Wellbutrin (Bupropion) Dosing
Start bupropion SR at 150 mg once daily for 3 days, then increase to 150 mg twice daily (300 mg total daily) for major depressive disorder, with a maximum dose of 400 mg/day for SR formulation and 450 mg/day for XL formulation. 1, 2
Standard Dosing by Formulation
Bupropion SR (Sustained Release)
- Initial dose: 150 mg once daily for 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 for 1 week 1, 2
- Maintenance dose: 300 mg once daily in the morning 1
- Maximum dose: 450 mg per day 1, 2
- Timing: Single morning dose 1
Indication-Specific Dosing
Major Depressive Disorder
- Target dose is 300 mg daily (150 mg twice daily for SR or 300 mg once daily for XL) 1, 2
- FDA trials demonstrated efficacy at 300-450 mg per day, with the 450 mg dose showing superior efficacy in fixed-dose studies 2
- Allow 6-8 weeks at an adequate dose before determining treatment response 1
Smoking Cessation
- Dose: 150 mg twice daily (300 mg total) of SR formulation 1
- Timing: Begin 1-2 weeks before target quit date to establish therapeutic drug levels 1
- Duration: 7-12 weeks, with efficacy assessed after this period 1
- Titration: Start 150 mg once daily for days 1-3, then increase to 150 mg twice daily 1
Special Population Dosing
Older Adults
- Initial dose: 37.5 mg once daily in the morning 1
- Titration: Increase by 37.5 mg every 3 days as tolerated 1
- Maximum dose: 150 mg twice daily (300 mg total daily) 1
- Rationale: Lower starting doses (approximately 50% of standard dose) minimize risk of adverse reactions in older adults 1
Hepatic Impairment
- Moderate to severe impairment: Maximum 150 mg daily (one tablet total) 1
- Rationale: Reduced hepatic metabolism requires dose limitation 1
Renal Impairment
- Moderate to severe impairment (GFR <90 mL/min): Reduce total daily dose by half 1
- Rationale: Bupropion and metabolites are cleared renally and may accumulate 1
Critical Safety Considerations
Absolute Contraindications
- Seizure disorders: Bupropion lowers seizure threshold and is contraindicated 1, 2
- Concurrent MAOI use or within 14 days of discontinuing MAOIs 1
- Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs: Increases seizure risk 1
- Bulimia or anorexia nervosa: Increased seizure risk 1
- Uncontrolled hypertension: Particularly with naltrexone/bupropion combinations 1
Maximum Dose Limits
- Do not exceed 450 mg per day to minimize seizure risk 1, 2
- At recommended doses ≤450 mg/day, seizure rates are comparable to other antidepressants (0.1% at 300 mg/day, 0.4% at 400 mg/day) 2, 3
- Doses exceeding 450 mg/day significantly increase seizure risk and risk of manic switch in bipolar disorder 4
Monitoring and Timeline
Early Monitoring (Weeks 1-2)
- Monitor for worsening depression, suicidal ideation, or behavioral changes, particularly in patients under 24 years 1
- Black box warning: Increased risk of suicidal thoughts and behavior in patients younger than 24 years requires close monitoring 1
- Monitor blood pressure and heart rate, especially in first 12 weeks, as bupropion can cause elevations 1
Response Assessment (Weeks 6-8)
- Assess for adequate response at 6-8 weeks before considering treatment modification 1, 2
- Energy levels may improve more rapidly, sometimes within first few weeks 1
- If no adequate response by 6-8 weeks at therapeutic doses, modify treatment approach 1
Long-Term Maintenance
- FDA maintenance trial demonstrated significantly lower relapse rates over 44 weeks with bupropion 300 mg/day versus placebo 2
- Continue monitoring for neuropsychiatric adverse effects and blood pressure 1
Clinical Pearls
Ideal Candidates
- Patients with depression characterized by low energy, apathy, or hypersomnia benefit from bupropion's activating properties 1
- Patients concerned about sexual dysfunction or weight gain, as bupropion has lower rates of these side effects compared to SSRIs 1
- Patients with comorbid depression and smoking cessation goals 1
Common Pitfalls
- Timing error: Administering second SR dose after 3 PM increases insomnia risk 1
- Premature discontinuation: Do not discontinue before 6-8 weeks unless significant adverse effects occur 1
- Formulation switching: Monitor closely when switching between brand and generic or between SR and XL formulations due to historical bioequivalence issues 1
- Polypharmacy caution: In patients on multiple psychotropic medications, start with 37.5 mg once daily and titrate slowly 1