VA Boston Healthcare System, Boston, Massachusetts, USA.
Department of Psychiatry, Harvard Medical School, Boston, Massachusetts, USA.
Acta Psychiatr Scand. 2022 May;145(5):423-441. doi: 10.1111/acps.13406. Epub 2022 Mar 16.
Clozapine is substantially underutilized in most countries and clinician factors including lack of knowledge and concerns about adverse drug effects (ADEs) contribute strongly to treatment reluctance. The aim of this systematic review was to provide clinicians with a comprehensive information source regarding clozapine ADEs.
PubMed and Embase databases were searched for English language reviews concerned with clozapine ADEs; publications identified by the automated search were manually searched for additional relevant citations. Following exclusion of redundant and irrelevant reports, pertinent information was summarized in evidence tables corresponding to each of six major ADE domains; two authors reviewed all citations for each ADE domain and summarized their content by consensus in the corresponding evidence table. This study was conducted in accordance with PRISMA principles.
Primary and secondary searches identified a total of 305 unique reports, of which 152 were included in the qualitative synthesis. Most clozapine ADEs emerge within 3 months, and almost all appear within 6 months, after initiation. Notable exceptions are weight gain, diabetic ketoacidosis (DKA), severe clozapine-induced gastrointestinal hypomotility (CIGH), clozapine-induced cardiomyopathy (CICM), seizures, and clozapine-induced neutropenia (CIN). Most clozapine ADEs subside gradually or respond to dose reduction; those that prompt discontinuation generally do not preclude rechallenge. Rechallenge is generally inadvisable for clozapine-induced myocarditis (CIM), CICM, and clozapine-induced agranulocytosis (CIA). Clozapine plasma levels >600-1000 μg/L appear more likely to cause certain ADEs (e.g., seizures) and, although there is no clear toxicity threshold, risk/benefit ratios are generally unfavorable above 1000 μg/L.
Clozapine ADEs rarely require discontinuation.
氯氮平在大多数国家的应用都严重不足，临床医生的因素，包括缺乏知识和对药物不良反应 (ADEs) 的担忧，是导致治疗犹豫不决的主要原因。本系统评价的目的是为临床医生提供一个关于氯氮平 ADEs 的综合信息来源。
检索了 PubMed 和 Embase 数据库中关于氯氮平 ADEs 的英文评论；通过自动搜索确定的出版物，手动搜索其他相关引文。排除重复和不相关的报告后，将相关信息总结在对应于六个主要 ADE 领域的证据表中；两位作者审查了每个 ADE 领域的所有引用，并在相应的证据表中通过共识总结了其内容。本研究按照 PRISMA 原则进行。
初级和次级搜索共确定了 305 篇独特的报告，其中 152 篇被纳入定性综合分析。大多数氯氮平 ADEs 在开始后 3 个月内出现，几乎所有 ADEs 在 6 个月内出现。值得注意的例外是体重增加、糖尿病酮症酸中毒 (DKA)、严重的氯氮平诱导的胃肠道低动力 (CIGH)、氯氮平诱导的心肌病 (CICM)、癫痫发作和氯氮平诱导的中性粒细胞减少症 (CIN)。大多数氯氮平 ADEs 逐渐缓解或对剂量减少有反应；那些导致停药的 ADE 通常不排除重新挑战。氯氮平诱导的心肌炎 (CIM)、CICM 和氯氮平诱导的粒细胞缺乏症 (CIA) 一般不建议重新挑战。氯氮平血浆水平>600-1000μg/L 似乎更有可能引起某些 ADEs（如癫痫发作），尽管没有明确的毒性阈值，但超过 1000μg/L 时，风险/效益比通常不利。
氯氮平 ADEs 很少需要停药。
