What is the difference between Wellbutrin (bupropion) SL and XL formulations?

Wellbutrin SR vs XL: Key Formulation Differences

The primary difference between Wellbutrin SR (Sustained Release) and XL (Extended Release) is the dosing frequency: SR requires twice-daily administration (typically 150 mg twice daily for a total of 300 mg/day), while XL is dosed once daily in the morning (typically 300 mg once daily). 1

Pharmacokinetic Differences

• SR formulation reaches peak concentration (Tmax) at approximately 3 hours, while XL has a prolonged absorption with Tmax at approximately 5 hours 2
• Despite different absorption profiles, all three bupropion formulations (IR, SR, and XL) are bioequivalent in terms of systemic exposure to bupropion and its active metabolites 3, 2
• The extended absorption of XL allows for once-daily dosing convenience compared to SR's twice-daily requirement 2

Dosing Schedules and Administration

SR (Sustained Release) Formulation:

• Start with 150 mg once daily for 3 days, then increase to 150 mg twice daily (300 mg total) 1
• The second dose must be administered before 3 PM to minimize insomnia risk 1
• Maximum dose is 400 mg per day 1

XL (Extended Release) Formulation:

• Initial dose of 150 mg once daily, with maintenance dose of 150-300 mg once daily 1
• Administered in the morning as a single dose 1
• Maximum dose is 450 mg per day 1

Clinical Efficacy Considerations

• Both formulations demonstrate comparable efficacy for major depressive disorder, with SR showing consistent effectiveness across multiple trials 3
• XL established efficacy in two of six well-designed placebo-controlled studies for primary outcomes, though it demonstrated efficacy in secondary outcomes in five studies 3
• SR was as effective as SSRIs with advantages of less somnolence and sexual dysfunction 3

Practical Clinical Decision-Making

Choose SR formulation when:

• Patients require more flexible dosing due to side effects or need dose adjustments for hepatic or renal impairment 1
• Patients can reliably take medications twice daily
• Lower maximum daily doses are needed (400 mg vs 450 mg for XL)

Choose XL formulation when:

• Once-daily dosing improves medication adherence 3, 4
• Patients prefer simplified medication regimens
• Higher maximum doses may be needed (up to 450 mg daily) 1

Critical Safety Monitoring

• Historical bioequivalence issues existed with some generic SR formulations; monitor patients closely when switching between brand and generic or between SR and XL formulations 1
• Both formulations lower seizure threshold and are contraindicated in patients with seizure disorders 1
• For hepatic impairment (moderate to severe), total daily dose should not exceed 150 mg daily regardless of formulation 1
• For renal impairment (moderate to severe), reduce total daily dose by half 1

Common Pitfalls to Avoid

• Do not administer SR's second dose after 3 PM, as this significantly increases insomnia risk 1
• Avoid switching formulations without close monitoring, as loss of antidepressant effect may occur 1
• Do not exceed maximum daily doses (400 mg for SR, 450 mg for XL) to minimize seizure risk 1