medications, 1
 

Center for Drug Evaluation and 

Research, 38
 

pregnancy Category C, 13, 31, 53
 

Index 107
 
Vitamin deficiencies, 47–48 

Vivitrol®. See Naltrexone, extendedrelease injectable 

Wernicke-Korsakoff’s Syndrome, 85

Withdrawal, 82–85
 

Women for Sobriety, Inc., 56
 

108 Index 
 

CSAT TIPs and Publications Based on TIPs 

What Is a TIP? 

Treatment Improvement Protocols (TIPs) are the products of a systematic and innovative process that brings together 

clinicians, researchers, program managers, policymakers, and other Federal and non-Federal experts to reach consensus on state-of-the-art treatment practices. TIPs are developed under CSAT’s Knowledge Application Program to 

improve the treatment capabilities of the Nation’s alcohol and drug abuse treatment service system. 

What Is a Quick Guide? 

A Quick Guide clearly and concisely presents the primary information from a TIP in a pocket-sized booklet. Each 

Quick Guide is divided into sections to help readers quickly locate relevant material. Some contain glossaries of terms 

or lists of resources. Page numbers from the original TIP are referenced so providers can refer back to the source document for more information. 

What Are KAP Keys?

Also based on TIPs, KAP Keys are handy, durable tools. Keys may include assessment or screening instruments, checklists, and summaries of treatment phases. Printed on coated paper, each KAP Keys set is fastened together with a key

ring and can be kept within a treatment provider’s reach and consulted frequently. The Keys allow you—the busy clinician or program administrator—to locate information easily and to use this information to enhance treatment services. 

TIP 1	 State Methadone Treatment Guidelines— 

Replaced by TIP 43 

TIP 2* Pregnant, Substance-Using Women—BKD107 

Quick Guide for Clinicians QGCT02 

KAP Keys for Clinicians KAPT02 

TIP 3	 Screening and Assessment of Alcohol- and 

Other Drug-Abusing Adolescents—Replaced

by TIP 31 

TIP 4	 Guidelines for the Treatment of Alcoholand Other Drug-Abusing Adolescents—

Replaced by TIP 32 

TIP 5	 Improving Treatment for Drug-Exposed 

Infants—BKD110 

TIP 6* Screening for Infectious Diseases Among 

Substance Abusers—BKD131 

Quick Guide for Clinicians QGCT06 

KAP Keys for Clinicians KAPT06 

TIP 7	 Screening and Assessment for Alcohol and 

Other Drug Abuse Among Adults in the 

Criminal Justice System—Replaced by TIP 44 

TIP 8	 Intensive Outpatient Treatment for Alcohol 

and Other Drug Abuse—Replaced by TIPs 46 

and 47 

TIP 9	 Assessment and Treatment of Patients With 

Coexisting Mental Illness and Alcohol and 

Other Drug Abuse—Replaced by TIP 42 

TIP 10 Assessment and Treatment of CocaineAbusing Methadone-Maintained Patients—

Replaced by TIP 43 

TIP 11*Simple Screening Instruments for Outreach 

for Alcohol and Other Drug Abuse and 

Infectious Diseases—BKD143 

Quick Guide for Clinicians QGCT11 

KAP Keys for Clinicians KAPT11 

TIP 12 Combining Substance Abuse Treatment 

With Intermediate Sanctions for Adults in 

the Criminal Justice System—Replaced by 

TIP 44 

TIP 13 Role and Current Status of Patient 

Placement Criteria in the Treatment of 

Substance Use Disorders—BKD161 

Quick Guide for Clinicians QGCT13 

Quick Guide for Administrators QGAT13 

KAP Keys for Clinicians KAPT13 

TIP 14 Developing State Outcomes Monitoring 

Systems for Alcohol and Other Drug Abuse 

Treatment—BKD162 

TIP 15 Treatment for HIV-Infected Alcohol and 

Other Drug Abusers—Replaced by TIP 37 

TIP 16 Alcohol and Other Drug Screening of 

Hospitalized Trauma Patients—BKD164 

Quick Guide for Clinicians QGCT16 

KAP Keys for Clinicians KAPT16 

TIP 17 Planning for Alcohol and Other Drug 

Abuse Treatment for Adults in the Criminal 

Justice System—Replaced by TIP 44 

TIP 18 The Tuberculosis Epidemic: Legal and 

Ethical Issues for Alcohol and Other Drug 

Abuse Treatment Providers—BKD173 

Quick Guide for Clinicians QGCT18 

KAP Keys for Clinicians KAPT18 

TIP 19 Detoxification From Alcohol and Other 

Drugs—Replaced by TIP 45 

TIP 20 Matching Treatment to Patient Needs in 

Opioid Substitution Therapy—Replaced by 

TIP 43 

TIP 21 Combining Alcohol and Other Drug Abuse 

Treatment With Diversion for Juveniles in 

the Justice System—(SMA) 08-4073 

Quick Guide for Clinicians and 

Administrators QGCA21 

TIP 22 LAAM in the Treatment of Opiate 

Addiction—Replaced by TIP 43 

TIP 23 Treatment Drug Courts: Integrating 

Substance Abuse Treatment With Legal 

Case Processing—(SMA) 08-3917 

Quick Guide for Administrators QGAT23 

TIP 24 A Guide to Substance Abuse Services for 

Primary Care Clinicians—(SMA) 08-4075 

Concise Desk Reference Guide (SMA)

08-3740 

Quick Guide for Clinicians QGCT24 

KAP Keys for Clinicians KAPT24 

TIP 25 Substance Abuse Treatment and Domestic 

Violence—(SMA) 08-4076 

A Guide for Treatment Providers MS668 

A Guide for Administrators MS667 

Quick Guide for Clinicians QGCT25 

KAP Keys for Clinicians KAPT25 

TIP 26 Substance Abuse Among Older Adults—

(SMA) 08-3918 

A Guide for Treatment Providers MS669 

A Guide for Social Service Providers MS670 

Physician’s Guide MS671 

*Under revision 

109 
 

 

 

 

 

 

TIP 26 Substance Abuse Among Older Adults—

(SMA) 08-3918 

Good Mental Health is Ageless PHD881 

(English), (SMA) 08-3897 (Spanish)
 

Aging, Medicines and Alcohol (SMA) 08-3169 

(English), (SMA) 08-3898 (Spanish)
 

Quick Guide for Clinicians QGCT26
 

KAP Keys for Clinicians KAPT26
 

TIP 27 Comprehensive Case Management for 

Substance Abuse Treatment—(SMA) 08-4215
 

A Guide for Treatment Providers MS673
 

Quick Guide for Clinicians QGCT27
 

Quick Guide for Administrators QGAT27
 

TIP 28 Naltrexone and Alcoholism Treatment— 

Replaced by TIP 49
 

TIP 29 Substance Use Disorder Treatment for 

People With Physical and Cognitive 

Disabilities—(SMA) 08-4078
 

Quick Guide for Clinicians QGCT29
 

Quick Guide for Administrators (SMA)

08-3592
 

KAP Keys for Clinicians KAPT29
 

TIP 30 Continuity of Offender Treatment for 

Substance Use Disorders From Institution 

to Community—(SMA) 08-3920
 

Quick Guide for Clinicians QGCT30 

KAP Keys for Clinicians KAPT30 

TIP 31 Screening and Assessing Adolescents for 

Substance Use Disorders—(SMA) 08-4079
 

See companion products for TIP 32. 

TIP 32 Treatment of Adolescents With Substance 

Use Disorders—(SMA) 08-4080
 

Quick Guide for Clinicians QGC312
 

KAP Keys for Clinicians KAPT312
 

TIP 33 Treatment for Stimulant Use Disorders— 

BKD289 

Quick Guide for Clinicians QGCT33 

KAP Keys for Clinicians KAPT33 

TIP 34 Brief Interventions and Brief Therapies for 

Substance Abuse—(SMA) 07-3952
 

Quick Guide for Clinicians QGCT34
 

KAP Keys for Clinicians KAPT34
 

TIP 35 Enhancing Motivation for Change in 

Substance Abuse Treatment—(SMA) 08-4212
 

Faces of Change (SMA) 08-4174
 

Inservice Training (SMA) 08-4190
 

Quick Guide for Clinicians QGCT35
 

KAP Keys for Clinicians KAPT35
 

TIP 36 Substance Abuse Treatment for Persons 

With Child Abuse and Neglect Issues—

(SMA) 08-3923
 

Helping Women Heal—(SMA) 08-4132 

(English), PHD981S (Spanish)
 

Helping Men Heal—(SMA) 07-4134 (English), 

PHD1059S (Spanish)
 

Quick Guide for Clinicians QGCT36
 

KAP Keys for Clinicians KAPT36
 

TIP 37 Substance Abuse Treatment for Persons 

With HIV/AIDS—(SMA) 08-4137
 

HIV/AIDS: Is Your Client at Risk? MS965
 

Drugs, Alcohol and HIV/AIDS (SMA) 08-4127 

(English), (SMA) 08-4181 (Spanish)
 

Drugs, Alcohol and HIV/AIDS for African 

Americans (SMA) 07-4248
 

Quick Guide for Clinicians QGCT37
 

KAP Keys for Clinicians KAPT37 

TIP 38 Integrating Substance Abuse Treatment 

and Vocational Services—BKD381 

Quick Guide for Clinicians QGCT38 

Quick Guide for Administrators QGAT38 

KAP Keys for Clinicians KAPT38 

TIP 39 Substance Abuse Treatment and Family 

Therapy—(SMA) 08-4219
 

Quick Guide for Clinicians QGCT39
 

Quick Guide for Administrators QGAT39 

TIP 40 Clinical Guidelines for the Use of 

Buprenorphine in the Treatment of Opioid 

Addiction—(SMA) 07-3939
 

Quick Guide for Physicians QGPT40
 

KAP Keys for Physicians KAPT40 

TIP 41 Substance Abuse Treatment: Group 

Therapy—BKD507 

Quick Guide for Clinicians QGCT41 

TIP 42 Substance Abuse Treatment for Persons 

With Co-Occurring Disorders—(SMA)

08-3992
 

Inservice Training (SMA) 08-4262
 

Quick Guide for Clinicians (SMA) 07-4034
 

Quick Guide for Administrators QGAT42
 

KAP Keys for Clinicians (SMA) 08-4036
 

TIP 43 Medication-Assisted Treatment for Opioid

Addiction in Opioid Treatment Programs—

(SMA) 08-4214
 

Inservice Training (SMA) 08-4341
 

Quick Guide for Clinicians QGCT43
 

KAP Keys for Clinicians (SMA) 07-4108
 

TIP 44 Substance Abuse Treatment for Adults in 

the Criminal Justice System—BKD526
 

Alcohol & Drug Treatment (SMA) 07-4292 

(English), (SMA) 08-4320 (Spanish)
 

Quick Guide for Clinicians QGCT44
 

KAP Keys for Clinicians (SMA) 07-4150 

TIP 45 Detoxification and Substance Abuse 

Treatment—(SMA) 08-4131
 

Inservice Training (SMA) 08-4331
 

Quick Guide for Clinicians (SMA) 06-4225
 

Quick Guide for Administrators (SMA)

06-4226
 

KAP Keys for Clinicians (SMA) 06-4224
 

TIP 46 Substance Abuse: Administrative Issues in 

Outpatient Treatment—BKD545
 

Quick Guide for Administrators (SMA)

07-4232
 

TIP 47 Substance Abuse: Clinical Issues in 

Intensive Outpatient Treatment—BKD551
 

Quick Guide for Clinicians (SMA) 07-4233
 

KAP Keys for Clinicians (SMA) 07-4251
 

TIP 48 Managing Depressive Symptoms in 

Substance Abuse Clients During Early 

Recovery—(SMA) 08-4353
 

TIP 49 Incorporating Alcohol Pharmacotherapies 

Into Medical Practice—(SMA) 09-4380
 

TIP 50 Addressing Suicidal Thoughts and 

Behaviors With Clients in Substance Abuse 

Treatment—(SMA) 09-4381
 

110 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Treatment Improvement Protocols (TIPs) from the Substance Abuse and Mental Health Services Administration’s (SAMHSA’s) 

Center for Substance Abuse Treatment (CSAT) 

Place the quantity (up to 5) next to the publications you would like to receive and print your mailing address below. 

___TIP 2* BKD107 ___TIP 27 (SMA) 08-4215 ___TIP 38 BKD381 

___QG† for Clinicians QGCT02 ___Guide for Treatment Providers ___QG for Clinicians QGCT38 

___KK† for Clinicians KAPT02 MS673 ___QG for Administrators QGAT38 

___Guide for Administrators MS672 ___KK for Clinicians KAPT38 

___TIP 5 BKD110 ___QG for Clinicians QGCT27 

___QG for Administrators QGAT27 ___TIP 39 (SMA) 08-4219 

___TIP 6* BKD131 ___QG for Clinicians QGCT39 

___QG for Clinicians QGCT06 ___TIP 29 (SMA) 08-4078 ___QG for Administrators QGAT39 

___KK for Clinicians KAPT06 ___QG for Clinicians QGCT29 

___QG for Administrators ___TIP 40 (SMA) 07-3939 

___TIP 11* BKD143 (SMA) 08-3592 ___QG for Physicians QGPT40 

___QG for Clinicians QGCT11 ___KK for Clinicians KAPT29 ___KK for Physicians KAPT40 

___KK for Clinicians KAPT11 

___TIP 30 (SMA) 08-3920 ___TIP 41 BKD507 

___TIP 13 BKD161 ___QG for Clinicians QGCT30 ___QG for Clinicians QGCT41 

___QG for Clinicians QGCT13 ___KK for Clinicians KAPT30 

___QG for Administrators QGAT13 ___TIP 42 (SMA) 08-3992 

___KK for Clinicians KAPT13 ___TIP 31 (SMA) 08-4079 ___Inservice Training (SMA) 08-4262 

___QG for Clinicians (SMA) 07-4034 

___TIP 14 BKD162 ___TIP 32 (SMA) 08-4080 ___QG for Administrators QGAT42 

___QG for Clinicians QGC312 ___KK for Clinicians KAPT42 

___TIP 16 BKD164 ___KK for Clinicians KAPT312 

___QG for Clinicians QGCT16 ___TIP 43 (SMA) 08-4214

___KK for Clinicians KAPT16 ___TIP 33 BKD289 ___Inservice Training (SMA) 08-4341 

___QG for Clinicians QGCT33 ___QG for Clinicians QGCT43 

___TIP 18 BKD173 ___KK for Clinicians KAPT33 ___KK for Clinicians (SMA) 07-4108 

___QG for Clinicians QGCT18 

___KK for Clinicians KAPT18 ___TIP 34 (SMA) 07-3952 ___TIP 44 BKD526 

___QG for Clinicians QGCT34 ___Alcohol & Drug Treatment 

___TIP 21 (SMA) 08-4073 ___KK for Clinicians KAPT34 (SMA) 07-4292

___QG for Clinicians & Administrators ___Alcohol & Drug Treatment (Spanish)

QGCA21 ___TIP 35 (SMA) 08-4212 (SMA) 08-4320 

___Faces (SMA) 08-4174 ___QG for Clinicians QGCT44 

___TIP 23 (SMA) 08-3917 ___Inservice Training (SMA) 08-4190 ___KK for Clinicians (SMA) 07-4150 

___QG for Administrators QGAT23 ___QG for Clinicians QGCT35 

___KK for Clinicians KAPT35 ___TIP 45 (SMA) 08-4131 

___TIP 24 (SMA) 08-4075 ___Inservice Training (SMA) 08-4331 

___Desk Reference (SMA) 08-3740 ___TIP 36 (SMA) 08-3923 ___QG for Clinicians (SMA) 06-4225 

___QG for Clinicians QGCT24 ___Brochure for Women ___QG for Administrators (SMA) 06-

___KK for Clinicians KAPT24 (SMA) 08-4132 4226 

___Brochure for Women (Spanish) ___KK for Clinicians (SMA) 06-4224 

___TIP 25 (SMA) 08-4076 PHD981S 

___Guide for Treatment Providers ___Brochure for Men ___TIP 46 BKD545 

MS668 (SMA) 07-4134 ___QG for Administrators (SMA) 07-

___Guide for Administrators MS667 ___Brochure for Men (Spanish) 4232 

___QG for Clinicians QGCT25 PHD1059S 

___KK for Clinicians KAPT25 ___QG for Clinicians QGCT36 ___TIP 47 BKD551 

___KK for Clinicians KAPT36 ___QG for Clinicians (SMA) 07-4233 

___TIP 26 (SMA) 08-3918 ___KK for Clinicians (SMA) 07-4251 

___Guide for Treatment Providers ___TIP 37 (SMA) 08-4137 

 MS669 ___Your Client At Risk MS965 ___TIP 48 (SMA) 08-4353 

___Guide for Social Service Providers ___Drugs, Alcohol & HIV/AIDS 

 MS670 (SMA) 08-4127 ___TIP 49 (SMA) 09-4380 

___Physician’s Guide MS671 ___Drugs, Alcohol & HIV/AIDS 

___Good Mental Health PHD881 (Spanish) (SMA) 08-4181 ___TIP 50 (SMA) 09-4381 

___Good Mental Health (SMA) 08-3897 –––Drugs, Alcohol & HIV/AIDS for 

(Spanish) African Americans (SMA) 07-4248 

___Aging, Medicine (SMA) 08-3169 ___QG for Clinicians QGCT37 

___Aging, Medicine (SMA) 08-3898 ___KK for Clinicians KAPT37 

(Spanish) 

___QG for Clinicians QGCT26 *Under revision 

___KK for Clinicians KAPT26 †QG = Quick Guide; KK = KAP Keys 

Name: ______________________________________________ Address:_________________________________________________ 

City, State, Zip: ____________________________________ Phone and e-mail: _______________________________________ 

You can either mail this form or fax it to (240) 221-4292. Publications also can be ordered by calling SAMHSA’s Health 

Information Network at 877-SAMHSA-7 (877-726-4727) (English and Español) or by visiting http://www.samhsa.gov/shin. 

TIPs can also be accessed on line at http://www.kap.samhsa.gov. 
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SAMHSA’s Health Information Network 

P.O. Box 2345
 

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Incorporating Alcohol 


Pharmacotherapies
 

Into Medical Practice
 

TIP 49, Incorporating Alcohol Pharmacotherapies Into Medical 

Practice, provides clinical guidelines for the proper use of medications 

in the treatment of alcohol use disorders. The underlying objective 

is to expand access to information about the effective use of these 

medications, not only in specialty substance abuse treatment programs but also in physicians’ offices and other general medical care 

settings. The TIP includes discussions of acamprosate, disulfiram, oral 

naltrexone, and extended-release injectable naltrexone. The U.S. Food 

and Drug Administration has approved these medications for treating 

alcohol use disorders. The TIP explains each medication’s history, the 

reasons for its use, how to use it, who should use it, and other clinical 

information about the medication. 

Most of the fundamental research that forms the evidence basis for 

this TIP is not provided in the TIP itself. Those who wish to review the 

supporting research can access a full bibliography, an annotated bibliography of select references, and a literature review via the Internet 

at http://www.kap.samhsa.gov. The online bibliography and literature 

review are updated every 6 months for 5 years after publication of 

the TIP. 

HHS Publication No. (SMA) 09-4380
 

Printed 2009
 

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
 

Substance Abuse and Mental Health Services Administration
 

Center for Substance Abuse Treatment