Is it safe to combine Vyvanse (lisdexamfetamine), Vraylar (cariprazine), and Auvelity (dextromethanol and bupropion)?

Safety of Combining Vyvanse, Vraylar, and Auvelity

The combination of Vyvanse (lisdexamfetamine), Vraylar (cariprazine), and Auvelity (dextromethorphan-bupropion) is not recommended due to significant risk of drug interactions and potential for serious adverse effects, particularly cardiovascular complications and increased seizure risk.

Medication Interactions and Risks

Stimulant + Bupropion Combination

• Bupropion (in Auvelity) lowers the seizure threshold, and when combined with stimulants like Vyvanse, this risk may be further increased 1
• While there are no explicit warnings against combining bupropion and stimulants in the literature, clinical guidelines advise caution until further studies are available 1

Cardiovascular Concerns

• Both Vyvanse (stimulant) and the bupropion component of Auvelity can increase blood pressure and heart rate
• When combined, these medications may cause additive cardiovascular effects
• Research shows that combining stimulants with other agents can lead to significant increases in vital signs - with combinations showing pulse rate increases of +17.67 to 20.85 beats/min and systolic BP increases of +12.96 to 13.78 mmHg 2

Pharmacokinetic Interactions

• Auvelity contains bupropion, which is a CYP2D6 inhibitor 3
• This inhibition could potentially affect the metabolism of cariprazine (Vraylar), altering its plasma concentrations and increasing risk of side effects

Specific Concerns by Medication

Vyvanse (Lisdexamfetamine)

• Schedule II controlled substance with significant cardiovascular effects
• Can cause increased heart rate, blood pressure, and risk of cardiac events
• May worsen anxiety, which could be problematic if combined with other psychotropic medications

Vraylar (Cariprazine)

• Second-generation antipsychotic approved for bipolar disorder and schizophrenia, and as adjunctive therapy for major depressive disorder 3
• Common side effects include akathisia, fatigue, and nausea
• Adding this to a stimulant may create opposing pharmacological actions

Auvelity (Dextromethorphan-Bupropion)

• Novel antidepressant combining dextromethorphan (NMDA receptor antagonist) with bupropion 3, 4
• Bupropion component increases seizure risk and has cardiovascular effects
• Dextromethorphan has NMDA receptor and sigma-1 receptor activity that may interact unpredictably with other psychotropics 3

Clinical Decision-Making Algorithm

1. Assess for absolute contraindications:

   • History of seizures (contraindication for bupropion in Auvelity)
   • Uncontrolled hypertension (risk with both Vyvanse and Auvelity)
   • Current use of MAOIs (contraindicated with both Vyvanse and Auvelity)

2. Consider alternative approaches:

   • Treat one condition at a time with monotherapy before adding additional agents
   • If multiple disorders are present, consider medications with efficacy for multiple conditions
   • For ADHD + depression: Consider non-stimulant options for ADHD if using Auvelity

3. If combination therapy is deemed necessary:

   • Start with the medication treating the most severe/impairing condition
   • Add second agent at low dose with careful titration
   • Monitor vital signs weekly during initiation and dose changes
   • Perform regular ECG monitoring
   • Consider consultation with both psychiatry and cardiology

Monitoring Recommendations

If despite risks, this combination is used, implement rigorous monitoring:

• Weekly blood pressure and heart rate checks during initiation and dose changes
• Baseline and follow-up ECG
• Regular assessment for neuropsychiatric symptoms
• Monitor for signs of serotonin syndrome (confusion, high fever, tremor, muscle rigidity)
• Seizure precautions and education for patient and family

Conclusion

The combination of Vyvanse, Vraylar, and Auvelity presents significant risks without established safety data. According to clinical practice guidelines, prescribers need a clear rationale for using medication combinations 1, and combinations with overlapping adverse effects or potential for pharmacodynamic interactions require formal evaluation 1. This specific three-medication combination lacks such evaluation and carries substantial theoretical risks.