CLOZAPINE-INDUCED ELECTROENCEPHALOGRAM CHANGES AS A FUNCTION OF CLOZAPINE SERUM LEVELS

Specific electroencephalogram (EEG) changes during clozapine therapy w ere prospectively studied in a cohort of 50 chronic state hospital pat ients with schizophrenia who were randomly assigned to one of three no noverlapping clozapine serum level ranges (50-150 ng/mL, 200-300 ng/mL , and 350-450 ng/mL). EEGs were obtained before clozapine was institut ed, and after 10 weeks of treatment. Fifty-three percent of patients s howed EEG changes during the 10-week study period. We observed three s eizures (6%), one in a patient on 900 mg (serum level 320 ng/mL) cloza pine, and two in patients with lower clozapine serum levels (200-300 n g/mL) who had prior histories of seizures and inadequate valproate cov erage. Thirteen percent of patients developed spikes with no relations hip to dose or serum level of clozapine. Fifty-three percent developed slowing on EEG. Compared to plasma levels below 300 ng/mL, a clozapin e serum level between 350 and 450 ng/mL led to more frequent and more severe slowing. The EEG slowing correlated with observed sleepiness, a lthough this factor was not sufficient to explain the severity of high -dose effects. (C) 1997 Society of Biological Psychiatry.