What is the starting dose for Wellbutrin (bupropion) in adults with depression or for smoking cessation, considering factors such as medical history and impaired liver or kidney function?

Starting Dose for Wellbutrin (Bupropion)

For major depressive disorder, start Wellbutrin SR at 150 mg once daily in the morning, then increase to 150 mg twice daily after 3-4 days if tolerated. 1, 2

Standard Adult Dosing for Depression

• Initial dose: 150 mg once daily for the first 3-4 days 1, 2
• Target maintenance dose: 150 mg twice daily (300 mg total daily) 1, 2
• The gradual titration minimizes seizure risk while achieving therapeutic drug levels 1
• Maximum dose is 400 mg/day for SR formulation or 450 mg/day for XL formulation 1

Formulation-Specific Considerations

• Wellbutrin SR (Sustained Release): Dosed 150 mg twice daily at maintenance, with doses separated and the second dose given before 3 PM to minimize insomnia 1
• Wellbutrin XL (Extended Release): Can be given as 150 mg once daily initially, then increased to 300 mg once daily in the morning 1
• The XL formulation offers improved adherence compared to twice-daily dosing, with nonadherence rates of only 15% for once-daily versus 37% for twice-daily users 3

Special Population Dose Adjustments

Older Adults

• Start with 37.5 mg once daily in the morning, then increase by 37.5 mg every 3 days as tolerated 1
• Maximum dose for older adults is 150 mg twice daily (300 mg total) 1
• This conservative approach reduces risk of adverse reactions in this vulnerable population 1

Hepatic Impairment

• Moderate to severe hepatic impairment: Maximum 150 mg every other day 1, 2
• Mild hepatic impairment: Reduce dose and/or frequency 1, 2
• Bupropion and metabolites accumulate in hepatic dysfunction, requiring careful dose reduction 1

Renal Impairment

• Reduce total daily dose by 50% for moderate to severe renal impairment (GFR <90 mL/min) 1, 2
• Bupropion metabolites are cleared renally and accumulate with renal dysfunction 1
• Consider reducing frequency of dosing 2

Smoking Cessation Dosing

• Initial dose: 150 mg once daily for 3 days 1
• Maintenance dose: 150 mg twice daily (300 mg total) 1
• Critical timing: Start bupropion 1-2 weeks BEFORE the target quit date to establish therapeutic drug levels 1
• Maximum dose: 300 mg/day for smoking cessation (lower than depression dosing) to maintain seizure risk at 0.1% 1
• Treatment duration is typically 7-12 weeks after the quit date 1

Timing of Administration

• First dose: Always in the morning to leverage activating properties 1
• Second dose (if SR formulation): Must be given before 3 PM to prevent insomnia 1
• The most common reason for missed doses is simply forgetting, occurring in 49% of twice-daily users 3

Critical Safety Screening Before Initiation

Absolute Contraindications

• Seizure disorder or any condition predisposing to seizures 1
• Current or recent MAOI use (within 14 days) 1
• Eating disorders (bulimia or anorexia nervosa) due to increased seizure risk 1
• Abrupt discontinuation of alcohol, benzodiazepines, or antiepileptic drugs 1
• Uncontrolled hypertension 1

Monitoring Parameters

• Blood pressure and heart rate, especially during first 12 weeks 1
• Neuropsychiatric symptoms and suicidal ideation, particularly in patients under 24 years old 1
• The risk for suicide attempts is greatest during the first 1-2 months of treatment 1

Expected Timeline for Response

• Begin monitoring within 1-2 weeks of initiation for adverse effects and worsening depression 1
• Allow 6-8 weeks at adequate dose before determining treatment response 1
• Energy levels may improve more rapidly than mood, sometimes within the first few weeks 1
• If no adequate response by 6-8 weeks, consider treatment modification rather than premature discontinuation 1

Common Pitfalls to Avoid

• Do not exceed maximum daily doses: 400 mg/day for SR or 450 mg/day for XL to keep seizure risk at 0.1% 1, 2
• Do not give second dose late in the day: This causes insomnia, the most common adverse effect 1, 4
• Do not start at full dose: Gradual titration reduces seizure risk and improves tolerability 1, 2
• Do not switch between brand and generic formulations without close monitoring: Historical bioequivalence issues may lead to loss of antidepressant effect 1