Dextromethorphan ( think cough syrup) for OCD: A Promising Glutamate-Targeted Augmentation Strategy?

A small 2026 randomized controlled trial found that adding low-dose dextromethorphan (DXM, 15 mg twice daily) to ongoing SSRI treatment significantly reduced Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores in adults with SSRI-resistant OCD, dropping from about 26.6 to 16.3 over 12 weeks versus little change on placebo. Strengths include its double-blind, placebo-controlled design, strong statistical effect size, excellent tolerability with no reported side effects, and alignment with the glutamatergic hypothesis of OCD. Limitations center on the tiny sample size (n=40), single-center location in Iran, lack of secondary outcomes or long-term follow-up, and potential pharmacokinetic variability from SSRI interactions; broader evidence from meta-analyses of other glutamatergic agents supports the approach but calls for larger confirmatory trials.