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

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

Auvelity (dextromethorphan-bupropion) is recommended as an effective treatment option for major depressive disorder (MDD) in adults, particularly for patients who need rapid symptom improvement or have failed previous antidepressant trials. This novel medication combines an NMDA receptor antagonist with a norepinephrine-dopamine reuptake inhibitor, offering a different mechanism of action compared to traditional antidepressants.

Dosing and Administration

• Initial titration schedule:

  • Week 1: 1 tablet (45 mg dextromethorphan/105 mg bupropion) in the morning
  • Week 2: Increase to 1 tablet twice daily
  • Week 3: Increase to 2 tablets in morning, 1 tablet in afternoon
  • Week 4 and beyond: Maintenance dose of 2 tablets twice daily

• Important administration notes:

  • The second daily dose should not be taken late in the day to minimize insomnia risk 1
  • For patients with moderate to severe renal impairment, reduce total daily dose by half (1 tablet twice daily) 1
  • For patients with moderate to severe hepatic impairment, limit to 1 tablet daily 1
  • Evaluate treatment response within 1-2 weeks of initiation 1, 2

Efficacy and Monitoring

• Auvelity has demonstrated significant reductions in depression scores within two weeks of treatment initiation 3
• Clinical trials showed higher remission and response rates compared to placebo and bupropion monotherapy 3
• Long-term studies demonstrated maintained efficacy with remission rates approaching 70% and response rates exceeding 80% over 12-15 months 3
• Monitor patients regularly during the first 1-2 weeks of therapy 1
• If inadequate response after 6-8 weeks at the maintenance dose, consider modifying treatment 1
• If 5% weight loss is not achieved after 12 weeks at maintenance dose, consider discontinuation as patient may be a poor responder 1

Treatment Duration

• Continue treatment for 4-9 months after satisfactory response for first episode of MDD 1
• For patients with 2 or more previous episodes, longer duration therapy is beneficial 1, 2

Special Considerations

Potential Benefits in Specific Populations:

• May be particularly beneficial for patients requiring rapid symptom improvement 3
• Can be used as monotherapy (28.8% of real-world patients) or as add-on therapy (71.2%) 4
• 10.1% of patients in real-world settings initiated Auvelity without prior treatment in the preceding 12 months 4

Precautions and Contraindications:

• Boxed warning: May increase risk of suicidal thoughts and behaviors, particularly in young adults 5
• Seizure risk: Higher risk at higher doses; use caution in patients with seizure history 5
• Opioid interactions: Due to dextromethorphan component, avoid in patients requiring opioid therapy; discontinue before procedures requiring opiates 1
• Hypertension: Monitor vital signs; avoid in patients with uncontrolled hypertension 1
• Drug interactions: Avoid use with monoamine oxidase inhibitors (MAOIs) or within 14 days of stopping MAOIs 1, 2

Common Side Effects:

• Dizziness, nausea, headache, diarrhea, somnolence, dry mouth, sexual dysfunction, hyperhidrosis, anxiety, constipation, decreased appetite, and insomnia 5
• Most adverse events in clinical trials were rated as mild-to-moderate 3

Place in Treatment Algorithm

1. First-line option: Can be considered as initial therapy, especially when rapid onset of action is desired
2. Second-line option: After failure of traditional SSRIs/SNRIs
3. Add-on therapy: Most commonly added to SSRIs (10.7%) or SNRIs (6.5%) in real-world practice 4
4. Treatment-resistant depression: Consider for patients who have failed multiple medication trials 2, 6

Clinical Pearls

• Auvelity represents a novel mechanism of action for MDD through glutamatergic modulation 3, 6
• The combination of dextromethorphan and bupropion creates both pharmacokinetic and pharmacodynamic synergy, with bupropion increasing dextromethorphan bioavailability through CYP2D6 inhibition 3, 6
• Consider Auvelity for patients who need rapid symptom improvement, as changes can be seen within two weeks 3
• The American College of Physicians recommends modifying treatment if patients do not have adequate response to pharmacotherapy within 6-8 weeks 1