ABSTRACT
BackgroundInnovative 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
ABSTRACT
BackgroundIn 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