Rankings / Mood, Anxiety & Stress
Dextromethorphan-bupropion (Auvelity / AXS-05)
Mood, Anxiety & Stress · NMDA antagonist + sigma-1 agonist + NDRI
Tier B
What this is
Axsome Therapeutics. First-in-class oral rapid-acting antidepressant — onset within 1-2 weeks vs 4-6 for SSRIs. Notable advance for treatment-resistant depression. The bupropion serves dual purpose: own antidepressant effect + CYP2D6 inhibition that slows DXM clearance, allowing meaningful steady-state levels orally.
Mechanism
Combines dextromethorphan (NMDA receptor antagonist + sigma-1 agonist + serotonin/norepinephrine reuptake inhibitor) with bupropion (NDRI + CYP2D6 inhibitor that also slows DXM metabolism); rapid antidepressant effect via NMDA pathway similar to ketamine but oral
Dose & route
45 mg DXM + 105 mg bupropion PO once daily x 3 days then 2x daily
Citations
- https://pubmed.ncbi.nlm.nih.gov/39150594/
- https://pubmed.ncbi.nlm.nih.gov/38917770/
- https://pubmed.ncbi.nlm.nih.gov/36423706/
- https://pubmed.ncbi.nlm.nih.gov/40282849/
- https://pubmed.ncbi.nlm.nih.gov/39329027/
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This is an independent synthesis of published research by a non-clinician. Scores are opinions supported by citations, not prescriptions. See the full disclaimer and methodology for how this score was produced and what it does and doesn't mean.