What is the recommended treatment plan for major depressive disorder using Auvelity (dextromethorphan-bupropion)?

Treatment Plan for Major Depressive Disorder Using Auvelity (Dextromethorphan-Bupropion)

Auvelity (dextromethorphan-bupropion) is an effective, fast-acting, and well-tolerated first-line or add-on treatment option for adults with major depressive disorder, with significant antidepressant effects observed within two weeks of initiation. 1

Dosing and Titration

• Initial dosing: Start with 1 tablet (45 mg dextromethorphan/105 mg bupropion) once daily in the morning
• Titration schedule:
  • Week 1: 1 tablet once daily in the morning
  • Week 2: Increase to 1 tablet twice daily
  • Week 3: Increase to 2 tablets in morning and 1 in afternoon
  • Week 4 and beyond: Maintenance dose of 2 tablets twice daily
• Important administration notes:
  • The second dose should not be taken late in the day to minimize insomnia risk
  • Take tablets whole; do not crush, divide, or chew

Dosage Adjustments for Special Populations

• Renal impairment:
  • Moderate to severe impairment: Reduce total daily dose by half (1 tablet twice daily)
  • End-stage renal disease: Avoid use
• Hepatic impairment:
  • Moderate to severe impairment: Maximum 1 tablet daily

Monitoring and Treatment Duration

• Evaluate initial response within 1-2 weeks of starting treatment 2
• Use standardized measurement tools (PHQ-9, HAMD, MADRS) to track symptoms
• If patient has not lost 5% of body weight after 12 weeks on maintenance dose, consider discontinuation as they may be a poor responder 3
• Continue treatment for 4-9 months after satisfactory response for first episode of MDD
• For patients with 2 or more previous episodes, longer duration therapy is beneficial 3
• Monitor vital signs regularly, especially blood pressure

Efficacy

• Clinical trials demonstrated significant reductions in Montgomery-Åsberg Depression Rating Scale (MADRS) scores compared to placebo within two weeks 1
• Long-term studies showed maintained efficacy through 12-15 months with remission rates approaching 70% 1
• Real-world data shows Auvelity is being used both as monotherapy (28.8%) and as an add-on treatment (71.2%) 4

Contraindications and Precautions

• Absolute contraindications:

  • Concomitant use with MAOIs or within 14 days of stopping MAOIs
  • Seizure disorders or conditions that lower seizure threshold
  • Bulimia or anorexia nervosa
  • Uncontrolled hypertension

• Use with caution in:

  • Patients requiring opioid therapy (due to naltrexone component)
  • Patients with history of seizures
  • Patients younger than 24 years (monitor for suicidal thoughts)

Common Side Effects

• Dizziness, nausea, headache, diarrhea, somnolence
• Dry mouth, sexual dysfunction, hyperhidrosis
• Anxiety, constipation, decreased appetite, insomnia 5

Clinical Pearls

• Auvelity works through a novel mechanism as an NMDA receptor antagonist and sigma-1 receptor agonist, offering a different approach from traditional monoamine-based antidepressants 1
• The bupropion component increases dextromethorphan bioavailability through CYP2D6 inhibition 1
• Consider Auvelity for patients who have failed to achieve remission with serotonin-targeting agents 6
• If patient does not have adequate response to pharmacotherapy within 6-8 weeks, modify treatment 3
• Auvelity may be particularly beneficial for patients with comorbid depression and need for smoking cessation

Potential Pitfalls

• Monitor closely for suicidal thoughts and behaviors, especially in younger adults (boxed warning)
• Seizure risk increases at higher doses; adhere to recommended dosing
• Avoid concomitant use with drugs that lower seizure threshold
• Discontinue before procedures requiring opioid analgesia
• Do not abruptly discontinue; taper gradually to minimize withdrawal symptoms

Auvelity represents a novel treatment option for MDD with a different mechanism of action than traditional antidepressants, potentially offering benefits for patients who have not responded adequately to other treatments.