Switching from Wellbutrin (Bupropion) to an SSRI
When switching from bupropion to an SSRI, you can initiate the SSRI immediately without any washout period, as bupropion is not a monoamine oxidase inhibitor and does not require a drug-free interval. 1
Direct Switch Protocol
Immediate transition strategy:
- Stop bupropion on day 1 and start the SSRI (e.g., escitalopram 10 mg, sertraline 50 mg) on the same day 1
- No tapering of bupropion is required for most patients, though a gradual taper may minimize potential withdrawal symptoms in some individuals 2
- The 14-day washout requirement applies only to MAOI transitions, not to bupropion-to-SSRI switches 1
SSRI Selection and Dosing
Preferred SSRIs for the switch:
- Escitalopram: Start 10 mg daily, may increase to 20 mg after 1 week if tolerated (maximum 20 mg to avoid QT prolongation) 3, 1
- Sertraline: Start 50 mg daily, titrate to 100-200 mg based on response 3, 4
- Citalopram: Start 20 mg daily, may increase to 40 mg 3
All SSRIs demonstrate equivalent efficacy for major depressive disorder, with response rates of 50-60% and remission rates of approximately 25% after switching from another antidepressant 3, 4. Choose based on side-effect profile, cost, and patient preference 3.
Critical Safety Monitoring
First 1-2 weeks after the switch:
- Assess for suicidal ideation at every contact, as the risk for suicide attempts is greatest during the first 1-2 months after any antidepressant change 1, 2
- Monitor for early signs of serotonin syndrome within 24-48 hours: confusion, agitation, tremor, hyperreflexia, fever, tachycardia 1
- Evaluate for SSRI-emergent side effects: nausea, sexual dysfunction, sedation, weight gain 3
Contraindications to verify before initiating SSRI:
- No MAOI use within the preceding 14 days 1
- Avoid concurrent serotonergic agents (tramadol, meperidine, methadone, fentanyl, dextromethorphan, St. John's wort) 1
- Screen for QT-prolongation risk factors if using escitalopram, especially at doses >20 mg 1
Expected Timeline and Response Assessment
Week 1: Contact patient to assess adherence, tolerability, and early adverse events 1
Weeks 2-4: Monitor weekly during the active transition phase for withdrawal symptoms or emerging adverse events 1
Week 6-8: Formal efficacy assessment—allow a full 6-8 weeks at therapeutic SSRI dose before declaring treatment failure 3, 1, 2
Approximately 21-25% of patients achieve remission when switching from one antidepressant to another SSRI after an adequate trial 3, 1. If no response occurs by 8 weeks, consider switching to a different class (SNRI such as venlafaxine) or augmentation strategies 3, 1.
Common Pitfalls to Avoid
- Do not make the switch before ensuring bupropion has been tried at adequate doses (300-400 mg/day) for 6-8 weeks 2, 5
- Do not exceed escitalopram 20 mg daily without cardiac monitoring due to QT prolongation risk 1
- Do not combine multiple serotonergic agents during the transition period 1
- Do not skip the intensive monitoring window in weeks 1-2, as this carries the highest risk for emergent suicidal ideation 1, 2
Continuation Therapy Duration
After achieving remission on the SSRI, continue treatment for 4-9 months for a first episode of major depression 3, 1. For recurrent depression (≥2 episodes), maintain therapy for ≥1 year or longer to prevent relapse 3, 1.
Alternative Consideration: Why Not Augment Instead?
If the patient had a partial response to bupropion, consider augmenting with an SSRI rather than switching 3, 6. The STAR*D trial demonstrated that augmenting with an SSRI achieves similar remission rates (approximately 30%) to switching, with the advantage of retaining any partial benefit from bupropion 3, 6. However, if bupropion provided no benefit or caused intolerable side effects, a direct switch is appropriate 7, 4.