Should I start a patient on bupropion (Bupropion) SR (Sustained Release) or XL (Extended Release)?

Bupropion XL Formulation is Preferred Over SR for Initial Treatment

For most patients, bupropion XL (extended-release) formulation should be initiated rather than SR (sustained-release) due to its once-daily dosing, improved adherence potential, and comparable efficacy with potentially fewer side effects. 1

Formulation Comparison

Dosing Schedule

• XL formulation: Once-daily dosing 1, 2
• SR formulation: Twice-daily dosing 1, 2
• IR formulation: Three-times-daily dosing (mentioned for reference) 1, 2

Pharmacokinetics

• XL formulation: Prolonged absorption (Tmax ~5 hours) 2
• SR formulation: Intermediate absorption (Tmax ~3 hours) 2
• Bioequivalence: All formulations are bioequivalent, with differences primarily in release characteristics 2

Clinical Decision Algorithm

1. Default choice: Start with XL formulation 150mg once daily

   • Advantages: Improved adherence, simpler regimen, potentially fewer peak-related side effects 1
   • Most commonly prescribed formulation (62% of new prescriptions) 3

2. Consider SR formulation when:

   • Patient has previously experienced hypersensitivity reaction to XL formulation 4
   • Cost/insurance coverage favors SR formulation
   • Patient requires more flexible dosing schedule

3. Dosing considerations:

   • Start with 150mg (XL once daily or SR twice daily)
   • Optimal therapeutic dose is 300mg daily for most patients 5
   • Maximum daily dose should not exceed 450mg 6
   • Reduce dose by 50% in patients with moderate to severe renal impairment 6

Special Considerations

Tolerability Profile

• Both formulations have similar side effect profiles: insomnia, dry mouth, anxiety, decreased appetite, headache 6, 1
• XL formulation may provide more stable blood levels, potentially reducing peak-related side effects 1, 2

Rare but important case scenario

• There is case evidence of a patient who developed urticaria and angioedema with XL formulation but subsequently tolerated SR formulation well 4. This suggests that in rare cases of formulation-specific hypersensitivity, switching between formulations might be an option rather than discontinuing bupropion altogether.

Monitoring Requirements

• Regular monitoring of blood pressure and heart rate is necessary for all formulations, especially during the first 12 weeks 6
• Monitor for anxiety, agitation, insomnia, and increased vigilance for suicidal thoughts, particularly in patients under 24 years 6

Common Pitfalls to Avoid

1. Seizure risk: All formulations carry seizure risk. Avoid in patients with seizure disorders or conditions that lower seizure threshold 6

2. Contraindications for all formulations:

   • Uncontrolled hypertension
   • History of seizures
   • Current use of MAO inhibitors
   • Brain metastases
   • Concurrent tamoxifen use
   • Closed-angle glaucoma 6

3. Abrupt discontinuation: Gradual tapering is recommended when discontinuing any bupropion formulation to minimize withdrawal symptoms 6