基于自发呈报系统的选择性5-羟色胺再摄取抑制剂不良反应信号挖掘

Pharmacovigilance study on signal detection of adverse drug reactions associated with selective serotonin reuptake inhibitors using spontaneous reporting system data

摘要

目的: 基于FAERS数据库报告挖掘选择性5-羟色胺再摄取抑制剂(selective serotonin reuptake inhibitors, SSRIs)药物不良反应信号,为该类药物的安全性评价提供参考。方法: 采用比例报告比值法(proportional reporting ratio,PRR)、报告比值比(reporting odds ratio, ROR)和贝叶斯置信传递神经网络法(Bayesian confidence propagation neural network, BCPNN)挖掘不良反应信号。结果: SSRIs的不良反应报告主要累及的器官系统为精神异常、神经系统异常、全身性疾病及给药部位各种反应、各类损伤、中毒及操作并发症和胃肠系统异常。共发现70个阳性信号,氟伏沙明存在溢乳[信息成分(information component,IC) 95%CI下限0.79,PRR 95%CI下限3.88,ROR 95%CI下限3.88]、高催乳素血症(信息成分95%CI下限0.78,PRR 95%CI下限3.57,ROR 95%CI下限3.57)潜在不良反应信号;其余4种药物均发现妊娠过程中胎儿暴露的潜在不良反应信号;西酞普兰存在小样儿(信息成分95%CI下限3.38,PRR 95%CI下限2.47,ROR 95%CI下限2.48)潜在不良反应信号。结论: 本研究发现SSRIs类药物的潜在药物不良反应,提示妊娠期SSRIs用药需谨慎,氟伏沙明用药期间需监测患者溢乳或高催乳素血症,为临床安全用药提供参考。

Abstract

Objective: To detect adverse drug reaction (ADR) signals of selective serotonin reuptake inhibitors (SSRIs) based on the FDA Adverse Event Reporting System (FAERS) database, and to provide a reference for the safety evaluation of these drugs. Methods: The proportional reporting ratio (PRR), reporting odds ratio (ROR), and Bayesian confidence propagation neural network (BCPNN) methods were used to detect ADR signals. Results: The adverse reaction reports of SSRIs mainly involved the following system organ classes: psychiatric disorders, nervous system disorders, general disorders and administration siteconditions, injury, poisoning and procedural complications, and gastrointestinal disorders. A total of 70 positive signals were detected. Fluvoxamine showed potential ADR signals for galactorrhea (IC 95%CI lower limit 0.79, PRR 95%CI lower limit 3.88, ROR 95%CI lower limit 3.88) and hyperprolactinemia (IC 95%CI lower limit 0.78, PRR 95%CI lower limit 3.57, ROR 95%CI lower limit 3.57). The other four SSRIs all showed potential ADR signals of fetal exposure during pregnancy. Citalopram showed a potential ADR signal for small for gestational age (IC 95%CI lower limit 3.38, PRR 95%CI lower limit 2.47, ROR 95%CI lower limit 2.48). Conclusion: This study identified potential ADR signals of SSRIs, suggesting that caution should be exercised when using SSRIs during pregnancy and that patients receiving fluvoxamine should be monitored for galactorrhea or hyperprolactinemia, so as to provide a reference for clinical safe medication.

关键词

选择性5-羟色胺再摄取抑制剂 / 不良反应 / FAERS

Key words

selective serotonin reuptake inhibitors / adverse drug reaction / FAERS

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基金资助

中国毒理学会临床毒理专项研究课题资助项目(CST2020CT103);重庆市药品不良反应监测中心药物警戒开放课题资助项目(Y0120240004)