Impact of AXS-05 (Dextromethorphan-Bupropion) on Patient-Reported Insomnia Symptoms: Results from the GEMINI Trial

This work was sponsored by Axsome Therapeutics Background: Insomnia is prevalent among individuals with major depressive disorder (MDD), and certain antidepressants may exacerbate this condition. AXS-05 [dextromethorphan-bupropion (Auvelity™ extended-release tablet)] is a novel, oral NMDA receptor antagonist with multimodal activity approved by the FDA for the treatment of MDD. We assessed the impact of AXS-05 compared to placebo on patient-reported insomnia symptoms. Methods: GEMINI (Nf327) was a 6-week, randomized, double-blind, placebo-controlled U.S. study. Adult MDD patients were randomized 1:1 to receive AXS-05 or placebo twice daily. A post-hoc analysis was performed using the Insomnia Subscale of the Quick Inventory of Depressive Symptomatology (QIDS-SR-16). The three insomnia-related items of the QIDS (falling asleep, sleeping during the night, waking up too early) were combined into a single score ranging from 0-9. Results: At baseline, 4.7%, 42.1%, and 52.7% of patients reported no insomnia, mild insomnia, and moderate-severe insomnia, respectively. AXS-05 exhibited statistically higher response (50% reduction in QIDS insomnia score) rates starting at Week 3, through all subsequent timepoints. At Week 6, 40% of AXS-05-treated individuals achieved a response on the QIDS insomnia subscale, compared to 26% in the placebo group (p=0.013). The LS mean change-from-baseline in the QIDS insomnia subscale score at Week 6 was comparable between AXS-05 and placebo (1.93 vs. 1.59, p=0.22). Common adverse reactions included dizziness, headache, diarrhea, somnolence, dry mouth, sexual dysfunction, and hyperhidrosis. Conclusion: AXS-05 demonstrated significant improvements in insomnia response rates compared to placebo in the GEMINI study. These findings provide additional evidence of AXS-05's efficacy on patient-centric outcomes in MDD.