What is the maximum recommended dose of bupropion (Wellbutrin) for treating depression and smoking cessation?

Maximum Recommended Dose of Bupropion

The maximum recommended dose of bupropion should not exceed 450 mg per day, as exceeding this dose significantly increases seizure risk. 1

Dosage Guidelines for Different Formulations

• Bupropion for Depression:

  • Immediate-release (IR): Maximum 450 mg per day 2
  • Sustained-release (SR): Maximum 400 mg per day 2
  • Extended-release (XL): 150-300 mg once daily 1

• Bupropion for Smoking Cessation:

  • Standard dosing: 150 mg twice daily (300 mg total) 3
  • Initiation schedule:
    • Days 1-3: 150 mg once daily
    • Day 4-12 weeks: 150 mg twice daily, if tolerated 3
  • Treatment duration: 7-12 weeks 3

Important Safety Considerations

Seizure Risk

The most serious adverse effect of bupropion is seizures, with risk increasing significantly at doses above 450 mg daily 1, 2. The seizure incidence is approximately 0.1% at therapeutic doses (≤450 mg/day) 1, 4.

Contraindications

Bupropion is contraindicated in patients with:

• History of seizures 1
• Brain lesions or structural abnormalities 1
• Current alcohol/substance abuse 1
• Brain metastases 3, 1
• Patients taking MAO inhibitors (risk of hypertensive reactions) 3
• Patients taking tamoxifen 3
• Closed-angle glaucoma 3

Dose Adjustments for Special Populations

• Renal impairment: Reduce total daily dose by half for moderate to severe impairment 1
• Hepatic impairment: Maximum 1 tablet daily 1
• Elderly patients: Consider lower starting doses due to increased risk of adverse effects 1

Common Side Effects

• Insomnia
• Dry mouth
• Anxiety/jitteriness
• Decreased appetite
• Headache
• Potential for increased blood pressure and heart rate 1
• Nausea (particularly relevant when used for smoking cessation during chemotherapy) 3

Clinical Pearls

1. Titration is essential: Always start with a lower dose and gradually increase to minimize side effects and reduce seizure risk 1, 2

2. Monitor for neuropsychiatric symptoms: Although uncommon, watch for development or worsening of depression and suicidal ideation/behavior, especially in younger patients 3, 1

3. Combination therapy: When used for smoking cessation, bupropion can be combined with nicotine replacement therapy (NRT) for enhanced efficacy 3

4. Timing of administration: For patients experiencing insomnia, avoid taking the medication close to bedtime 1

5. Discontinuation: If stopping treatment, implement gradual tapering (e.g., reduction to 150mg once daily for 1-2 weeks before complete discontinuation) to minimize withdrawal symptoms 1

Remember that while the maximum dose is 450 mg daily, many patients achieve therapeutic benefit at lower doses. The National Comprehensive Cancer Network guidelines specifically note that for smoking cessation, the maximum dose is 300 mg per day (150 mg twice daily) 3.