Can Abrupt Discontinuation of Clozapine Cause Seizures?

Abrupt discontinuation of clozapine can result in serious and potentially life-threatening psychiatric and physical complications, including psychotic rebound, increased risk of suicide, catatonia, cholinergic rebound, and autonomic instability. Although exceedingly rare, the literature contains case reports describing seizures following abrupt clozapine withdrawal. We report and discuss an additional case of this phenomenon. A 45-year-old man with a diagnosis of paranoid schizophrenia, treated with clozapine 300 mg/day for at least 20 years, abruptly discontinued the medication. Two weeks later, he experienced two generalized tonic-clonic seizures. No alternative medical cause was identified, and the temporal association suggests clozapine withdrawal as the precipitating factor. This case highlights the importance of preventing abrupt clozapine discontinuation. In clinical situations where abrupt discontinuation is unavoidable, it should be performed in a hospital setting. When feasible, gradual tapering is recommended to minimize withdrawal-related complications.