Topiramate for the treatment of cocaine addiction

Bankole A. Johnson, Nassima Ait-Daoud, Xin Qun Wang, J. Kim Penberthy, Martin A. Javors, Chamindi Seneviratne, Lei Liu

Research output: Contribution to journalArticlepeer-review

98 Scopus citations


IMPORTANCE: 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. DESIGN, SETTING, AND PARTICIPANTS: 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. INTERVENTIONS: 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. MAIN OUTCOMESAND MEASURES: 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 AND RELEVANCE: 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. TRIAL REGISTRATION Identifier: NCT00249691.

Original languageEnglish
Pages (from-to)1338-1346
Number of pages9
JournalJAMA psychiatry
Issue number12
StatePublished - Dec 2013


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