Rapid Antidepressant Effects and MADRS Item Improvements With AXS-05 (Dextromethorphan-Bupropion), an Oral NMDA Receptor Antagonist, in Major Depressive Disorder: Results from Two Randomized, Double-Blind, Controlled Trials

Abstract: Background: AXS-05 (dextromethorphan-bupropion) is a novel, oral, investigational, NMDA receptor antagonist with multimodal activity being developed for MDD. The dextromethorphan component of AXS-05 is an NMDA receptor antagonist and a sigma-1 receptor agonist. The bupropion component of AXS-05 serves primarily to increase the bioavailability of dextromethorphan. Methods: AXS-05 was evaluated in two double-blind, randomized, controlled, 6-week trials. The GEMINI trial was placebo-controlled and the ASCEND trial used bupropion as the control. Here we focus on efficacy in the first 2 weeks of treatment and present a pooled analysis of the individual items of the MADRS for AXS-05 as compared to control. Results: In GEMINI, starting at Week 1, AXS 05 was superior (p