Ondansetron augmentation in treatment-resistant obsessive-compulsive disorder: a preliminary, single-blind, prospective study

CNS Drugs. 2009 Dec;23(12):1047-55. doi: 10.2165/11530240-000000000-00000.


Serotonin and dopamine neuronal systems have been implicated in the modulation of obsessive-compulsive disorder (OCD) symptoms. About 40% of OCD patients do not respond to first-line selective serotonin reuptake inhibitor (SSRI) treatment; among those, dopamine blocker augmentation has been reported to improve the rate of response by an additional one-third. Given that serotonin 5-HT(3) receptors are indirect inhibitors of cortico-mesolimbic dopamine release, augmentation with the 5-HT(3) receptor antagonist ondansetron in combination with SSRIs and antipsychotics has potential efficacy in treatment-resistant OCD patients. To assess the efficacy and tolerability of ondansetron in combination with SSRIs and antipsychotics in patients with treatment-resistant OCD. In total, 14 patients with a DSM-IV diagnosis of OCD, who were treatment resistant and receiving stable treatment with SSRIs and antipsychotic augmentation, entered a 12-week, single-blind trial of ondansetron. The drug was initiated at a dosage of 0.25 mg twice daily for 6 weeks and was then titrated to 0.5 mg twice daily for 6 weeks. Of the 14 patients, nine (64.3%) experienced a treatment response (> or =25% reduction in the Yale-Brown Obsessive Compulsive Scale [YBOCS] score and a Clinical Global Impressions-Improvement [CGI-I] score of 1 or 2) at 12 weeks. The average reduction in YBOCS-rated symptoms for the whole group was 23.2%. None of the treated patients experienced symptom exacerbation or significant adverse effects. These results suggest that low-dose ondansetron may have promise as an augmentation strategy for some patients with OCD resistant to SSRIs and antipsychotic augmentation, but further controlled trials are required. Trial registration number (ClinicalTrials.gov): NCT00796497.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antipsychotic Agents / adverse effects
  • Antipsychotic Agents / therapeutic use
  • Drug Resistance
  • Drug Therapy, Combination
  • Female
  • Humans
  • Male
  • Middle Aged
  • Obsessive-Compulsive Disorder / drug therapy*
  • Obsessive-Compulsive Disorder / physiopathology
  • Ondansetron / adverse effects
  • Ondansetron / pharmacology
  • Ondansetron / therapeutic use*
  • Pilot Projects
  • Psychiatric Status Rating Scales
  • Selective Serotonin Reuptake Inhibitors / adverse effects
  • Selective Serotonin Reuptake Inhibitors / therapeutic use
  • Serotonin 5-HT3 Receptor Antagonists
  • Serotonin Antagonists / adverse effects
  • Serotonin Antagonists / pharmacology
  • Serotonin Antagonists / therapeutic use*
  • Severity of Illness Index
  • Single-Blind Method
  • Young Adult


  • Antipsychotic Agents
  • Serotonin 5-HT3 Receptor Antagonists
  • Serotonin Antagonists
  • Serotonin Uptake Inhibitors
  • Ondansetron

Associated data

  • ClinicalTrials.gov/NCT00796497