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 an and sigma-1 agonist. bupropion serves primarily to increase the bioavailability dextromethorphan. Methods was evaluated in two double-blind, randomized, controlled, 6-week trials. GEMINI trial (N=327) placebo-controlled ASCEND (N=80) used as control. Here we focus on efficacy first 2 weeks treatment present pooled analysis individual items MADRS compared Results In GEMINI, starting at Week 1, AXS 05 superior (p < 0.05) placebo on: mean improvement (7.3 vs. 4.9), response (15% 7%), CGI-I (22% 13%), CGI-S (0.7 0.4) Q-LES-Q-SF (9.0% 5.8%). At 2, also statistically remission (17% vs.8%) SDS (6.8 4.5). ASCEND, from (p< (12.5vs. 7.8), (26% 3%), (1.41 0.9). resulted greater improvements reported sadness, inner tension, inability feel, pessimistic thoughts, suicidal 6, demonstrated significant over control seven ten items. trial, most commonly adverse events were dizziness, nausea, headache, diarrhea, somnolence, dry mouth. Conclusions Treatment rapid broad antidepressant efficacy. Funding Axsome Therapeutics