Starting Dose of Bupropion Sustained-Release
For bupropion sustained-release (SR) in adults, start with 150 mg once daily in the morning for 3 days, then increase to 150 mg twice daily (300 mg total daily dose). 1, 2
Dosing Algorithm by Indication
For Depression (MDD)
- Days 1-3: 150 mg once daily in the morning
- Day 4 onward: 150 mg twice daily (300 mg/day total)
- Maximum dose: 200 mg twice daily (400 mg/day) if needed 3
The FDA label for bupropion extended-release (XL) specifies starting at 150 mg once daily for 4 days before increasing to 300 mg daily 4, but for sustained-release formulations, the 3-day titration is standard 1, 2.
For Smoking Cessation
- Days 1-3: 150 mg once daily in the morning
- Day 4 through 7-12 weeks: 150 mg twice daily (300 mg/day)
- Timing: Initiate 1-2 weeks prior to quit date 5
- Give second dose before 3 PM to minimize insomnia risk 3
For Weight Management (Bupropion/Naltrexone Combination)
When bupropion is used in the naltrexone-bupropion ER combination (each tablet contains 90 mg bupropion):
- Week 1: 1 tablet daily (morning)
- Week 2: 1 tablet twice daily
- Week 3: 2 tablets (morning) + 1 tablet (afternoon)
- Week 4+: 2 tablets twice daily (maintenance dose = 360 mg bupropion/day) 6
Critical Dosing Adjustments
Hepatic Impairment
- Moderate to severe (Child-Pugh 7-15): Maximum 150 mg every other day
- Mild (Child-Pugh 5-6): Consider reducing dose and/or frequency 4
Renal Impairment
- GFR <90 mL/min: Consider reducing dose and/or frequency
- Moderate to severe renal impairment: When using naltrexone-bupropion, reduce to 1 tablet twice daily
- End-stage renal disease: Avoid naltrexone-bupropion entirely 6, 4
Key Safety Considerations
Seizure risk minimization: The gradual dose escalation is essential to minimize seizure risk, which is dose-dependent. Never exceed 200 mg as a single dose for SR formulations 3, 4.
Contraindications for bupropion:
- History of seizures or conditions that lower seizure threshold (stroke, brain metastases)
- Current or recent (within 14 days) MAOI use
- Eating disorders (bulimia, anorexia)
- Abrupt discontinuation of alcohol or benzodiazepines 3, 5, 4
Timing of second dose: Always give the second daily dose before mid-afternoon (3 PM) to avoid insomnia 3.
Drug interactions: Exercise caution with CYP 2D6 inhibitors and avoid concurrent MAOI therapy. Allow 14 days between discontinuing an MAOI and starting bupropion 1, 4.
Common Pitfall
The most common error is starting at too high a dose or escalating too rapidly, which significantly increases seizure risk. The therapeutic seizure rate at appropriate doses (up to 300 mg/day SR) is approximately 0.1%, which is within the range of other antidepressants 7. However, this risk increases substantially with higher doses or rapid titration.