What are the risks of taking Vraylar (cariprazine) and Wellbutrin (bupropion) together?

Combining Vraylar (Cariprazine) and Wellbutrin (Bupropion)

The combination of Vraylar and Wellbutrin can be used together safely with appropriate monitoring, as no direct pharmacokinetic interactions or contraindications exist between these medications, but requires vigilant seizure risk assessment and neuropsychiatric monitoring. 1, 2

Primary Safety Considerations

Seizure Risk Management

• Bupropion lowers the seizure threshold with a documented 0.1% seizure risk in clinical trials, making this the most critical safety concern when combining with any medication 3, 1, 2
• Screen for absolute contraindications before initiating or continuing this combination:
  • Active seizure disorder or seizure history 1, 2
  • Brain metastases or structural brain lesions 3, 1
  • Eating disorders (anorexia or bulimia) 1, 2
  • Alcohol withdrawal or abrupt benzodiazepine discontinuation 1, 2
  • Recent head trauma 1, 2

Neuropsychiatric Monitoring

• Both medications require monitoring for worsening depression, suicidal ideation (especially in patients under 24 years), and increased agitation, though large-scale trials show bupropion does not significantly increase neuropsychiatric events compared to placebo 3, 1, 2
• Bupropion is an activating medication that can cause agitation, while Vraylar (an atypical antipsychotic) may have sedating or activating effects depending on the individual 1, 2

Cardiovascular Effects

• Monitor blood pressure regularly, as bupropion can cause mild elevations in blood pressure and heart rate 1, 2
• Avoid this combination in patients with uncontrolled hypertension 1, 2

Dosing Considerations

Bupropion Dosing

• Standard therapeutic dose for depression is 300mg daily (bupropion XL), with maximum dose of 450mg daily 1
• Initial dosing: 150mg once daily, then increase to 300mg once daily after 3-7 days if tolerated 3, 1
• Administer in the morning or ensure any second dose is given before 3 PM to minimize insomnia 1

Special Population Dose Adjustments

• In moderate to severe hepatic impairment, maximum bupropion dose is 150mg daily (AUC increases 3.12-fold) 1, 4
• In moderate to severe renal impairment, reduce bupropion dose by 50% (exposure approximately doubles) 1, 4

Common Side Effects to Monitor

• Headache, dizziness, and insomnia are common with bupropion 2
• Gastrointestinal effects including nausea, dry mouth, and constipation should be monitored 2
• Nausea from either medication may need management, especially if the patient is on other medications that cause GI upset 3

Critical Drug Interactions to Avoid

• Never combine bupropion with MAOIs or within 14 days of stopping MAOIs due to hypertensive crisis risk 1, 2
• Avoid tramadol, meperidine, or other serotonergic opioids if the patient is also on SSRIs 1
• Bupropion inhibits CYP2D6, which can affect metabolism of other medications metabolized by this pathway 1

Clinical Benefits of This Combination

• This combination may be particularly effective for treatment-resistant depression, as Vraylar is FDA-approved as an augmentation agent for major depressive disorder 1
• Bupropion addresses depression through norepinephrine/dopamine pathways and is beneficial for patients with low energy, apathy, or who want to quit smoking 1, 2

Monitoring Protocol

• Establish baseline blood pressure and monitor regularly 1, 2
• Assess for neuropsychiatric symptoms at each visit, especially during dose adjustments 2
• Regular follow-up visits to assess efficacy and side effects 2
• Discontinue or adjust dosing if significant side effects occur 2

Important Caveat About Seizure Risk Duration

• The seizure risk associated with bupropion may persist until metabolites are cleared, which takes approximately 7-9 days after discontinuation 4
• This extended clearance time is relevant if the medication needs to be stopped due to adverse effects or before procedures 4