A Multisite, Double-blind, Placebo-Controlled Clinical Trial to Evaluate the Safety and Efficacy of Vigabatrin for Treating Cocaine Dependence | Clinical Pharmacy and Pharmacology | JAMA Psychiatry | JAMA Network
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Original Article
June 2013

A Multisite, Double-blind, Placebo-Controlled Clinical Trial to Evaluate the Safety and Efficacy of Vigabatrin for Treating Cocaine Dependence

Author Affiliations

Author Affiliations: Department of Veterans Affairs Medical Center (Dr E. C. Somoza) and Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, and Cincinnati Addiction Research Center (Drs E. C. Somoza and Winhusen, Mr Lewis, and Ms P. Somoza), Cincinnati, Ohio; Catalyst Pharmaceutical Partners, Inc, Coral Gables (Mr Winship and Drs Gorodetzky and Miller), and Operation PAR, Inc, Largo (Dr Sheehan), Florida; Division of Psychiatry, Boston University School of Medicine, Boston, Massachusetts (Dr Ciraulo); Addiction Pharmacology Research Laboratory, St Luke's Hospital, San Francisco (Dr Galloway), and Pacific Coast Research Associates, Culver City (Dr Watson), California; Be Well Center, The University of Texas Health Science Center at San Antonio (Dr Roache); Virginia Tech Carilion Research Institute, Roanoke (Dr Bickel); and Center for Chemical Dependence, The Johns Hopkins Bayview Medical Center, Baltimore, Maryland (Dr Jasinski). Dr Segal is in private practice at Segal Institute for Clinical Research, North Miami, Florida.

JAMA Psychiatry. 2013;70(6):630-637. doi:10.1001/jamapsychiatry.2013.872

Importance Cocaine dependence is a significant public health problem, yet no validated pharmacological treatment exists. The potent γ-aminobutyric acid (GABA)ergic medication vigabatrin has previously been shown to be effective in a double-blind single-site study conducted in Mexico.

Objective To evaluate the safety and efficacy of vigabatrin for the treatment of cocaine dependence in a US sample.

Design and Setting Multisite, randomized, double-blind, placebo-controlled, 12-week clinical trial with follow-up visits at weeks 13, 16, 20, and 24 in 11 US sites.

Participants In total, 186 treatment-seeking participants with cocaine dependence (mean age, 45 years). Approximately 67% were male, and about 60% were of African American race/ethnicity.

Interventions Participants received twice-daily doses of vigabatrin (total dosage, 3.0 g/d) or matched placebo, plus weekly computerized cognitive behavioral therapy and biweekly individual counseling for 13 weeks. Contingency management encouraged the provision of urine samples.

Main Outcomes and Measures The primary outcome measure was the proportion of participants with cocaine abstinence during the last 2 weeks of the 12-week treatment phase as assessed by self-reports and quantitative urine drug screens. The weekly fraction of cocaine use days and the number of drug-free urine samples during weeks 1 through 13 were key secondary measures.

Results No significant differences were observed between the vigabatrin group and the placebo group on the primary outcome measure (P = .67), key secondary measures (P > .99), or other outcome measures. However, while pill counts and self-reports indicated that more than 66% of all participants (and >63% of the vigabatrin group) took more than 70% of their medication, post hoc vigabatrin urine concentration levels suggested that approximately 40% to 60% of patients taking vigabatrin may not have been adherent. This lack of adherence may have obscured any evidence of vigabatrin efficacy. No visual acuity or visual field deterioration occurred in any of the participants.

Conclusions and Relevance No protocol-defined differences in efficacy between vigabatrin treatment and placebo were detected for any outcome variable. This may have been due to medication nonadherence or, alternatively, due to the weak efficacy of vigabatrin.

Trial Registration clinicaltrials.gov Identifier: NCT00611130