Topiramate for Treating Alcohol Dependence<SUBTITLE>A Randomized Controlled Trial</SUBTITLE>

ContextHypothetically, topiramate can improve drinking outcomes among alcohol-dependent individuals by reducing alcohol&#39;s reinforcing effects through facilitation of γ-aminobutyric acid function and inhibition of glutaminergic pathways in the corticomesolimbic system.ObjectiveTo determine if topiramate is a safe and efficacious treatment for alcohol dependence.Design, Setting, and ParticipantsDouble-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.InterventionsUp to 300 mg/d of topiramate (n = 183) or placebo (n = 188), along with a weekly compliance enhancement intervention.Main Outcome MeasuresPrimary 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 γ-glutamyltransferase).ResultsTreating 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