What is the dose of dextromethorphan in Auvelity (dextromethorphan-bupropion)?

Dextromethorphan Dosage in Auvelity

Auvelity contains 45 mg of dextromethorphan per tablet, administered twice daily for a total daily dose of 90 mg dextromethorphan. 1, 2, 3

Formulation and Dosing Details

• Auvelity is a fixed-dose combination medication containing 45 mg dextromethorphan and 105 mg bupropion in an extended-release formulation per tablet 1, 3
• The standard dosing regimen is one tablet twice daily, resulting in a total daily dose of 90 mg dextromethorphan 2, 3
• The initial dosing typically starts with one tablet once daily for the first 3 days, then increases to one tablet twice daily thereafter 3

Mechanism of Action

• Dextromethorphan in Auvelity functions as an uncompetitive NMDA receptor antagonist and sigma-1 receptor agonist, modulating glutamate signaling 1
• Bupropion serves a dual purpose in this formulation:
  • It provides its own antidepressant effect as a norepinephrine-dopamine reuptake inhibitor 2
  • It inhibits CYP2D6, preventing the rapid metabolism of dextromethorphan and increasing its bioavailability 1, 2

Clinical Context

• Dextromethorphan has traditionally been used as a cough suppressant at doses ranging from 15-30 mg for acute cough 4
• In Auvelity, the higher dose of 45 mg twice daily (90 mg total) is specifically formulated for the treatment of major depressive disorder, not for cough suppression 1, 3
• The dextromethorphan dose in Auvelity (45 mg) is higher than typical cough suppressant doses (30 mg) because:
  1. The antidepressant effect requires higher doses than the antitussive effect 2, 3
  2. The combination with bupropion allows for higher dextromethorphan blood levels through CYP2D6 inhibition 1

Efficacy Evidence

• In clinical trials, the 45 mg dextromethorphan/105 mg bupropion combination demonstrated significant improvements in depression scores compared to bupropion alone 3
• Remission rates with this dextromethorphan dosage approached 70% in long-term studies 1
• The onset of antidepressant effect was observed within two weeks of treatment initiation 1, 3

Safety Considerations

• The most common adverse effects at this dextromethorphan dosage include dizziness, headache, nausea, dry mouth, and somnolence 1, 5
• Unlike when used as a cough suppressant, the dextromethorphan in Auvelity is not associated with significant respiratory depression at the 45 mg dose 4
• Like all antidepressants, Auvelity carries a boxed warning regarding increased risk of suicidal thoughts and behaviors in pediatric and young adult patients 5

The 45 mg dextromethorphan dose in Auvelity represents a specific therapeutic dosing for depression that differs from its traditional use as a cough suppressant, with the bupropion component serving to both enhance dextromethorphan levels and provide additional antidepressant effects.