Abstracts
3427201
(#31) Effects of Dextromethorphan-Bupropion (45mg/105mg) in Participants with Major Depressive Disorder and Anxious Distress
Abstract: Background: Anxiety symptoms are common in major depressive disorder (MDD) and are associated with poor treatment response to conventional antidepressants. Dextromethorphan-bupropion (45mg/105mg; Auvelity®) is an NMDA receptor antagonist and CYP2D6 inhibitor approved for adults with MDD. This posthoc analysis evaluated the antidepressant efficacy of dextromethorphan-bupropion in patients with MDD and anxious distress.
Methods: Data were analyzed from the 6-week, Phase 3 GEMINI trial of dextromethorphan-bupropion versus placebo in adults with MDD. Anxious distress (proxy definition) required ≥2 of the following: MADRS Inner Tension ≥3; MADRS Concentration Difficulties ≥3 with QIDS Concentration Difficulties ≥2; QIDS Restlessness ≥2. The primary endpoint was change from baseline in MADRS total score at Week 6; secondary endpoints included MADRS response and remission, CGI-S/I, patient-reported outcomes (Q-LES-Q, SDS), and PGI-I. Safety outcomes included TEAEs and discontinuations.
Results: Among participants with anxious distress (dextromethorphan-bupropion n=115/156; placebo n=102/161), dextromethorphan-bupropion produced significantly greater reductions in MADRS total score versus placebo at all timepoints (all P ≤ 0.001). Dextromethorphan-bupropion was associated with higher response rates at all visits (all P 0.05) and higher remission rates from Week 2 onward (all P 0.01). Improvements in CGI-S, CGI-I, Q-LES-Q, SDS, and PGI-I were also observed. Anxiety-related TEAEs were uncommon (4.3% vs 1.2%), with low anxiety-related discontinuations (1.9% vs 0%).
Conclusions: Dextromethorphan-bupropion demonstrated robust antidepressant efficacy in participants with MDD and anxious distress. It was generally well‑tolerated, with low rates of anxiety‑related discontinuations. These findings support dextromethorphan-bupropion as a clinically meaningful and well‑tolerated treatment option for patients with MDD and anxious distress.
Short Description: Anxiety is common in MDD and linked to poor antidepressant response. This post-hoc analysis of the GEMINI trial assessed dextromethorphan-bupropion in participants with MDD and anxious distress (defined by proxy criteria aligned to the DSM-V-TR). Dextromethorphan‑bupropion was associated with reductions in MADRS, higher response/remission rates, and improvements in clinician‑rated and patient‑reported outcomes, with low rates of anxiety‑related TEAEs. Findings support dextromethorphan-bupropion as a clinically meaningful and well‑tolerated treatment for patients with MDD and anxious distress.
Name of Sponsoring Organization(s): Axsome Therapeutics, Inc.
Methods: Data were analyzed from the 6-week, Phase 3 GEMINI trial of dextromethorphan-bupropion versus placebo in adults with MDD. Anxious distress (proxy definition) required ≥2 of the following: MADRS Inner Tension ≥3; MADRS Concentration Difficulties ≥3 with QIDS Concentration Difficulties ≥2; QIDS Restlessness ≥2. The primary endpoint was change from baseline in MADRS total score at Week 6; secondary endpoints included MADRS response and remission, CGI-S/I, patient-reported outcomes (Q-LES-Q, SDS), and PGI-I. Safety outcomes included TEAEs and discontinuations.
Results: Among participants with anxious distress (dextromethorphan-bupropion n=115/156; placebo n=102/161), dextromethorphan-bupropion produced significantly greater reductions in MADRS total score versus placebo at all timepoints (all P ≤ 0.001). Dextromethorphan-bupropion was associated with higher response rates at all visits (all P 0.05) and higher remission rates from Week 2 onward (all P 0.01). Improvements in CGI-S, CGI-I, Q-LES-Q, SDS, and PGI-I were also observed. Anxiety-related TEAEs were uncommon (4.3% vs 1.2%), with low anxiety-related discontinuations (1.9% vs 0%).
Conclusions: Dextromethorphan-bupropion demonstrated robust antidepressant efficacy in participants with MDD and anxious distress. It was generally well‑tolerated, with low rates of anxiety‑related discontinuations. These findings support dextromethorphan-bupropion as a clinically meaningful and well‑tolerated treatment option for patients with MDD and anxious distress.
Short Description: Anxiety is common in MDD and linked to poor antidepressant response. This post-hoc analysis of the GEMINI trial assessed dextromethorphan-bupropion in participants with MDD and anxious distress (defined by proxy criteria aligned to the DSM-V-TR). Dextromethorphan‑bupropion was associated with reductions in MADRS, higher response/remission rates, and improvements in clinician‑rated and patient‑reported outcomes, with low rates of anxiety‑related TEAEs. Findings support dextromethorphan-bupropion as a clinically meaningful and well‑tolerated treatment for patients with MDD and anxious distress.
Name of Sponsoring Organization(s): Axsome Therapeutics, Inc.
