Wellbutrin (Bupropion) Dosing
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), with a maximum dose of 400 mg/day for SR formulation or 450 mg/day for XL formulation. 1, 2
Standard Dosing by Formulation
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, 2
- 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 1
- Maintenance dose: 150-300 mg once daily 1
- Maximum dose: 450 mg per day 1, 2
- Timing: Single morning dose 1
Indication-Specific Dosing
Smoking Cessation
- Dose: 150 mg twice daily (300 mg total) using SR formulation 1
- Timing: Begin 1-2 weeks before target quit date to establish therapeutic drug levels 1
- Duration: 7-12 weeks, with efficacy assessed at end of treatment period 1
- Weight gain mitigation: Higher doses (300 mg/day) associated with less weight gain during cessation (1.5 kg vs 2.9 kg with placebo) 3
Obesity/Weight Management (Naltrexone-Bupropion ER)
- Titration schedule: 4
- Week 1: 8/90 mg (naltrexone/bupropion) once daily in morning
- Week 2: 8/90 mg twice daily
- Week 3: 16/180 mg morning, 8/90 mg evening
- Week 4 and beyond: 16/180 mg twice daily (maintenance)
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
- Rationale: Reduced hepatic clearance increases drug accumulation risk 1
Renal Impairment
- Moderate to severe impairment (GFR <90 mL/min): Reduce total daily dose by 50% 1
- Rationale: Bupropion and metabolites are renally cleared and may accumulate 1
Critical Safety Considerations
Seizure Risk
- Maximum daily dose: Do not exceed 450 mg/day to minimize seizure risk 1, 2
- Absolute contraindications: 1, 5
- Current seizure disorder
- History of anorexia or bulimia nervosa (increased seizure risk)
- Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs
- Seizure incidence: Less than 0.1% at doses ≤450 mg/day, comparable to other antidepressants 5, 6
Drug Interactions
- MAOI use: Contraindicated within 14 days of MAOI discontinuation 1
- Tamoxifen: Avoid concurrent use (bupropion inhibits CYP2D6, reducing tamoxifen efficacy) 1
Monitoring Requirements
- Blood pressure: Monitor regularly, avoid in uncontrolled hypertension 1
- Neuropsychiatric effects: Increased monitoring in patients <24 years old 1
- Agitation: Watch for increased agitation due to activating properties 1
Clinical Pearls
Timing Optimization
- Morning dosing: Leverages activating properties, beneficial for patients with low energy or apathy 1
- Second dose cutoff: Administer before 3 PM to prevent insomnia 1
Efficacy Assessment
- Depression: Allow 6-8 weeks at adequate dose before determining treatment response 1
- Energy improvement: May occur within first few weeks, faster than mood improvement 1
- Smoking cessation: Assess efficacy after 7-12 weeks of treatment 1
Ideal Candidates
- Depression with: Low energy, apathy, hypersomnia, or atypical features 1
- Comorbid conditions: Depression with smoking cessation goals, or depression with weight concerns 1
- Sexual dysfunction concerns: Minimal sexual side effects compared to SSRIs 7