Effects of AXS-05 (Auvelity®) in Improving Anhedonia and Interest-Activity Symptoms of MDD and the Associated Improvements in Functional Impairment
Background: Traditional antidepressant monotherapies are associated with poor outcomes in patients with impaired symptom domains of anhedonia and interest-activity. AXS-05 (dextromethorphan-bupropion; AUVELITY) is a novel, oral N-methyl-D-aspartate (NMDA) receptor antagonist and sigma-1 receptor agonist approved in the US for treatment of major depressive disorder (MDD) in adults.
Methods: GEMINI and ASCEND assessed AXS-05 vs controls (placebo and 105 mg bupropion, respectively) in six-week randomized controlled studies of MDD. This post hoc analysis pooled GEMINI and ASCEND populations to evaluate the effect of AXS-05 on anhedonia (Montgomery Asberg Depression Rating Scale [MADRS] Anhedonia subscale: Items 1, 2, 6, 7, 8) and interest-activity (Interest-Activity symptoms score: MADRS Items 6, 7, 8 and Quick Inventory of Depressive Symptomatology-Self Report Items 10, 13, 14; doubled to match MADRS). Least-squares mean difference (LSMD) in MADRS Anhedonia subscale and Interest-Activity Symptom scores, response (≥50% improvement), and correlations between anhedonia improvements and Sheehan Disability Scale (SDS) scores were assessed.
Results: AXS-05 (n=199) showed significant improvement vs control (n=199) in both the anhedonia and interest-activity domain scores, beginning as early as Week 1 (LSMD; both P < 0.001). Proportion of responders were 51.3% (AXS-05) vs 36.7% (control) for anhedonia and 51.8% (AXS-05) vs 36.7% (control) for interest-activity. AXS-05 treatment showed consistent benefits regardless of baseline Interest-Activity Symptom scores. Improvements in anhedonia and disability were positively correlated.
Conclusions: AXS-05 significantly improved anhedonia and impairments in interest-activity vs. control. AXS-05 significantly improved MDD symptoms regardless of baseline interest-activity symptom severity. Improvements in anhedonia symptoms were strongly correlated with improvements in functional impairment.
