What is the usual dosing regimen of Auvelity (dextromethorphan/bupropion) for an adult with major depressive disorder not taking other bupropion or dextromethorphan, and how does it compare to typical Wellbutrin (bupropion) dosing?

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Auvelity Dosing Compared to Standard Wellbutrin

Auvelity contains only 105 mg of bupropion per tablet—substantially less than the typical 150–300 mg daily doses used in standard Wellbutrin therapy for depression. 1

Standard Auvelity Dosing Regimen

The FDA-approved dosing for Auvelity is one tablet (45 mg dextromethorphan/105 mg bupropion) twice daily, providing a total daily bupropion dose of 210 mg. 2, 3, 4 This represents approximately 70% of the standard 300 mg daily bupropion dose used for major depressive disorder. 1

  • No titration is required—patients start directly at the maintenance dose of one tablet twice daily. 3, 4
  • Therapeutic effects appear within 1–2 weeks, significantly faster than the 6–8 weeks typically required for standard antidepressants including bupropion monotherapy. 3

Comparison to Standard Wellbutrin Dosing

Wellbutrin SR (Sustained Release)

  • Initial dose: 150 mg once daily for 3 days, then increase to 150 mg twice daily (300 mg total). 1
  • Maximum dose: 400 mg per day. 1
  • Requires gradual titration to minimize seizure risk and assess tolerability. 1

Wellbutrin XL (Extended Release)

  • Initial dose: 150 mg once daily, with maintenance at 150–300 mg once daily. 1
  • Maximum dose: 450 mg per day. 1

Why the Lower Bupropion Dose in Auvelity Works

In Auvelity, bupropion serves a dual role: it provides antidepressant effects through noradrenergic/dopaminergic pathways AND inhibits CYP2D6 to increase dextromethorphan bioavailability by approximately 20-fold. 3, 4 The dextromethorphan component—an NMDA receptor antagonist and sigma-1 receptor agonist—provides the primary rapid antidepressant mechanism, allowing for lower bupropion dosing than traditional monotherapy. 2, 3, 4

Critical Safety Considerations

  • Seizure risk remains present despite the lower bupropion dose; all standard bupropion contraindications apply (seizure disorders, eating disorders, abrupt alcohol/benzodiazepine withdrawal, MAOI use within 14 days). 1, 5
  • Black box warning for suicidal ideation applies to all patients, especially those under 24 years, with highest risk in the first 1–2 months. 1, 5
  • Most common adverse effects include dizziness, nausea, headache, diarrhea, somnolence, dry mouth, sexual dysfunction, and insomnia—similar to bupropion but with additional dextromethorphan-related effects. 5

Clinical Use Patterns

Real-world data show that 28.8% of patients initiate Auvelity as monotherapy, while 71.2% use it as add-on therapy, most commonly added to SSRIs (10.7%) or SNRIs (6.5%). 6 Notably, 10.1% of patients were treatment-naïve, suggesting clinicians are comfortable using Auvelity as first-line therapy despite its novelty. 6

Patients previously treated with standard bupropion (40.4% in real-world cohorts) can safely transition to Auvelity, though the lower total bupropion dose (210 mg vs. typical 300 mg) should be considered when making this switch. 6

References

Guideline

Bupropion Dosing and Administration

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

Research

Dextromethorphan-bupropion (Auvelity) for the Treatment of Major Depressive Disorder.

Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology, 2023

Research

New Combination Drug for Depression.

The American journal of nursing, 2023

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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