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A Randomized, Double-Blind, Placebo-Controlled Trial of Long-Acting Risperidone in Cocaine-Dependent Men

Tsafrir Loebl, M.D.; Gustavo A. Angarita, M.D.; Gladys N. Pachas, M.D.; Kai-Lin Huang, M.D.; Sang H. Lee, B.Sc.; Johanna Nino, M.D.; Tanya Logvinenko, Ph.D.; Melissa A. Culhane, M.P.H.; and A. Eden Evins, M.D., M.P.H.

Objective: There is no approved pharmacotherapy for cocaine dependence. Risperidone is an atypical antipsychotic drug with combined dopamine-2/serotonin-2 (D2/5-HT2) antagonist activity that has been effective in reducing cocaine use in some animal studies. We tested the efficacy of a long-acting, injectable preparation of risperidone on cocaine use in active cocaine users.

Method: Thirty-one cocaine-dependent men who met DSM-IV diagnostic criteria for current cocaine dependence entered a 12-week, randomized, double-blind, placebo-controlled trial of intramuscular risperidone, 25 mg every other week. The primary outcome measure was cocaine use as measured by urinary concentration of cocaine metabolites. Secondary outcomes were self-report of cocaine use and craving, depressive symptoms as measured by the Hamilton Rating Scale for Depression (HAM-D), and adverse events. Participants were recruited during a 12-month period from October 2005 to September 2006.

Results: Both groups reduced their cocaine use during the study. There were no between-group differences in the primary measure of cocaine use (urinary metabolites [F = 0.7, p = .41]) or on craving measures. Those assigned to risperidone reported significantly worsened depressive symptoms (mean SD HAM-D change scores: +7.4 8.8 vs. -2.3 5.8, respectively, F = 7.5, p = .018) and gained significantly more weight (mean weight change: +6.3 9.4 lb vs. -4.0 8.9 lb, respectively, F = 4.65, p = .044) than those assigned to placebo.

Conclusion: Treatment with long-acting injectable risperidone in active cocaine users was not associated with reduction in cocaine use or craving and was associated with worsening of depressive symptoms and weight gain.

Trial Registration: Identifier: NCT00385801

(J Clin Psychiatry 2008;69:480-486. Online Ahead of Print February 20, 2008.)

Received Oct. 15, 2007; accepted Jan. 7, 2008. From the Center for Addiction Medicine of the Department of Psychiatry and the Biostatistics Center of Massachusetts General Hospital, Harvard Medical School, Boston, Mass (all authors). Dr. Angarita is currently in psychiatry residency training at Yale Medical School, New Haven, Conn., and Dr. Huang is currently in Child and Adolescent Psychiatry fellowship training at the Taipei Veterans General Hospital, Taipei, Taiwan.

This work was supported by a grant from Janssen Pharmaceutica to Dr. Evins. Dr. Loebl was supported by an Invest Fellowship from the National Institute on Drug Abuse (NIDA) International Program.

Dr. Evins has received grant/research support from GlaxoSmithKline and NIDA. Drs. Loebl, Angarita, Pachas, Huang, Nino, and Logvinenko and Mr. Lee and Ms. Culhane report no additional financial affiliations or other relationships relevant to the subject of this article.

Corresponding author and reprints: Tsafrir Loebl, M.D., Center for Addiction Medicine, Massachusetts General Hospital, 60 Staniford St., Boston, MA 02114 (e-mail: