How do I safely discontinue bupropion extended‑release 150 mg and start sertraline?

Switching from Bupropion XL 150 mg to Sertraline

You can stop bupropion XL 150 mg abruptly and start sertraline the next day without any washout period or taper, because bupropion does not cause a classic withdrawal syndrome and neither drug is an MAOI. 1

Discontinuing Bupropion XL 150 mg

Direct Discontinuation (Preferred Approach)

• Stop bupropion XL 150 mg immediately without tapering, as it does not produce physical dependence requiring a structured weaning protocol like SSRIs or benzodiazepines. 1
• Bupropion can typically be discontinued abruptly in most patients without a formal taper because it does not cause a classic withdrawal syndrome. 1

Optional Conservative Taper (If Concerned About Symptom Recurrence)

• If you are concerned about depression relapse, reduce bupropion XL from 150 mg once daily to 150 mg every other day for 1 week, then stop. 1
• This conservative approach is optional and not medically necessary for most patients. 1

Post-Discontinuation Monitoring

• Monitor for depression relapse weekly for 4 weeks after stopping bupropion, particularly watching for return of low energy, apathy, or depressive symptoms. 1

Starting Sertraline

No Washout Required

• Begin sertraline immediately the day after stopping bupropion—no washout period is needed because neither drug is an MAOI. 2
• The 14-day washout requirement applies only to transitions involving MAOIs and does not apply to bupropion-to-sertraline switches. 2

Initial Dosing

• Start sertraline 50 mg once daily in the morning. 3
• This starting dose allows assessment of tolerability while providing therapeutic benefit in many patients. 4

Dose Titration Strategy

• Continue sertraline 50 mg daily for 6–8 weeks before considering dose escalation, as evidence shows that continued treatment at 50 mg yields response rates comparable to immediate escalation to 150 mg. 4
• If inadequate response after 6–8 weeks at 50 mg, increase to 100 mg daily for another 4 weeks, then to 150 mg if needed. 3
• Maximum dose is 200 mg daily. 3

Critical Safety Screening Before Starting Sertraline

Absolute Contraindications

• Confirm the patient has not taken an MAOI within the preceding 14 days, as concurrent use can precipitate serotonin syndrome within 24–48 hours. 2
• Screen for concurrent use of other serotonergic agents (tramadol, meperidine, methadone, fentanyl, dextromethorphan, St. John's wort) that increase serotonin syndrome risk. 3, 2

Baseline Assessment

• Assess for QT-interval prolongation risk factors, as sertraline can prolong QT at higher doses. 2
• Evaluate suicidal ideation, especially in patients younger than 24 years who require close monitoring during the first 1–2 months. 3

Monitoring During the Transition

First 1–2 Weeks (Critical Window)

• Monitor for early signs of serotonin syndrome: mental-status changes (confusion, agitation), neuromuscular hyperactivity (tremor, clonus), and autonomic hyperactivity (hypertension, tachycardia, diaphoresis). 2
• Assess for suicidal ideation, agitation, irritability, or unusual behavioral changes, as the risk of suicide attempts is highest during the first 1–2 months of antidepressant therapy. 3

Weeks 2–8

• Continue weekly monitoring for treatment response and adverse effects. 3
• Common sertraline side effects include nausea (31%), diarrhea (26%), insomnia (18%), and sexual dysfunction (41% in women, 63% in men). 5, 6

Week 6–8 Assessment

• Formally assess treatment response at 6–8 weeks; if inadequate response, consider dose escalation or augmentation rather than switching. 3

Important Clinical Considerations

Advantages of This Switch

• Sertraline is first-line for depression with prominent anxiety, whereas bupropion is preferred for depression with low energy and apathy. 3
• If sexual dysfunction was a concern on bupropion (unlikely, as bupropion has low rates), sertraline will have significantly higher rates (63% vs 15% in men, 41% vs 7% in women). 5, 6

Discontinuation Syndrome Risk

• Sertraline is associated with discontinuation syndrome characterized by dizziness, fatigue, nausea, sensory disturbances, and anxiety when stopped abruptly—unlike bupropion. 3
• When eventually discontinuing sertraline, a gradual taper will be required. 3

Drug Interactions

• Sertraline may interact with drugs metabolized by CYP2D6, though to a lesser extent than fluoxetine or paroxetine. 3

Common Pitfalls to Avoid

• Do not wait 14 days between stopping bupropion and starting sertraline—this washout is unnecessary and prolongs untreated depression. 2
• Do not escalate sertraline dose before 6–8 weeks unless tolerability issues arise, as early escalation does not improve response rates. 4
• Do not skip intensive monitoring during weeks 1–2, as this period carries the highest risk for emergent suicidal ideation and serotonin syndrome. 3, 2
• Do not misinterpret early serotonin syndrome symptoms (confusion, myoclonus, agitation) as worsening depression—this can lead to inappropriate dose escalation. 7