Is Ondansetron Augmentation Effective in Obsessive-Compulsive Disorder?

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To the Editors
Serotonin reuptake inhibitors (SRIs) are the preferred drugs for treating obsessive-compulsive disorder (OCD). However, 40% to 60% of patients do not respond to an initial SRI trial, and many do not benefit even after switching to other SRIs.1 Atypical antipsychotics are frequently used to augment therapeutic effect of SRIs, but they are effective only in approximately 30% of patients and are often poorly tolerated.1 There is a pressing need for additional pharmacological options to treat OCD.
Serotonin (5-HT3) receptors have been located on γ-aminobutyric acid interneurons in the ventral tegmental area. Ondansetron, a commonly used antiemetic, is a selective 5-HT3 blocker. It may have an indirect inhibitory action on corticomesolimbic dopaminergic release and thus reduce striatal dopamine–related repetitive behavior.2 This property may be beneficial in treating OCD, as dopaminergic-related repetitive behavior such as grooming in animals is a putative model for OCD.3 Furthermore, ondansetron may act on 5-HT3 receptors located in cingulate cortex, amygdala, nucleus accumbens, and hippocampus, which have been implicated in OCD.4 Ondansetron also has significant activity on 5-HT4 receptors, which in turn may influence dopaminergic activity in the mesolimbic system.5,6
In line with this, some studies have found ondansetron to be an effective augmenting agent to SRIs in treating OCD.7–11 Moderate-to-high doses (3–8 mg/d)7,8,11 and low doses of ondansetron (1 mg/d)9,10 have been found beneficial. However, observing important limitations in current literature, reviews2,12 have opined that ondansetron is a promising albeit experimental treatment for OCD, whose role needs further clarification. In this context, we sought to examine the effectiveness of ondansetron augmentation of SRIs in a real-world setting, from the database of an OCD clinic in India.
We conducted a chart review of all patients who registered at the OCD clinic at the National Institute of Mental Health and Neurosciences, Bangalore, India, between 2004 and 2014 after obtaining approval from the institutional ethics committee. All patients attending the clinic are routinely evaluated with the Mini International Neuropsychiatric Interview plus, the Yale-Brown Obsessive Compulsive Scale (YBOCS), and the Clinical Global Impressions - severity scale (CGI-S) by trained postgraduate psychiatry residents. Improvement is monitored by administering the YBOCS and the CGI-S during each follow-up visit. Diagnoses and ratings are confirmed by experienced psychiatrists. We included patients initiated on ondansetron for nonremission of symptoms (defined as YBOCS score of ≥12) despite an adequate trial with an SRI.13 Only patients who were on a stable dose of SRI for 12 weeks or longer before ondansetron augmentation were included. Patients who were concurrently treated with cognitive behavioral therapy or medications with augmenting effects were excluded.1 Although comorbidities were not excluded for clinical care, patients with comorbid psychosis, mental retardation, or bipolar disorder were not included in our sample.
All-cause discontinuation was used as a primary outcome measure. Because medication discontinuation integrates patient and clinician judgments of efficacy and tolerability, it might be considered as a global measure of effectiveness relevant to clinical practice.14 Change in the YBOCS score from baseline was used as secondary outcome measure. Response was defined as a reduction of 25% or more in YBOCS total score after initiation of ondansetron augmentation. Although most of the patients received twice-daily ondansetron, some were on once-daily treatment. Outcomes were measured for all eligible patients and were also compared between those on once-daily and twice-daily regimens. Statistical analysis was conducted using the Statistical Package for Social Sciences (version 13.0).
Ondansetron was initiated in 55 patients.
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