How do I transition from sertraline 50mg to bupropion?

Transitioning from Sertraline 50mg to Bupropion

You should perform a direct switch from sertraline 50mg to bupropion SR 150mg once daily, discontinuing sertraline on the same day you start bupropion, then increase bupropion to 150mg twice daily after 3-4 days if tolerated. 1, 2

Rationale for Direct Switch Strategy

At the low dose of sertraline 50mg, a direct switch without cross-tapering is appropriate and minimizes the period of suboptimal antidepressant coverage. 3 The STAR*D trial demonstrated that switching between antidepressants after SSRI failure yields approximately 25% remission rates regardless of the specific agent chosen, supporting the safety and efficacy of direct switching strategies. 3

Step-by-Step Transition Protocol

Day 1: Initiation

• Discontinue sertraline 50mg completely 1, 2
• Start bupropion SR 150mg once daily in the morning 1, 2
• Take with or without food 2

Days 4-7: Dose Escalation

• Increase to bupropion SR 150mg twice daily (total 300mg/day) if the initial dose is well-tolerated 4, 1, 2
• Administer second dose before 3 PM to minimize insomnia risk 1
• This gradual titration minimizes seizure risk while achieving therapeutic levels 1

Weeks 6-8: Efficacy Assessment

• Evaluate response after 6-8 weeks at adequate dosing 1
• If no response, consider alternative treatment strategies 1

Critical Safety Considerations

Absolute Contraindications to Bupropion

• Seizure disorders or conditions that lower seizure threshold 1, 2
• Current or recent (within 14 days) MAOI use 2
• Eating disorders (bulimia or anorexia nervosa) due to increased seizure risk 1
• Abrupt discontinuation of alcohol or benzodiazepines 2

Important Drug Interaction Warning

While transitioning, be aware that bupropion inhibits cytochrome P450 2D6, which can increase blood levels of residual sertraline during the first few days. 5 Although serotonin syndrome with this combination is rare, monitor for early signs including myoclonic jerks, confusion, agitation, or autonomic instability during the first week. 5

Monitoring Requirements

• Blood pressure monitoring - bupropion should be avoided in uncontrolled hypertension 1
• Neuropsychiatric symptoms - particularly in patients under 24 years old 1
• Seizure precautions - maximum dose should not exceed 400mg/day for SR formulation 1, 2

Advantages of This Transition

Bupropion offers significant advantages over sertraline for sexual function, with only 7-15% of patients developing sexual dysfunction compared to 41-63% with sertraline. 6, 7, 8 This makes bupropion particularly appropriate if sexual side effects were a concern with sertraline.

Both medications demonstrate similar antidepressant efficacy, with no significant differences in remission rates when used as second-step treatments after SSRI failure. 3

Special Population Adjustments

Hepatic Impairment

• Moderate to severe (Child-Pugh 7-15): Maximum 150mg every other day 2
• Mild (Child-Pugh 5-6): Consider dose/frequency reduction 2

Renal Impairment

• GFR <90 mL/min: Reduce total daily dose by half 1, 2

Older Adults

• Start with 37.5mg daily, increase by 37.5mg every 3 days as tolerated 1
• Maximum 150mg twice daily (300mg total) 1

Common Pitfalls to Avoid

• Do not crush, divide, or chew bupropion SR tablets - this increases seizure risk by causing rapid drug release 2
• Do not exceed 150mg per single dose - doses should be spaced at least 8 hours apart 2
• Do not misinterpret early withdrawal symptoms from sertraline (dizziness, irritability, flu-like symptoms) as bupropion side effects - these typically resolve within 1-2 weeks
• Do not add venlafaxine or other serotonergic agents if symptoms worsen during transition, as this increases serotonin syndrome risk 5