Clozapine and seizures: a review.

Clozapine, a novel antipsychotic agent, is an alternative to standard neuroleptic therapy for psychotic disorders. Some advantages of clozapine over neuroleptics are that it may be a more effective antipsychotic in treatment resistant patients and has a lower incidence of extrapyramidal side effects. However, seizures associated with clozapine treatment occur at a rate of about three percent. Factors which seem to increase the likelihood of seizures include high doses of clozapine, rapid dose titration, the concurrent use of other epileptogenic agents and a previous history of neurological abnormalities. A strategy that has been proposed to reduce the occurrence of seizures is the addition of an anticonvulsant agent. At present, little rigorous scientific evidence exists to establish the effectiveness of this strategy or the choice of an anticonvulsant. However, based on what evidence there is and the side effect profiles of the various anticonvulsants, the authors propose the use of valproic acid for the prophylaxis and management of clozapine related seizures.