Wellbutrin SR vs. XL: Key Differences
The primary difference between Wellbutrin SR and XL is the dosing frequency and duration of action: SR requires twice-daily dosing (typically 150 mg twice daily) while XL is administered once daily in the morning (typically 300 mg), with both formulations being bioequivalent in terms of total systemic exposure to bupropion. 1, 2, 3
Pharmacokinetic Differences
Absorption and Peak Timing:
- Wellbutrin XL has a prolonged absorption with peak plasma concentration (Tmax) occurring at approximately 5 hours after administration 4
- Wellbutrin SR reaches peak concentration more rapidly at approximately 3 hours 4
- Both formulations are bioequivalent in terms of overall systemic exposure to bupropion and its active metabolites 2, 3, 4
Dosing Schedules
Wellbutrin SR (Sustained Release):
- Initial dose: 150 mg once daily for 3-4 days 5, 6
- Maintenance dose: 150 mg twice daily (300 mg total daily) 5, 6
- Maximum dose: 400 mg per day 5
- Critical timing requirement: The second dose must be administered before 3 PM to minimize insomnia risk 5, 6
Wellbutrin XL (Extended Release):
- Initial dose: 150 mg once daily in the morning 1
- Maintenance dose: 300 mg once daily in the morning (after 4 days) 1
- Maximum dose: 450 mg per day 5, 1
- Administered in the morning with or without food 1
Clinical Advantages and Considerations
Medication Adherence:
- Once-daily XL formulation demonstrates superior persistence compared to twice-daily SR in real-world practice 7
- Patients on XL had significantly longer duration between first and last prescription (128 days vs. 82 days for SR) 7
- Medication possession ratio was higher with XL (0.50 vs. 0.36 for SR), indicating better adherence 7
- Patients were almost twice as likely to maintain medication possession ratio >0.7 with XL (32.0%) compared to SR (17.0%) 7
Formulation Selection Strategy:
- Choose SR formulation when patients need more flexible dosing due to side effects or require dose adjustments for hepatic or renal impairment, as it allows easier titration in smaller increments 6
- Choose XL formulation for improved adherence and simplified dosing regimen, particularly beneficial for patients with compliance concerns 7
- When switching between formulations, maintain the same total daily dose when possible, but monitor closely due to historical bioequivalence issues between brand and generic formulations 5, 1
Efficacy Profile
Both formulations demonstrate equivalent efficacy:
- SR and XL formulations show comparable effectiveness in treating major depressive disorder 2, 3
- Both are as effective as SSRIs (escitalopram) and SNRIs (venlafaxine XR) in most comparative trials 2, 3
- Both formulations have advantages of less somnolence and sexual dysfunction compared to SSRIs 2, 3
- Clinical response should be assessed after 6-8 weeks at adequate doses 5
Safety Considerations Common to Both
Seizure Risk:
- Maximum daily dose must not exceed 450 mg to minimize seizure risk (approximately 0.1% at recommended doses) 5, 6
- Both formulations are contraindicated in patients with seizure disorders 6, 1
Special Population Dosing:
- For moderate to severe hepatic impairment: maximum 150 mg every other day (SR) or 150 mg daily (XL) 1
- For renal impairment (GFR <90 mL/min): reduce total daily dose by half for both formulations 6
- For older adults: start with 37.5 mg every morning, increase by 37.5 mg every 3 days, with maximum 300 mg daily 6
Practical Clinical Pearls
- The XL formulation eliminates the need for midday dosing, which is particularly advantageous for patients in school, work, or structured settings where medication administration may be challenging 7
- SR formulation's twice-daily dosing may provide more stable plasma levels throughout the day for some patients, though this has not translated to superior efficacy 4
- Both formulations should be swallowed whole and not crushed, divided, or chewed 1
- When discontinuing either formulation at 300 mg daily, taper to 150 mg daily before complete discontinuation 1