Bupropion (Wellbutrin) 450 mg Dosing Guidelines
The maximum recommended dose of Wellbutrin (bupropion) is 450 mg per day, which is appropriate for major depressive disorder when using the extended-release (XL) formulation as a once-daily dose. 1
Formulation-Specific Dosing
- For Wellbutrin XL (extended-release), the maximum dose is 450 mg once daily in the morning 1
- For Wellbutrin SR (sustained-release), the maximum dose is 400 mg per day (200 mg twice daily) 1
- Clinical trials have demonstrated efficacy of the 450 mg dose for major depressive disorder, with significant improvements in Hamilton Depression Rating Scale total score and Clinical Global Impressions-Severity score 2
Titration Schedule
- For Wellbutrin XL: Start with 150 mg once daily for the first week, then increase to 300 mg once daily, with further increase to 450 mg once daily if clinically indicated 1
- For Wellbutrin SR: Start with 150 mg once daily for 3 days, then increase to 150 mg twice daily, with further titration if needed (maximum 200 mg twice daily) 1
- Allow at least 24 hours between dose increases to minimize seizure risk 2
Safety Considerations
- The 450 mg daily dose should not be exceeded due to increased seizure risk 1, 2
- Bupropion lowers the seizure threshold in a dose-dependent manner; risk is minimized by limiting daily dose to 450 mg and gradually increasing the dose 2
- Discontinue immediately if a seizure occurs 2
- Monitor for neuropsychiatric adverse events including changes in mood, psychosis, hallucinations, and suicidal ideation 2
- Monitor blood pressure before and during treatment as bupropion can increase blood pressure 2
Special Population Considerations
- For patients with moderate to severe hepatic impairment, the total daily dose should not exceed 150 mg daily 1
- For patients with moderate to severe renal impairment, reduce the total daily dose by half 1
- For older adults, consider starting with lower doses (approximately 50% of standard dose) and titrating more slowly 1
Drug Interactions
- Bupropion is a CYP2D6 inhibitor and may increase levels of medications metabolized by this enzyme 2
- Avoid concurrent use with monoamine oxidase inhibitors (MAOIs) or within 14 days of discontinuing MAOIs 1, 2
- Use caution when combining with other medications that lower seizure threshold 2
Clinical Pearls
- Administer the last dose of the day before 3 PM to minimize risk of insomnia 1
- The extended-release formulation (XL) offers the convenience of once-daily dosing while maintaining similar bioavailability to other formulations 2, 3
- If no response is seen after 6-8 weeks at an adequate dose, consider alternative treatment 1
- Bupropion has a lower incidence of sexual dysfunction and weight gain compared to many other antidepressants 4, 5