What is the recommended dosing for Wellbutrin (bupropion) as an adjunct therapy in adults?

Bupropion Dosing as Adjunct Therapy

When using bupropion as adjunct therapy for major depressive disorder, start with 150 mg once daily for 3 days, then increase to 150 mg twice daily (300 mg total daily dose) for the SR formulation, or 150 mg once daily initially with titration to 300 mg once daily for the XL formulation. 1, 2

Standard Dosing Regimens by Formulation

Bupropion SR (Sustained Release)

• Initial dose: 150 mg once daily for the first 3 days 1
• Maintenance dose: 150 mg twice daily (300 mg total daily) 1, 2
• Maximum dose: 400 mg per day 1
• Timing: First dose in the morning, second dose before 3 PM to minimize insomnia risk 1

Bupropion XL (Extended Release)

• Initial dose: 150 mg once daily in the morning 1
• Maintenance dose: 300 mg once daily 1, 2
• Maximum dose: 450 mg per day 1, 2

Dose Adjustments for Special Populations

Older Adults

• Start with 37.5 mg every morning 1
• Increase gradually by 37.5 mg every 3 days as tolerated 1
• Maximum dose: 150 mg twice daily (300 mg total daily) 1
• Administer second dose before 3 PM to prevent sleep disturbances 1

Hepatic Impairment

• Moderate to severe hepatic impairment: Maximum 150 mg daily (one tablet total) 1

Renal Impairment

• GFR <90 mL/min: Reduce total daily dose by half 1
• Close monitoring required as bupropion and metabolites accumulate with renal clearance 1

Critical Timing Considerations

• First dose: Always administer in the morning to leverage activating properties 1
• Second dose (SR formulation): Must be given before 3 PM to minimize insomnia risk 1
• Titration interval: Allow 3 days between dose increases when using gradual titration 1

Efficacy Assessment Timeline

• Initial monitoring: Begin within 1-2 weeks of initiation for adverse effects and worsening depression 1
• Energy improvement: May occur within first few weeks, faster than other antidepressants 1
• Full response assessment: Allow 6-8 weeks at adequate dose before determining treatment failure 1
• Treatment modification: If no response by 6-8 weeks at therapeutic doses, consider alternative approaches 1

Absolute Contraindications

• Seizure disorders: Bupropion lowers seizure threshold (risk approximately 1 in 1,000 at therapeutic doses) 1, 2
• Current or recent MAOI use: Avoid within 14 days of discontinuing MAOIs 1
• Eating disorders: Bulimia or anorexia nervosa increase seizure risk 1
• Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs: Dramatically increases seizure risk 1
• Pregnancy (for weight management formulations): All naltrexone-bupropion combinations contraindicated 1

Critical Safety Monitoring

Cardiovascular

• Monitor blood pressure and heart rate periodically, especially during first 12 weeks 1
• Uncontrolled hypertension is a relative contraindication, particularly with naltrexone-bupropion combinations 1

Neuropsychiatric

• Black box warning: Increased risk of suicidal thoughts and behavior in patients <24 years old 1
• Monitor for agitation, anxiety, panic attacks, insomnia, irritability, hostility, impulsivity, mania 2
• Risk for suicide attempts is greatest during first 1-2 months of treatment 1

Seizure Risk Factors

• Maximum dose of 450 mg/day for XL or 400 mg/day for SR to minimize seizure risk 1, 2
• Alcohol consumption significantly lowers seizure threshold when combined with bupropion 3
• Doses ≥2.7g in overdose can cause seizures, encephalopathy, and cardiovascular effects 4

Clinical Advantages as Adjunct

• Lower sexual dysfunction rates compared to SSRIs 1
• Favorable for patients with: Low energy, apathy, hypersomnia, or concerns about weight gain 1
• Dual benefit: Addresses both depression and smoking cessation when applicable 1
• Complementary mechanism: Works via noradrenergic/dopaminergic pathways when combined with serotonergic agents 1

Important Clinical Pitfalls

• Do not exceed maximum daily doses: 450 mg/day for XL or 400 mg/day for SR to maintain seizure risk at 0.1% 1, 2
• Bioequivalence concerns: Monitor closely when switching between brand and generic formulations or between SR and XL, as historical bioequivalence issues may lead to loss of effect 1
• Avoid late-day dosing: Second SR dose after 3 PM significantly increases insomnia risk 1
• Gradual titration essential: Rapid dose escalation increases seizure risk 1
• Alcohol warning: Patients must be counseled that alcohol consumption lowers seizure threshold 3