Switching from Sertraline (Zoloft) to Bupropion (Wellbutrin)
Use a cross-taper approach over 2-3 weeks: start bupropion at 37.5 mg daily (increasing by 37.5 mg every 3 days to target 150 mg twice daily), while simultaneously reducing sertraline by approximately 50% in the first week, then discontinuing it completely in the second week. 1, 2
Titration Protocol
Week 1: Initiate Cross-Taper
- Start bupropion SR at 37.5 mg every morning 2
- Reduce sertraline dose by 50% (e.g., from 150 mg to 75 mg daily) 1
- Increase bupropion by 37.5 mg every 3 days as tolerated 2
- Give the second bupropion dose before 3 PM to minimize insomnia risk 2
Week 2: Complete Sertraline Discontinuation
- Discontinue sertraline completely 1
- Continue titrating bupropion to target dose of 150 mg twice daily (maximum 300 mg/day) 2
- Monitor closely for withdrawal symptoms during this transition period 1, 3
Week 3 and Beyond
- Maintain bupropion at therapeutic dose (typically 150 mg twice daily) 2
- Continue monitoring for at least 4-6 weeks to assess full therapeutic response 2
Critical Monitoring Requirements
Sertraline Withdrawal Symptoms (First 10-14 Days)
- Watch for discontinuation syndrome: dizziness, vertigo, sensory disturbances, irritability, anxiety, headache, nausea, fatigue, and insomnia 1
- The gradual taper over 10-14 days significantly reduces withdrawal symptom severity 1
Bupropion-Specific Precautions
- Contraindicated in patients with seizure disorders or brain metastases due to dose-dependent seizure risk 2
- Do not use in agitated patients as bupropion is activating 2
- Monitor for neuropsychiatric symptoms including depression, suicidal ideation, or hostility, though these are uncommon 2
Rationale for This Approach
Why Cross-Taper Rather Than Direct Switch
- Cross-tapering maintains antidepressant coverage while minimizing withdrawal risk 1, 3
- Abrupt sertraline cessation is problematic due to well-documented discontinuation syndrome 1, 4
- Conservative "washout period" approaches leave patients untreated and risk life-threatening depression exacerbations 3
Pharmacological Considerations
- Bupropion and sertraline have different mechanisms: bupropion is a norepinephrine-dopamine reuptake inhibitor, while sertraline is an SSRI 2
- No significant drug-drug interaction concerns between these two agents during overlap 2
- Bupropion has significantly lower sexual dysfunction rates (15% men, 7% women) compared to sertraline (63% men, 41% women), which may be a key reason for switching 5, 6
Common Pitfalls to Avoid
- Do not titrate bupropion too rapidly: the 37.5 mg every 3 days schedule minimizes seizure risk and allows tolerance to develop 2
- Do not give second bupropion dose after 3 PM: this increases insomnia risk 2
- Do not abruptly stop sertraline: always taper over at least 10-14 days 1
- Do not exceed 300 mg/day total bupropion dose to minimize seizure risk 2