Clozapine-induced electroencephalogram changes as a function of clozapine serum levels

Oliver Freudenreich, Richard D. Weiner, Joseph P. McEvoy

Research output: Contribution to journalArticlepeer-review

99 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)132-137
Number of pages6
JournalBiological Psychiatry
Issue number2
StatePublished - Jul 15 1997
Externally publishedYes


  • Clozapine
  • Electroencephalogram
  • Schizophrenia
  • Seizures
  • Serum level

ASJC Scopus subject areas

  • Biological Psychiatry


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