What is the maximum recommended dose of Wellbutrin (bupropion) for a patient with no significant medical history?

Maximum Dose of Wellbutrin (Bupropion)

The maximum dose of bupropion depends on the formulation: 400 mg/day for sustained-release (SR) and 450 mg/day for extended-release (XL), with these limits established to minimize seizure risk to approximately 0.1%. 1, 2

Formulation-Specific Maximum Doses

• Bupropion SR (Wellbutrin SR): Maximum dose is 400 mg per day, typically administered as 200 mg twice daily 1, 3
• Bupropion XL (Wellbutrin XL): Maximum dose is 450 mg per day, administered as a single morning dose 1, 2
• Immediate-release formulation: Maximum dose is 450 mg per day in divided doses, though this formulation is less commonly used 3

The difference in maximum dosing between formulations relates to pharmacokinetic profiles and seizure risk management, with the sustained-release formulation having a slightly lower ceiling to maintain safety 3.

Critical Safety Considerations

Seizure risk is the primary limiting factor for bupropion dosing. The incidence of seizures at recommended doses (≤300 mg/day for SR) is approximately 0.1%, comparable to other antidepressants 4. However, this risk increases substantially at higher doses:

• At doses ≤450 mg/day in divided schedules, seizure rates remain comparable to other antidepressants in patients without risk factors 5
• Doses exceeding these maximums significantly increase seizure risk 2, 3
• The drug lowers the seizure threshold and is absolutely contraindicated in patients with seizure disorders 1, 4

Dose Adjustments for Special Populations

Hepatic impairment requires significant dose reduction:

• Moderate to severe hepatic impairment (Child-Pugh score 7-15): Maximum dose is 150 mg every other day 2
• Mild hepatic impairment (Child-Pugh score 5-6): Consider reducing dose and/or frequency 2
• For naltrexone-bupropion combinations in hepatic impairment: Maximum 150 mg daily (one tablet) 6, 1

Renal impairment also necessitates dose reduction:

• Moderate to severe renal impairment (GFR <90 mL/min): Reduce total daily dose by 50% 6, 1, 2
• Bupropion and metabolites are cleared renally and may accumulate, requiring close monitoring 2, 7
• Avoid in end-stage renal disease 6

Older adults may require lower starting doses (approximately 50% of standard) due to increased risk of adverse reactions and likely decreased renal function, though the maximum dose can still be reached if tolerated 1, 2

Indication-Specific Dosing

For major depressive disorder:

• Standard therapeutic dose: 300 mg/day (SR: 150 mg twice daily; XL: 300 mg once daily) 6, 1
• Maximum dose: 400 mg/day (SR) or 450 mg/day (XL) 1, 3

For smoking cessation:

• Standard dose: 300 mg/day (150 mg twice daily of SR formulation) 6, 1, 4
• Maximum dose should not exceed 300 mg/day for smoking cessation to maintain seizure risk at 0.1% 1, 4
• Higher doses for smoking cessation are not recommended and provide no additional benefit 8

For obesity management (naltrexone-bupropion ER):

• Maintenance dose: 32 mg naltrexone/360 mg bupropion daily (two 8/90 mg tablets twice daily) 6
• This represents the maximum dose for this combination product 6

Practical Dosing Algorithm

1. Start low: Begin with 150 mg once daily (SR) or 150 mg once daily (XL) for 3-7 days 1, 3
2. Titrate gradually: Increase to 150 mg twice daily (SR) or 300 mg once daily (XL) after initial tolerance is established 1
3. Assess response: Allow 6-8 weeks at therapeutic dose before considering further increases 1
4. Consider maximum dose only if needed: Increase to 400 mg/day (SR) or 450 mg/day (XL) only if inadequate response at 300 mg/day and patient has no seizure risk factors 1, 3
5. Never exceed formulation-specific maximums: 400 mg/day for SR, 450 mg/day for XL 1, 2

Common Pitfalls to Avoid

• Do not exceed maximum doses even in treatment-resistant cases, as seizure risk increases substantially 2, 5
• Screen carefully for seizure risk factors before prescribing, including history of head trauma, CNS tumor, eating disorders, or abrupt discontinuation of alcohol/benzodiazepines 1, 4
• Avoid late-day dosing of the second SR dose (administer before 3 PM) to minimize insomnia risk 1
• Do not combine with MAOIs or use within 14 days of MAOI discontinuation 1
• Monitor blood pressure regularly, especially in the first 12 weeks, as bupropion can elevate blood pressure and should be avoided in uncontrolled hypertension 6, 1
• Adjust doses appropriately in hepatic or renal impairment—failure to do so significantly increases adverse event risk 6, 2