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

An open-label study tested AXS-05, a combination of dextromethorphan and bupropion, in 146 directly enrolled patients with major depressive disorder and comorbid anxiety. Mean baseline HAM-A anxiety scores were 15.6. Reductions from baseline were 3.4 points at Week 1, 5.5 at Week 2, and 8.6 at Week 6, with improvements lasting through Month 12. Remission rates (HAM-A ≤7) reached 58.1% by Week 6 and 78.3% at Month 12. Common side effects included COVID-19 infection, nausea, headache, dry mouth, insomnia, and dizziness. The authors suggest the treatment is useful for patients with both depression and anxiety.

Study at a glance

Abstract

AbstractBackgroundInnovative therapies to treat individuals with MDD, especially those with comorbid anxiety, are urgently needed.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.ObjectiveTo evaluate the effects of AXS-05 on anxiety in MDD.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. A total of 186 patients were enrolled. Efficacy endpoints included MADRS and HAM-A. Here we present the results for the directly enrolled patients (n =146).ResultsMean baseline HAM-A scores were 15.6. Reductions from baseline to Weeks 1, 2, and 6 were 3.4±5.34 (p< 0.001), 5.5±5.81 (p< 0.001), and 8.6±5.75 (p< 0.001), respectively. Improvements on the HAM-A were durable through Month 12 (-10.2±6.33; p< 0.001). Remission (HAM-A ≤7) rates on the HAM-A at Weeks 1, 2, and 6 were 19.9%, 36.0%, and 58.1%, respectively. Remission at Month 12 was 78.3%.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%).ConclusionsThese data support the use of AXS-05 in patients with comorbid depression and anxiety.FundingAxsome Therapeutics