Starting Wellbutrin Dose
For major depressive disorder, start bupropion XL at 150 mg once daily in the morning, then increase to the target dose of 300 mg once daily after 4 days. 1
Standard Dosing by Formulation
Bupropion XL (Extended-Release)
- Initial dose: 150 mg once daily in the morning 1
- Titration: After 4 days, increase to 300 mg once daily in the morning 1
- Maximum dose: 450 mg per day 2
- Administration: Take in the morning, with or without food; swallow whole, do not crush, divide, or chew 1
Bupropion SR (Sustained-Release)
- Initial dose: 150 mg once daily for 3 days 2
- Titration: Increase to 150 mg twice daily (300 mg total) 2
- Maximum dose: 400 mg per day 2
- Timing: First dose in the morning, second dose before 3 PM to minimize insomnia risk 2
Special Population Dosing
Older Adults (≥65 years)
- Initial dose: 37.5 mg once daily in the morning 2
- Titration: Increase by 37.5 mg every 3 days as tolerated 2
- Target dose: 150 mg twice daily (maximum 300 mg/day) 2
- Rationale: Lower starting doses reduce risk of adverse reactions in this population 2
Hepatic Impairment
- Moderate to severe (Child-Pugh 7-15): Maximum 150 mg every other day 1
- Mild (Child-Pugh 5-6): Consider reducing dose and/or frequency 1
Renal Impairment
- GFR <90 mL/min: Reduce total daily dose by 50% 2
- Hemodialysis: Consider 150 mg every 3 days rather than daily 3
- Rationale: Bupropion metabolites accumulate in renal impairment and are not effectively cleared by dialysis 2, 3
Critical Safety Considerations
Seizure Risk Minimization
- Never exceed 450 mg/day to maintain seizure risk at 0.1% (1 in 1,000) 2, 4
- Gradual dose titration is essential to minimize seizure risk 1
- Screen for predisposing factors before initiating treatment 4
Absolute Contraindications
- Seizure disorders or conditions lowering seizure threshold 2, 1
- Eating disorders (bulimia, anorexia nervosa) due to increased seizure risk 2
- Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs 2
- Current MAOI use or within 14 days of discontinuing MAOIs 1
- Uncontrolled hypertension 2
Monitoring Requirements
- Suicidal ideation: Close monitoring in patients <24 years old, especially during first 1-2 months when suicide risk is highest 2, 1
- Blood pressure and heart rate: Monitor periodically, especially during first 12 weeks 2
- Early follow-up: Begin monitoring within 1-2 weeks of initiation for therapeutic response and adverse effects 2
Common Adverse Effects
- Most frequent: Insomnia, dry mouth, headache, nausea, anxiety 4
- Management: These effects are typically transient and resolve without intervention; if needed, reduce dose 4
- Insomnia prevention: Ensure second dose (SR formulation) is taken before 3 PM 2
Time to Clinical Effect
- Initial assessment: Monitor within 1-2 weeks for adverse effects 2
- Adequate trial: Allow 6-8 weeks at therapeutic dose before determining treatment response 2
- Energy improvement: May occur within first few weeks, earlier than mood improvement 2
Clinical Advantages
- Lower sexual dysfunction rates compared to SSRIs 2
- Weight neutral or weight loss rather than weight gain 2
- Lower sedation rates than SSRIs 2
- Beneficial for patients with: Depression with low energy, apathy, hypersomnia, or comorbid smoking 2
Important Pitfalls to Avoid
- Do not crush or divide XL tablets - this destroys the extended-release mechanism and increases seizure risk 1
- Do not start at full dose - gradual titration is mandatory for safety 1
- Do not combine with naltrexone-bupropion if patient is on opioid therapy - this is an absolute contraindication 2
- Monitor for bioequivalence issues when switching between brand and generic formulations 2