Bupropion SR 450 mg Daily Dosing Assessment
The proposed regimen of 300 mg in the morning and 150 mg in the evening (450 mg total daily) exceeds the recommended maximum dose for bupropion SR and should not be prescribed. 1
Maximum Dosing Limits
The standard maximum dose for bupropion SR is 400 mg per day, not 450 mg. 1 The guidelines are explicit:
- Bupropion SR maximum: 400 mg/day (typically 200 mg twice daily) 1
- Bupropion XL maximum: 450 mg/day (given once daily) 1
The confusion likely stems from the fact that bupropion XL can be dosed up to 450 mg, but this applies only to the once-daily extended-release formulation, not the SR formulation. 1
Seizure Risk Considerations
The primary safety concern with exceeding recommended doses is significantly increased seizure risk:
- At doses ≤450 mg/day with proper divided dosing, seizure rates are comparable to other antidepressants 2
- Doses >450 mg/day are associated with substantially elevated seizure risk 2, 3
- The maximum daily dose should not exceed 450 mg to minimize seizure risk, and this applies specifically to formulations designed for once-daily dosing 1
Additionally, case reports demonstrate that exceeding 450 mg/day may trigger manic episodes in patients with bipolar disorder, suggesting a dose-related threshold for adverse psychiatric effects. 3
Correct Dosing for Bupropion SR
The appropriate regimen for bupropion SR in major depressive disorder is:
- Starting dose: 150 mg once daily for 3 days 1
- Maintenance dose: 150 mg twice daily (300 mg total) 1
- Maximum dose: 200 mg twice daily (400 mg total) if needed 1
Timing Recommendations
If prescribing bupropion SR twice daily:
The activating properties of bupropion make late-day dosing problematic for sleep. 1
Alternative if Higher Dosing Needed
If the patient requires doses approaching 450 mg daily for adequate therapeutic effect, consider switching to bupropion XL 450 mg once daily in the morning rather than exceeding the SR maximum. 1 The XL formulation is specifically designed for once-daily administration at this dose level and maintains appropriate drug levels throughout the day. 4, 5
Critical Safety Monitoring
Regardless of formulation chosen:
- Contraindicated in patients with seizure disorders 1
- Avoid in patients with eating disorders (bulimia/anorexia) due to increased seizure risk 1
- Monitor blood pressure, as bupropion should be avoided in uncontrolled hypertension 1
- Watch for neuropsychiatric adverse effects, especially in patients <24 years 1
- Reduce dose by 50% in moderate-to-severe renal impairment 1
- Do not exceed 150 mg daily in moderate-to-severe hepatic impairment 1
Common Pitfall to Avoid
Do not confuse the maximum doses between formulations. The 450 mg maximum applies only to bupropion XL (once daily), not bupropion SR (twice daily). 1 Prescribing 450 mg of SR formulation places the patient at unnecessary risk without guideline support.