Is ondansetron augmentation of SSRI useful in OCD? Eur Neuropsypharm. 2014 Mar.


SSRIs are the first line of treatment in OCD. It is considered that 40% of patients do not respond to SSRI treatment, and that less than 30% of patients experienced substantial symptom improvement.Augmentation with antipsychotics help by blocking the effects of striatal dopamine release which result in improvement of repetitive thoughts and behaviours.  Only a third of patients receiving such augmentation benefit from that.We need to look at other ways of augmenting SSRIs. Would medications acting on 5HT3  system be beneficial? 

Odansetron modulates dopamine turnover in the nucleus accumbens  in the mesolimbic reward pathway.5HT3 receptors are co-localised  with GABA interneurons in the ventral tegmental area, and thus can exert indirect inhibitory action on cortico-mesolimbic dopaminergic release. Soltani et al., 2010 reported the results of the first double blind RCT and showed that odansetron is effective in OCD. Odansetron and fluoxetine were started together in this study and hence is not be reflective of the usual augmentation practices.

Stefano Pallantia,Silvia Bernardia, Sarah Antoninib, Nikhilesh Singh and Eric Hollander report the results of  the first study to examine efficacy of low-dose ondansetron augmentation to ongoing SSRI therapy in OCD patients who have not adequately responded to SSRI therapy.  They also sought to see  whether symptoms would recur when the drug was discontinued.

Study: Participants were poor responders to SSRI. ( CGI score of 4 or more, Yale Brown score 24 or more). SSRI doses were moderate to high.(Eg: sertraline 250, fluoxetine 60,escitalopram up to 60). In phase 1 of the trial, participants received oral ondansetron 0.25 mg in twice daily  for 2 weeks. Then the dose was titrated to 0.5 mg  twice daily for another 10 weeks. During phase II, ondansetron was discontinued and the patients were followed for an additional 4 weeks. Relapse was defined as a worsening of YBOCS total score more than 25% with respect to the last evaluation and/or CGI score = 6–7  after discontinuation.

Results: 21 patients participated in the study. one patient dropped out due to constipation. 57% patients experienced a treatment response at 12 weeks based on 25% improvement in YBOCS score and CGI-I = 1–2. Responders (n=12) reached an average reduction in YBOCS scores of 44%. During the discontinuation phase  symptoms worsened by an average of 36.4% in responders. At Week 16, 8 out of 12 (67%) responders relapsed after discontinuation.  

Limitations:  Observation period  after discontinuation  is short.  The possible influences of comorbid tic or personality disorder not taken in to account. Correlations of  specific OCD dimensions with treatment response cannot be determined due to small sample size.Patients were not blind to the intervention.

Conclusion:  Low dose odansetron is likely to be beneficial in half of the SSRI poor responders.

Summary of the article:

Ondansetron augmentation in patients with obsessive-compulsive disorder who are inadequate responders to serotonin reuptakeinhibitorsImprovement with treatment and worsening following discontinuation.

Pallanti S, Bernardi S, Antonini S, Singh N, Hollander E. Eur Neuropsychopharmacol. 2014 Mar;24(3):375-80




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