Topiramate for treating alcohol dependence: a randomized controlled trial.
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.
Johnson
Bankole A
BA
Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, Charlottesville, VA 22908, USA. bankolejohnson@virginia.edu
Rosenthal
Norman
N
Capece
Julie A
JA
Wiegand
Frank
F
Mao
Lian
L
Beyers
Karen
K
McKay
Amy
A
Ait-Daoud
Nassima
N
Anton
Raymond F
RF
Ciraulo
Domenic A
DA
Kranzler
Henry R
HR
Mann
Karl
K
O'Malley
Stephanie S
SS
Swift
Robert M
RM
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
D018691:Excitatory Amino Acid Antagonists; D018757:GABA Modulators; D000077236:Topiramate; D005632:Fructose