Topiramate for Treating Alcohol Dependence: A Randomized Controlled Trial.
JAMA, 298(14), 1641--1651.
Keywords: alcohol dependence, alcohol use disorders, pharmacotherapy, randomized controlled trials, rct, and topiramate
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. Objective To
determine if topiramate is a safe and efficacious treatment for alcohol
dependence. Design, Setting, and Participants 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. Interventions Up to 300 mg/d
of topiramate (n = 183) or placebo (n = 188), along with a weekly
compliance enhancement intervention. Main Outcome Measures 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). Results 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%). Conclusion Topiramate is a promising treatment for
alcohol dependence. Trial Registration clinicaltrials.gov Identifier: