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

Hye Sung Kim, Tak Youn, Se Hyun Kim, Seong Hoon Jeong, Hee Yeon Jung, Sang Wuk Jeong, Kwang Ki Kim, Yong Sik Kim, In Won Chung

Research output: Contribution to journalArticleResearchpeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)131-137
Number of pages7
JournalInternational clinical psychopharmacology
Volume34
Issue number3
DOIs
StatePublished - 1 May 2019

Fingerprint

Clozapine
Electroencephalography
norclozapine
Valproic Acid
Bipolar Disorder
Schizophrenia
Observational Studies
Seizures
Retrospective Studies
Logistic Models
Regression Analysis

Cite this

Kim, Hye Sung ; Youn, Tak ; Kim, Se Hyun ; Jeong, Seong Hoon ; Jung, Hee Yeon ; Jeong, Sang Wuk ; Kim, Kwang Ki ; Kim, Yong Sik ; Chung, In Won. / Association between electroencephalogram changes and plasma clozapine levels in clozapine-treated patients. In: International clinical psychopharmacology. 2019 ; Vol. 34, No. 3. pp. 131-137.
@article{6a057d36c55c4b4aba6491957a71fa0d,
title = "Association between electroencephalogram changes and plasma clozapine levels in clozapine-treated patients",
abstract = "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.",
author = "Kim, {Hye Sung} and Tak Youn and Kim, {Se Hyun} and Jeong, {Seong Hoon} and Jung, {Hee Yeon} and Jeong, {Sang Wuk} and Kim, {Kwang Ki} and Kim, {Yong Sik} and Chung, {In Won}",
year = "2019",
month = "5",
day = "1",
doi = "10.1097/YIC.0000000000000255",
language = "English",
volume = "34",
pages = "131--137",
journal = "International Clinical Psychopharmacology",
issn = "0268-1315",
publisher = "Lippincott Williams and Wilkins Ltd.",
number = "3",

}

Association between electroencephalogram changes and plasma clozapine levels in clozapine-treated patients. / Kim, Hye Sung; Youn, Tak; Kim, Se Hyun; Jeong, Seong Hoon; Jung, Hee Yeon; Jeong, Sang Wuk; Kim, Kwang Ki; Kim, Yong Sik; Chung, In Won.

In: International clinical psychopharmacology, Vol. 34, No. 3, 01.05.2019, p. 131-137.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Association between electroencephalogram changes and plasma clozapine levels in clozapine-treated patients

AU - Kim, Hye Sung

AU - Youn, Tak

AU - Kim, Se Hyun

AU - Jeong, Seong Hoon

AU - Jung, Hee Yeon

AU - Jeong, Sang Wuk

AU - Kim, Kwang Ki

AU - Kim, Yong Sik

AU - Chung, In Won

PY - 2019/5/1

Y1 - 2019/5/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85063713707&partnerID=8YFLogxK

U2 - 10.1097/YIC.0000000000000255

DO - 10.1097/YIC.0000000000000255

M3 - Article

VL - 34

SP - 131

EP - 137

JO - International Clinical Psychopharmacology

JF - International Clinical Psychopharmacology

SN - 0268-1315

IS - 3

ER -