Wellbutrin XL vs SR: Key Differences
Wellbutrin XL is dosed once daily (300 mg in the morning) while Wellbutrin SR is dosed twice daily (150 mg BID), with both formulations being bioequivalent in terms of systemic exposure but differing significantly in their dosing convenience and timing requirements. 1
Dosing Differences
Wellbutrin SR (Sustained Release)
- Initial dose: 150 mg once daily for 3 days, then increase to 150 mg twice daily (300 mg total daily) 2
- Timing requirement: First dose in the morning, second dose must be taken before 3 PM to minimize insomnia risk 2
- Maximum dose: 400 mg per day 2, 3
- Dosing frequency: Twice daily administration required 1
Wellbutrin XL (Extended Release)
- Initial dose: 150 mg once daily in the morning 2
- Target dose: 300 mg once daily after 4-7 days 1
- Maximum dose: 450 mg per day 2, 1
- Dosing frequency: Once daily administration 1
- Timing: Administered in the morning, may be taken with or without food 1
Pharmacokinetic Differences
The primary distinction lies in absorption kinetics rather than overall bioavailability:
- XL formulation: Prolonged absorption with Tmax approximately 5 hours 4
- SR formulation: Faster absorption with Tmax approximately 3 hours 4
- Bioequivalence: All three formulations (IR, SR, XL) are bioequivalent in terms of systemic exposure to bupropion and produce the same active metabolites (hydroxybupropion, threohydrobupropion, erythrohydrobupropion) 5, 4
Side Effect Profile
Both formulations share similar adverse effect profiles, as they are bioequivalent:
- Common side effects include headache, dry mouth, nausea, insomnia, constipation, and dizziness 6
- Seizure risk: Both formulations lower seizure threshold; risk is dose-dependent and requires gradual titration 1, 3
- Activating properties: Both can cause insomnia if dosed late in the day, which is why SR requires the second dose before 3 PM 2
- Sexual dysfunction: Both formulations have among the lowest incidence of sexual dysfunction compared to SSRIs 6
- Weight effects: Both are associated with minimal weight gain compared to other antidepressants 6
Clinical Considerations for Formulation Selection
Choose SR formulation when:
- Flexible dosing needed: Patients requiring dose adjustments for hepatic or renal impairment may benefit from twice-daily dosing 2
- Titration flexibility: The ability to split doses may help manage side effects during initial treatment 2
- Cost considerations: SR formulations may be less expensive in some settings 5
Choose XL formulation when:
- Adherence concerns: Once-daily dosing improves medication compliance 5
- Convenience preferred: Single morning dose eliminates need to remember afternoon administration 1
- Seasonal Affective Disorder: XL is specifically FDA-approved for SAD prevention 1
Critical Safety Warnings (Both Formulations)
Maximum dosing limits must be strictly observed to minimize seizure risk:
- SR maximum: 400 mg/day (200 mg per dose) 3
- XL maximum: 450 mg/day 1
- Contraindications: Seizure disorders, eating disorders (bulimia/anorexia), abrupt discontinuation of alcohol or benzodiazepines 2, 1
- MAOI interaction: At least 14 days must elapse between MAOI discontinuation and bupropion initiation 1
Special Population Dosing (Both Formulations)
Dose reductions required for:
- Hepatic impairment (moderate to severe): Maximum 150 mg daily for XL; 150 mg every other day for severe impairment 2, 1
- Renal impairment (GFR <90 mL/min): Reduce total daily dose by half 2
- Older adults: Start with lower doses (37.5 mg) and titrate slowly 2
Formulation Switching Considerations
When switching between SR and XL, maintain the same total daily dose when possible 1. However, clinicians should monitor closely when switching between brand and generic formulations or between SR and XL, as historical bioequivalence issues have been reported that may lead to loss of antidepressant effect 2.
Discontinuation Protocol
For patients on 300 mg daily of either formulation, taper to 150 mg once daily before complete discontinuation 1. This applies to both SR (reducing to 150 mg once daily) and XL formulations to minimize withdrawal effects.