How to taper off Wellbutrin (bupropion) from 450mg daily to 150mg daily?

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Tapering Bupropion from 450mg to 150mg Daily

When discontinuing bupropion from 450mg to 150mg daily, reduce the dose to 150mg once daily for at least several days before complete discontinuation, as recommended by the FDA. 1

Recommended Tapering Protocol

For patients on 450mg daily (typically bupropion XL 450mg once daily or bupropion SR 150mg three times daily), decrease directly to 150mg once daily. 1

  • The FDA label explicitly states: "When discontinuing treatment in patients treated with bupropion hydrochloride extended-release tablets (XL) 300 mg once daily, decrease the dose to 150 mg once daily prior to discontinuation." 1
  • This same principle applies when reducing from 450mg to 150mg—a single-step dose reduction is the standard approach. 1

Formulation-Specific Considerations

If the patient is on bupropion XL 450mg once daily:

  • Switch directly to bupropion XL 150mg once daily, taken in the morning. 2
  • The extended-release formulation allows for once-daily dosing, simplifying the taper. 2

If the patient is on bupropion SR (150mg three times daily to achieve 450mg):

  • Reduce to bupropion SR 150mg once daily in the morning. 2
  • Alternatively, switch to bupropion XL 150mg once daily for equivalent dosing. 2, 1
  • When switching between formulations, give the same total daily dose when possible and monitor closely for loss of antidepressant effect, as historical bioequivalence issues have been documented with some generic formulations. 2

Timing and Administration

Administer the 150mg dose in the morning to minimize insomnia risk. 2

  • Bupropion has activating properties that can interfere with sleep if taken later in the day. 2
  • If using SR formulation with twice-daily dosing during any intermediate step, ensure the second dose is before 3 PM. 2

Monitoring During Dose Reduction

Monitor for worsening depression, suicidal ideation, or behavioral changes within 1-2 weeks of dose reduction, particularly in patients under 24 years of age. 2

  • The risk for suicide attempts is greatest during treatment changes, especially in the first 1-2 months. 2
  • Assess blood pressure periodically, as bupropion can elevate blood pressure, and dose reduction may affect this. 3
  • Watch for return of depressive symptoms including low energy, apathy, or hypersomnia, as these may indicate inadequate dosing. 2

Duration at Reduced Dose

Maintain the 150mg daily dose for at least several days to weeks before considering complete discontinuation, if that is the ultimate goal. 1

  • The FDA label does not specify an exact duration at the reduced dose, but clinical practice suggests maintaining the lower dose long enough to assess symptom stability. 1
  • If 150mg is the target maintenance dose (not complete discontinuation), continue indefinitely and reassess periodically for the need for ongoing treatment. 2

Critical Safety Considerations

Do not abruptly discontinue bupropion, especially in patients with seizure risk factors or those taking other medications that lower seizure threshold. 2

  • While bupropion withdrawal is generally well-tolerated compared to other antidepressants, gradual dose reduction minimizes risk of symptom recurrence. 1
  • Patients with hepatic impairment (moderate to severe) should not exceed 150mg daily as their maximum dose. 2, 3
  • Patients with renal impairment (GFR <90 mL/min) may require dose reduction by half and closer monitoring during any dose changes. 2, 3

Common Pitfalls to Avoid

Do not switch between brand and generic formulations or between SR and XL formulations during the taper without close monitoring. 2

  • Historical bioequivalence issues with some generic bupropion SR formulations have led to loss of antidepressant effect. 2
  • If a formulation switch is necessary during tapering, monitor the patient closely for changes in efficacy or side effects. 2

Do not assume the patient needs complete discontinuation—reassess whether ongoing treatment at 150mg is appropriate for maintenance. 2

  • Acute depressive episodes require several months or longer of antidepressant treatment beyond the initial response. 1
  • The dose needed for maintenance may differ from the dose that provided initial response. 1

References

Guideline

Bupropion Dosing and Administration

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Bupropion Initiation and Dosing Guidelines

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

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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