AXS-05 (Dextromethorphan-Bupropion) Significantly Improved Functioning in Major Depressive Disorder: Analysis of the Domains of the Sheehan Disability Scale

This work was sponsored by Axsome Therapeutics Background: Major Depressive Disorder (MDD) is the leading global cause of disability, with a significant economic burden, particularly in workplace costs. AXS-05 [dextromethorphan-bupropion (Auvelity™ extended-release tablet)] is a novel, oral, NMDA receptor antagonist with multimodal activity approved by the FDA for the treatment of MDD in adults. To explore the effects of AXS-05 on patient function, this post-hoc analysis evaluated functional disability assessed by Sheehan Disability Scale (SDS) subdomain scores over 6 and 52 weeks in two phase 3 studies in MDD. Methods: Two clinical trials of AXS-05 in MDD (GEMINI and COMET) assessed functional disability using the Sheehan Disability Scale (SDS). GEMINI, a 6-week, randomized, double-blind, placebo-controlled trial, enrolled 327 patients. COMET, an open-label study, enrolled 609 patients without prior AXS-05 treatment, for up to one year. Results: Patients reported moderate-to-marked disability across all SDS domains at baseline. In GEMINI, AXS-05 demonstrated significant improvement beginning at Week 2, reaching significance in all 3 domains by week 6 with AXS-05, showing rapid, substantial changes from baseline compared to placebo. In the COMET trial, treatment with AXS-05 improved SDS scores across all the domains as early as Week 1 with improvements maintained for up to one year. The most common adverse reactions in GEMINI (vs. placebo) were: dizziness, headache, diarrhea, somnolence, dry mouth, sexual dysfunction, and hyperhidrosis. Long-term safety in COMET was consistent with the controlled trials. Conclusions: Treatment with AXS-05 significantly improved functional disability in the SDS domains of Work/School, Social Life and Family Life/Home Responsibilities in patients with MDD.