Bupropion Dosing for Depression
For major depressive disorder, start bupropion SR at 150 mg once daily for 3 days, then increase to 150 mg twice daily (300 mg total daily dose), or use bupropion XL 150 mg once daily for 1 week, then increase to 300 mg once daily. 1, 2
Standard Adult Dosing
Bupropion SR (Sustained-Release)
- Initial dose: 150 mg once daily in the morning for 3 days 1
- Maintenance dose: 150 mg twice daily (300 mg total daily) 1
- Maximum dose: 400 mg per day 1
- Timing: First dose in the morning, second dose before 3 PM to minimize insomnia risk 1
Bupropion XL (Extended-Release)
- Initial dose: 150 mg once daily in the morning for 1 week 1, 2
- Maintenance dose: 300 mg once daily 1, 2
- Maximum dose: 450 mg per day 1
- Timing: Single morning dose 1
The FDA clinical trials demonstrated efficacy at 300 mg/day for most patients, though one trial showed efficacy only at 450 mg/day 2. The bioavailability is similar between SR and XL formulations under steady-state conditions 2.
Special Population Dosing
Older Adults
- Initial dose: 37.5 mg once daily in the morning 1
- Titration: Increase by 37.5 mg every 3 days as tolerated 1
- Maximum dose: 150 mg twice daily (300 mg total daily) 1
- Rationale: Lower starting doses reduce risk of adverse reactions in this population 1
Hepatic Impairment
- Moderate to severe impairment: Maximum 150 mg daily (one tablet total) 1
- Mechanism: Reduced hepatic metabolism requires dose reduction 1
Renal Impairment
- Moderate to severe impairment (GFR <90 mL/min): Reduce total daily dose by 50% 1
- Rationale: Bupropion and metabolites are cleared renally and may accumulate 1
Critical Safety Considerations
Absolute Contraindications
- Seizure disorders: Bupropion lowers seizure threshold 1, 2
- Eating disorders (bulimia, anorexia nervosa): Increased seizure risk 1
- MAOI use: Avoid within 14 days of MAOI discontinuation 1
- Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs: Dramatically increases seizure risk 1
- Uncontrolled hypertension: Monitor blood pressure closely 1
Maximum Dose Limits
Never exceed 450 mg per day to minimize seizure risk 1. The observed seizure rate at doses up to 300 mg/day is 0.06-0.10%, well within the range of other antidepressants 3.
Timing and Administration
Optimal Dosing Schedule
- Morning administration: Leverages bupropion's activating properties 1
- Second dose (SR formulation): Must be given before 3 PM to prevent insomnia 1
- Rationale: Bupropion improves energy and reduces apathy, making late-day dosing problematic for sleep 1
Efficacy Assessment
Timeline for Response
- Energy improvement: May occur within first few weeks 1
- Full antidepressant effect: Allow 6-8 weeks at adequate dose before determining treatment response 1
- Action if no response: Consider alternative treatment after 6-8 weeks at therapeutic dose 1
Clinical Advantages and Patient Selection
Ideal Candidates
- Depression with low energy, apathy, or hypersomnia: Bupropion's activating properties are particularly beneficial 1
- Concerns about sexual dysfunction: Lower rates compared to SSRIs 1
- Concerns about weight gain: Bupropion associated with mean weight loss of 0.5-1.0 kg versus 0.2 kg with placebo 4
- Comorbid smoking cessation needs: Addresses both conditions simultaneously 1
Important Clinical Pitfalls
Formulation Switching
Monitor patients closely when switching between brand and generic formulations or between SR and XL formulations 1. Historical bioequivalence issues with some generic bupropion SR versions have led to loss of antidepressant effect 1.
Neuropsychiatric Monitoring
- Young adults (<24 years): Increased monitoring for suicidal ideation and behavioral changes 1
- All patients: Watch for agitation, as bupropion is an activating medication 1
Drug Interactions
Bupropion is a CYP2D6 inhibitor and can increase levels of drugs metabolized by this pathway (e.g., desipramine levels increased 2-5 fold) 2. Consider dose adjustments of concomitant CYP2D6 substrates 2.