title: A preliminary randomized, double-blind, placebo-controlled study of the safety and efficacy of ondansetron in the treatment of cocaine dependence.
abstract: Prior studies have demonstrated inefficacy among dopamine receptor antagonists for treating cocaine dependence. An alternative approach would be to investigate the ability of indirect inhibitors of cortico-mesolimbic dopamine release, such as the 5-HT(3) receptor antagonist ondansetron, to reduce cocaine's reinforcing effects. We hypothesized that ondansetron might be more efficacious than placebo at reducing cocaine intake and promoting abstinence in cocaine-dependent individuals. In a pilot randomized, double-blind, 10-week controlled trial, 63 treatment-seeking, cocaine-dependent men and women received ondansetron (0.25 mg, 1.0 mg, or 4.0 mg twice daily) or placebo. Up to three times per week, participants were assessed on several measures of cocaine use, including urine benzoylecgonine. Cognitive behavioral therapy was administered weekly. Ondansetron was well tolerated, causing no serious adverse events. The ondansetron 4.0 mg group had the lowest dropout rate among all treatment groups and a greater rate of improvement in percentage of participants with a cocaine-free week compared with the placebo group (p = 0.02), whereas the ondansetron 1.0 mg group had a lower rate of improvement in percentage of weekly mean non-use days than did placebo recipients (p = 0.04). These results suggest the possibility of a non-linear dose-response function, with evidence supporting efficacy for the 4.0 mg group.
authors.affiliation: Department of Psychiatric Medicine, University of Virginia, P.O. Box 800623, Charlottesville, VA 22908-0623, USA. bankolejohnson@virginia.edu
authors.forename: Bankole A
authors.initials: BA
authors.lastname: Johnson
authors.forename: John D
authors.initials: JD
authors.lastname: Roache
authors.forename: Nassima
authors.initials: N
authors.lastname: Ait-Daoud
authors.forename: Martin A
authors.initials: MA
authors.lastname: Javors
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Harrison
authors.forename: Ahmed
authors.initials: A
authors.lastname: Elkashef
authors.forename: Jurij
authors.initials: J
authors.lastname: Mojsiak
authors.forename: Shou-Hua
authors.initials: SH
authors.lastname: Li
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Bloch
mesh_terms: D000328:Adult; D019970:Cocaine-Related Disorders / Q000534:rehabilitation* / Q000628:therapy; D015928:Cognitive Behavioral Therapy / Q000379:methods*; D003131:Combined Modality Therapy; D003710:Demography; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D017294:Ondansetron / Q000009:adverse effects* / Q000627:therapeutic use; D012702:Serotonin Antagonists / Q000009:adverse effects* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D012702:Serotonin Antagonists; D017294:Ondansetron