基于美国食品药品监督管理局不良事件报告系统数据库的老年人药源性认知障碍信号挖掘^*

Research on signal mining of drug-induced cognitive impairment in elderly people basedon the Food and Drug Administration Adverse Event Reporting System

摘要

目的 挖掘与分析美国食品药品监督管理局不良事件报告系统数据库(FAERS)中导致65岁及以上老年人产生认知障碍的药品不良反应风险信号,为临床用药安全提供参考。方法 采用比例失衡法对FAERS数据库中2004年第1季度至2025年第1季度报告的目标药物不良事件进行分析,旨在发现可能诱发特定药品不良反应的药物。结果 65岁及以上患者发生目标药物不良事件共10 847例,药源性认知障碍相关药物不良事件自2010年以来呈波动性增长,2021年达到最高峰。其中阳性信号的药物包括神经系统、抗肿瘤和免疫调节剂、心血管系统、消化和代谢系统、生殖泌尿系统和性激素、皮肤病、感觉器官系统、血液和造血器官、全身使用的抗感染药物、呼吸系统、肌肉骨骼系统、全身用激素类药物(不包括性激素和胰岛素)、其他、抗寄生虫药/杀虫药和驱虫药。阳性信号按频数排名前50的药物中,神经系统药物占比最多,包括抗帕金森病药卡比多巴/左旋多巴、抗精神病药奥氮平、抗癫痫药丙戊酸、抗痴呆药多奈哌齐、抗抑郁药及苯二氮类等。结论 65岁以上老年人群需警惕因神经系统药物导致的认知障碍及多重用药的风险,优先选择低风险替代方案。

Abstract

Objective To mine and analyze risk signals of adverse drug reactions leading to cognitive impairment in adults aged 65 and older from the US Food and Drug Administration Adverse Event Reporting System(FAERS) database, providing references for clinical medication safety. Methods The disproportionality analysis was used to analyze target adverse drug events in the FAERS database to identify drugs potentially inducing specific adverse drug events. Results A total of 10 847 patients aged 65 and older experienced the target adverse drug events, drug-induced cognitive impairment-related adverse drug events showed fluctuating growth since 2010. Among the positive signal drugs, include those for the nervous system, anti-tumor and immunomodulators, cardiovascular system, digestive and metabolic system, reproductive and urinary system and sex hormones, skin diseases, sensory organ system, blood and hematopoietic organs, systemic anti-infective drugs, respiratory system, musculoskeletal system, systemic hormonal drugs (excluding sex hormones and insulin), others, antiparasitic drugs/pesticides and anthelmintics. Among the top 50 drugs by report frequency with positive signals, nervous system agents constituted the largest proportion. These included anti-Parkinson drugs like carbidopa/levodopa, antipsychotics such as olanzapine, antiepileptics like valproic acid, anti-dementia drugs including donepezil, as well as antidepressants and benzodiazepines, among others. Conclusion The elderly population aged 65 and older should be vigilant regarding cognitive impairment associated with nervous system drugs and the cognitive risks of polypharmacy, prioritizing lower-risk alternative therapeutic options when possible.

关键词

药源性认知障碍 / 不良反应 / 比例失衡法

Key words

Drug-induced cognitive impairment / Adverse reaction / Disproportionality analysis

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基金资助

^*北京慢性病防治与健康教育研究会2024年药学专项科研课题(MBZX0082024001)