Improvement in Anxiety Symptoms in Depressed Patients Treated With AXS-05 (DEXTROMETHORPHAN-BUPROPION): Results From the Evolve Open-Label, Long-Term Study

Abstract Background Innovative therapies to treat individuals with MDD, especially those comorbid anxiety, are urgently needed. AXS-05 (dextromethorphan HBr 45 mg-bupropion HCl 105 mg) is a novel, oral, investigational NMDA receptor antagonist multimodal activity. The dextromethorphan component of an and sigma-1 agonist. bupropion serves primarily increase the bioavailability dextromethorphan. Objective To evaluate effects on anxiety in MDD. Methods EVOLVE was open-label study, which patients were treated twice daily for up 15 months. Subjects had either rolled after prior study or directly enrolled DSM-5 diagnosis MADRS score ≥25, been ≥ 1 antidepressant current major depressive episode. A total 186 enrolled. Efficacy endpoints included HAM-A. Here we present results (n =146). Results Mean baseline HAM-A scores 15.6. Reductions from Weeks 1, 2, 6 3.4±5.34 (p< 0.001), 5.5±5.81 8.6±5.75 respectively. Improvements durable through Month 12 (-10.2±6.33; p< 0.001). Remission (HAM-A ≤7) rates at 19.9%, 36.0%, 58.1%, 78.3%. 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 These data support use depression anxiety. Funding Axsome Therapeutics