REVIEW OF: Hamanaka S et al, J Psychiatr Res 2023;167:132–138

STUDY TYPE: Systematic review and meta-analysis

Ondansetron (Zofran), a serotonin 3 receptor antagonist (5-HT3 RA), is a common and effective treatment for nausea. It has also been investigated for the treatment of OCD, and a recent meta-analysis looked at whether it’s worth using for this diagnosis. 

The authors performed a systematic review and meta-analysis of double-blind, randomized, placebo-controlled trials of 5-HT3 RAs in adults with OCD. They reviewed 10 studies with a total of 628 patients with severe OCD at baseline (average Yale–Brown Obsessive–Compulsive Scale [Y-BOCS] score = 29.6) who were predominantly female (60.7%) and had a mean age of 33.4 years. The studies used ondansetron, granisetron, and tropisetron (not available in the US) over 4–12 weeks. Most participants (8 of 10 studies) also received selective serotonin reuptake inhibitors (SSRIs), but psychotherapy was either excluded or not reported. Of the 10 studies, 7 were conducted in Iran.

5-HT3 RAs improved Y-BOCS totals by 5.08 points more than placebo (95% confidence interval: -7.04, -3.12). Individually, all three outperformed placebo as well (ondansetron: mean difference [MD] = -5.72, 6 studies, 331 patients; granisetron: MD = -5.59, 3 studies, 178 patients; tropisetron: MD = -2.87, 1 study, 96 patients). Dosages varied: ondansetron 4–24 mg/day, granisetron 2 mg/day, and tropisetron 10 mg/day. Interestingly, lower doses of 5-HT3 RAs showed larger effect sizes for the primary outcome (p = 0.02).

Secondary outcomes, including the Y-BOCS obsession subscale, Y-BOCS compulsive subscale, remission rate, and treatment response, also favored 5-HT3 RAs. Additionally, these treatments were well tolerated, with no significant differences in discontinuation or adverse effects compared to placebo. 

CARLAT TAKE
These studies were relatively short and don’t offer any information about combining these meds with psychotherapy. However, for patients who have tried SSRIs and clomipramine but still have high Y-BOCS scores, it is reasonable to consider augmenting with 5-HT3 RAs.