What is the recommended protocol for switching from Trintellix (vortioxetine) to bupropion?

Switching from Vortioxetine (Trintellix) to Bupropion

When switching from vortioxetine to bupropion, you can perform a direct switch without a washout period or cross-taper, starting bupropion SR at 150 mg once daily for 3 days while discontinuing vortioxetine, then increasing to 150 mg twice daily (300 mg total daily dose). 1, 2

Rationale for Direct Switch Strategy

The American College of Physicians' systematic review found no significant differences in efficacy between various switch strategies, including switches to bupropion SR, making a direct transition approach reasonable and evidence-based. 1 Both medications have distinct mechanisms—vortioxetine affects multiple serotonin receptors while bupropion acts on norepinephrine and dopamine without serotonergic activity—which minimizes concerns about overlapping pharmacodynamic effects. 3, 4

Specific Switching Protocol

Step 1: Discontinue Vortioxetine

• Stop vortioxetine on the day you initiate bupropion, as vortioxetine's 66-hour half-life allows for gradual clearance without requiring a taper in most patients. 4
• No washout period is necessary between medications. 1

Step 2: Initiate Bupropion SR

• Days 1-3: Start bupropion SR 150 mg once daily in the morning. 2
• Day 4 onward: Increase to 150 mg twice daily (300 mg total), with the second dose taken before 3 PM to minimize insomnia risk. 1, 2
• Maximum dose is 400 mg/day for SR formulation if needed after 6-8 weeks of adequate dosing. 2, 3

Critical Safety Considerations

Absolute Contraindications for Bupropion

• Seizure disorders or conditions lowering seizure threshold (including brain metastases, stroke history, or eating disorders). 1, 2
• Current MAOI use or within 14 days of MAOI discontinuation due to hypertensive crisis risk. 1, 2
• Uncontrolled hypertension—monitor blood pressure closely during the switch. 2

Dose Adjustments for Special Populations

• Hepatic impairment (moderate to severe): Maximum 150 mg daily total. 2
• Renal impairment (moderate to severe): Reduce total daily dose by 50%. 2
• Older adults (≥65 years): Start at 37.5 mg daily, increase by 37.5 mg every 3 days as tolerated, maximum 300 mg/day. 2

Monitoring During the Switch

Weeks 1-2

• Monitor for neuropsychiatric symptoms including depression worsening, agitation, hostility, or suicidal ideation—particularly in patients under 24 years old. 1, 2
• Assess for common side effects: insomnia, agitation, dry mouth, headache, nausea, and tremor. 3
• Check blood pressure at baseline and during titration. 2

Weeks 2-8

• Expect initial antidepressant response by week 2, with full efficacy at 4-6 weeks. 3
• If no response after 6-8 weeks at adequate dose (300 mg/day), consider alternative strategies. 2

Important Clinical Pearls

Drug interaction consideration: If the patient was taking vortioxetine with a strong CYP2D6 inhibitor, be aware that bupropion itself is a strong CYP2D6 inhibitor, which may affect other medications the patient is taking. 4

Advantage of this switch: Bupropion may be particularly beneficial if the patient has comorbid smoking cessation needs, low energy, or experienced sexual dysfunction on vortioxetine. 1, 2, 5

Weight considerations: Unlike many antidepressants, bupropion is associated with modest weight loss (0.5-1.0 kg) rather than weight gain. 6

Discontinuation of bupropion: If bupropion needs to be stopped due to adverse effects (occurs in approximately 6-15% of patients), it can be discontinued abruptly without a taper. 3, 5