Pharmacotherapy for Alcohol Use Disorder: A Systematic Review and Meta-Analysis

Abstract

Importance: Alcohol use disorder affects more than 28.3 million people in the United States and is associated with increased rates of morbidity and mortality.

Objective: To compare efficacy and comparative efficacy of therapies for alcohol use disorder.

Data sources: PubMed, the Cochrane Library, the Cochrane Central Trials Registry, PsycINFO, CINAHL, and EMBASE were searched from November 2012 to September 9, 2022 Literature was subsequently systematically monitored to identify relevant articles up to August 14, 2023, and the PubMed search was updated on August 14, 2023.

Study selection: For efficacy outcomes, randomized clinical trials of at least 12 weeks' duration were included. For adverse effects, randomized clinical trials and prospective cohort studies that compared drug therapies and reported health outcomes or harms were included.

Data extraction and synthesis: Two reviewers evaluated each study, assessed risk of bias, and graded strength of evidence. Meta-analyses used random-effects models. Numbers needed to treat were calculated for medications with at least moderate strength of evidence for benefit.

Main outcomes and measures: The primary outcome was alcohol consumption. Secondary outcomes were motor vehicle crashes, injuries, quality of life, function, mortality, and harms.

Results: Data from 118 clinical trials and 20 976 participants were included. The numbers needed to treat to prevent 1 person from returning to any drinking were 11 (95% CI, 1-32) for acamprosate and 18 (95% CI, 4-32) for oral naltrexone at a dose of 50 mg/d. Compared with placebo, oral naltrexone (50 mg/d) was associated with lower rates of return to heavy drinking, with a number needed to treat of 11 (95% CI, 5-41). Injectable naltrexone was associated with fewer drinking days over the 30-day treatment period (weighted mean difference, -4.99 days; 95% CI, -9.49 to -0.49 days) Adverse effects included higher gastrointestinal distress for acamprosate (diarrhea: risk ratio, 1.58; 95% CI, 1.27-1.97) and naltrexone (nausea: risk ratio, 1.73; 95% CI, 1.51-1.98; vomiting: risk ratio, 1.53; 95% CI, 1.23-1.91) compared with placebo.

Conclusions and relevance: In conjunction with psychosocial interventions, these findings support the use of oral naltrexone at 50 mg/d and acamprosate as first-line pharmacotherapies for alcohol use disorder.

Figure 1.. Study Identification and Review for Medications Used in the Treatment of Alcohol Use Disorder

Figure 2.. Return to Any Drinking, Acamprosate vs Placebo

Figure 3.. Return to Any Drinking, Disulfiram vs Placebo

Multiple comparisons within publications are presented separately.

Figure 4.. Return to Any Drinking, Naltrexone vs Placebo

“Overall” refers to pooled estimate for all forms of naltrexone (50 mg/d oral, 100 mg/d oral, and injection).

Figure 5.. Return to Heavy Drinking, Acamprosate vs Placebo

Heavy drinking is defined as ≥4 drinks/d for women and ≥5 drinks/d for men. Multiple comparisons within publications are presented separately.

Figure 6.. Return to Heavy Drinking, Naltrexone vs Placebo

“Overall” refers to pooled estimate for all forms of naltrexone (50 mg/d oral, 100 mg/d oral, and injection). Heavy drinking is defined as ≥4 drinks/d for women and ≥5 drinks/d for men.

Figure 7.. Summary of Strength-of-Evidence Assessments for Harms Outcomes

IE indicates insufficient evidence; NA, not assessed. This figure includes all drugs with a rating of at least low strength of evidence for adverse events for at least 1 outcome. All doses of naltrexone were assessed together.