Ondansetron Augmentation in Treatment-Resistant Obsessive-Compulsive Disorder

Abstract

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.

Avances en el tratamiento farmacológico del trastorno obsesivo-compulsivo.

“…El ondansetrón parece ser útil para potenciar el tratamiento de pacientes con TOC resistente a ISRS y antipsicóticos según un estudio no controlado (17). Asimismo, un estudio abierto sugiere que el ondansetrón como monoterapia (18) puede disminuir síntomas del TOC.…”

Ondansetron Augmentation of Serotonin Reuptake Inhibitors as a Treatment Strategy in Obsessive-Compulsive Disorder

“…Pallanti et al 17 specifically examined the benefits of low-dose ondansetron in OCD. The sample comprised 14 adults who had not responded to the combination of an SRI with an atypical antipsychotic drug.…”

“…In contrast with usual findings in psychopharmacology studies, ondansetron augmentation was more strikingly effective in the RCTs 19,20 than in the uncontrolled studies. 17,18 There are 2 possible explanations. One is that patients in the uncontrolled studies 17,18 had a documented history of poor response to ongoing and/or previous anti-OCD medications; in contrast, previous medication history was not reported in the controlled trials, 19,20 and patients were off all psychotropic medications for at least the previous 6 weeks.…”

“…17,18 There are 2 possible explanations. One is that patients in the uncontrolled studies 17,18 had a documented history of poor response to ongoing and/or previous anti-OCD medications; in contrast, previous medication history was not reported in the controlled trials, 19,20 and patients were off all psychotropic medications for at least the previous 6 weeks. The other is that ondansetron was dosed at higher levels in the RCTs 19,20 as compared with the uncontrolled trials.…”

“…Finally, independent confirmation of ondansetron benefits is necessary. Both of the 12-week uncontrolled augmentation trials in inadequate responders were published by the same team, 17,18 and both of the impressively positive RCTs 19,20 in patients with undocumented past treatment history were conducted in the same country.…”