Ondansetron in OCD

A novel, tolerable option for OCD

STUDY: Mohammad A et al, European Journal of Clinical Pharmacology 2026

STUDY TYPE: Systematic review and meta-analysis

FUNDING: Independent

Background

Up to 60% of OCD patients don’t respond adequately to SSRIs, and antipsychotic augmentation, the best-studied next step, helps only about one-third. Ondansetron is a serotonin-3 (5-HT3) receptor antagonist widely used for nausea, and that mechanism may help it treat OCD in the brain.

The Study

• Five randomized, double-blind, placebo-controlled trials; 289 adults with OCD on stable background SSRI therapy
• Ondansetron (4–24 mg/day, most use 4mg) versus placebo, added to ongoing treatment
• Follow-up: 4 to 12 weeks
• Primary outcome: change in OCD severity scale (Y-BOCS)

Results

Ondansetron outperformed placebo at every time point measured. By week 8, the difference in Y-BOCS scores was about 5.5 points. By week 12, the gap held at about 6 points. Obsessional symptoms improved first, by week 4. Compulsive symptoms followed later, reaching significance by week 8.

The findings were consistent after excluding outlying trials, though several individual studies drove much of the heterogeneity.

Limitations

Four of the five trials were conducted in Iran and India, limiting generalizability. Safety data were inconsistently reported across trials. Publication bias can’t be excluded.

Practice Implications

1. Side effects are difficult for patients with OCD to tolerate, so this low-risk option is a useful addition. Constipation is the main side effect; QTc prolongation the main risk.
2. Although the data support it as SSRI-augmentation, I have used it successfully as monotherapy in patients who do not tolerate or cannot take SSRIs, such as bipolar with OCD.

—Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report

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