Berger Stefan J, Hofer Alex
Department für Psychiatrie, Psychotherapie, Psychosomatik und Medizinische Psychologie, Univ.-Klinik für Psychiatrie I, Medizinische Universität Innsbruck, Anichstr. 35, 6020, Innsbruck, Österreich.
Neuropsychiatr. 2023 Sep;37(3):122-129. doi: 10.1007/s40211-023-00474-z. Epub 2023 Jun 22.
According to current guidelines, clozapine should be used as a third step in treatment resistant schizophrenia (TRS). In everyday clinical practice, however, it is frequently used at a much later stage, which leads to a significant deterioration of prognosis. The first part of this narrative overview focuses on the most frequent side effects of clozapine, on the relevance of slow titration, and on specific aspects of therapeutic drug monitoring (TDM).
Medline, the Guideline for the use of clozapine 2013 of the Netherlands Clozapine Collaboration Group, and the S3 Guideline for Schizophrenia of the German Association for Psychiatry, Psychotherapy and Psychosomatics were searched for relevant literature, the last query dating from April 28th, 2023.
Despite its unique efficacy clozapine is underused in clinical practice and prescription varies between and within countries. Next to hematological, metabolic, and vegetative side effects, clozapine induced inflammation manifesting in the form of pneumonia or myocarditis, which is mainly associated with rapid titration, represents a major clinical challenge with CRP monitoring being of particular relevance. In this context, it also has to be noted that sex, smoking behavior, and ethnic origin impact clozapine metabolism, thus requiring personalized dosing.
Slow titration when possible, TDM, and CYP diagnostics when appropriate increase patient safety during treatment with clozapine and thus the likelihood of early prescription of this compound in TRS.
根据当前指南，氯氮平应作为难治性精神分裂症（TRS）治疗的第三步使用。然而，在日常临床实践中，它经常在更晚的阶段使用，这导致预后显著恶化。本叙述性综述的第一部分重点关注氯氮平最常见的副作用、缓慢滴定的相关性以及治疗药物监测（TDM）的具体方面。
检索了Medline、荷兰氯氮平协作组2013年氯氮平使用指南以及德国精神病学、心理治疗和身心医学协会的精神分裂症S3指南，最后一次检索日期为2023年4月28日。
尽管氯氮平具有独特的疗效，但在临床实践中使用不足，且不同国家之间以及国家内部的处方存在差异。除血液学、代谢和植物神经副作用外，氯氮平引起的以肺炎或心肌炎形式表现的炎症主要与快速滴定有关，这是一个重大的临床挑战，CRP监测尤为重要。在此背景下，还必须注意性别、吸烟行为和种族对氯氮平代谢有影响，因此需要个性化给药。
尽可能缓慢滴定、进行TDM以及在适当的时候进行CYP诊断可提高氯氮平治疗期间的患者安全性，从而增加在TRS中早期使用该药物的可能性。
