What is the recommended treatment protocol for Auvelity (dextromethorphan/bupropion) in adults with major depressive disorder?

Treatment Protocol for Auvelity (Dextromethorphan/Bupropion) in Adults with Major Depressive Disorder

The recommended treatment protocol for Auvelity (dextromethorphan/bupropion) in adults with major depressive disorder begins with a starting dose of one tablet (45 mg dextromethorphan/105 mg bupropion) once daily in the morning for the first week, followed by weekly escalation to the maintenance dose of two tablets twice daily (total daily dose: 180 mg dextromethorphan/420 mg bupropion).

Dosing Schedule and Administration

• Week 1: One tablet once daily in the morning
• Week 2: One tablet twice daily (morning and afternoon)
• Week 3: Two tablets in the morning, one tablet in the afternoon
• Week 4 and beyond: Two tablets twice daily (maintenance dose)

Important Administration Considerations:

• The second daily dose should not be taken late in the day to minimize insomnia risk 1
• Tablets should be swallowed whole and not crushed, divided, or chewed
• Evaluate treatment response after 12 weeks at the maintenance dose; if the patient has not lost at least 5% of body weight (when used for weight management) or shown significant improvement in depressive symptoms, consider discontinuation 1

Dosage Adjustments

• Moderate to severe renal impairment: Reduce total daily dose by half (one tablet twice daily) 1
• End-stage renal disease: Avoid use 1
• Moderate to severe hepatic impairment: Do not exceed one tablet daily 1

Monitoring and Follow-up

• Assess initial response within 1-2 weeks of starting treatment using standardized measurement tools (PHQ-9, HAMD, MADRS, or QIDS-SR) 2
• Monitor vital signs regularly, particularly blood pressure, as bupropion may increase blood pressure 1
• Treatment duration should include:
  • Acute phase: 6-8 weeks
  • Continuation phase: 4-9 months
  • Maintenance phase: Longer duration for patients with 2+ previous episodes 2

Efficacy Profile

Auvelity demonstrates several advantages over traditional antidepressants:

• Rapid onset: Significant improvement in depressive symptoms as early as 1 week after initiation 3, 4
• High response rates: Clinical trials showed response rates >80% in long-term studies 3
• High remission rates: Approaching 70% in long-term studies 3
• Sustained efficacy: Reductions in MADRS scores maintained through 12-15 months of treatment 3

Safety and Adverse Effects

The most common adverse effects include:

• Dizziness, headache, somnolence 5
• Nausea, diarrhea, dry mouth, constipation 5
• Decreased appetite 5
• Anxiety and insomnia 5
• Sexual dysfunction and hyperhidrosis 5

Most adverse events are mild to moderate in severity 3.

Contraindications and Precautions

• Boxed warning: May increase risk of suicidal thoughts and behaviors, particularly in pediatric and young adult patients 5
• Seizure risk: Higher risk at higher doses; avoid in patients with seizure disorders 5
• Opioid antagonism: Due to the dextromethorphan component, avoid in patients requiring opioid therapy; discontinue before procedures requiring opioid analgesia 1
• Monoamine Oxidase Inhibitors (MAOIs): Avoid concomitant use or within 14 days of stopping MAOIs 2
• Uncontrolled hypertension: Avoid use 1

Clinical Positioning

Auvelity can be used in various clinical scenarios:

• First-line therapy for MDD 6
• Second-line option when patients fail to achieve remission with serotonin-targeting agents 6
• Treatment-resistant depression 6

Real-world data shows that among 22,288 patients with MDD who initiated Auvelity:

• 28.8% initiated as monotherapy
• 71.2% initiated as add-on therapy (most commonly to SSRIs or SNRIs)
• 10.1% were treatment-naïve 7

Special Considerations

• Consider Auvelity for patients with depressed mood, as the bupropion component has demonstrated antidepressant properties 1
• May be beneficial for patients who need assistance with smoking cessation due to the bupropion component 1
• The unique mechanism of action (NMDA receptor antagonism and sigma-1 receptor agonism) offers an alternative for patients who haven't responded to traditional antidepressants 3, 4

By following this protocol, clinicians can optimize the safety and efficacy of Auvelity treatment for adults with major depressive disorder while minimizing adverse effects.