AXS-05 (DEXTROMETHORPHAN-BUPROPION) Improves Depressive Symptoms and Functioning in Patients With One Prior Treatment Failure: Results From the Evolve Long-Term, Open Label Study

Abstract Background In STAR*D, following non-remission with an SSRI, remission rates for second-line treatments were ~ 25%, regardless of the switch strategy employed. Antidepressants novel mechanisms may improve outcomes in MDD. AXS-05 (dextromethorphan HBr 45 mg- bupropion HCl 105 mg) is a novel, oral, investigational, NMDA receptor antagonist multimodal activity. The dextromethorphan component and sigma-1 agonist. serves primarily to increase bioavailability dextromethorphan. Methods EVOLVE was open-label study, which patients treated twice daily up 15 months. Subjects had either rolled after prior study or directly enrolled DSM-5 diagnosis MDD, MADRS score ≥25, been ≥1 antidepressant current major depressive episode (MDE). A total 186 enrolled. Here we present results (n =146). Results Mean change from baseline 32.2 -9.1±7.64, -13.3±8.58, -20.4±7.79 points at Weeks 1, 2, 6, respectively (p< 0.001 all). Remission (MADRS ≤10) achieved by 5.7%, 16.2%, 46.0% respectively. Improvement functioning, measured SDS, seen starting Week 1 (p < 0.001). Improvements SDS sustained Month 12. Long-term treatment generally well tolerated. most commonly reported adverse events COVID-19 infection (8.9%), nausea headache (7.5%), dry mouth (6.2%), insomnia (5.5%), dizziness (5.5%). Conclusions improved depression functioning who failed one MDE. Funding Axsome Therapeutics