De Las Cuevas Carlos, Sanz Emilio J, de Leon Jose
Department of Internal Medicine, Dermatology, and Psychiatry and Instituto Universitario de Neurociencia (IUNE), Universidad de La Laguna, La Laguna, Canary Islands, Spain.
Department of Physical Medicine and Pharmacology, Universidad de La Laguna, La Laguna, Canary Islands, Spain.
Patient Prefer Adherence. 2024 Nov 12;18:2261-2280. doi: 10.2147/PPA.S495254. eCollection 2024.
Clozapine is an antipsychotic which was approved in 1989 for treatment-resistant schizophrenia in the United States (US). There were few randomized trials before its approval and potentially lethal clozapine adverse drug reactions (ADRs), such as agranulocytosis and myocarditis were identified by pharmacovigilance. VigiBase, the WHO global database, is a cornerstone of international pharmacovigilance efforts for ADR identification during post-marketing surveillance. This systematic review of the literature explores additional contributions to the knowledge of clozapine ADRs from recent VigiBase studies.
Using the terms "clozapine AND VigiBase" we conducted an article search in PubMed on September 5, 2024. Of the 29 articles, 11 were excluded and 18 described in the Results section.
All clozapine ADRs were described in two VigiBase studies. One on pregnancy indicated no increased risk with clozapine compared with other antipsychotics; the other reported 191,557 clozapine ADRs, including 22,956 fatal outcomes through January 15, 2023, and paid attention to the reporting style of the top 4 reporting countries (the US, the United Kingdom, Canada and Australia). Infections were described in three VigiBase studies where clozapine treatment was associated with infections, respiratory aspiration, and pneumonia. Rapid titration can lead to localized clozapine-induced inflammations including myocarditis, pericarditis or pancreatitis, or generalized inflammations such as drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome. Clozapine-induced inflammation was described in four VigiBase studies, two focused on all ages (myocarditis and DRESS) and two on youth (myocarditis and another on pericarditis and pancreatitis). Other specific ADRs were described in nine VigiBase studies (hematological malignancies, rhabdomyolysis, sialorrhea, seizures, diabetes mellitus, drug-induced parkinsonism, withdrawal symptoms, and suicidal behaviors).
The spectrum of respiratory aspiration - aspiration pneumonia - pneumonia and other infections are significant causes of fatal outcomes in clozapine-treated patients. Clozapine had anti-suicidal effects versus other antipsychotics across all VigiBase labels of suicidal behavior.
氯氮平是一种抗精神病药物，1989年在美国被批准用于治疗难治性精神分裂症。在其获批之前几乎没有随机试验，并且通过药物警戒识别出了潜在致命的氯氮平药物不良反应（ADR），如粒细胞缺乏症和心肌炎。世界卫生组织全球数据库VigiBase是上市后监测期间国际药物警戒工作中识别ADR的基石。本系统文献综述探讨了近期VigiBase研究对氯氮平ADR知识的其他贡献。
2024年9月5日，我们使用“氯氮平AND VigiBase”这两个术语在PubMed上进行了文献检索。在29篇文章中，排除了11篇，结果部分描述了18篇。
两项VigiBase研究描述了所有氯氮平ADR。一项关于妊娠的研究表明，与其他抗精神病药物相比，氯氮平不会增加风险；另一项研究报告了截至2023年1月15日的191,557例氯氮平ADR，包括22,956例致命结局，并关注了前4个报告国家（美国、英国、加拿大和澳大利亚）的报告风格。三项VigiBase研究描述了感染情况，其中氯氮平治疗与感染、呼吸道误吸和肺炎有关。快速滴定可导致局部性氯氮平诱导的炎症，包括心肌炎、心包炎或胰腺炎，或全身性炎症，如伴有嗜酸性粒细胞增多和全身症状的药物反应（DRESS）综合征。四项VigiBase研究描述了氯氮平诱导的炎症，两项针对所有年龄段（心肌炎和DRESS），两项针对青年（心肌炎，另一项针对心包炎和胰腺炎）。九项VigiBase研究描述了其他特定的ADR（血液系统恶性肿瘤、横纹肌溶解、流涎、癫痫发作、糖尿病、药物性帕金森综合征、戒断症状和自杀行为）。
呼吸道误吸-误吸性肺炎-肺炎以及其他感染是氯氮平治疗患者致命结局的重要原因。在所有关于自杀行为的VigiBase标签中，与其他抗精神病药物相比，氯氮平具有抗自杀作用。
