Bupropion and Risk of Seizures

Q: Bupropion is contraindicated in patients with seizure disorder. What is the maximum recommended total daily dose to reduce the risk of seizure with Bupropion?


What is the Incidence of seizure risk with Buproprion?

  • With the IR formulation, the rate is 0.4% (4/1000) at doses of 300 to 450 mg/day.
  • With the SR formulation, the rate is 0.1% (1/1000) at the target dose of 300 mg/day.
  • Incidence of seizure with bupropion XL has not been evaluated.
  • This incidence of seizures may exceed that of other antidepressants by as much as 4-fold.
  • Incidence increases to ~10 folds between 450-600 mg/day dose.




What patient factors may increase the risk of seizure with bupropion?

  • History of Head Trauma
  • Prior Seizure
  • CNS tumor
  • Severe Hepatic Cirrhosis
  • Concomitant Medications that lowers seizure threshold
  • Metabolic disorders (e.g., hypoglycemia, hyponatremia, severe hepatic impairment, and hypoxia)
  • Use of illicit drugs (e.g., cocaine).
  • Abuse or misuse of prescription drugs such as CNS stimulants.


Which co-morbid conditions are associated with increased risk of seizure?

  • Excessive use of alcohol or sedatives (including benzodiazepines)
  • Addiction to opiates, cocaine, or stimulants
  • Use of over-the-counter stimulants and anorectics
  • Diabetes treated with oral hypoglycemics or insulin


What are the recommendations for reducing the risk of seizure with Bupropion?

  • Total daily dose of Bupropion should not exceed 450 mg/daily.
  • Daily dose is administered 3 times daily, with each single dose not to exceed 150 mg to avoid high peak concentrations of bupropion and/or its metabolites.
  • Rate of incrementation of dose should be very gradual.



  1. Bupropion Package Insert.
  2. J Clin Psychiatry. 1998 Jul; 59(7):366-73.
  3. Prim Care Companion J Clin Psychiatry. 2005; 7(3): 106–113.

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Dr. Harvinder Singh, M.D. (Admin)

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