AXS-05 Demonstrates Efficacy and Manageable Adverse Effects in Major Depressive Disorder Treatment

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Key Takeaways

AXS-05, combining dextromethorphan and bupropion, acts as an NMDA receptor antagonist and sigma-1 receptor agonist.
Rapid symptom reduction was observed within the first week, with sustained efficacy over six weeks.
Significant improvement in depressive symptoms was consistent across diverse demographic groups.
Common adverse events included dizziness, nausea, and headache, resolving within 2.5 to 16 days.
AXS-05 was generally well tolerated, with a low discontinuation rate due to adverse effects.

A pooled analysis of two clinical trials highlights AXS-05’s rapid and sustained effectiveness in reducing depressive symptoms, offering a promising new treatment option for major depressive disorder with a manageable safety profile.

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CONFERENCE REPORTER

A pooled analysis of 2 clinical trials evaluating AXS-05, an investigational treatment for major depressive disorder (MDD), shows that the drug is effective in reducing depressive symptoms while maintaining a manageable safety profile. The findings, presented at the Nevada Psychiatric Association’s 30th Annual National Psychopharmacology Update, highlight AXS-05’s potential as a new treatment option for patients struggling with MDD.¹

AXS-05: A Novel Approach to Depression Treatment

AXS-05 is a combination of dextromethorphan and bupropion, acting as an N-methyl-_D-aspartate receptor antagonist, sigma-1 receptor agonist, and aminoketone CYP2D6 inhibitor.¹Unlike many antidepressants that may take weeks to show benefit, AXS-05 was effective in reducing depression symptoms within the first week.

Effective Symptom Reduction Across Diverse Patient Groups

AXS-05 demonstrated significant improvement in depressive symptoms across different demographic groups, including sex, race, and prior antidepressant therapy history.¹ The study pooled data from 2 6-week, double-blind, randomized controlled trials (GEMINI and ASCEND), in which 327 patients with moderate to severe MDD were enrolled.

The primary efficacy measure was the Montgomery-Åsberg Depression Rating Scale (MADRS) total score, which showed a greater reduction in symptoms among AXS-05-treated patients compared with placebo or bupropion. Symptom relief was evident as early as week 1, and superiority over the control group was maintained through week 6.¹

Manageable Adverse Effects with Early Onset and Resolution

The most common treatment-emergent adverse events associated with AXS-05 were dizziness (17.1%), nausea (13.8%), and headache (8.1%).¹ Most treatment-emergent adverse events appeared within the first week of treatment and resolved within 2.5 to 16 days. The study found that only 7.6% of patients discontinued treatment due to adverse effects, indicating that AXS-05 was generally well tolerated.¹

Other less common adverse effects included dry mouth (6.7%), somnolence (5.7%), anxiety (5.7%), and decreased appetite (5.2%). Sexual dysfunction was reported in 5.2% of participants, but its onset was later than other adverse effects.¹ Serious or severe adverse events were rare, with a total of 5.

Study Findings

The study demonstrated AXS-05 was effective in reducing depressive symptoms while maintaining a manageable safety profile. MADRS scores reduced consistently over 6 weeks and showed an improvement in score after week 1. This remained true across all demographics given AXS-05.

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Reference

1. Chepke C, Iosifescu D, Eglit GML, et al. AXS-05 (Auvelity®) in major depressive disorder: pooled data from two six-week controlled trials (GEMINI and ASCEND). Presented at: Nevada Psychiatric Association 30^th Annual Psychopharmacology Update; February 13, 2025.