A randomized, double-blind, placebo-controlled trial of long-acting risperidone in cocaine-dependent men.
OBJECTIVE
There is no approved pharmaco-therapy for cocaine dependence. Risperidone is an atypical antipsychotic drug with combined dopamine-2/serotonin-2 (D(2)/5-HT(2)) 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.


METHODS
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 risperi-done 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.


CONCLUSIONS
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.


BACKGROUND
clinicaltrials.gov Identifier: NCT00385801.
Loebl
Tsafrir
T
Center for Addiction Medicine of the Department of Psychiatry and the Biostatistics Center of Massachusetts General Hospital, Harvard Medical School, Boston, Mass. 02114, USA. tloebl@partners.org
Angarita
Gustavo A
GA
Pachas
Gladys N
GN
Huang
Kai-Lin
KL
Lee
Sang H
SH
Nino
Johanna
J
Logvinenko
Tanya
T
Culhane
Melissa A
MA
Evins
A Eden
AE
D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D019970:Cocaine-Related Disorders / Q000453:epidemiology*; D003692:Delayed-Action Preparations; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000453:epidemiology*; D039721:Diagnostic and Statistical Manual of Mental Disorders; D065127:Dopamine D2 Receptor Antagonists; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D006801:Humans; D007273:Injections, Intramuscular; D008133:Long QT Syndrome / Q000139:chemically induced / Q000453:epidemiology; D008297:Male; D011618:Psychotic Disorders / Q000188:drug therapy* / Q000453:epidemiology*; D018967:Risperidone / Q000008:administration & dosage / Q000627:therapeutic use*
D014150:Antipsychotic Agents; D003692:Delayed-Action Preparations; D065127:Dopamine D2 Receptor Antagonists; D018967:Risperidone