Zhan Zhi-Qing, Li Jia-Xin, Zhang Wei-Gang, Huang Shu-Yi, Fang Xixi
Division of Gastroenterology and Hepatology, NHC Key Laboratory of Digestive Diseases, State Key Laboratory for Oncogenes and Related Genes, Shanghai Institute of Digestive Disease, School of Medicine, Renji Hospital, Shanghai Jiao Tong University, Shanghai, China.
Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu, China.
CNS Neurosci Ther. 2025 May;31(5):e70436. doi: 10.1111/cns.70436.
Limited research has been conducted on the association between proton pump inhibitors (PPIs) use and psychiatric adverse events (AEs), leaving the understanding of PPIs-related psychiatric AEs in real-world settings unclear.
We aim to identify psychiatric AEs highly relevant to five commonly prescribed PPIs and to delve into the clinical characteristics of the population experiencing psychiatric AEs, as well as the time-to-onset pattern of the reported AEs.
We performed disproportionality analysis to evaluate the PPI-related psychiatric AEs risk signal using data from the FDA adverse event reporting system. Linkage disequilibrium score regression, high-definition likelihood, and Bidirectional MR analyses were employed to evaluate genetic correlations and causality for the pairwise traits between indications for PPI therapy and three common psychiatric disorders.
Psychiatric AEs were reported in 12.83% of all AE reports on PPIs. Disproportionality analysis identified multiple PPI-related psychiatric AE risk signals such as depressive disorder, bipolar disorder, and sleep disorder, with Omeprazole exhibiting the highest number of positive signals and cases (N = 386) and Rabeprazole the fewest (N = 28). Notably, we detected positive signals for suicide or self-injury-related AEs in three types of PPIs. Significant genetic correlations were revealed in peptic ulcer with major depressive disorder, peptic ulcer with schizophrenia, and gastroesophageal reflux disease (GERD) with major depressive disorder. Bidirectional MR analyses identified significant causal relationships between MDD and peptic ulcer, and a potential bidirectional causal association between GERD and MDD.
PPI-related psychiatric AEs may represent a non-negligible portion of overall PPI-related AEs. It is recommended to monitor and evaluate the safety of long-term PPI use in relation to psychiatric AEs.
关于质子泵抑制剂（PPIs）使用与精神科不良事件（AEs）之间关联的研究有限，使得对现实环境中与PPIs相关的精神科AEs的理解尚不清楚。
我们旨在识别与五种常用PPIs高度相关的精神科AEs，并深入研究经历精神科AEs人群的临床特征以及所报告AEs的发病时间模式。
我们使用来自美国食品药品监督管理局（FDA）不良事件报告系统的数据进行不成比例分析，以评估与PPI相关的精神科AEs风险信号。采用连锁不平衡评分回归、高清似然性和双向孟德尔随机化（MR）分析来评估PPI治疗适应症与三种常见精神障碍之间成对性状的遗传相关性和因果关系。
在所有关于PPIs的AE报告中，12.83%报告了精神科AEs。不成比例分析确定了多个与PPI相关的精神科AE风险信号，如抑郁症、双相情感障碍和睡眠障碍，其中奥美拉唑显示出最多的阳性信号和病例（N = 386），雷贝拉唑最少（N = 28）。值得注意的是，我们在三种类型的PPIs中检测到与自杀或自我伤害相关AEs的阳性信号。在消化性溃疡与重度抑郁症、消化性溃疡与精神分裂症以及胃食管反流病（GERD）与重度抑郁症之间发现了显著的遗传相关性。双向MR分析确定了重度抑郁症与消化性溃疡之间的显著因果关系，以及GERD与重度抑郁症之间潜在的双向因果关联。
与PPI相关的精神科AEs可能在总体与PPI相关的AEs中占不可忽视的比例。建议监测和评估长期使用PPI与精神科AEs相关的安全性。
