Seizure Associated with Clozapine: Incidence, Etiology, and Management

Seizures are a known adverse effect of clozapine therapy. The literature varies on incidence rates of seizures, secondary to varying time frames in which each seizure occurred. Tonic-clonic seizures comprise the majority of seizures experienced secondary to clozapine use, but it is imperative to recognize the potential variety of seizure presentation. The exact etiology of clozapine-induced seizure is unknown. Conflicting reports regarding total oral dose, serum concentration, dose titration, and concomitant medications make it difficult to identify a single cause contributing to seizure risk. Following seizure occurrence, it may be in the best interests of the patient to continue clozapine treatment. In this clinical situation, the use of an antiepileptic drug (AED) for seizure prophylaxis may be required. The AED of choice appears to be valproate, but several successful case reports also support the use of lamotrigine, gabapentin and topiramate. Well-designed clinical trials regarding clozapine seizure prophylaxis are lacking. Given clozapine’s strong evidence for efficacy in the treatment of schizophrenia and schizoaffective disorder, every attempt to manage side effects, including seizure, should be implemented to allow for therapeutic continuation.