title: Clozapine-induced electroencephalogram changes as a function of clozapine serum levels.
abstract: Specific electroencephalogram (EEG) changes during clozapine therapy were prospectively studied in a cohort of 50 chronic state hospital patients with schizophrenia who were randomly assigned to one of three nonoverlapping clozapine serum level ranges (50-150 ng/mL, 200-300 ng/mL, and 350-450 ng/mL). EEGs were obtained before clozapine was instituted, and after 10 weeks of treatment. Fifty-three percent of patients showed EEG changes during the 10-week study period. We observed three seizures (6%), one in a patient on 900 mg (serum level 320 ng/mL) clozapine, and two in patients with lower clozapine serum levels (200-300 ng/mL) who had prior histories of seizures and inadequate valproate coverage. Thirteen percent of patients developed spikes with no relationship to dose or serum level of clozapine. Fifty-three percent of patients developed slowing on EEG. Compared to plasma levels below 300 ng/mL, a clozapine serum level between 350 and 450 ng/mL led to more frequent and more severe slowing. The EEG slowing correlated with observed sleepiness, although this factor was not sufficient to explain the severity of high-dose effects.
authors.affiliation: John Umstead Hospital, Butner, North Carolina 27509, USA.
authors.forename: O
authors.initials: O
authors.lastname: Freudenreich
authors.forename: R D
authors.initials: RD
authors.lastname: Weiner
authors.forename: J P
authors.initials: JP
authors.lastname: McEvoy
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D002908:Chronic Disease; D003024:Clozapine / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004569:Electroencephalography / Q000187:drug effects*; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders / Q000097:blood / Q000188:drug therapy*; D012559:Schizophrenia / Q000097:blood / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D012640:Seizures / Q000097:blood / Q000139:chemically induced
chemical_list: D014150:Antipsychotic Agents; D003024:Clozapine