Restart at Lower Dose After 2-Week Bupropion Hiatus
After a 2-week discontinuation of Wellbutrin 300mg ER, you should restart at the lower dose of 150mg once daily and titrate back up to 300mg after 4 days, following the standard initiation protocol. 1
Rationale for Dose Reduction
The FDA label explicitly states that bupropion XL should be started at 150mg once daily in the morning, with dose escalation to 300mg after 4 days of dosing to minimize seizure risk. 1 This gradual titration is necessary even in patients previously tolerating higher doses because:
- Seizure risk minimization is paramount - The primary safety concern with bupropion is dose-related seizure risk, which requires gradual dose escalation regardless of prior exposure. 1
- Two weeks represents sufficient washout - After 2 weeks off medication, the patient's system has cleared the drug and its metabolites, effectively resetting their tolerance profile. 1
- No exception exists for previously stable patients - The FDA labeling makes no distinction between treatment-naive patients and those restarting after a hiatus; the same initiation protocol applies. 1
Specific Dosing Protocol
Week 1 (Days 1-4):
- Administer 150mg once daily in the morning. 1
- Take with or without food. 1
- Swallow whole; do not crush, divide, or chew. 1
Week 1 (Day 5 onward):
- Increase to 300mg once daily in the morning if the 150mg dose is well tolerated. 1
- This represents the target maintenance dose for major depressive disorder. 1
Critical Safety Considerations
Seizure threshold protection requires:
- Adherence to the gradual titration schedule, as abrupt initiation at 300mg bypasses the safety buffer built into the dosing protocol. 1
- Maximum daily dose must not exceed 450mg to maintain seizure risk at approximately 0.1%. 2, 3
- Screening for new seizure risk factors that may have developed during the 2-week hiatus (alcohol withdrawal, new benzodiazepine use, head trauma, etc.). 4
Monitor for neuropsychiatric effects:
- Increased suicide risk is highest during the first 1-2 months of treatment, particularly in patients under 24 years old. 4
- Begin monitoring within 1-2 weeks of reinitiation for worsening depression, suicidal ideation, or behavioral changes. 4
Common Pitfalls to Avoid
Do not restart at 300mg directly - Even though the patient previously tolerated this dose, the 2-week gap necessitates retitration. The FDA provides no exemption for previously stable patients, and the seizure risk reduction strategy depends on gradual dose escalation. 1
Do not assume tolerance persists - Medication tolerance can diminish after discontinuation, and adverse effects like insomnia, dry mouth, or anxiety may reemerge during reinitiation. 2, 5
Timing matters for the second dose consideration - If the patient were on SR formulation (twice daily), the second dose must be given before 3 PM to minimize insomnia risk, though this patient is on XL (once daily). 4
Expected Timeline for Response
- Early monitoring (1-2 weeks): Assess for adverse effects and neuropsychiatric symptoms. 4
- Therapeutic assessment (6-8 weeks): Evaluate for adequate antidepressant response at the target dose before considering treatment modification. 4
- Energy improvement may occur earlier: Some patients experience improvement in energy levels within the first few weeks, though full antidepressant effect requires 6-8 weeks. 4