A case of pharmacokinetic interference in comedication of clozapine and valproic acid

In 4-6% of treatment histories, clozapine induces generalized seizures by r educing the seizure threshold. Despite the knowledge of high risks combined therapy (such as bone marrow suppression, pathological EEG changes), some authors even suggest the prophylactic combination with anticonvulsants in h igh dose treatment of clozapine. We report a case of a 33-year-old female p atient, a heavy smoker, suffering from mixed schizoaffective disorder from 1989 onwards. At her 8th admission in 1998, she was rehospitalized after ex periencing her first generalized seizure under clozapine treatment. althoug h no seizure phenomenon or other relevant side-effects under several previo us clozapine therapies had been observed. Therefore, she received a valproi c acid co-medication during her clozapine therapy. Based on therapeutic dru g monitoring of clozapine (weekly) under compliance-controlled conditions, the serum levels of clozapine significantly decreased, probably induced by valproic acid. According to the literature. this case report might support the clinical relevance of therapeutic drug monitoring when clozapine therap y is combined with valproic acid as comedication.