What is the recommended protocol for decreasing the dose of Wellbutrin (bupropion)?

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Tapering Wellbutrin (Bupropion): Recommended Protocol

When discontinuing bupropion XL 300 mg once daily, decrease the dose to 150 mg once daily prior to complete discontinuation. 1

FDA-Approved Tapering Protocol

The FDA label provides explicit guidance for discontinuing bupropion extended-release formulations:

  • For patients on 300 mg daily: Reduce to 150 mg once daily before stopping completely 1
  • Timing: The FDA does not specify a minimum duration at the reduced dose, but the taper should be gradual to minimize seizure risk 1

This represents the only evidence-based tapering protocol specifically outlined in official prescribing information for bupropion.

Formulation-Specific Considerations

Bupropion SR (sustained-release): If tapering from 300 mg daily (150 mg twice daily), reduce to 150 mg once daily before discontinuation 2

Bupropion XL (extended-release): Reduce from 300 mg once daily to 150 mg once daily before stopping 1

The key principle is to avoid abrupt discontinuation, particularly from higher doses, as bupropion lowers seizure threshold and gradual dose reduction minimizes this risk 1

Special Population Adjustments During Tapering

Hepatic impairment: Patients with moderate to severe hepatic impairment (Child-Pugh score 7-15) should not exceed 150 mg every other day, making the taper even more gradual 1

Renal impairment: Consider reducing dose and/or frequency more gradually in patients with GFR <90 mL/min 1

Older adults: May require slower tapering with smaller dose reductions (consider 37.5 mg decrements) due to increased risk of adverse reactions 2

Clinical Monitoring During Taper

Withdrawal symptoms to monitor: While bupropion is not associated with the same withdrawal syndrome as SSRIs or opioids, monitor for:

  • Return of depressive symptoms 1
  • Changes in mood or behavior, particularly in patients under 24 years old 3
  • Vital signs, especially blood pressure 3

Duration at reduced dose: Although not specified in FDA labeling, maintaining the reduced dose (150 mg) for at least 1-2 weeks before complete discontinuation is reasonable based on the drug's elimination half-life of 11-14 hours and the need to allow neuroadaptations to resolve 4

Critical Safety Considerations

Do not abruptly discontinue: The gradual taper is essential to minimize seizure risk, which is dose-dependent with bupropion 1

MAOI interactions: Allow at least 14 days after stopping bupropion before starting an MAOI antidepressant 1

Opioid considerations: If bupropion is part of naltrexone-bupropion combination therapy for weight management, discontinue before any procedure requiring opioid analgesia 3

Common Pitfalls to Avoid

  • Stopping too quickly from 300 mg: Always step down to 150 mg first rather than stopping abruptly 1
  • Ignoring formulation differences: SR formulations require twice-daily dosing adjustments, while XL is once daily 2
  • Inadequate monitoring period: Observe patients for at least several weeks after complete discontinuation for emergence of depressive symptoms 1

References

Guideline

Bupropion Dosing and Administration

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Review of bupropion.

Clinical pharmacy, 1983

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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