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

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

Initial Recommendation

Auvelity (dextromethorphan-bupropion) is recommended for adults with major depressive disorder (MDD) as either first-line monotherapy or as an add-on treatment for patients who have not achieved adequate response with other second-generation antidepressants, with significant improvement in depressive symptoms observed as early as 1-2 weeks after initiation. 1, 2

Dosing and Administration

• Initial titration schedule:

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

• Important administration considerations:

  • Take second dose earlier in the day to minimize insomnia risk
  • For patients with moderate to severe renal impairment: Reduce total daily dose by half (1 tablet twice daily)
  • For patients with moderate to severe hepatic impairment: Do not exceed 1 tablet daily
  • If patient has not lost 5% body weight after 12 weeks on maintenance dose, consider discontinuation 3

Efficacy Assessment

• Assess response within 1-2 weeks of initiating treatment 4
• Use standardized measurement tools like Montgomery-Åsberg Depression Rating Scale (MADRS) or PHQ-9 to track symptoms 4
• Clinical trials demonstrated:
  • Significant reduction in MADRS scores within 2 weeks compared to placebo and bupropion monotherapy 2
  • Higher remission rates (46.5% vs. 16.2%) and response rates (60.5% vs. 40.5%) compared to bupropion alone at 6 weeks 2
  • Long-term studies showed remission rates approaching 70% and response rates greater than 80% maintained through 12-15 months 1

Duration of Treatment

• Continue treatment for 4-9 months after satisfactory response for first episode of MDD
• For patients with 2 or more previous depressive episodes, longer duration of therapy is recommended 3
• If no adequate response after 6-8 weeks on maintenance dose, modify treatment 3

Special Considerations

Preferred Patient Populations:

• Patients with comorbid depressed mood (bupropion component has antidepressant properties) 3
• Patients who need assistance with smoking cessation (bupropion component may help) 3
• Patients concerned about sexual dysfunction (bupropion has lower rates of sexual adverse events than SSRIs) 3, 4
• Real-world data shows 28.8% of patients initiate Auvelity as monotherapy and 71.2% as add-on therapy 5

Contraindications and Precautions:

• Do not use with:

  • Monoamine oxidase inhibitors (MAOIs) or within 14 days of stopping MAOIs 3
  • Opioid therapy (due to naltrexone component that may reduce efficacy or precipitate withdrawal) 3
  • Uncontrolled hypertension 3
  • History of seizures or epilepsy (bupropion may lower seizure threshold) 3

• Monitor:

  • Vital signs, particularly blood pressure
  • Neuropsychiatric adverse effects, including suicidal thoughts (especially in patients under 24 years) 3
  • Discontinue before procedures requiring opiates 3

Adverse Effects

• Most common adverse events are mild to moderate and include:

  • Dizziness
  • Nausea
  • Dry mouth
  • Decreased appetite
  • Anxiety 2

• Advantages over other antidepressants:

  • Not associated with psychotomimetic effects
  • Not associated with weight gain
  • Not associated with sexual dysfunction 2
  • Fewer adverse effects than many SGAs 3

Treatment Algorithm

1. First-line options:

   • Either cognitive behavioral therapy (CBT) or second-generation antidepressants including Auvelity based on patient preference, cost, accessibility, and adverse effect profiles 3
   • Consider Auvelity as first-line for patients concerned about sexual dysfunction or who may benefit from smoking cessation

2. If inadequate response to initial SGA after 6-8 weeks:

   • Switch to Auvelity if not already tried
   • Consider Auvelity as add-on therapy (71.2% of real-world patients use it this way) 5

3. If inadequate response to Auvelity after 6-8 weeks:

   • Consider augmentation strategies such as adding lithium or an atypical antipsychotic 4
   • Consider switching to another antidepressant with a different mechanism of action 4
   • Consider adding CBT 4

Clinical Pearls and Pitfalls

• Unique mechanism: Auvelity works through NMDA receptor antagonism and sigma-1 receptor agonism, differing from traditional monoamine-based antidepressants 1, 6
• Rapid onset: Unlike many traditional antidepressants that take 4-6 weeks, Auvelity may show effects within 1-2 weeks 1, 2
• Avoid late dosing: Second daily dose should not be taken late in the day to minimize insomnia risk 3
• Discontinuation before procedures: Must be discontinued before procedures requiring opioid pain management 3
• Cardiovascular monitoring: Long-term cardiovascular safety remains unclear as cardiovascular outcome trials were terminated early 3

Auvelity represents a novel approach to treating MDD with its unique mechanism of action targeting glutamatergic neurotransmission, offering rapid onset of action and favorable side effect profile compared to traditional antidepressants.