dextromethorphan + selective serotonin reuptake inhibitors

Dextromethorphan + selective serotonin reuptake inhibitors (SSRIs) is a combination therapy being investigated for the treatment of major depressive disorder (MDD). Dextromethorphan, a small molecule traditionally used as an over-the-counter antitussive, is being repurposed as an adjunct to standard SSRI treatment to address therapeutic latency and treatment resistance. Dextromethorphan acts as a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, a sigma-1 receptor agonist, and an inhibitor of both the serotonin transporter (SERT) and norepinephrine transporter (NET). By modulating glutamatergic signaling in addition to the monoaminergic effects of SSRIs, this combination is hypothesized to provide enhanced and potentially more rapid antidepressant efficacy. The All India Institute of Medical Sciences (AIIMS), Bhubaneswar, is evaluating this regimen in a Phase 2 randomized, double-blind, placebo-controlled trial (NCT05181527) using a 30 mg daily dose of dextromethorphan in patients with mild to moderate MDD.

Other names

Dextromethorphan as adjunct to SSRIsDextromethorphan add-on therapy