2005]. A comparison of clozapine use in Korean and Caucasian patients found a greater change in the Brief Psychiatric Rating Scale (BPRS) scores in Korean patients while on significantly lower doses of clozapine [Matsuda et al. 1996]. It appears that lower maintenance doses of clozapine might be enough to treat Asian patients successfully but that seizures (which are usually associated with higher clozapine doses) might present at much lower clozapine Inhibitors,research,lifescience,medical doses. The use of valproate

for prophylaxis of clozapine-induced seizure Valproate is an effective GABA-ergic antiepileptic drug (AED) [McElroy et al. 1989]. It has been widely regarded as the drug of choice for the treatment and prophylaxis of clozapine-induced seizures [Foster and Olajide, 2005; Iqbal et al. 2003; Miller, 2000;

Littrell et al. 1995; Kando et al. 1994; Toth and Frankenburg, 1994; Liukkonen et al. 1992], and is the most commonly used AED for this indication. There are, however, very few studies prospectively Inhibitors,research,lifescience,medical examining the efficacy of valproate in preventing clozapine-related seizures. Valproate has advantages over other AEDs: it has a broad spectrum of Inhibitors,research,lifescience,medical antiepileptic activity; it is effective in primary generalized seizures such as tonic—clonic, tonic, clonic, myoclonic (seizures and jerks) and both simple and complex absence seizures [McElroy et al. 1989]. Valproate has been used successfully in one case of clozapine-induced tonic—clonic seizure in a patient with treatment-resistant schizophrenia [Foster

and Olajide, 2005]; the authors noted an improved outcome in treatment-resistant schizophrenia with the concomitant use of an antiepileptic/ mood-stabilizing agent. Clozapine-associated myoclonic seizures seem to respond well to valproate. Two cases reporting myoclonic seizures with clozapine therapy Inhibitors,research,lifescience,medical described successful treatment with valproic acid [Taner et al. 1998]. This allowed the patients to continue with their effective clozapine treatment whilst remaining seizure-free. The authors of Inhibitors,research,lifescience,medical another case report [Meltzer and Ranjan, 1994] also advocate the use of valproic acid in the treatment of clozapine-induced myoclonic jerks. Meltzer and Ranjan suggested that it may be the serotonergic receptor blocking properties of clozapine that Metalloexopeptidase causes myoclonus, with valproic acid displaying an antimyoclonic effect. It is the dual effect of valproate when added to clozapine treatment that is PI3K inhibitor attractive to clinicians. It acts prophylactically against seizures and also has psychotropic properties; it acts as a mood stabilizer and as an antimanic agent [Brodtkorb and Mula, 2006]. This can add greatly to the potential therapeutic benefits for the patient. A retrospective study of 55 patients examined the safety of the concurrent clozapine and valproate [Kando et al. 1994]; valproate was used as a mood stabilizer in 25 of the patients, as seizure prophylaxis in 12 patients, and as an antiepileptic in 5 patients with a history of a seizure disorder.