Can Wellbutrin (bupropion) lower the seizure threshold?

Bupropion and Seizure Threshold

Yes, bupropion (Wellbutrin) definitively lowers the seizure threshold, with meta-analyses of trial data showing a 0.1% seizure risk among those receiving the drug for smoking cessation. 1

Mechanism and Risk

• Bupropion reduces the seizure threshold through its effects on the dopaminergic and adrenergic systems, as well as its inhibition of nicotinic acetylcholinergic receptors 1
• The risk of seizures is dose-dependent, with higher incidence observed at doses exceeding the recommended maximum 2, 3
• At doses of 450 mg/day or less, the observed incidence of seizures ranges from 0.35% to 0.44% 2
• At doses above 450 mg/day, the seizure risk increases significantly 2, 4

Risk Factors for Seizures with Bupropion

• History of seizure disorders (absolute contraindication) 5
• Brain metastases 1
• Elevated risk of seizure due to other conditions 1
• Concomitant use of medications that lower seizure threshold 6
• Recent discontinuation of benzodiazepines or other medications that raise seizure threshold when stopped 5

Drug Interactions That Increase Seizure Risk

• Extreme caution is needed when coadministering bupropion with other drugs that lower the seizure threshold 6
• These include:
  • Other bupropion products 6
  • Antipsychotics 6
  • Antidepressants 6
  • Theophylline 6
  • Systemic corticosteroids 6

Clinical Considerations

• Seizures can occur even in patients with no personal or family history of seizure disorders 5, 7
• Seizures have been reported to occur within days of starting bupropion therapy 5, 7
• Even at therapeutic doses and blood levels, seizures can occur in patients without predisposing factors 4
• The FDA label specifically warns about the risk of seizures and recommends using low initial doses of bupropion and increasing the dose gradually in patients at risk 6

Case Reports and Evidence

• Multiple case reports document new-onset seizures in patients without seizure risk factors shortly after starting bupropion 5, 7
• A 66-year-old female experienced new-onset seizure 4 days after starting bupropion for smoking cessation, despite having no personal or family history of seizure disorders 5
• In another report, two patients with no personal or family seizure history developed generalized tonic-clonic seizures after taking bupropion 300 mg per day for a few days 7

Recommendations

• Avoid bupropion in patients with a history of seizures or elevated seizure risk 1
• Use low initial doses and increase gradually in patients with risk factors 6
• Discontinue bupropion if a seizure occurs during treatment 5
• Consider alternative medications for patients with seizure disorders or risk factors 1
• Minimize or avoid alcohol consumption during treatment with bupropion, as there have been reports of adverse neuropsychiatric events with concurrent use 6