Oral topiramate for treatment of alcohol dependence: a randomised controlled trial.
BACKGROUND
Topiramate, a sulphamate fructopyranose derivative, might antagonise alcohol's rewarding effects associated with abuse liability by inhibiting mesocorticolimbic dopamine release via the contemporaneous facilitation of gamma-amino-butyric acid activity and inhibition of glutamate function. We aimed to see whether topiramate was more effective than placebo as a treatment for alcohol dependence.


METHODS
We did a double-blind randomised controlled 12-week clinical trial comparing oral topiramate and placebo for treatment of 150 individuals with alcohol dependence. Of these 150 individuals, 75 were assigned to receive topiramate (escalating dose of 25-300 mg per day) and 75 had placebo as an adjunct to weekly standardised medication compliance management. Primary efficacy variables were: self-reported drinking (drinks per day, drinks per drinking day, percentage of heavy drinking days, percentage of days abstinent) and plasma gamma-glutamyl transferase, an objective index of alcohol consumption. The secondary efficacy variable was self-reported craving.


RESULTS
At study end, participants on topiramate, compared with those on placebo, had 2.88 (95% CI -4.50 to -1.27) fewer drinks per day (p=0.0006), 3.10 (-4.88 to -1.31) fewer drinks per drinking day (p=0.0009), 27.6% fewer heavy drinking days (p=0.0003), 26.2% more days abstinent (p=0.0003), and a log plasma gamma-glutamyl transferase ratio of 0.07 (-0.11 to -0.02) less (p=0.0046). Topiramate-induced differences in craving were also significantly greater than those of placebo, of similar magnitude to the self-reported drinking changes, and highly correlated with them.


CONCLUSIONS
Topiramate (up to 300 mg per day) is more efficacious than placebo as an adjunct to standardised medication compliance management in treatment of alcohol dependence.
Johnson
Bankole A
BA
Department of Psychiatry, University of Texas Health Science Center at San Antonio, TX 78229-3900, USA. bjohnson@uthscsa.edu <bjohnson@uthscsa.edu>
Ait-Daoud
Nassima
N
Bowden
Charles L
CL
DiClemente
Carlo C
CC
Roache
John D
JD
Lawson
Kevin
K
Javors
Martin A
MA
Ma
Jennie Z
JZ
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000428:Alcohol Drinking / Q000517:prevention & control; D000437:Alcoholism / Q000097:blood / Q000188:drug therapy*; D018492:Dopamine Antagonists / Q000008:administration & dosage*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005632:Fructose / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015813:Substance Abuse Detection; D000077236:Topiramate; D005723:gamma-Glutamyltransferase / Q000097:blood
D018492:Dopamine Antagonists; D000077236:Topiramate; D005632:Fructose; D005723:gamma-Glutamyltransferase