Vortioxetine and Bupropion Interaction
Dose adjustment of vortioxetine is required when combining with bupropion due to a clinically significant pharmacokinetic interaction that increases vortioxetine exposure by approximately 28%. 1, 2, 3
Mechanism of Interaction
- Bupropion is a strong CYP2D6 inhibitor that significantly increases vortioxetine plasma concentrations 2, 3
- When co-administered, vortioxetine steady-state AUC increases by 128% and Cmax increases by 114% 3
- This interaction occurs because vortioxetine is primarily metabolized by CYP2D6, and bupropion potently inhibits this enzyme 2, 4
Dosing Recommendations
When combining these medications, reduce the vortioxetine dose by half: 1, 2
- If a patient is on vortioxetine 20 mg daily, reduce to 10 mg daily when adding bupropion 2
- If a patient is on vortioxetine 10 mg daily, reduce to 5 mg daily when adding bupropion 2
- For bupropion dosing, start at 150 mg once daily and increase to 150 mg twice daily after 3-7 days if tolerated, with a maximum of 300 mg/day 5
Safety Monitoring
Monitor for the following when using this combination: 5
- Seizure risk: Bupropion lowers the seizure threshold and should be avoided in patients with seizure disorders or brain metastases, with maximum dose not exceeding 300 mg per day 6, 5
- Cardiovascular effects: Both medications can affect heart rate and blood pressure; monitor vital signs at baseline and periodically 5
- Serotonin syndrome: Although vortioxetine has a relatively low risk, monitor for mental status changes, autonomic hyperactivity, and neuromuscular abnormalities when combining with other serotonergic agents 4
- Neuropsychiatric effects: Monitor for suicidal ideation, depression, agitation, and behavioral changes, particularly in patients under 24 years old 6, 5
Contraindications to This Combination
Do not use this combination in patients with: 5
- Active seizure disorder or conditions lowering seizure threshold 5
- Uncontrolled hypertension 5
- Concurrent MAO inhibitor use (within 14 days) 6
- Pregnancy or active attempts to conceive 5
Clinical Context
- This combination is commonly used in clinical practice, particularly for treatment-resistant depression and bipolar depression 5
- The interaction is predictable and manageable with appropriate dose adjustment 2, 3
- Unlike many other antidepressants, vortioxetine itself has minimal effect on CYP enzymes and does not significantly affect plasma concentrations of other medications 2, 4
- Concomitant therapy is generally well tolerated when doses are appropriately adjusted, with most adverse events being mild or moderate in intensity 3
Common Pitfall to Avoid
The most critical error is failing to reduce vortioxetine dose when adding bupropion. Without dose adjustment, patients experience significantly elevated vortioxetine levels (128% increase in AUC), which increases the risk of adverse effects including nausea, sexual dysfunction, constipation, and vomiting. 2, 3