What are the differences between SR (Sustained Release) and XL (Extended Release) formulations of bupropion (Wellbutrin) in terms of dosing and safety?

Bupropion SR vs XL: Key Dosing and Safety Differences

Bupropion SR requires twice-daily dosing (150 mg BID for 300 mg total daily), while XL is administered once daily in the morning (300 mg QD), with both formulations being bioequivalent in terms of systemic exposure but differing critically in their dosing schedules and timing requirements. 1, 2, 3

Dosing Schedules

SR (Sustained Release) Formulation

• Initial dose: 150 mg once daily for 3-4 days 1, 2
• Maintenance dose: 150 mg twice daily (300 mg total daily) 1, 2
• Maximum dose: 400 mg per day 1
• Critical timing requirement: The second dose must be administered before 3 PM to minimize insomnia risk 1

XL (Extended Release) Formulation

• Initial dose: 150 mg once daily in the morning 1, 2
• Maintenance dose: 300 mg once daily in the morning 1, 2
• Maximum dose: 450 mg per day 1, 2
• Administration: Single morning dose, may be taken with or without food 2

Clinical Decision-Making Between Formulations

Choose SR formulation when patients need more flexible dosing due to side effects or require dose adjustments for hepatic or renal impairment. 1 The twice-daily dosing allows for easier titration in 37.5 mg increments, particularly beneficial for older adults or those on multiple psychotropic medications 1.

Choose XL formulation for improved adherence and convenience, as once-daily dosing reduces pill burden and eliminates the need to remember afternoon doses 2, 3.

Safety Considerations Common to Both Formulations

Seizure Risk

• Maximum daily dose must not exceed 450 mg to minimize seizure risk 1
• Both formulations are contraindicated in patients with seizure disorders 1, 2
• The seizure incidence at recommended doses (300 mg/day) is approximately 0.1% 4

Contraindications (Identical for Both)

• Use within 14 days of MAOI discontinuation 1, 2
• Seizure disorders 1, 2
• Bulimia or anorexia nervosa (increased seizure risk) 1
• Abrupt discontinuation of alcohol, benzodiazepines, or antiepileptic drugs 1

Monitoring Requirements

• Blood pressure monitoring (avoid in uncontrolled hypertension) 5, 1
• Neuropsychiatric adverse effects, especially in patients under 24 years 1
• Vital signs during treatment 1

Special Population Dosing (Applies to Both Formulations)

Hepatic Impairment

• Moderate to severe (Child-Pugh 7-15): Maximum 150 mg every other day 2
• Mild (Child-Pugh 5-6): Consider dose reduction and/or frequency adjustment 2

Renal Impairment

• GFR <90 mL/min: Reduce total daily dose by half 1
• Close monitoring required as bupropion and metabolites are cleared renally 1

Older Adults

• Start with 37.5 mg every morning 1
• Increase by 37.5 mg every 3 days as tolerated 1
• Maximum dose: 150 mg twice daily (300 mg total) for SR formulation 1

Discontinuation Protocol

When discontinuing either formulation at 300 mg daily, taper to 150 mg once daily before complete discontinuation. 2 For SR formulation, this means reducing from 150 mg BID to 150 mg once daily; for XL, reduce from 300 mg QD to 150 mg QD 6, 2.

Common Adverse Effects (Similar Between Formulations)

• Insomnia (most common, dose-related) 4, 7
• Dry mouth (20% in obesity trials) 5, 4
• Headache 4, 7
• Nausea 4, 7
• Anxiety (also a nicotine withdrawal symptom) 4

Key advantage: Both formulations have significantly lower rates of sexual dysfunction and weight gain compared to SSRIs 3, 8

Critical Formulation Switching Considerations

When switching between SR and XL formulations, maintain the same total daily dose when possible. 2 However, monitor patients closely as historical bioequivalence issues between brand and generic formulations have led to loss of antidepressant effect in some cases 1. Some generic versions of bupropion SR were previously found not bioequivalent to brand-name Wellbutrin SR 1.

Clinical Pearls

• SR formulation's twice-daily dosing allows for more gradual dose adjustments, making it preferable for patients requiring careful titration (older adults, multiple medications, hepatic/renal impairment) 1
• XL formulation's once-daily dosing improves adherence and eliminates the risk of late-day dosing causing insomnia 2, 3
• Both formulations are bioequivalent in systemic exposure but not interchangeable without monitoring 3
• The activating properties of bupropion make morning administration ideal for both formulations 1