Adding 30 mg of dextromethorphan daily to standard SSRI treatment for eight weeks led to significantly greater reductions in depression severity, higher response and remission rates, and better clinical global improvement in patients with mild to moderate major depressive disorder, compared to adding a placebo. The combination was well-tolerated, with adverse events comparable between groups. No significant difference in serum BDNF levels was observed. These results suggest that early augmentation of SSRIs with dextromethorphan may improve clinical outcomes.
Adding dextromethorphan to ongoing SSRI treatment may improve outcomes for major depressive disorder. A randomized, double-blind, placebo-controlled trial will assign patients to receive either 30 mg dextromethorphan or placebo once daily for 8 weeks alongside their SSRI. The primary outcome is change in depression severity measured by the Montgomery-Åsberg Depression Rating Scale; secondary outcomes include response and remission rates, clinical global impression, and serum biomarkers. The trial aims to address therapeutic latency, lack of efficacy, and adverse drug reactions in current antidepressant therapies.