What are the guidelines for long-term use of Auvelity (dextromethorphan/bupropion) for major depressive disorder?

Long-Term Use of Auvelity for Major Depressive Disorder

For patients with major depressive disorder, Auvelity (dextromethorphan/bupropion) should be continued for 4 to 9 months after a satisfactory response in patients with a first episode of depression, while those with 2 or more previous episodes should receive even longer treatment durations. 1

Duration of Treatment Guidelines

The American College of Physicians provides clear guidance on antidepressant treatment duration that applies to Auvelity:

• First episode of MDD: Continue treatment for 4-9 months after achieving a satisfactory response 1
• Multiple episodes (≥2): Longer duration therapy is beneficial, potentially extending into years 1

This recommendation is based on the understanding of depression as having three distinct phases:

1. Acute phase (6-12 weeks)
2. Continuation phase (4-9 months)
3. Maintenance phase (≥1 year)

Discontinuing treatment too early increases the risk of relapse (return of symptoms during acute/continuation phases) or recurrence (return of symptoms during maintenance phase) 1.

Monitoring and Assessment

When using Auvelity long-term:

• Regular monitoring: Begin assessment within 1-2 weeks of starting therapy and continue throughout treatment 1
• Evaluate for:
  • Therapeutic response
  • Adverse effects
  • Emergence of suicidal thoughts or behaviors (particularly important in first 1-2 months)
  • Changes in agitation, irritability, or unusual behavior 1

Efficacy of Long-Term Auvelity Treatment

Recent research supports the long-term efficacy of Auvelity:

• Two long-term, open-label studies showed large reductions in Montgomery-Åsberg Depression Rating Scale (MADRS) scores maintained through 12-15 months of treatment 2
• Long-term remission rates approached 70%, with response rates exceeding 80% 2
• Real-world data shows increasing adoption of Auvelity, with 22,288 patients initiating treatment within a year of approval 3

Safety Considerations for Long-Term Use

When using Auvelity long-term, be aware of these safety concerns:

• Boxed warning: Increased risk of suicidal thoughts and behaviors, particularly in pediatric and young adult patients 4
• Seizure risk: More likely at higher doses 4
• Common adverse effects: Dizziness, nausea, headache, diarrhea, somnolence, dry mouth, sexual dysfunction, hyperhidrosis, anxiety, constipation, decreased appetite, and insomnia 4

Treatment Selection and Modification

• The American College of Physicians recommends selecting between cognitive behavioral therapy or second-generation antidepressants (including Auvelity) after discussing effects, adverse profiles, cost, accessibility, and preferences with patients 1
• If inadequate response occurs within 6-8 weeks of initiating therapy, treatment modification is strongly recommended 1

Clinical Pitfalls to Avoid

1. Premature discontinuation: Stopping treatment too soon after symptom improvement significantly increases relapse risk
2. Inadequate monitoring: Failing to assess for adverse effects or suicidality, especially in early treatment
3. Overlooking comorbidities: Mental health comorbidities are common (53.5% of Auvelity users), with anxiety disorders present in 47.6% 3
4. Not recognizing treatment-resistant depression: Most patients prescribed Auvelity (83.7%) had previously received other antidepressants, including SSRIs, bupropion, or SNRIs 3

Auvelity's unique mechanism as an NMDA receptor antagonist and sigma-1 receptor agonist offers a different approach for patients who may not have responded adequately to traditional antidepressants, with the potential benefit of faster onset of action (as early as 1-2 weeks) compared to conventional options 5.