Clozapine is more effective than other atypical antipsychotics for treatment resistant schizophrenia, but has serious side effects. Clozapine has an estimated cumulative seizure risk of 10% in patients treated for 3.8 years. Bupropion can also induce seizures and its estimated risk is 0.4% at recommended doses. While some risk factors for seizures are known, much remains unknown about predicting seizure risk.We present 2 cases of seizures in patients treated with clozapine and bupropion without a seizure history. In the first case, a patient with schizoaffective disorder treated with dual antipsychotic therapy had a witnessed generalized tonic-clonic seizure. With the exception of bupropion/naltrexone which was started 2.5 months prior for weight loss, she had not had any recent medication changes. In the second case, a patient with schizoaffective disorder was treated with clozapine and was prescribed bupropion SR for smoking cessation for an extended duration. He had cut back on cigarette use in the 2 months prior to reporting "spells." The neurologist's assessment was probable epileptic seizures which resolved after the bupropion was stopped and divalproex was started for seizure prophylaxis.Clozapine and bupropion are known to lower the seizure threshold, but little information is available regarding the risk when used in combination. It is unclear whether these agents, when used in combination, have additive seizure risk or possible synergistic effects. Bupropion should be used cautiously in patients treated with clozapine. Safer agents that do not lower the seizure threshold should be utilized whenever possible.
