Department of Pharmacy, Mayo Clinic, Rochester, Minnesota, USA.
Department of Experimental and Clinical Pharmacology, University of Minnesota College of Pharmacy, Minneapolis, Minnesota, USA.
Pharmacotherapy. 2023 Dec;43(12):1364-1396. doi: 10.1002/phar.2887. Epub 2023 Oct 31.
Clozapine is an effective antipsychotic medication used for treatment-resistant schizophrenia. However, it is underutilized due to rigorous hematologic monitoring requirements and many adverse drug reactions. Publications have highlighted the occurrence of inflammatory reactions, some life-threatening, particularly during the early stages of clozapine treatment. Although guidelines have suggested monitoring for inflammatory processes during clozapine initiation, screening in clinical practice is not universal. This systematic review aimed to investigate the relationship between clozapine and inflammation and assess the importance of monitoring for inflammatory reactions. A comprehensive literature search yielded 6915 unique publication records after removal of duplicates. After a rigorous screening process, 75 publications were included in the review, which focused on three main aspects: (i) the impact of clozapine on inflammatory markers, (ii) monitoring cardiac and other organ function during clozapine-associated inflammatory processes, and (iii) monitoring non-specific signs and symptoms of inflammation. Elevated levels of C-reactive protein (CRP) and several proinflammatory cytokines have been observed in association with clozapine treatment. However, the practicality of measuring specific markers in clinical practice remains uncertain. Current evidence supports monitoring CRP levels during the first 4-8 weeks of treatment, especially to facilitate myocarditis screening. Further research is needed to establish clinically relevant CRP thresholds for intervention. The implementation of monitoring protocols during the early phase of clozapine treatment may mitigate adverse reactions and allow for continued use of clozapine. Future studies should also explore the association between clozapine-associated inflammation and pneumonia, as well as investigate the impact of inflammation on clozapine metabolism to predict the need for dose adjustment. These endeavors may facilitate the development and implementation of evidence-based guidelines for the monitoring of clozapine-associated inflammation.
氯氮平是一种有效的抗精神病药物，用于治疗抵抗性精神分裂症。然而，由于严格的血液监测要求和许多药物不良反应，它的应用并不广泛。已有出版物强调了炎症反应的发生，其中一些是威胁生命的，特别是在氯氮平治疗的早期阶段。尽管指南建议在氯氮平开始治疗时监测炎症过程，但在临床实践中并非普遍进行筛查。本系统评价旨在研究氯氮平和炎症之间的关系，并评估监测炎症反应的重要性。经过彻底的文献筛选，去除重复项后共获得 6915 条独特的出版物记录。最终有 75 篇出版物被纳入本综述，主要集中在三个方面：（i）氯氮平对炎症标志物的影响，（ii）在氯氮平相关炎症过程中监测心脏和其他器官功能，（iii）监测非特异性炎症迹象和症状。在氯氮平治疗期间观察到 C 反应蛋白 (CRP) 和几种促炎细胞因子水平升高。然而，在临床实践中测量特定标志物的实用性仍不确定。目前的证据支持在治疗的前 4-8 周监测 CRP 水平，特别是为了促进心肌炎筛查。需要进一步研究以确定临床相关的 CRP 干预阈值。在氯氮平治疗的早期阶段实施监测方案可能会减轻不良反应，并允许继续使用氯氮平。未来的研究还应探讨氯氮平相关炎症与肺炎之间的关系，并研究炎症对氯氮平代谢的影响，以预测需要调整剂量。这些努力可能有助于制定和实施监测氯氮平相关炎症的循证指南。
