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Association between electroencephalogram changes and plasma clozapine levels in clozapine-treated patients

Kim, Hye Sunga; Youn, Taka,,b; Kim, Se Hyuna,,b; Jeong, Seong Hoonc; Jung, Hee Yeond,,e; Jeong, Sang-Wukf; Kim, Kwang Kif; Kim, Yong Sika,,b; Chung, In Wona,,b

International Clinical Psychopharmacology: May 2019 - Volume 34 - Issue 3 - p 131–137
doi: 10.1097/YIC.0000000000000255
Original Articles

This retrospective observational study was performed to investigate electroencephalogram abnormalities in clozapine-treated patients with refractory schizophrenia or bipolar disorder. The electroencephalogram and plasma clozapine and norclozapine levels in 71 patients were measured on the same day. Fifty-nine patients (85.9%) had a diagnosis of schizophrenia, and 12 patients (14.1%) had a diagnosis of bipolar disorder. The mean daily clozapine dose was 242.9 ± 105.5 mg (range 25–500 mg), and the mean plasma clozapine and norclozapine levels were 429.4 ± 264.1 and 197.8 ± 132.6 ng/ml, respectively. Twenty-five patients (35.2%) were taking valproate in combination with clozapine. electroencephalogram abnormalities were found in 51 (71.8%) patients. No patient reported clinical seizures. Plasma clozapine level was significantly associated with electroencephalogram abnormalities and was identified as a significant predictor of electroencephalogram abnormalities in a logistic regression analysis. The plasma norclozapine levels of patients taking both clozapine and valproic acid were significantly lower than those of patients treated with clozapine alone. These results demonstrate that electroencephalogram abnormalities are closely correlated with plasma clozapine levels. Valproate reduced plasma norclozapine levels. Simultaneous monitoring of electroencephalogram and plasma clozapine levels was useful for adjusting clozapine doses, improving clinical efficacy, and preventing the side effects of clozapine treatment.

aDepartment of Psychiatry, Dongguk University International Hospital, Goyang

bInstitute of Clinical Psychopharmacology, Dongguk University College of Medicine, Goyang

cDepartment of Psychiatry, Eulji University Hospital, Daejeon

dDepartment of Psychiatry, SMG-SNU Boramae Medical Center, Seoul

eDepartment of Psychiatry and Behavioral Science, Institute of Human Behavioral Medicine, Seoul National University College of Medicine, Seoul

fDepartment of Neurology, Dongguk University International Hospital, Goyang, Korea

Received 1 October 2018 Accepted 19 February 2019

Correspondence to In Won Chung, MD, PhD, Department of Psychiatry, Dongguk University International Hospital, Institute of Clinical Psychopharmacology, Dongguk University School of Medicine, 27 Dongguk-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do 10326, Korea, Tel: +82 31 961 7231; fax: +82 31 961 7236; e-mail:

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