Ondansetron augmentation in patients with obsessive-compulsive disorder who are inadequate responders to serotonin reuptake inhibitors: Improvement with treatment and worsening following discontinuation

Object: The aim of this study was to evaluate low-dose ondansetron as an augmentation strategy in patients with obsessive-compulsive disorder (OCD) who do not adequately respond to serotonin reuptake inhibits (SRIs). Methods: Twenty-one OCD patients who had not responded adequately to an SRI received 12 weeks of single-blind ondansetron augmentation initiated at 0.25 mg BID for 2 weeks, and titrated to 0.5 mg BID for an additional 10 weeks. Patients were rated every two weeks using the Yale-Brown Obsessive Compulsive Scale (YBOCS) and Clinical Global Impressions Scale (CGI). Treatment response was defined as an additional 25% reduction in YBOCS score from the score at the initiation of ondansetron augmentation, an end of treatment YBOCS score of ≤24 and a CGI-Improvement (CGI-I) score of ≤2. Upon completion of treatment course patients were followed for 4 weeks. Results: At week 12, twelve of the 21 (57%) patients were responders. The average reduction in the YBOCS score for the overall group was 27.2%. Responders had an average 44% YBOCS score reduction and 76.9% CGI-I reduction. After discontinuation of ondansetron the YBOCS worsened an average of 15.5% in the entire sample and 38.3% in the responder subsample. No clinically meaningful side effects were reported. Conclusion: OCD patients who do not adequately respond to an SRI may benefit from augmentation with a low-dose of ondansetron. This may provide an alternative approach to augmentation with atypical antipsychotic agents, with a more favorable safety profile.