Improvement in Anxiety Symptoms in Depressed Patients Treated With AXS-05 (DEXTROMETHORPHAN-BUPROPION): Results From the Evolve Open-Label, Long-Term Study
Amanda Jones, Caroline Streicher, Shawn Alter, Zachariah Thomas, Herriot Tabuteau
CNS Spectrums April 1, 2023 DOI: 10.1017/s1092852923002080 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Open-label study Peer reviewed |
|---|---|
| Sample size | 146 |
| Population | Directly enrolled patients with DSM-5 diagnosis of MDD, MADRS score ≥25, treated with at least one antidepressant in the current major depressive episode |
| Intervention | AXS-05 (dextromethorphan HBr 45 mg-bupropion HCl 105 mg) |
| Dose | 45 mg dextromethorphan HBr and 105 mg bupropion HCl twice daily |
| Duration | Up to 15 months |
| Measures | MADRS, HAM-A |
| Topics | Anxiety |
| Key points | AXS-05 treatment was associated with reductions in anxiety symptoms that were durable through 12 months, with high remission rates. |
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