Initial Dosing Directions for Wellbutrin (Bupropion)
For starting Wellbutrin (bupropion), begin with 150 mg once daily for the first 3-4 days, then increase to 150 mg twice daily if tolerated, with a maximum dose of 300 mg per day. 1
Standard Dosing Protocol
Immediate Release (IR) Formulation
- Not typically used as first-line due to three-times-daily dosing requirement
Sustained Release (SR) Formulation
- Initial dose: 150 mg once daily in the morning 2, 1
- Days 4 and beyond: Increase to 150 mg twice daily if tolerated 1
- Maximum dose: 300 mg per day (150 mg twice daily) 2, 1
Extended Release (XL) Formulation
- Initial dose: 150 mg once daily in the morning 1
- After 4 days: May increase to target dose of 300 mg once daily in the morning 1
- Maximum dose: 300 mg per day 1
Administration Guidelines
- Take in the morning (for once-daily dosing) 1
- May be taken with or without food 1
- Swallow tablets whole - do not crush, divide, or chew extended-release formulations 1
- Space doses at least 8 hours apart for twice-daily dosing 2
Important Monitoring and Safety Considerations
Seizure Risk
- Gradual dose titration is essential to minimize seizure risk 1
- Contraindicated in patients with seizure disorders, stroke, or brain metastases 2
- Avoid in patients with closed-angle glaucoma 2
Drug Interactions
- Contraindicated with MAO inhibitors (must allow 14 days between discontinuing MAOIs and starting bupropion) 1
- Avoid in patients taking tamoxifen 2
Psychiatric Monitoring
- Monitor closely for worsening depression or emergence of suicidal thoughts, especially during initial treatment or dose changes 1
- Although uncommon, watch for development of neuropsychiatric issues including depression and suicidal ideation/behavior 2
- In bipolar patients, doses exceeding 450 mg/day may increase risk of manic switch 3
Common Side Effects
- Dry mouth, insomnia, headache, nausea
- Activation/agitation - to minimize risk of insomnia, administer second dose before 3 PM 2
Special Populations
Hepatic Impairment
- Moderate to severe impairment: Maximum 150 mg every other day 1
- Mild impairment: Consider reducing dose and/or frequency 1
Renal Impairment
- Consider reducing dose and/or frequency in patients with GFR <90 mL/min 1
Discontinuation
- For patients on 300 mg daily, taper to 150 mg daily before discontinuing 1
- Gradual discontinuation helps minimize withdrawal symptoms
Bupropion has a unique mechanism as a dopamine-norepinephrine reuptake inhibitor and is effective for depression with less sexual dysfunction and sedation compared to many other antidepressants 4. The gradual titration schedule is crucial for minimizing adverse effects and optimizing treatment outcomes.