Topiramate for treating alcohol dependence: a randomized controlled trial.

Abstract

Hypothetically, topiramate can improve drinking outcomes among alcohol-dependent individuals by reducing alcohol's reinforcing effects through facilitation of gamma-aminobutyric acid function and inhibition of glutaminergic pathways in the corticomesolimbic system. To determine if topiramate is a safe and efficacious treatment for alcohol dependence. Double-blind, randomized, placebo-controlled, 14-week trial of 371 men and women aged 18 to 65 years diagnosed with alcohol dependence, conducted between January 27, 2004, and August 4, 2006, at 17 US sites. Up to 300 mg/d of topiramate (n = 183) or placebo (n = 188), along with a weekly compliance enhancement intervention. Primary efficacy variable was self-reported percentage of heavy drinking days. Secondary outcomes included other self-reported drinking measures (percentage of days abstinent and drinks per drinking day) along with the laboratory measure of alcohol consumption (plasma gamma-glutamyltransferase). Treating all dropouts as relapse to baseline, topiramate was more efficacious than placebo at reducing the percentage of heavy drinking days from baseline to week 14 (mean difference, 8.44%; 95% confidence interval, 3.07%-13.80%; P = .002). Prespecified mixed-model analysis also showed that topiramate compared with placebo decreased the percentage of heavy drinking days (mean difference, 16.19%; 95% confidence interval, 10.79%-21.60%; P < .001) and all other drinking outcomes (P < .001 for all comparisons). Adverse events that were more common with topiramate vs placebo, respectively, included paresthesia (50.8% vs 10.6%), taste perversion (23.0% vs 4.8%), anorexia (19.7% vs 6.9%), and difficulty with concentration (14.8% vs 3.2%). Topiramate is a promising treatment for alcohol dependence. clinicaltrials.gov Identifier: NCT00210925.