Vortioxetine Dose Adjustment When Increasing Bupropion
When increasing bupropion from 150 mg to 300 mg XL in a patient taking vortioxetine 10 mg, reduce the vortioxetine dose to 5 mg daily because bupropion is a strong CYP2D6 inhibitor that significantly increases vortioxetine plasma concentrations.
Pharmacokinetic Rationale
Bupropion acts as a strong CYP2D6 inhibitor, which is the primary metabolic pathway for vortioxetine clearance, and doubling the bupropion dose will substantially increase this inhibitory effect 1.
Vortioxetine exposure increases significantly when co-administered with strong CYP2D6 inhibitors like bupropion, requiring dose reduction to maintain therapeutic levels and avoid adverse effects 1.
The recommended dose adjustment for vortioxetine when combined with strong CYP2D6 inhibitors is to reduce the dose by half—from 10 mg to 5 mg daily 1.
Specific Dosing Algorithm
Step 1: Reduce vortioxetine from 10 mg to 5 mg daily on the same day you plan to increase bupropion 1.
Step 2: Simultaneously increase bupropion XL from 150 mg to 300 mg once daily in the morning 2.
Step 3: Monitor for vortioxetine-related adverse effects (nausea, sexual dysfunction, constipation, vomiting) during the first 2 weeks, as steady-state concentrations of the new regimen will be achieved within this timeframe 3, 1.
Critical Safety Monitoring
Assess blood pressure and heart rate at baseline and periodically during the first 12 weeks after increasing bupropion, as the medication can elevate both parameters 2.
Screen for seizure risk factors before dose escalation: the maximum bupropion dose of 450 mg/day should never be exceeded, and the 300 mg dose maintains seizure risk at approximately 0.1% 2, 4.
Monitor for neuropsychiatric symptoms including agitation, restlessness, and suicidal ideation, particularly during the first 1–2 weeks after the dose change 2.
Expected Timeline for Clinical Effect
Full antidepressant efficacy of the increased bupropion dose should be assessed at 6–8 weeks after reaching the 300 mg dose, not earlier 2.
Vortioxetine steady-state plasma concentrations at the reduced 5 mg dose will be achieved within 2 weeks (approximately 5 half-lives of vortioxetine's 66-hour terminal half-life) 1.
Common Pitfall to Avoid
Do not maintain vortioxetine at 10 mg when increasing bupropion to 300 mg, as this combination will result in excessive vortioxetine exposure equivalent to taking a much higher dose, significantly increasing the risk of nausea, sexual dysfunction, and other adverse effects 1.
Do not increase bupropion above 300 mg/day for depression, as the maximum dose for bupropion XL is 450 mg/day, but doses above 300 mg increase seizure risk without proportional efficacy gains for most patients 2, 5.