Clozapine Related EEG Changes

Background: Clozapine is an “atypical” neuroleptic drug with low affinity at most dopamine receptors, and interact at several other classes of receptors. Although it has less adverse effects, clozapine has profound impact on EEG, and may cause seizures. We retrospectively reviewed medical records and EEGs in patients with clozapine to evaluate the prevalence and risk factors of EEG abnormalities and seizures. Methods: 163 EEGs of 44 patients and their medical records were reviewed from Jan. 2000 to Jul. 2006. EEG was graded as follows: (0: Normal, 1: Less than 50% of theta waves, 2: More than 50% of theta or less than 50% of delta waves or grade 0/1 plus epileptic discharge, 3: More than 50% of delta waves or grade 2 plus epileptic discharge, and 4: Electroclinical seizure or marked low amplitude EEGs). Relation between the dosage of clozapine and EEG abnormalities, effect of anticonvulsant on seizure prevention were reviewed. Results: Dosage of clozapine and EEG abnormality was closely related (P<.001). 82% (23/28) of the EEGs with less than 100 mg of clozapine were grade 0, whereas 8/83 (9.7%) EEGs were grade 0 with more than 400 mg of clozapine. Epileptic discharges were frequently found when clozapine dosage was 200 mg or more [27/130 EEGs (21%)]. Valproate administration did not prevent EEG deterioration in 4/13 patients as long as clozapine was increased. Although preventive treatment with valproate was done in 11 patients, seizures occurred in 2 patients. Conclusions: Abnormal EEGs were significantly correlated with dosage of clozapine. Efficacy of valproate can not be determined in the prevention of seizure induced by clozapine. (J Korean Epilep Soc 2007;11(1):50-53)