Psychiatry Unit, Department of Health Sciences, University Magna Graecia of Catanzaro, Catanzaro, 88100, Italy; Department of Psychiatry, Psychotherapy and Psychosomatics, Hospital of Psychiatry, University of Zurich, Zurich, Switzerland.
The Zucker Hillside Hospital, Psychiatry Research, Northwell Health, Glen Oaks, New York, USA; Department of Psychiatry, Zucker School of Medicine at Northwell/Hofstra, Hempstead, NY, USA; Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, Manhasset, NY, USA.
Eur Neuropsychopharmacol. 2022 Jul;60:25-37. doi: 10.1016/j.euroneuro.2022.04.009. Epub 2022 May 26.
Clozapine-related drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare adverse reaction. We aimed to screen a large pharmacovigilance database to identify clozapine-related DRESS cases, even if otherwise reported and provide a clinical overview. We screened spontaneous reports of clozapine-related DRESS syndrome in EudraVigilance database applying the European Registry on Severe Cutaneous Adverse Drug Reactions (RegiSCAR) criteria and scores to identify probable/definite DRESS syndrome cases. Clinical and demographic characteristics of included cases were provided and associations between RegiSCAR scores, and time to develop/recover DRESS were assessed. In a total of 262,146 adverse drug reactions reports for 75,190 clozapine-treated patients, 596 cases fulfilled RegiSCAR criteria; ultimately, 51 cases were rated as probable/definite DRESS according to RegiSCAR scores, of which 4 were previously published as case reports. The mean age of patients was 41.06 years (43.1% females), with 13 patients (25.5%) receiving reported co-medication with other DRESS culprit drugs. Median time between clozapine initiation and DRESS symptoms was 25 days. Clozapine dose was associated with days to develop symptoms (Spearman's ρ 0.40, p = 0.03). Organ involvement was reported in all cases followed by fever (n = 49; 96.1%) and eosinophilia (n = 47; 92.2%). Treatment involved clozapine discontinuation for 37 patients (72.5%), while 3.9% (n = 2) of cases ended fatally. Clozapine rechallenge was undertaken in 25 patients (49.0%). The screening of the EudraVigilance database revealed 47 novel clozapine-related DRESS cases, and only one was originally reported as DRESS. Clozapine-related DRESS may occur with clozapine monotherapy not only during dose titration, but also during maintenance treatment.
氯氮平相关药物反应伴嗜酸性粒细胞增多和全身症状（DRESS）综合征是一种罕见的不良反应。我们旨在筛选一个大型药物警戒数据库，以确定氯氮平相关 DRESS 病例，即使这些病例是以其他方式报告的，并提供临床概述。我们应用欧洲严重皮肤不良反应登记处（RegiSCAR）标准和评分，筛选 EudraVigilance 数据库中氯氮平相关 DRESS 综合征的自发报告，以确定可能/确定的 DRESS 综合征病例。提供了纳入病例的临床和人口统计学特征，并评估了 RegiSCAR 评分与出现/恢复 DRESS 时间之间的关联。在 75190 例氯氮平治疗患者的 262146 例药物不良反应报告中，有 596 例符合 RegiSCAR 标准；最终，根据 RegiSCAR 评分，有 51 例被评为可能/确定的 DRESS，其中 4 例之前作为病例报告发表。患者的平均年龄为 41.06 岁（43.1%为女性），有 13 例（25.5%）接受了其他 DRESS 致病药物的报告合并用药。氯氮平开始使用与 DRESS 症状出现之间的中位时间为 25 天。氯氮平剂量与出现症状的天数相关（Spearman ρ 0.40，p=0.03）。所有病例均有器官受累，随后出现发热（n=49；96.1%）和嗜酸性粒细胞增多（n=47；92.2%）。37 例（72.5%）患者停止使用氯氮平进行治疗，而 3.9%（n=2）的病例死亡。25 例（49.0%）患者进行了氯氮平再挑战。筛选 EudraVigilance 数据库显示了 47 例新的氯氮平相关 DRESS 病例，其中只有 1 例最初报告为 DRESS。氯氮平相关 DRESS 不仅在剂量滴定期间，而且在维持治疗期间，均可发生于氯氮平单药治疗。
