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A Randomized Controlled Trial

Bankole A. Johnson, DSc, MD, PhD; Norman Rosenthal, MD; Julie A. Capece, BA; Frank Wiegand, MD; Lian Mao, PhD; Karen Beyers, MS; Amy McKay, PharmD; Nassima Ait-Daoud, MD; Raymond F. Anton, MD; Domenic A. Ciraulo, MD; Henry R. Kranzler, MD; Karl Mann, MD; Stephanie S. O’Malley, PhD; Robert M. Swift, MD, PhD; for the Topiramate for Alcoholism Advisory Board and the Topiramate for Alcoholism Study Group

JAMA. 2007;298:1641-1651.

Context  Hypothetically, topiramate can improve drinking outcomes among alcohol-dependent individuals by reducing alcohol's reinforcing effects through facilitation of -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 -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: NCT00210925

Author Affiliations: Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, Charlottesville (Drs Johnson and Ait-Daoud); Ortho-McNeil Janssen Scientific Affairs LLC, Raritan, New Jersey (Drs Rosenthal, Wiegand, Mao, and McKay and Mss Capece and Beyers); Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston (Dr Anton); Division of Psychiatry, Boston University, Boston, Massachusetts (Dr Ciraulo); Department of Psychiatry, University of Connecticut, Farmington (Dr Kranzler); Department of Addictive Behavior and Addiction Medicine, University of Heidelberg, Mannheim, Germany (Dr Mann); Department of Psychiatry, Yale University, New Haven, Connecticut (Dr O’Malley); and Department of Psychiatry and Human Behavior, Brown University, Providence, Rhode Island (Dr Swift).

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