What is the starting dose of Auvelity (dextromethorphan/bupropion) for an adult patient with major depressive disorder?

Starting Dose of Auvelity for Major Depressive Disorder

The starting dose of Auvelity (dextromethorphan/bupropion) is one tablet (45 mg dextromethorphan/105 mg bupropion) taken orally once daily in the morning for the first 3 days, then increased to one tablet twice daily (morning and afternoon) starting on day 4. 1

Initial Dosing Protocol

• Days 1-3: Begin with one tablet (45 mg/105 mg) once daily in the morning 1
• Day 4 onward: Increase to one tablet twice daily, with the second dose taken before 3 PM to minimize insomnia risk 2, 3
• The medication is administered as an extended-release fixed combination formulation 4

Critical Timing Considerations

• The morning administration leverages the activating properties of the bupropion component 2
• The second daily dose must be taken before 3 PM to prevent sleep disturbances, as bupropion has stimulating effects that can cause insomnia if taken later in the day 2, 3

Expected Timeline for Clinical Response

• Significant reductions in Montgomery-Åsberg Depression Rating Scale (MADRS) scores were observed within 2 weeks in phase 2 and phase 3 clinical trials, demonstrating faster onset compared to traditional antidepressants 1
• Full therapeutic assessment should occur at 6-8 weeks, consistent with standard antidepressant evaluation timelines 2
• Response rates exceeded 80% and remission rates approached 70% in long-term studies extending to 12-15 months 1

Pre-Treatment Screening Requirements

Before initiating Auvelity, you must evaluate for:

• Seizure history or risk factors: Auvelity is contraindicated in patients with seizure disorders, eating disorders (anorexia/bulimia), or conditions that lower seizure threshold 2, 4
• Current medications: Contraindicated with MAOIs or within 14 days of MAOI discontinuation; avoid in patients on chronic opioids (due to the naltrexone component in some bupropion combinations) 2
• Cardiovascular status: Monitor baseline blood pressure, as bupropion can elevate blood pressure and heart rate 2, 3
• Hepatic and renal function: Dose adjustments are required for moderate to severe impairment 2
• Suicidal ideation: Particularly critical in patients under 24 years old, who require close monitoring for increased suicidal thoughts during the first 1-2 months 2, 4

Common Pitfalls to Avoid

• Do not skip the 3-day titration period: Starting directly at twice-daily dosing increases the risk of adverse effects, particularly seizures 1
• Do not administer the second dose late in the day: This commonly causes insomnia and treatment discontinuation 2, 3
• Do not use in patients with uncontrolled hypertension: Blood pressure elevation is a known effect that can worsen cardiovascular outcomes 2, 3
• Do not combine with other medications that lower seizure threshold without extreme caution, as this significantly increases seizure risk 2

Monitoring During Initial Treatment

• Assess patient status within 1-2 weeks of initiation for worsening depression, suicidal ideation, or behavioral changes 2
• Monitor blood pressure and heart rate, especially during the first 12 weeks 2, 3
• Evaluate for common adverse effects including dizziness, nausea, headache, diarrhea, somnolence, dry mouth, sexual dysfunction, hyperhidrosis, anxiety, constipation, decreased appetite, and insomnia 4
• Most adverse events in clinical trials were rated as mild-to-moderate and well-tolerated 1

Treatment Context

Real-world data from 22,288 patients showed that 28.8% initiated Auvelity as monotherapy, while 71.2% used it as add-on therapy (most commonly added to SSRIs or SNRIs) 5. Approximately 10% of patients were treatment-naïve when starting Auvelity 5. This suggests Auvelity is being used across the treatment spectrum, from first-line to treatment-resistant depression.