What is the maximum recommended dose of Wellbutrin (bupropion) SR/SL?

Maximum Dose of Wellbutrin SR

The maximum recommended dose of Wellbutrin SR (bupropion sustained-release) is 400 mg per day, administered as 200 mg twice daily, while the XL formulation has a maximum dose of 450 mg once daily. 1

Standard Dosing for Wellbutrin SR

• For major depressive disorder, the typical maintenance dose is 150 mg twice daily (300 mg total daily), starting with 150 mg once daily for 3 days before increasing 1
• For smoking cessation, the standard dose is 150 mg twice daily (300 mg total daily), initiated 1-2 weeks before the target quit date 1
• The maximum daily dose should not exceed 400 mg per day for the SR formulation to minimize seizure risk 1

Critical Safety Considerations

Seizure risk is the primary dose-limiting factor with bupropion. The incidence of seizures at the recommended 300 mg/day dose is approximately 0.1% in carefully screened patients 2. This risk increases substantially with higher doses:

• Doses above 450 mg/day of immediate-release formulation or 400 mg/day of SR formulation significantly increase seizure risk 3
• Single doses should not exceed 200 mg for SR formulation to maintain safety 2
• Patients must be screened for predisposing seizure risk factors including history of seizure disorder, eating disorders (bulimia/anorexia), abrupt discontinuation of alcohol or benzodiazepines, and concurrent medications that lower seizure threshold 1, 2

Dose Adjustments for Special Populations

Hepatic impairment requires significant dose reduction:

• Moderate to severe hepatic impairment (Child-Pugh 7-15): maximum 150 mg every other day 4
• Mild hepatic impairment (Child-Pugh 5-6): consider reducing dose and/or frequency 4

Renal impairment necessitates dose reduction:

• GFR <90 mL/min: reduce total daily dose by half 1
• Bupropion and metabolites accumulate with renal dysfunction, requiring close monitoring 4

Older adults may require lower starting doses:

• Start with 37.5 mg every morning, increasing by 37.5 mg every 3 days as tolerated 1
• Maximum dose of 150 mg twice daily (300 mg total) for geriatric patients 1
• Elderly patients have higher risk of decreased renal function requiring dose adjustment 4

Timing Considerations to Minimize Adverse Effects

• The second daily dose of SR formulation must be administered before 3 PM to minimize insomnia risk 1
• This timing is critical as bupropion has activating properties that can interfere with sleep 1

Common Pitfalls to Avoid

Do not confuse formulations: The maximum dose differs between SR (400 mg/day) and XL (450 mg/day) formulations 1. Switching between brand and generic formulations requires close monitoring due to historical bioequivalence issues 1.

Avoid rapid titration: Gradual dose escalation is necessary to assess tolerability and minimize seizure risk 1. The standard approach is increasing by 37.5-75 mg increments every 3 days 1.

Monitor for drug interactions: Bupropion is contraindicated with MAOIs or within 14 days of MAOI discontinuation 1. It should not be used in patients taking tamoxifen due to metabolic interactions 1.

Overdose Experience

Overdoses up to 30 grams have been reported, with seizures occurring in approximately one-third of cases 4. Other serious reactions include hallucinations, loss of consciousness, sinus tachycardia, and cardiac conduction disturbances 4. The most common adverse effects at therapeutic doses are insomnia and dry mouth, which are generally transient 2.