Background and Objectives

Despite the evidence that no other antipsychotic is effective as clozapine for the treatment of resistant schizophrenia, it is associated with various metabolic, neuroendocrine, cardiovascular, and gastrointestinal adverse effects. Guidelines aiming to address the monitoring of clozapine’s (serious) adverse effects can be helpful to prevent and treat these effects. However, many of these guidelines seem to lack one or more important monitoring recommendations. We aimed to systematically review the content and quality of existing monitoring guidelines/recommendations for clozapine-induced adverse effects.

Methods

A comprehensive and systematic literature search, using the MEDLINE, Embase, Web of Science, and Cochrane databases, was conducted for guidelines/recommendations on the monitoring of clozapine-induced adverse events, published between January 2004 and April 2023 (last search 16 April 2023). Only peer-reviewed published guidelines reporting on the comprehensive monitoring of all major clozapine-induced adverse effects and including evidence-based recommendations, developed after the year 2004, were included. Studies reporting on the monitoring of adverse effects of clozapine without being a formal guideline, guidelines reporting on the monitoring of one or a limited number of adverse effects of clozapine, guidelines that were not peer reviewed or published, expert opinion papers without formal consensus guideline development, or guidelines developed before the year 2004, were excluded. The Appraisal of Guidelines for Research and Evaluation II (AGREE-II) tool was used to evaluate the guidelines/recommendations’ quality.

Results

Only one guideline met the inclusion criteria. This consensus statement made recommendations for hematological monitoring, and the monitoring of metabolic, cardiac, and three other adverse effects. Highest scores for the qualitative assessment were found for the domains “scope and purpose” (66.7%), “clarity of presentation” (44.4%), and “editorial independence” (66.7%). Lowest scores were found for “rigor of development” (14.6%) and “applicability” (0%).

Conclusions

Future guidelines should develop more comprehensive recommendations about specific clozapine-induced adverse effects, including constipation, myocarditis, tachycardia, and seizures, as well as include a rechallenge policy. There is an urgent need for well-developed, methodologically stringent, guidelines.

Registration

PROSPERO registration number, CRD42023402480.

中文翻译：

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评估氯氮平引起的不良反应的监测指南：系统评价

背景和目标

尽管有证据表明没有其他抗精神病药能像氯氮平一样有效治疗难治性精神分裂症，但它与各种代谢、神经内分泌、心血管和胃肠道不良反应有关。旨在监测氯氮平（严重）不良反应的指南有助于预防和治疗这些影响。然而，其中许多指南似乎缺乏一项或多项重要的监测建议。我们的目的是系统地审查现有氯氮平引起的不良反应监测指南/建议的内容和质量。

方法

使用 MEDLINE、Embase、Web of Science 和 Cochrane 数据库对 2004 年 1 月至 2023 年 4 月期间发布的氯氮平引起的不良事件监测指南/建议进行了全面、系统的文献检索（最后一次检索于 2023 年 4 月 16 日） ）。仅包括 2004 年之后制定的经同行评审的已发表指南，该指南报告了对氯氮平引起的所有主要不良反应的全面监测，并包括基于证据的建议。报告氯氮平不良反应监测但没有正式指南的研究、报告氯氮平一种或有限数量不良反应监测的指南、未经同行评审或发表的指南、未制定正式共识指南的专家意见文件，或 2004 年之前制定的指南被排除在外。研究和评估指南 II (AGREE-II) 工具用于评估指南/建议的质量。

结果

只有一项指南符合纳入标准。该共识声明对血液学监测以及代谢、心脏和其他三种不良反应的监测提出了建议。定性评估得分最高的领域是“范围和目的”（66.7%）、“演示清晰度”（44.4%）和“编辑独立性”（66.7%）。得分最低的是“开发的严谨性”（14.6%）和“适用性”（0%）。

结论

未来的指南应针对氯氮平引起的特定不良反应（包括便秘、心肌炎、心动过速和癫痫发作）制定更全面的建议，并包括重新挑战政策。迫切需要制定完善、方法严格的指南。

登记

PROSPERO 注册号，CRD42023402480。