Aygün Ertuğrul , A. Elif Anıl Yağcıoğlu , Esen Ağaoğlu , Ahmet Alp Karakaşlı , Sertaç Ak , M. Kâzım Yazıcı , Jose de Leon
{"title":"丙戊酸盐、肥胖和其他氯氮平代谢不良的原因在快速滴定的背景下可以解释氯氮平诱导的心肌炎:对土耳其病例系列的重新分析","authors":"Aygün Ertuğrul , A. Elif Anıl Yağcıoğlu , Esen Ağaoğlu , Ahmet Alp Karakaşlı , Sertaç Ak , M. Kâzım Yazıcı , Jose de Leon","doi":"10.1016/j.rpsm.2021.10.003","DOIUrl":null,"url":null,"abstract":"<div><h3>Introduction</h3><p>Clozapine-induced myocarditis or any clozapine-induced inflammation may be a hypersensitivity reaction due to titration that was too rapid for the patient's clozapine metabolism. Clozapine metabolism is influenced by ancestry, sex, smoking and the presence of confounders including obesity, infections, and inhibitors (e.g., valproate) causing the patient to behave as a clozapine poor metabolizer (PM). A published study in a Turkish hospital identified 1 case of clozapine-induced pancreatitis and hepatitis and 9 cases of clozapine-induced myocarditis. To explore the hypothesis that the 10 patients were clozapine PMs, their serum clozapine concentrations were investigated using concentration-to-dose (C/D) ratios and their titrations carefully reviewed.</p></div><div><h3>Methods</h3><p>Dividing the trough serum concentration by the dose produces the clozapine C/D ratio. The dose required to reach 350<!--> <!-->ng/ml was considered the minimum therapeutic dosage and was used to classify patients according to clozapine PM status. Titration speed was assessed.</p></div><div><h3>Results</h3><p>All 10 patients were possibly clozapine PMs (3 of them had as minimum therapeutic doses: 72, 82 or 83<!--> <!-->mg/day). Nine of the 10 patients may have behaved as clozapine PMs due to obesity and/or valproate co-prescription during titration. One also had an undiagnosed infection. Of the 10 patients, 9 had at least 1 of 3 factors: too-rapid titration in the first or second weeks, or a final dosage that was too high.</p></div><div><h3>Conclusions</h3><p>Future studies using clozapine levels and considering the role of clozapine PM status should explore whether or not all cases of clozapine-induced inflammation could be explained by lack of individualized titration.</p></div>","PeriodicalId":21391,"journal":{"name":"Revista de psiquiatria y salud mental","volume":null,"pages":null},"PeriodicalIF":5.2000,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"11","resultStr":"{\"title\":\"Valproate, obesity and other causes of clozapine poor metabolism in the context of rapid titration may explain clozapine-induced myocarditis: A re-analysis of a Turkish case series\",\"authors\":\"Aygün Ertuğrul , A. Elif Anıl Yağcıoğlu , Esen Ağaoğlu , Ahmet Alp Karakaşlı , Sertaç Ak , M. Kâzım Yazıcı , Jose de Leon\",\"doi\":\"10.1016/j.rpsm.2021.10.003\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Introduction</h3><p>Clozapine-induced myocarditis or any clozapine-induced inflammation may be a hypersensitivity reaction due to titration that was too rapid for the patient's clozapine metabolism. Clozapine metabolism is influenced by ancestry, sex, smoking and the presence of confounders including obesity, infections, and inhibitors (e.g., valproate) causing the patient to behave as a clozapine poor metabolizer (PM). A published study in a Turkish hospital identified 1 case of clozapine-induced pancreatitis and hepatitis and 9 cases of clozapine-induced myocarditis. To explore the hypothesis that the 10 patients were clozapine PMs, their serum clozapine concentrations were investigated using concentration-to-dose (C/D) ratios and their titrations carefully reviewed.</p></div><div><h3>Methods</h3><p>Dividing the trough serum concentration by the dose produces the clozapine C/D ratio. The dose required to reach 350<!--> <!-->ng/ml was considered the minimum therapeutic dosage and was used to classify patients according to clozapine PM status. Titration speed was assessed.</p></div><div><h3>Results</h3><p>All 10 patients were possibly clozapine PMs (3 of them had as minimum therapeutic doses: 72, 82 or 83<!--> <!-->mg/day). Nine of the 10 patients may have behaved as clozapine PMs due to obesity and/or valproate co-prescription during titration. One also had an undiagnosed infection. Of the 10 patients, 9 had at least 1 of 3 factors: too-rapid titration in the first or second weeks, or a final dosage that was too high.</p></div><div><h3>Conclusions</h3><p>Future studies using clozapine levels and considering the role of clozapine PM status should explore whether or not all cases of clozapine-induced inflammation could be explained by lack of individualized titration.</p></div>\",\"PeriodicalId\":21391,\"journal\":{\"name\":\"Revista de psiquiatria y salud mental\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":5.2000,\"publicationDate\":\"2022-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"11\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Revista de psiquiatria y salud mental\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S188898912100121X\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PSYCHIATRY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Revista de psiquiatria y salud mental","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S188898912100121X","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PSYCHIATRY","Score":null,"Total":0}
Valproate, obesity and other causes of clozapine poor metabolism in the context of rapid titration may explain clozapine-induced myocarditis: A re-analysis of a Turkish case series
Introduction
Clozapine-induced myocarditis or any clozapine-induced inflammation may be a hypersensitivity reaction due to titration that was too rapid for the patient's clozapine metabolism. Clozapine metabolism is influenced by ancestry, sex, smoking and the presence of confounders including obesity, infections, and inhibitors (e.g., valproate) causing the patient to behave as a clozapine poor metabolizer (PM). A published study in a Turkish hospital identified 1 case of clozapine-induced pancreatitis and hepatitis and 9 cases of clozapine-induced myocarditis. To explore the hypothesis that the 10 patients were clozapine PMs, their serum clozapine concentrations were investigated using concentration-to-dose (C/D) ratios and their titrations carefully reviewed.
Methods
Dividing the trough serum concentration by the dose produces the clozapine C/D ratio. The dose required to reach 350 ng/ml was considered the minimum therapeutic dosage and was used to classify patients according to clozapine PM status. Titration speed was assessed.
Results
All 10 patients were possibly clozapine PMs (3 of them had as minimum therapeutic doses: 72, 82 or 83 mg/day). Nine of the 10 patients may have behaved as clozapine PMs due to obesity and/or valproate co-prescription during titration. One also had an undiagnosed infection. Of the 10 patients, 9 had at least 1 of 3 factors: too-rapid titration in the first or second weeks, or a final dosage that was too high.
Conclusions
Future studies using clozapine levels and considering the role of clozapine PM status should explore whether or not all cases of clozapine-induced inflammation could be explained by lack of individualized titration.
期刊介绍:
The Spanish Journal of Psychiatry and Mental Health (SJPMH), incorporated into ISSN 1888-9891, is the official scientific publication of the Spanish Society of Psychiatry and Mental Health. The journal focuses on studying mental illnesses, their pathological processes, and their psychosocial consequences, and aims to disseminate scientific advances in all areas related to mental health and illness. SJPMH accepts unpublished works on psychiatry and mental health, including their medical and social implications. The journal provides space for research in the biological, clinical, and psychosocial fields. Manuscripts undergo peer-review by external reviewers before being accepted for publication. SJPMH is indexed in Index Medicus/Medline, IBECS, Social Sciences Citation Index Journal Citation Reports/Social Sciences Edition, and Current Contents/Social and Behavioral Sciences.