Pharmacotherapy for Alcohol Dependence

West SL, Garbutt JC, Carey TS, et al. Pharmacotherapy for alcohol dependence. Evidence report number 3. (Contract 290-97-0011 to Research Triangle Institute, University of North Carolina, Chapel Hill). AHCPR publication no. 99-E004. Rockville, MD: Agency for Health Care Policy and Research; January 1999.




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The pharmacotherapy of alcohol dependence was selected for review because of its timeliness, the severity and impact of the disease, and the need for careful evaluation of new therapeutic modalities for alcoholism. Alcoholism is a prevalent disease that will affect on the order of 10 percent of the adult population of the United States. An estimated 100,000 Americans die each year secondary to alcohol-related disease or injury. The serious financial and nonfinancial impact of this disease extends to family members and society in general. Its annual dollar cost to the Nation has been estimated to exceed $166 billion (as of 1995).

Alcoholism affects all segments of society and all ethnic groups. It is more common in men than women, but many women also suffer from alcoholism. Treatments for alcoholism and their outcomes are quite variable. Because so many individuals relapse rapidly after completing treatment, the need is great to identify a wider variety of more effective alcoholism treatments. The objective of this report was to review the efficacy of five major categories of pharmacotherapies that have historically been used for or recently identified as enhancing the treatment of patients with alcoholism. To achieve this objective, the project team conducted a systematic and unbiased review of the literature, graded the evidence as a whole, completed a synthesis of this review, and provided suggestions for future research.

Search Strategy

A detailed search of the literature was conducted using the following databases: MEDLINE┬«, HealthSTAR, the American Society of Health-System Pharmacists’ International Pharmaceutical Abstracts database, EMBASE, Alcohol and Alcohol Problems Database, and PsycINFO┬«. The Medical Subject Headings (MeSH) used for the search included the key therapies (disulfiram, the opiate antagonists [naltrexone and nalmefene], acamprosate, serotonergic agents such as ondansetron, buspirone, and the selective serotonin reuptake inhibitors [SSRIs], and lithium), alcoholism, alcohol drinking, study characteristics, and study design. The project librarian defined study characteristics and study design before using them in the search. An extensive gray literature search also was conducted to identify symposia proceedings, industry reports, and unpublished documents that contained efficacy data.

Selection Criteria

Inclusion criteria were: studies published from 1966 through November 1997 in English, French, or German; studies on adults 18 years of age or older with alcohol dependence; studies with sample sizes of 10 or more subjects; and studies with a control group for comparison. Reviews, letters to the editor, and studies that did not address the efficacy of the key therapies were excluded.

Data Collection and Analysis

Four separate data collection forms were developed and pretested: the primary Data Extraction Form with attached Quality Rating Score; the Followup Results Form; the Comorbid Study Results Form; and the Adverse Events Form. An Extraction Guide was developed for use during the formal training session to ensure consistency of abstraction among the abstractors/reviewers. Each article was dually reviewed and graded; a third conflict-resolution review was also conducted. After the evidence tables were developed, the literature was graded using an adjudication procedure to arrive at two separate scores, one for the efficacy data and the other for harms data.

Main Results

Our systematic and comprehensive review of the literature coupled with evaluation of the quality of the evidence reveals the following:

Disulfiram has been widely used as a deterrent for relapse, but the evidence for its efficacy in treating alcohol dependence is mixed. Although disulfiram appears to reduce drinking days in alcohol-dependent subjects, there is only minimal evidence that it enhances abstinence. Data on disulfiram implants and supervised disulfiram administration are limited. The blinded design of disulfiram efficacy trials has made their interpretation more complex; disulfiram’s psychological deterrent effect is present in both treatment groups. Thus, medication compliance is an important predictor of treatment outcome.

There is good evidence that naltrexone reduces relapse rates and frequency and quantity of drinking in alcohol-dependent individuals and may decrease craving and enhance abstinence. The quality of the naltrexone studies is good, although the total sample size across all trials is modest.

There is good evidence that acamprosate enhances abstinence and reduces drinking rates in alcoholism. Although the trials are limited to European populations, they involved more than 2,000 patients.

The evidence is insufficient to evaluate the efficacy of SSRIs, buspirone, or ondansetron in the treatment of primary alcoholism or alcoholism complicated by comorbid mood and anxiety disorders. The limited evidence available to date indicates that these agents are not efficacious for the treatment of primary alcohol dependence.

There is ample evidence that lithium is not effective for the treatment of primary alcoholism based on data from one well-designed, large controlled trial.

Future studies of the pharmacotherapy of alcoholism should use standard outcome definitions and methods, control for comorbidity, and describe and control for psychosocial interventions.


Pharmacotherapy is emerging as an important component of treatment for people with alcohol dependence. Two relatively new medications, naltrexone and acamprosate, show good evidence of being superior to placebo in the treatment of alcoholism. Disulfiram is less clearly superior to placebo than are naltrexone or acamprosate, although positive effects are found. To date, serotonergic agents have not been demonstrated to show efficacy in treating alcohol-dependent patients who do not have depression or anxiety.

Even when depressive and anxiety disorders are present, the efficacy of serotonergic agents in treating alcoholism is not established. Lithium does not show efficacy for the treatment of alcoholism. Additional work is needed to extend these findings and to investigate new agents in an effort to improve the treatment of and outcomes for people with alcohol dependence.