Wellbutrin Formulation Differences
The primary difference between Wellbutrin formulations is the dosing frequency and release mechanism: Wellbutrin SR (sustained-release) is dosed twice daily at 150 mg per dose (300 mg total), while Wellbutrin XL (extended-release) is dosed once daily in the morning at 300 mg, with both formulations being bioequivalent in terms of systemic bupropion exposure. 1, 2
Release Kinetics and Pharmacokinetics
- Wellbutrin SR has a time to maximum concentration (Tmax) of approximately 3 hours and requires twice-daily administration 3
- Wellbutrin XL has a prolonged absorption with Tmax of approximately 5 hours, allowing for once-daily dosing 3
- All three bupropion formulations (immediate-release, SR, and XL) are bioequivalent in terms of systemic exposure to bupropion and its active metabolites 2, 4, 3
Dosing Schedules
Wellbutrin SR Dosing
- Starting dose: 150 mg once daily for 3 days, then increase to 150 mg twice daily (300 mg total) 5
- Timing: First dose in the morning, second dose before 3 PM to minimize insomnia risk 5
- Maximum dose: 400 mg per day 5
Wellbutrin XL Dosing
- Starting dose: 150 mg once daily in the morning 1
- Target dose: After 4 days, may increase to 300 mg once daily in the morning 1
- Maximum dose: 450 mg per day 5, 1
- Administration: Must be taken in the morning and may be taken with or without food 1
Clinical Considerations for Formulation Selection
- SR formulation may be preferred for patients requiring more flexible dosing due to side effects or those needing dose adjustments for hepatic or renal impairment 5
- XL formulation offers the advantage of once-daily dosing, which may improve medication adherence 2, 4
- Both formulations have comparable efficacy and tolerability profiles, with advantages over SSRIs including less somnolence and sexual dysfunction 2, 4
Important Safety Considerations
- Seizure risk: Both formulations lower the seizure threshold; maximum doses should not be exceeded (SR: 400 mg/day; XL: 450 mg/day) to minimize this risk 5, 1
- Tablets must be swallowed whole: Neither SR nor XL tablets should be crushed, divided, or chewed, as this alters the release rate and increases seizure risk 1
- Switching between formulations: When switching from SR to XL or vice versa, give the same total daily dose when possible 1
Special Population Adjustments
- Hepatic impairment (moderate to severe): Maximum dose is 150 mg every other day for XL formulation 1
- Renal impairment (GFR <90 mL/min): Consider reducing dose and/or frequency for both formulations 1
- Older adults: Start with lower doses (37.5 mg) and titrate gradually, with maximum of 300 mg total daily dose 5
Common Pitfall to Avoid
- Historical bioequivalence issues: Some generic versions of bupropion SR were previously found not to be bioequivalent to brand-name Wellbutrin SR, leading to reports of loss of antidepressant effect 6. While this issue has been addressed, clinicians should monitor patients closely when switching between brand and generic formulations or between SR and XL formulations 6