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

In patients with major depressive disorder who had not improved after one prior antidepressant in the current episode, treatment with AXS-05 (dextromethorphan HBr 45 mg-bupropion HCl 105 mg) led to rapid and sustained improvements in depression and functioning. Mean scores on the Montgomery-Åsberg Depression Rating Scale (MADRS) dropped by 9.1 points at one week, 13.3 points at two weeks, and 20.4 points at six weeks. Remission (MADRS score of 10 or less) was achieved by 5.7% of patients at one week, 16.2% at two weeks, and 46.0% at six weeks. Improvements in functioning were seen starting at one week and were maintained at 12 months. Common side effects included COVID-19 infection, nausea, headache, dry mouth, insomnia, and dizziness.

Study at a glance

Abstract

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