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Ondansetron Augmentation in Treatment-Resistant Obsessive-Compulsive Disorder

A Preliminary, Single-Blind, Prospective Study

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Abstract

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 0.25 mg twice daily for 6 weeks and was then titrated to 0.5 mg 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 patients 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. Trial registration number (ClinicalTrials.gov): NCT00796497

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Acknowledgements

Funding for this study was provided in part by Transcept Pharmaceuticals, Inc., Pt. Richmond, California, USA. Drs Hollander and Pallanti have served as consultants to Transcept Pharmaceuticals, Inc. Dr Singh is an employee of Transcept Pharmaceuticals, Inc. Drs Bernardi and Antonini have no conflicts of interest to report. Dr Bernardi’s current affiliation is Department of Psychiatry, Columbia University, New York, NY, USA. Dr Hollander’s current affiliation is Department of Psychiatry, Montefiore Medical Center, University Hospital of Albert Einstein College of Medicine, Bronx, NY, USA.

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Authors and Affiliations

  1. Department of Psychiatry, Mount Sinai School of Medicine, Box 1230, 1 Gustave Levy Place, New York, New York, 10029, USA

    Stefano Pallanti & Silvia Bernardi

  2. Department of Psychiatry, University of Florence, Florence, Italy

    Stefano Pallanti, Silvia Bernardi & Sarah Antonini

  3. Transcept Pharmaceuticals, Inc., Pt. Richmond, California, USA

    Nikhilesh Singh & Eric Hollander

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  1. Stefano Pallanti
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Correspondence to Stefano Pallanti.

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Pallanti, S., Bernardi, S., Antonini, S. et al. Ondansetron Augmentation in Treatment-Resistant Obsessive-Compulsive Disorder. CNS Drugs 23, 1047–1055 (2009). https://doi.org/10.2165/11530240-000000000-00000

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