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

Background: 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-HT₃ receptors are indirect inhibitors of corticomesolimbic dopamine release, augmentation with the 5-HT₃ receptor antagonist ondansetron in combination with SSRIs and antipsychotics has potential efficacy in treatment-resistant OCD patients. Objective: To assess the efficacy and tolerability of ondansetron in combination with SSRIs and antipsychotics in patients with treatment-resistant OCD. Method: 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 0.25mg twice daily for 6 weeks and was then titrated to 0.5mg twice daily for 6 weeks. Results: Of the 14 patients, nine (64.3%) experienced a treatment response (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 paients experienced symptom exacerbation or significant adverse effects. Conclusion: 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.