What are the contraindications for Wellbutrin (bupropion)?

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Wellbutrin (Bupropion) Contraindications

Bupropion is absolutely contraindicated in patients with seizure disorders, current or prior bulimia/anorexia nervosa, those undergoing abrupt discontinuation of alcohol/benzodiazepines/barbiturates/antiepileptics, concurrent MAOI use (or within 14 days), and uncontrolled hypertension. 1

Absolute Contraindications

Seizure-Related Contraindications

  • Any history of seizure disorder or epilepsy is an absolute contraindication due to bupropion's dose-dependent reduction of seizure threshold 2, 1
  • Current or prior diagnosis of bulimia or anorexia nervosa carries higher seizure incidence and is contraindicated 1, 2
  • Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs is contraindicated due to additive seizure risk 1
  • Patients with brain metastases should avoid bupropion due to increased seizure risk 2

The seizure risk is approximately 0.1% (1/1000 patients) at doses up to 300 mg/day, increasing at higher doses 2, 3. This risk is comparable to other antidepressants when dosing guidelines are followed 4, 5.

MAOI Interactions

  • Concurrent use with MAOIs or within 14 days of MAOI discontinuation is contraindicated due to hypertensive crisis risk 1, 2
  • Reversible MAOIs (linezolid, intravenous methylene blue) are also contraindicated; if urgent treatment is needed, stop bupropion promptly and monitor for 2 weeks or 24 hours after last MAOI dose 1

Cardiovascular Contraindications

  • Uncontrolled hypertension is a contraindication, as bupropion can elevate blood pressure and heart rate 6, 2

Other Absolute Contraindications

  • Acute angle-closure glaucoma (bupropion may worsen this condition) 6, 2
  • Chronic opioid use when bupropion is combined with naltrexone (due to opioid antagonism) 6, 2
  • Known hypersensitivity to bupropion, including anaphylactoid/anaphylactic reactions and Stevens-Johnson syndrome 1

Pregnancy and Lactation

  • Contraindicated in pregnancy and breastfeeding, particularly when used in combination formulations (naltrexone/bupropion) for obesity treatment 6, 2
  • Women of reproductive potential require counseling on reliable contraception 6

Critical Warnings

Black Box Warning

  • Risk of suicidal behavior/ideation in patients younger than 24 years with depression, requiring close monitoring especially during initial treatment months 6

Dose-Dependent Risks

  • Maximum dose should not exceed 450 mg/day to minimize seizure risk 7
  • Seizure incidence increases significantly above 300 mg/day 3

Common Pitfalls to Avoid

  • Do not overlook remote seizure history or family history of seizures - even patients without personal seizure history can develop new-onset seizures on bupropion 8, 3
  • Screen for eating disorders carefully - patients may not volunteer this history 1
  • Assess for recent benzodiazepine or alcohol discontinuation - this creates additive seizure risk 1
  • Check all concurrent medications for MAOI interactions and drugs that lower seizure threshold 7, 1
  • Monitor blood pressure before and during treatment, especially in patients with borderline hypertension 6

References

Guideline

Bupropion Contraindications and Precautions

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

[Bupropion-induced epileptic seizures].

Revue neurologique, 2004

Research

Overview of clinically significant adverse reactions to bupropion.

The Journal of clinical psychiatry, 1983

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Bupropion and DOT Certification

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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