Rankings / Mood, Anxiety & Stress

Dextromethorphan-bupropion (Auvelity / AXS-05)

Mood, Anxiety & Stress · NMDA antagonist + sigma-1 agonist + NDRI

Tier B

Reviewed by Read Off Label · Last reviewed · How we grade

serotoninpsychedelicnmda-modulatorprescription
6.8 / 10
Tier B
Ev 8 Bn 8 Sf 5

Bottom line

Read Off Label grades Dextromethorphan-bupropion (Auvelity / AXS-05) as B (6.8/10) based on strong evidence, high benefit magnitude, and a med-risk safety profile.

Axsome Therapeutics.

Studied, labeled, or reported-use context: 45 mg DXM + 105 mg bupropion PO once daily x 3 days then 2x daily — Rx; not individualized guidance.

What the evidence says

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

Studied, labeled, or reported dose & route

45 mg DXM + 105 mg bupropion PO once daily x 3 days then 2x daily

This records doses and routes described in studies, approved labeling, clinical practice, or documented use. It is not individualized guidance and does not establish safety; context changes with indication, formulation, health history, monitoring, and other medicines.

Citations

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Common questions

What does the evidence show about Dextromethorphan-bupropion (Auvelity / AXS-05)'s effects?
Read Off Label rates the evidence for Dextromethorphan-bupropion (Auvelity / AXS-05) as Strong and the benefit magnitude as high, producing an overall grade of B (6.8/10). Axsome Therapeutics.
What safety findings are reported for Dextromethorphan-bupropion (Auvelity / AXS-05)?
Dextromethorphan-bupropion (Auvelity / AXS-05) has a med risk profile in the database. Med (dizziness, headache, nausea, somnolence; serotonin syndrome risk with serotonergic agents; bupropion seizure risk in eating disorders or alcohol/benzo withdrawal; CYP2D6 considerations) Legal status: Rx.
What doses or routes are reported for Dextromethorphan-bupropion (Auvelity / AXS-05)?
45 mg DXM + 105 mg bupropion PO once daily x 3 days then 2x daily This is context from studies, approved labeling, clinical practice, or documented use; it is not individualized guidance and does not establish safety.
How does Dextromethorphan-bupropion (Auvelity / AXS-05) work?
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

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.