On December 7, 2022, the manufacturer, Axsome Therapeutics, Inc., announced that treatment with the recently FDA-approved agent, Auvelity (dextromethorphan HBr-bupropion HCl), produced swift, substantial, and durable improvements in cognitive and physical functioning in the EVOLVE (Evaluation of NMDA Modulation for Depressive Episodes) open-label trial in MDD. Treatment with Auvelity also resulted in diminished disability. Auvelity was approved by the FDA on August 19, 2022, as the first and only oral N-methyl D-aspartate (NMDA) receptor antagonist approved for the treatment of MDD in adults.
The new data were presented in a poster presentation titled "Improvements in Cognitive and Physical Functioning Outcomes in Depressed Patients Treated with AXS-05 (Dextromethorphan-Bupropion): Results from the EVOLVE Open-label, Long-Term Study" on December 6, 2022, at the American College of Neuropsychopharmacology 2022 Annual Meeting in Phoenix, Arizona.
The EVOLVE trial was an open-label, U.S. trial in which 146 patients with MDD who had received one or more prior antidepressants were treated with Auvelity twice daily for up to 15 months. The primary endpoint was the change from baseline to Week 6 on the Montgomery-Asberg Depression Rating Scale total score. Statistical analysis was performed comparing the measures at each timepoint to baseline values as prespecified (significance level of 0.05, two-sided).
In the trial, Auvelity swiftly, durably, and substantially improved symptoms of depression, including cognitive and physical functioning, and decreased disability in patients with MDD who had received one or more prior antidepressants. The change in cognitive and physical functioning was evaluated utilizing the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ), a patient-rated scale used to measure cognitive and executive dysfunction in mood and anxiety disorders.
The mean CPFQ score at baseline was 28.4. Mean improvements from baseline to Weeks 1, 2, and 6 in CPFQ scores were –2.0 points, –4.4 points, and –7.5 points, respectively (P <.001 for all). Improvements on the CPFQ were sustained through Month 6 (–9.5 points, P <.001) and Month 12 (–8.5 points, P <.001). Disability was measured using the Sheehan Disability Scale (SDS), a patient-facing questionnaire used to evaluate impairments in the domains of work, social life/leisure, and family life/home responsibility. The mean SDS score at baseline was 17.5. Mean improvements from baseline to Weeks 1, 2, and 6 in SDS scores were –2.9 points, –5.0 points, and –8.3 points, respectively (P <.001 for all). Improvements on the SDS were sustained through Month 6 (–10.1 points, P <.001) and Month 12 (–10.8 points, P <.001).
Among the trial participants, Auvelity was generally well tolerated with long-term treatment and exhibited a safety profile consistent with that observed in previously reported trials. The most common adverse events were COVID-19 infection (8.9%), nausea (8.9%), headache (7.5%), dry mouth (6.2%), dizziness (5.5%), and insomnia (5.5%).
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