At the recent American Society of Clinical Psychopharmacology Annual Meeting in June, researchers presented findings from a post hoc analysis entitled “AXS-05 (Dextromethorphan-Bupropion) Significantly Improved Functioning in Major Depressive Disorder: Analysis of the Domains of the Sheehan Disability Scale.” The post hoc analysis explored the effects of AXS-05 (dextromethorphan-bupropion [Auvelity extended-release tablet]) on patient function, evaluated by Sheehan Disability Scale (SDS) subdomain scores over 6 and 52 weeks in two phase III studies in MDD.

In the two clinical trials, GEMINI, a randomized, double-blind, placebo-controlled, 6-week trial, and COMET, an open-label study evaluating AXS-05 treatment for up to 1 year (NCT04039022), researchers evaluated AXS-05 (dextromethorphan 45 mg-bupropion 105 mg) in patients with MDD, and functional disability was measured utilizing SDS.

The researchers indicated that the SDS involves three domains (work/school, social life, and family life/home responsibilities), and each domain is scored from 0 to 10, with higher scores indicating a more significant disability. The GEMINI trial enrolled 327 patients, and the COMET trial enrolled 609 patients who did not previously participate in an AXS-05 study.

The results revealed that in both studies, patients reported moderate-to-marked disability on each domain at baseline: work/school (GEMINI: 6.2 for AXS-05 and 5.5 for placebo; COMET: 6.1 for AXS-05), social life (GEMINI: 7.2 for AXS-05 and 6.8 for placebo; COMET: 7.0 for AXS-05), and family life/home responsibilities (GEMINI: 6.7 for both AXS-05 and placebo; COMET: 6.7 for AXS-05).

At Week 6 in the GEMINI trial, treatment with AXS-05 substantially enhanced all SDS domains. The authors wrote, “Improvements (change from baseline, AXS-05 vs. placebo) were –2.6 vs. –1.8, P = .043, in the Work/School domain; –3.3 vs. –2.2, P = .001 in the Social Life domain; and –3.0 vs. –2.3, P = .029, in the Family Life/Home Responsibilities domain. Functional improvement across these domains was rapid, achieving improvement starting at Week 2.”

Beginning at Week 1 in the COMET trial, treatment with AXS-05 enhanced SDS scores across all the domains, and improvements were sustained for up to 1 year.

The most frequently reported adverse reactions (≥5% and more than twice the placebo rate) in the GEMINI trial included dizziness, headache, diarrhea, somnolence, dry mouth, sexual dysfunction, and hyperhidrosis. Long-term safety in the COMET open-label study was broadly consistent with the results detected in the controlled trials.

Based on their findings, the authors concluded, “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.”

Study presenter Andrew Cutler, MD, associate clinical professor of psychiatry at State University of New York Upstate Medical University and chief medical officer Neuroscience Education Institute, stated, “These data add to the existing clinical evidence for Auvelity in improving patient-centered outcomes in MDD and demonstrate the potential for Auvelity to improve functional impairment in MDD and to reduce key drivers of MDD-related costs.”

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