title: Topiramate for treating alcohol dependence: a randomized controlled trial.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  Up to 300 mg/d of topiramate (n = 183) or placebo (n = 188), along with a weekly compliance enhancement intervention.
  
  
  METHODS
  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%).
  
  
  CONCLUSIONS
  Topiramate is a promising treatment for alcohol dependence.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00210925.
authors.affiliation: Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, Charlottesville, VA 22908, USA. bankolejohnson@virginia.edu
authors.forename: Bankole A
authors.initials: BA
authors.lastname: Johnson
authors.forename: Norman
authors.initials: N
authors.lastname: Rosenthal
authors.forename: Julie A
authors.initials: JA
authors.lastname: Capece
authors.forename: Frank
authors.initials: F
authors.lastname: Wiegand
authors.forename: Lian
authors.initials: L
authors.lastname: Mao
authors.forename: Karen
authors.initials: K
authors.lastname: Beyers
authors.forename: Amy
authors.initials: A
authors.lastname: McKay
authors.forename: Nassima
authors.initials: N
authors.lastname: Ait-Daoud
authors.forename: Raymond F
authors.initials: RF
authors.lastname: Anton
authors.forename: Domenic A
authors.initials: DA
authors.lastname: Ciraulo
authors.forename: Henry R
authors.initials: HR
authors.lastname: Kranzler
authors.forename: Karl
authors.initials: K
authors.lastname: Mann
authors.forename: Stephanie S
authors.initials: SS
authors.lastname: O'Malley
authors.forename: Robert M
authors.initials: RM
authors.lastname: Swift
mesh_terms: D000328:Adult; D000437:Alcoholism / Q000188:drug therapy*; D001521:Behavior Therapy; D004311:Double-Blind Method; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D005632:Fructose / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018757:GABA Modulators / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D000077236:Topiramate
chemical_list: D018691:Excitatory Amino Acid Antagonists; D018757:GABA Modulators; D000077236:Topiramate; D005632:Fructose