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Cited by 444Substance Abuse Treatment and OutcomesAlcohol Consumption and Health EffectsAlcoholism and Thiamine Deficiency

Pharmacological Treatment of Alcohol Dependence: A Review of the Evidence

Garbutt, James C., West, Suzanne L., Carey, Timothy S., Lohr, Kathleen N., Crews, Fulton T.·1999·JAMA
DOI 10.1001/jama.281.14.1318
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Abstract

CONTEXT: Alcoholism affects approximately 10% of Americans at some time in their lives. Treatment consists of psychosocial interventions, pharmacological interventions, or both, but which drugs are most effective at enhancing abstinence and preventing relapse has not been systematically reviewed. OBJECTIVE: To evaluate the efficacy of 5 categories of drugs used to treat alcohol dependence--disulfiram, the opioid antagonists naltrexone and nalmefene, acamprosate, various serotonergic agents (including selective serotonergic reuptake inhibitors), and lithium. DATA SOURCES: Reports of randomized controlled trials, nonrandomized trials, and other study designs in English, French, and German identified from multiple searches of MEDLINE, EMBASE, and specialized databases; hand searching bibliographies of review articles; searches for unpublished literature; and discussions with investigators in the field. STUDY SELECTION: We included all studies on alcohol-dependent human subjects aged 18 years or older from all inpatient and outpatient settings between 1966 and December 1997 that met our inclusion criteria. DATA EXTRACTION: We abstracted the following information: study design and blinding, diagnostic instrument and severity assessment, drug interventions and cointerventions, demographic and comorbidity details about patients, compliance, and numerous outcome measures (eg, relapse, return to drinking, drinking or nondrinking days, time to first drink, alcohol consumed per unit of time, craving). We graded quality of the individual articles (scale, 0-100) independently from the strength of evidence for each drug class (A, strong and consistent evidence of efficacy in studies of large size and/or high quality; B, mixed evidence of efficacy; C, evidence of lack of efficacy; and I, insufficient evidence). DATA SYNTHESIS: Of 375 articles evaluated, we abstracted and analyzed data from 41 studies and 11 follow-up or subgroup studies. Naltrexone (grade A) reduces the risk of relapse to heavy drinking and the frequency of drinking compared with placebo but does not substantially enhance abstinence, ie, avoidance of any alcohol consumption. Acamprosate (grade A, from large-scale studies in Europe) reduces drinking frequency, although its effects on enhancing abstinence or reducing time to first drink are less clear. Controlled studies of disulfiram (grade B) reveal a mixed outcome pattern--some evidence that drinking frequency is reduced but minimal evidence to support improved continuous abstinence rates. The limited data on serotonergic agents were not very promising (grade I), although most studies were confounded by high rates of comorbid mood disorders. Lithium lacks efficacy (grade C) in the treatment of primary alcohol dependence. CONCLUSIONS: Recent reports documenting that naltrexone and acamprosate are more effective than placebo in the treatment of alcoholism justify clinical interest in use of these medications for alcohol-dependent patients. Use of disulfiram is widespread but less clearly supported by the clinical trial evidence; however, targeted studies on supervised administration of disulfiram may be warranted. Use of existing serotonergic agents or lithium for patients with primary alcohol dependence does not appear to be supported by the efficacy data available at this time; these medications may still have a positive effect in patients with coexisting psychiatric disorders.

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  • Altering euphoric and pleasurable effects of alcohol is hypothesized to underlie in part the efficacy of opioid receptor antagonists, including naltrexone and nalmefene.

    “The findings may have relevance to medication development, as altering euphoric and pleasurable effects of alcohol would be important targets for novel treatments and are hypothesized to underlie in part the efficacy of opioid receptor antagonists, including naltrexone and nalmefene(67–76).”

    From A Prospective 5-Year Re-examination of Alcohol Response in Heavy Drinkers Progressing in Alcohol Use Disorder (2016) · cites this paper as [69]

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Authors
Garbutt, J. C., West, S. L., Carey, T. S., Lohr, K. N., & Crews, F. T.
Affiliations
  • University of North Carolina at Chapel Hill (US)
  • RTI International (US)
ORCID
Venue
JAMA
Publisher
American Medical Association (AMA)
Published
1999-04-14
Volume
281
Issue
14
Pages
1318
ISSN
  • 0002-9955 (ISSN-L)
  • 0098-7484
DOI
10.1001/jama.281.14.1318
OpenAlex
W2082518171
Cited by
444
References
43
Citations by year
2025: 3 · 2024: 3 · 2023: 4 · 2022: 6 · 2021: 3 · 2020: 11 · 2019: 13 · 2018: 12 · 2017: 13 · 2016: 11 · 2015: 17 · 2014: 13 · 2013: 15 · 2012: 19
FWCI
21.16
Type
journal article
Language
en
Open access
closed
Locations
  • JAMA (publishedVersion)
  • PubMed (publishedVersion)
Funders
U.S. Public Health Service (290-97-0011)
Topics
  • Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
  • Health Sciences › Medicine › Neurology › Alcoholism and Thiamine Deficiency
Keywords
alcoholism, pharmacotherapy, disulfiram, naltrexone, nalmefene, acamprosate, selective serotonin reuptake inhibitors, lithium, relapse prevention, abstinence, drinking frequency, craving, treatment efficacy, quality of evidence grading, psychosocial interventions
MeSH terms
Acamprosate, Adult, Alcohol Deterrents, Alcoholism, Disulfiram, Humans, Lithium, Naltrexone, Narcotic Antagonists, Taurine, Serotonin Agents

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