Bupropion Dosing: Starting at 150 mg and Increasing to 300 mg
Yes, starting Wellbutrin (bupropion) at 150 mg for the first week and then increasing to 300 mg is an appropriate and FDA-approved dosing strategy for major depressive disorder. 1
Standard Titration Protocol
The FDA-approved dosing for bupropion XL (extended-release) follows this exact pattern you're describing:
- Days 1-4: Start with 150 mg once daily in the morning 1
- Day 4 onwards: May increase to 300 mg once daily 1
For the SR (sustained-release) formulation, the approach is slightly different but achieves the same total daily dose:
- Days 1-3: Start with 150 mg once daily 2
- Day 4 onwards: Increase to 150 mg twice daily (300 mg total) 2
Critical Timing Considerations
The second dose of bupropion SR must be given before 3 PM to minimize insomnia risk, as this is an activating medication that can significantly disrupt sleep if taken later in the day. 3, 2
Rationale for Gradual Titration
This stepwise approach serves two essential purposes:
- Seizure risk minimization: Gradual dose escalation reduces the risk of seizures, which is dose-dependent with bupropion 1, 4
- Tolerability assessment: Starting at 150 mg allows you to evaluate how the patient tolerates the medication before reaching the therapeutic target of 300 mg 5
Maximum Dosing and Safety Limits
- Maximum daily dose: 450 mg for XL formulation, 400 mg for SR formulation 1
- Standard therapeutic dose: 300 mg daily is the usual target for major depressive disorder 2, 1
- Seizure risk: When maintained at ≤450 mg/day in divided doses, the seizure rate is approximately 0.1%, comparable to other antidepressants 4, 6
Special Population Adjustments
For older adults or those at higher risk for adverse effects, consider an even more conservative approach:
- Start at 37.5 mg every morning 3, 2
- Increase by 37.5 mg every 3 days as tolerated 3, 2
- Target the same 300 mg daily maximum (150 mg twice daily for SR) 3
Efficacy Timeline
Allow 6-8 weeks at an adequate dose before determining treatment response. 2 However, bupropion may produce more rapid improvement in energy levels compared to other antidepressants, sometimes within the first few weeks. 3
Contraindications to This Dosing Strategy
Do not use bupropion at any dose in patients with:
- Current or prior seizure disorder 1
- Current or prior diagnosis of bulimia or anorexia nervosa 1
- Abrupt discontinuation of alcohol, benzodiazepines, or antiepileptic drugs 1
- Concurrent MAOI use or within 14 days of MAOI discontinuation 1
Clinical Pearls
- Bupropion is particularly beneficial for patients with depression characterized by low energy, apathy, or hypersomnia due to its activating properties 3, 2
- The most common adverse effects (insomnia and dry mouth) are generally transient and often resolve without intervention 4
- Monitor blood pressure periodically, as bupropion can cause hypertension 1
- Screen for bipolar disorder before initiating treatment, as bupropion can trigger manic episodes 1