Multidisciplinary consensus on prevention, screening and monitoring of clozapine-associated myocarditis and clozapine rechallenge after myocarditis

Elias Wagner, Nicole Korman, Marco Solmi, Matin Mortazavi, Zahra Aminifarsani, Douglas Dubrovin Leão, Matthew K. Burrage, Dan Siskind, Laura McMahon, Oliver D. Howes, Christoph U. Correll, CAM Expert Group, Alkomiet Hasan
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Abstract

Background

Clozapine is the antipsychotic of choice for people with treatment-resistant schizophrenia (TRS) but is associated with the uncommon but potentially life-threatening adverse effect of myocarditis. However, there are no criteria for diagnosing clozapine-associated myocarditis (CAM) or global guidelines on detection and risk reduction, or for restarting clozapine after CAM.

Aims

To develop criteria for CAM and algorithms for clozapine initiation and clozapine rechallenge after CAM in a multiprofessional consensus process.

Method

We conducted a systematic literature search for cases of clozapine rechallenge following CAM using the PubMed, EMBASE, CINAHL and PsycINFO databases, followed by a multidisciplinary international two-step Delphi consensus process in July and October 2024. The Delphi panel comprised psychiatrists, cardiologists, pharmacists, psychopharmacologists and nurses with expertise on clozapine or myocarditis.

Results

Ninety-three clinicians and academics with experience in prescribing clozapine from six continents participated in the Delphi process. A consensus was reached on a definition of CAM according to modified clinical criteria from the European Society of Cardiology for myocarditis associated with immune checkpoint inhibitors. Titration schemes slower than those given in the Summary of Product Characteristics for clozapine were recommended to minimise CAM risk. Minimum and enhanced requirements for screening and monitoring were developed to account for global perspectives and limited resources in certain healthcare systems, and an approach to clozapine rechallenge was elaborated.

Conclusions

This multidisciplinary project represents the first guidance for CAM and will inform clinicians, other caregivers and patients, as well as facilitating the development of national guidelines on CAM prevention, screening and monitoring and rechallenge after an index episode of myocarditis in individuals taking clozapine.

氯氮平相关性心肌炎的预防、筛查和监测以及心肌炎后氯氮平再挑战的多学科共识
背景氯氮平是治疗难治性精神分裂症(TRS)患者的首选抗精神病药物,但与罕见但可能危及生命的心肌炎不良反应相关。然而,目前还没有诊断氯氮平相关性心肌炎(CAM)的标准,也没有关于检测和降低风险的全球指南,也没有在CAM后重新使用氯氮平的指南。目的在多专业共识的过程中制定CAM的标准和氯氮平起始和CAM后氯氮平再挑战的算法。方法利用PubMed、EMBASE、CINAHL和PsycINFO数据库对氯氮平CAM后再挑战病例进行系统文献检索,并于2024年7月和10月进行多学科国际两步德尔菲共识过程。德尔菲小组由精神病学家、心脏病学家、药剂师、精神药理学家和具有氯氮平或心肌炎专业知识的护士组成。结果来自六大洲的93名具有氯氮平处方经验的临床医生和学者参与了德尔菲过程。根据欧洲心脏病学会对与免疫检查点抑制剂相关的心肌炎的修改临床标准,对CAM的定义达成了共识。推荐比氯氮平产品特性总结中给出的滴定方案慢的滴定方案以最小化CAM风险。考虑到全球视角和某些医疗保健系统有限的资源,制定了筛查和监测的最低和增强要求,并详细阐述了氯氮平再挑战的方法。该多学科项目代表了第一个CAM指南,将为临床医生、其他护理人员和患者提供信息,并促进有关服用氯氮平的个体发生心肌炎指数发作后CAM预防、筛查、监测和再挑战的国家指南的制定。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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