Seizure Risk with Wellbutrin (Bupropion)
Bupropion (Wellbutrin) carries a dose-dependent risk of seizures, with the highest risk occurring during initial dose titration and at doses exceeding 450 mg daily. 1
Seizure Risk Factors and Incidence
- The incidence of seizures with bupropion is dose-related, with approximately 0.1% (1/1000 patients) risk at doses up to 300 mg per day using the sustained-release formulation 1
- The risk increases to approximately 0.4% (13/3200) with immediate-release formulations at doses of 300-450 mg per day 1
- The seizure risk increases almost tenfold between 450 and 600 mg/day 1
- The cumulative 2-year risk of seizures in patients receiving the maximum recommended dose of 450 mg/day or less is approximately 0.48% 2
Timing of Seizure Risk
- The highest risk period is during initial dose titration, particularly when doses are increased rapidly 1, 3
- Seizures can occur even after just starting the medication - as reported in a case where seizure occurred 4 days after starting bupropion for smoking cessation 3
- Seizures can occur at any time during treatment, even at therapeutic doses (≤450 mg/day) 4
- Long-term use does not appear to increase seizure risk if the dose remains stable and below 450 mg daily 1
Risk Factors That Increase Seizure Susceptibility
- Pre-existing seizure disorder (contraindicated) 1
- History of head trauma, CNS tumor, or severe stroke 1
- Eating disorders (anorexia nervosa or bulimia) 1
- Abrupt discontinuation of alcohol, benzodiazepines, or barbiturates 1
- Concomitant use of medications that lower seizure threshold (antipsychotics, tricyclic antidepressants, theophylline, systemic corticosteroids) 1
- Metabolic disorders (hypoglycemia, hyponatremia, severe hepatic impairment, hypoxia) 1
- Use of illicit drugs, especially cocaine 1, 4
- Sleep deprivation 4
- History of attention deficit disorder 4
- Previous heavy alcohol use 4
Recommendations to Minimize Seizure Risk
- Start with low doses and increase gradually 1
- Never exceed 450 mg per day 1, 2
- For smoking cessation, follow the recommended titration schedule:
- Days 1-3: 150 mg orally once daily
- Day 4-12 weeks: 150 mg orally twice daily (maximum 300 mg per day) 5
- Avoid bupropion in patients with risk factors for seizures, especially those with brain metastases, history of seizures, or elevated seizure risk 5, 1
- Monitor for neuropsychiatric symptoms that may precede seizures 1
- Discontinue bupropion immediately if a seizure occurs 1, 3
Special Considerations
- Bupropion is contraindicated in patients with seizure disorder 1
- Bupropion should be used with caution in patients taking other medications that lower seizure threshold 1
- Drug interactions with anticonvulsants may affect bupropion levels - carbamazepine may decrease plasma bupropion to non-detectable levels 6
- Bupropion may increase sodium valproate levels 6
- Two case reports noted seizures in breastfed infants whose mothers were taking bupropion 5
Conclusion
Bupropion's seizure risk is most pronounced during initial titration and at higher doses. The risk can be minimized by gradual dose titration, keeping the daily dose at or below 450 mg, and avoiding use in patients with predisposing factors for seizures.