A pilot trial of topiramate for the treatment of cocaine dependence.
BACKGROUND
Both GABAergic and glutamatergic neurons appear to be important modulators of the brain reward system and medications that affect GABA and glutamatergic neurotransmission may reduce the rewarding properties of cocaine and reduce cocaine craving. Topiramate, an anticonvulsant, raises cerebral GABA levels, facilitates GABAergic neurotransmission and inhibits glutametergic activity at AMPA/kainite receptors. Thus, it may be useful for treating cocaine dependence.


METHODS
The efficacy of topiramate for cocaine dependence was tested in a 13-week, double-blind, placebo-controlled pilot trial (n = 40). Topiramate was titrated gradually over 8 weeks to a dose of 200 mg daily. The primary outcome measure was cocaine abstinence verified by twice weekly urine benzoylecgonine tests (UBT).


RESULTS
Eighty-two percent of subjects completed the trial. Analysis of the UBT using a GEE model showed that after week 8, when the dose titration was completed, topiramate-treated subjects were more likely to be abstinent from cocaine compared to placebo-treated subjects (Z = 2.67, P = 0.01). Topiramate-treated subjects were also more likely to attain 3 weeks of continuous abstinence from cocaine (chi2 = 3.9, d.f. = 1, P = 0.05).


CONCLUSIONS
Topiramate may be effective for the treatment of cocaine dependence.
Department of Psychiatry, University of Pennsylvania School of Medicine, 3900 Chestnut Street, Philadelphia, PA 19104, USA. kampman_k@mail.trc.upenn.edu
Kyle M
KM
Kampman
Helen
H
Pettinati
Kevin G
KG
Lynch
Charles
C
Dackis
Thorne
T
Sparkman
Catherine
C
Weigley
Charles P
CP
O'Brien
D000293:Adolescent; D000328:Adult; D016009:Chi-Square Distribution; D003042:Cocaine / Q000652:urine; D019970:Cocaine-Related Disorders / Q000188:drug therapy* / Q000523:psychology / Q000652:urine; D004311:Double-Blind Method; D005260:Female; D005632:Fructose / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D000077236:Topiramate
D000077236:Topiramate; D005632:Fructose; D003042:Cocaine