What is the difference between Wellbutrin (bupropion) SR and XL in terms of dosing and side effects?

Wellbutrin SR vs XL: Differences in Dosing and Side Effects

Bupropion XL (extended-release) is preferred over SR (sustained-release) due to once-daily dosing, which improves adherence and maintains more consistent blood levels with potentially fewer side effects. 1

Formulation Differences

• SR (Sustained-Release):

  • Administered twice daily 1
  • Initial dose: 150 mg once daily in the morning
  • Target dose: 150 mg twice daily (morning and afternoon, before 3 PM to minimize insomnia) 2
  • Duration of action: Approximately 12 hours per dose
  • Absorption: T-max approximately 3 hours 3

• XL (Extended-Release):

  • Administered once daily in the morning 1
  • Initial dose: 150 mg once daily
  • Target dose: 300 mg once daily in the morning
  • Duration of action: 24 hours
  • Absorption: T-max approximately 5 hours (more prolonged than SR) 3
  • Should be swallowed whole, not crushed, divided, or chewed 1

Bioequivalence and Switching

• All three formulations (IR, SR, XL) are bioequivalent in terms of systemic exposure to bupropion 4
• When switching from SR to XL, give the same total daily dose when possible 1
• Example: 150 mg SR twice daily (300 mg total) would convert to 300 mg XL once daily

Side Effect Profiles

Both formulations share similar side effects, but the XL formulation may provide more consistent blood levels, potentially reducing peak-related side effects:

• Common side effects for both formulations:

  • Insomnia
  • Dry mouth
  • Headache
  • Nausea
  • Constipation
  • Dizziness
  • Anxiety 1, 5

• Advantages of both SR and XL formulations:

  • Lower incidence of sexual dysfunction compared to SSRIs 6, 5
  • Minimal weight gain (may actually cause slight weight loss) 7
  • Less somnolence than some other antidepressants 5

Clinical Considerations

• Seizure risk: Both formulations carry a risk of seizures; dose should be increased gradually to minimize this risk 1

  • Contraindicated in patients with seizure disorders 2

• Dosage adjustments:

  • Hepatic impairment: Maximum dose 150 mg every other day for moderate to severe impairment 1
  • Renal impairment: Consider reducing dose and/or frequency 1

• Time to effect:

  • May take several weeks to feel the full antidepressant effect 1
  • Initial side effects may improve over 2-4 weeks as medication stabilizes 2

• Discontinuation:

  • When discontinuing XL 300 mg daily, taper to 150 mg daily before stopping 1

Practical Advantages of XL over SR

1. Improved adherence: Once-daily dosing is more convenient and improves medication compliance
2. Reduced peak-trough fluctuations: More consistent blood levels throughout the day
3. Simplified dosing schedule: No need to remember multiple doses
4. Potentially fewer side effects: Smoother pharmacokinetic profile may reduce peak-related adverse effects
5. Less risk of taking dose too late: No afternoon dose that could potentially worsen insomnia

Contraindications and Precautions (Both Formulations)

• Concurrent use with MAOIs (requires 14-day washout period) 2
• History of seizure disorders or conditions that lower seizure threshold 2
• Eating disorders (anorexia, bulimia) due to seizure risk
• Abrupt discontinuation of alcohol or sedatives
• Use with caution in patients with liver or kidney dysfunction 2

The choice between SR and XL should primarily be based on the patient's preference for dosing frequency, with XL offering the convenience of once-daily administration while maintaining equivalent efficacy to the SR formulation.