基于FAERS数据库对药源性帕金森综合征不良事件药物警戒信号的挖掘

Mining of pharmacovigilance signals for adverse events of drug-induced Parkinson""s syndrome based on FAERS database

关键词:  药源性帕金森综合征  FAERS  不良事件  信号挖掘

Key words:  Drug-induced Parkinsonism  FDA adverse event reporting system  Adverse events  Signal mining

摘要:

摘要：目的 基于美国食品药品管理局不良事件报告系统（FDA adverse event reporting system，FAERS）数据库，对引起药源性帕金森综合征的药物进行数据挖掘。方法 收集FAERS数据库2004年第1季度至2024年第1个季度共81个季度的发生药源性帕金森综合征的不良事件报告。采用ROR法、PRR法、BCPNN法以及MGPS法进行信号挖掘。结果 最终纳入分析的报告数为405755例。女性（239269例，58.97%）多于男性（135094例，33.29％）；在已知年龄的患者中，45-64岁人群中最多（23.83%），其次为≥65岁的老年人（20.75%）；四种方法取交集最终获得 107个DIP信号药物，涉及病例数183258例。其中以涉及神经系统药物最多（73个）。发现引起帕金森不良事件信号最有意义的药物有甲氧氯普胺[ROR=67.85, 95% CI(67.03-68.67)]、卡比多巴；左旋多巴[ROR=12.05, 95% CI(11.87-12.23)]、缬本那嗪[ROR=16.14, 95% CI(15.68-16.62)]、氟哌啶醇[ROR=12.30, 95% CI(11.90-12.71)]。临床转归结果：84.03％的病例发生严重不良事件；多数DIP事件在首次使用药物后的30天内显现（17.39%），其发病时间的中位数为9天；临床结局为死亡的病例共12062例（2.97％）；危及生命的病例有13852例（3.41％）；致残的病例有35309例（8.70％）。结论 第一代抗精神病药、甲氧氯普胺及含左旋多巴的抗帕金森药易引发DIP，多在30天内发生，且严重不良反应发生风险高。第二代抗精神病药和抗抑郁药也可能导致DIP，但其潜在风险仍需临床验证。

Abstract:

ABSTRACT：OBJECTIVE To conduct data mining on drugs causing drug-induced Parkinsonism based on the FDA Adverse Event Reporting System(FAERS). METHODS Collect adverse event reports of drug-induced Parkinson's syndrome from the FAERS database for a total of 81 quarters from Q1 2004 to Q1 2024. Using ROR, PRR, BCPNN, and MGPS methods for signal mining. RESULTS The final number of reports included in the analysis was 405755. There were more females (239269 cases, 58.97%) than males (135094 cases, 33.29%); Among patients of known age, the 45-64 age group has the highest proportion (23.83%), followed by elderly people aged 65 and above (20.75%); The intersection of four methods resulted in 107 DIP signal drugs, involving 183258 cases. Among them, the most commonly used drugs involve the nervous system, accounting for 73. The most significant drugs found to cause adverse event signals in Parkinson's disease are metoclopramide [OR=67.85, 95% CI (67.03-68.67)] and carbidopa; Levodopa [OR=12.05, 95% CI (11.87-12.23)], Valbenazine [OR=16.14, 95% CI (15.68-16.62)], Haloperidol [OR=12.30, 95% CI (11.90-12.71)]. Clinical outcome: 84.03% of cases experienced serious adverse events; Most DIP events manifest within 30 days after the first use of medication (17.39%), with a median onset time of 9 days; The clinical outcomes were as follows: a total of 12,062 cases resulted in death (2.97%); 13,852 cases were life-threatening (3.41%); and 35,309 cases led to disability (8.70%).CONCLUSIONS First-generation antipsychotics, metoclopramide, and Parkinson's medications containing levodopa are prone to inducing DIP, mostly within 30 days, with a high risk of severe adverse reactions. Second-generation antipsychotics and antidepressants may also lead to DIP, but their potential risks still require clinical verification.