What is the recommended initial dosing regimen for starting bupropion (Wellbutrin)?

Initiating Bupropion (Wellbutrin) Treatment

The recommended starting dose for bupropion (Wellbutrin) is 150 mg once daily in the morning for the first 4 days, after which the dose may be increased to the target dose of 300 mg once daily in the morning. 1

Initial Dosing Protocol

• First-line dosing:

  • Start with 150 mg once daily in the morning for 4 days
  • After 4 days, increase to target dose of 300 mg once daily in the morning
  • Take medication whole (do not crush, divide, or chew)
  • May be taken with or without food 1

• Special populations requiring dose adjustments:

  • Hepatic impairment:

    • Mild impairment (Child-Pugh score 5-6): Consider reducing dose/frequency
    • Moderate to severe impairment (Child-Pugh score 7-15): Maximum 150 mg every other day 1

  • Renal impairment:

    • For GFR <90 mL/min: Consider reducing dose and/or frequency
    • For severe impairment: Reduce dose by 50%
    • For end-stage renal disease: Avoid bupropion 2, 1

Administration Considerations

• Administer in the morning to minimize insomnia risk
• Increase dose gradually to minimize seizure risk 1
• Maximum daily dose should not exceed 450 mg per day 2
• When switching from immediate-release or sustained-release formulations, maintain the same total daily dose when possible 1

Monitoring During Initiation

• Monitor blood pressure and heart rate regularly, especially during the first 12 weeks 2
• Assess for common side effects: insomnia, dry mouth, anxiety/jitteriness, decreased appetite, headache 2
• Watch for neuropsychiatric symptoms, particularly in patients under 24 years (carries black box warning for suicidal thoughts) 2, 1

Contraindications and Precautions

• Absolute contraindications:

  • Seizure disorders or conditions lowering seizure threshold
  • Current use of MAO inhibitors (allow 14-day washout period)
  • Uncontrolled hypertension
  • Brain metastases
  • Concurrent tamoxifen use
  • Closed-angle glaucoma 2

• Use with caution in patients with:

  • History of seizures
  • Brain lesions or structural abnormalities
  • Current alcohol/substance abuse 2

Discontinuation Protocol

When discontinuing treatment with bupropion 300 mg daily, decrease the dose to 150 mg once daily prior to complete discontinuation to minimize withdrawal symptoms 1.

Clinical Pearls

• Bupropion is considered a preferred agent for depression due to its favorable adverse effect profile 3
• Unlike many antidepressants, bupropion is less likely to cause sexual dysfunction or weight gain 4
• Acute dystonia has been reported with rapid dose escalation, suggesting a dose-response relationship for this rare side effect 5
• Seizure risk appears comparable to therapeutic doses of tricyclic antidepressants (less than 1 per 1,000 at usual outpatient doses) 6

By following this structured approach to initiating bupropion, you can maximize therapeutic benefit while minimizing adverse effects for patients requiring treatment for depression.