Valproic acid for seizure prophylaxis during clozapine therapy: Where's the evidence?

Clozapine, a dibenzodiazepine derivative, is the prototype atypical antipsychotic indicated for treatment-resistant patients with schizophrenia. Although considered by many to be the most effective antipsychotic, its clinical use has been hindered by some serious adverse reactions, one of the more serious of which is seizures. In response to this inherent risk of clozapine-induced seizures, some clinicians have been advocating the use of prophylactic valproic acid treatment. This article reviews the available literature to assess the evidence to support this practice.