Is it safe to combine Auvelity (dextromethorphan/bupropion) and Vraylar (cariprazine)?

Safety of Combining Auvelity (Dextromethorphan/Bupropion) and Vraylar (Cariprazine)

The combination of Auvelity (dextromethorphan/bupropion) and Vraylar (cariprazine) should be used with caution due to potential pharmacodynamic interactions, though no absolute contraindication exists based on current evidence.

Understanding the Medications

Auvelity (Dextromethorphan/Bupropion)

• Auvelity is a fixed-dose combination medication containing dextromethorphan (45 mg) and bupropion (105 mg) approved for major depressive disorder in adults 1, 2
• Dextromethorphan acts as an NMDA receptor antagonist and sigma-1 receptor agonist, while bupropion inhibits CYP2D6, increasing dextromethorphan bioavailability 1, 3
• Common side effects include dizziness, headache, dry mouth, nausea, and insomnia 2, 3
• Carries a boxed warning regarding increased risk of suicidal thoughts and behaviors in pediatric and young adult patients 2

Vraylar (Cariprazine)

• Cariprazine is a second-generation antipsychotic approved for schizophrenia and as adjunctive treatment for major depressive disorder 1
• At 1.5 mg daily, cariprazine has shown efficacy as an adjunctive treatment for major depression with relatively low metabolic side effect burden 1
• Common side effects include akathisia/restlessness, fatigue, and nausea 1

Safety Considerations for This Combination

Potential Interactions

• There are no specific guidelines addressing the combination of Auvelity and Vraylar directly 4
• Both medications can affect the central nervous system, potentially leading to additive effects on:
  • CNS depression 4
  • Risk of seizures (bupropion component of Auvelity carries seizure risk) 2
  • Potential for serotonin syndrome (dextromethorphan has serotonergic properties) 4

Monitoring Recommendations

• Monitor for signs of excessive sedation or CNS depression 4
• Watch for symptoms of serotonin syndrome, especially within the first 24-48 hours after combining medications (confusion, agitation, tremors, hyperreflexia, autonomic hyperactivity) 4
• Be alert for increased risk of seizures, particularly in patients with a history of seizure disorder 4, 2
• Regular follow-up visits are recommended, similar to the monthly monitoring suggested for other psychotropic medications 4

Clinical Decision-Making

When This Combination Might Be Appropriate

• For patients with treatment-resistant depression who have failed to respond to monotherapy 4
• When the clinical benefits outweigh the potential risks of combination therapy 4
• For patients without a history of seizures, bipolar disorder, or other contraindications to either medication 4

Precautions and Contraindications

• Avoid in patients with:
  • History of seizure disorder 4, 2
  • Significant risk factors for seizures 2
  • History of bipolar disorder (caution with antidepressants) 4
  • Concomitant use of MAOIs (absolute contraindication with dextromethorphan) 4

Practical Recommendations

• Start with lower doses of both medications when using in combination 4
• Consider starting one medication first, stabilizing the patient, then adding the second medication 4
• Educate patients about potential side effects and when to seek medical attention 4
• Schedule more frequent follow-up visits initially (every 2-4 weeks) until the combination is established as effective and well-tolerated 4
• Monitor for both therapeutic effects and adverse reactions 4

Conclusion

While there is no absolute contraindication to combining Auvelity and Vraylar, caution is warranted due to potential additive CNS effects and limited direct evidence on this specific combination. The decision to use these medications together should be based on a careful assessment of the potential benefits versus risks for the individual patient, with close monitoring for adverse effects.