Wellbutrin (Bupropion) Dosing and Treatment for Depression
Recommended Starting Approach
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 if tolerated. 1
This represents the FDA-approved dosing strategy that balances efficacy with seizure risk minimization through gradual titration. 1
Formulation Selection and Dosing
Bupropion XL (Extended Release) - Preferred
- Initial dose: 150 mg once daily in the morning 1
- Target dose: 300 mg once daily after 4 days 2, 1
- Maximum dose: 450 mg once daily 2, 1
- Advantage: Once-daily dosing improves adherence 2
Bupropion SR (Sustained Release) - Alternative
- Initial dose: 150 mg once daily for 3 days 2
- Target dose: 150 mg twice daily (300 mg total) 3, 2
- Maximum dose: 400 mg per day 2
- Timing: First dose in morning, second dose before 3 PM to minimize insomnia 2
Special Population Dosing Adjustments
Hepatic Impairment
- Moderate to severe: Maximum 150 mg every other day 2, 1
- Mild: Consider reducing dose and/or frequency 1
Renal Impairment
Older Adults
- Initial dose: 37.5 mg once daily in morning 2
- Titration: Increase by 37.5 mg every 3 days as tolerated 2
- Maximum: 150 mg twice daily (300 mg total) 2
- Rationale: Increased risk of adverse reactions in elderly 2
Critical Monitoring and Safety
Initial Assessment Period
- Begin monitoring within 1-2 weeks of initiation for suicidal thoughts, agitation, irritability, or unusual behavioral changes 3, 1
- Risk for suicide attempts is greatest during the first 1-2 months 3
- Monitor blood pressure before and periodically during treatment 2, 1
Treatment Response Evaluation
- Assess efficacy at 6-8 weeks - if inadequate response, modify treatment 3
- Continue regular monitoring for therapeutic response and adverse effects 3
Neuropsychiatric Monitoring
- Watch for signs of hypomania/mania, especially in first 24-48 hours after dose changes 4
- Monitor for agitation, as bupropion has activating properties 2
- Particularly important in patients under 24 years old 2
Absolute Contraindications
Do not prescribe bupropion in patients with: 1
- Seizure disorder or history of seizures 2, 1
- Current or prior bulimia or anorexia nervosa 2, 1
- Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs 1
- Concurrent MAOI use or within 14 days of MAOI discontinuation 2, 1
- Known hypersensitivity to bupropion 1
Clinical Advantages Over Other Antidepressants
Sexual Function
- Bupropion has significantly lower rates of sexual dysfunction compared to SSRIs like fluoxetine, sertraline, and paroxetine 3
- This makes it particularly valuable for patients who have experienced sexual side effects with other antidepressants 3
Weight and Sedation
- Associated with less weight gain and somnolence compared to tricyclic antidepressants 5, 6
- Activating properties can improve energy levels and reduce apathy 2
Dual Indication Benefit
- Particularly beneficial for patients with comorbid depression and smoking cessation goals, addressing both conditions simultaneously 2
Seizure Risk Minimization
The seizure risk is dose-dependent and can be minimized through: 1, 7
- Never exceed 450 mg/day total dose 2, 1
- Gradual dose titration 1
- Avoiding use in high-risk populations 1
- Discontinue immediately if seizure occurs 1
At doses ≤450 mg/day with proper dosing schedule, seizure incidence is comparable to other antidepressants (approximately 0.1%) 7, 8
Efficacy Considerations
Comparative Effectiveness
- All second-generation antidepressants show equivalent efficacy for major depression - selection should be based on adverse effect profiles, cost, and patient preferences 3
- Bupropion demonstrates similar efficacy to SSRIs (escitalopram, fluoxetine) and SNRIs (venlafaxine) in head-to-head trials 5, 6
Treatment Duration
- Continue treatment through resolution of depressive episode 3
- For seasonal affective disorder, initiate in autumn and continue through winter season 1, 9
- Periodically reassess need for maintenance treatment 1
Common Pitfalls to Avoid
- Late-day dosing causing insomnia - always administer morning dose and second SR dose before 3 PM 2
- Rapid titration increasing seizure risk - follow gradual titration schedules 1
- Missing dose adjustments in hepatic/renal impairment - can lead to drug accumulation and toxicity 2, 1
- Inadequate monitoring in first 6-8 weeks - critical period for assessing response and suicidality 3
- Using in patients with uncontrolled hypertension - bupropion can elevate blood pressure 2, 1