Abstract
BACKGROUND: It is unknown whether women derive comparable benefits and have a similar safety and tolerability profile as men from acamprosate, a widely prescribed drug for the maintenance of abstinence in alcohol dependence. The objective of this study was to assess sex-specific differences in the efficacy, safety, and tolerability of acamprosate in the treatment of women and men with alcohol dependence. METHODS: A sex-specific meta-analysis was conducted based on individual patient data (IPD). Data were obtained from double-blind, randomized controlled trials with quantitative drinking measures in patients with alcohol dependence receiving oral acamprosate or placebo. Sources included PubMed, PsychInfo, and Cochrane electronic databases; reference lists from retrieved articles and presentations at professional meetings; and direct access to authors and companies who provided IPD. RESULTS: Individual records were obtained from 1,317 women and 4,794 men who participated in 22 eligible studies conducted in 18 countries. IPD meta-analyses found a significant beneficial effect of acamprosate relative to placebo across all 4 efficacy end points: an incremental gain of 10.4% (95% CI 7.1 to 13.7, p < 0.001) in percentage of abstinent days, an incremental gain of 11.0% (7.4 to 14.6, p < 0.001) in percentage of no heavy drinking days, an odds ratio of 1.9 (1.6 to 2.2, p < 0.001) for rate of complete abstinence, and an odds ratio of 1.9 (1.6 to 2.3, p < 0.001) for rate of no heavy drinking, over the study duration. Acamprosate was also associated with significantly higher rates of treatment completion (p = 0.004) and medication compliance (p < 0.001) than placebo. Men and women did not differ on any measure of acamprosate efficacy, safety, or tolerability. CONCLUSIONS: This sex-specific IPD meta-analysis provides evidence that acamprosate has a significant effect compared with placebo in improving rates of abstinence and no heavy drinking in both women and men with alcohol dependence. Further, acamprosate was associated with significantly higher rates of treatment completion and medication compliance than placebo among both women and men and had a comparable safety and tolerability profile.