title: Topiramate for the treatment of cocaine addiction: a randomized clinical trial.
abstract: OBJECTIVE
  No medication has been established as an efficacious treatment for cocaine dependence. We hypothesized that dual modulation of the mesocorticolimbic dopamine system by topiramate-a glutamate receptor antagonist and γ-aminobutyric acid receptor agonist-would result in efficacious treatment for cocaine dependence compared with placebo.
  
  
  OBJECTIVE
  To determine the efficacy of topiramate vs placebo as a treatment for cocaine dependence.
  
  
  METHODS
  Double-blind, randomized, placebo-controlled, 12-week trial of 142 cocaine-dependent adults in clinical research facilities at the University of Virginia between November 22, 2005, and July 25, 2011.
  
  
  METHODS
  Topiramate (n = 71) or placebo (n = 71) in escalating doses from 50 mg/d to the target maintenance dose of 300 mg/d in weeks 6 to 12, combined with weekly cognitive-behavioral treatment.
  
  
  METHODS
  For the efficacy period, weeks 6 to 12, the primary outcome was the weekly difference from baseline in the proportion of cocaine nonuse days; the secondary outcome was urinary cocaine-free weeks, and exploratory outcomes included craving and self- and observer-rated global functioning on the Clinical Global Impression scales.
  
  
  RESULTS
  Using an intent-to-treat analysis, topiramate was more efficacious than placebo at increasing the weekly proportion of cocaine nonuse days, irrespective of whether missing data were not or were imputed conservatively to the baseline value (13.3% vs 5.3%, 95% CI for the estimated mean difference, 1.4%-14.6%, P = .02 or 8.9% vs 3.7%, 95% CI for the estimated mean difference, 0.2%-10.1%, P = .04, respectively). Topiramate also was associated, significantly more than placebo, with increasing the likelihood of urinary cocaine-free weeks (16.6% vs 5.8%; odds ratio, 3.21; 95% CI, 1.24-8.32; P = .02), as well as decreasing craving and improving observer-rated global functioning (all P < .05).
  
  
  CONCLUSIONS
  Topiramate is more efficacious than placebo at increasing the mean weekly proportion of cocaine nonuse days and associated measures of clinical improvement among cocaine-dependent individuals.
authors.affiliation: Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, Charlottesville2now with Department of Psychiatry, University of Maryland School of Medicine, Baltimore.
authors.forename: Bankole A
authors.initials: BA
authors.lastname: Johnson
authors.forename: Nassima
authors.initials: N
authors.lastname: Ait-Daoud
authors.forename: Xin-Qun
authors.initials: XQ
authors.lastname: Wang
authors.forename: J Kim
authors.initials: JK
authors.lastname: Penberthy
authors.forename: Martin A
authors.initials: MA
authors.lastname: Javors
authors.forename: Chamindi
authors.initials: C
authors.lastname: Seneviratne
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
mesh_terms: D000328:Adult; D000927:Anticonvulsants / Q000008:administration & dosage / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000188:drug therapy* / Q000523:psychology / Q000652:urine; D015928:Cognitive Behavioral Therapy / Q000379:methods; D003131:Combined Modality Therapy; D004311:Double-Blind Method; D005260:Female; D005632:Fructose / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011569:Psychiatric Status Rating Scales; D012720:Severity of Illness Index; D013997:Time Factors; D000077236:Topiramate; D016896:Treatment Outcome
chemical_list: D000927:Anticonvulsants; D010919:Placebos; D000077236:Topiramate; D005632:Fructose