Min Wang, Xiaohong Chen, Zaiqiang Liu, Ziyi Li, Zhihong Zhu, Shao Liu, Sa Xiao
{"title":"探索GLP-1RAs与抑郁症之间的潜在关联：一项基于FAERS和VigiBase数据的药物警戒研究","authors":"Min Wang, Xiaohong Chen, Zaiqiang Liu, Ziyi Li, Zhihong Zhu, Shao Liu, Sa Xiao","doi":"10.1016/j.eclinm.2025.103385","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>GLP-1 receptor agonists (GLP-1RAs) are increasingly prescribed for diabetes and obesity management. Recent pharmacovigilance reports have raised concerns about potential neuropsychiatric adverse events, yet comprehensive safety assessments focusing on depressive disorders remain limited. This study investigated associations between specific GLP-1RAs and depressive disorders using real-world post-marketing surveillance data.</p><p><strong>Methods: </strong>We analyzed individual case safety reports (ICSRs) for liraglutide, semaglutide, and tirzepatide from the FDA Adverse Event Reporting System (FAERS) and WHO VigiBase databases through December 2024. Disproportionality analysis using reporting odds ratio (ROR) and information component (IC) identified signals of disproportionate reporting (SDRs) for depressive disorders. Time-to-onset analysis, stratified analyses, active comparator assessments, and co-medication evaluations were conducted to characterize these associations.</p><p><strong>Findings: </strong>Only semaglutide demonstrated statistically significant SDRs for depressive disorders in both databases (FAERS: ROR 1.26, 95% confidence interval (CI) 1.15-1.37; IC 0.33, 95% CI 0.20-0.45; VigiBase: ROR 1.38, 95% CI 1.27-1.49; IC 0.46, 95% CI 0.34-0.57), while liraglutide and tirzepatide showed no SDRs. Stratified analyses revealed increased disproportionality in females and healthcare professional reports. WSP analysis showed semaglutide-associated depression followed an early failure pattern, with no significant drug interactions identified with psychotropic medications.</p><p><strong>Interpretation: </strong>This pharmacovigilance investigation identified a semaglutide-specific SDR for depressive disorders across both databases, while liraglutide and tirzepatide showed no SDRs. Although inconsistent with reported protective effects in existing studies of GLP-1RAs, these findings suggest drug-specific rather than class-wide safety monitoring is warranted.</p><p><strong>Funding: </strong>This work was supported by grants from the Foshan \"Fourteen Five\" Key Medical Specialty Construction Project (grant number FSZD145035) and Natural Science Foundation of Hunan Province (grant number 2023JJ60520).</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"86 ","pages":"103385"},"PeriodicalIF":10.0000,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12329256/pdf/","citationCount":"0","resultStr":"{\"title\":\"Exploring potential associations between GLP-1RAs and depressive disorders: a pharmacovigilance study based on FAERS and VigiBase data.\",\"authors\":\"Min Wang, Xiaohong Chen, Zaiqiang Liu, Ziyi Li, Zhihong Zhu, Shao Liu, Sa Xiao\",\"doi\":\"10.1016/j.eclinm.2025.103385\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>GLP-1 receptor agonists (GLP-1RAs) are increasingly prescribed for diabetes and obesity management. Recent pharmacovigilance reports have raised concerns about potential neuropsychiatric adverse events, yet comprehensive safety assessments focusing on depressive disorders remain limited. This study investigated associations between specific GLP-1RAs and depressive disorders using real-world post-marketing surveillance data.</p><p><strong>Methods: </strong>We analyzed individual case safety reports (ICSRs) for liraglutide, semaglutide, and tirzepatide from the FDA Adverse Event Reporting System (FAERS) and WHO VigiBase databases through December 2024. Disproportionality analysis using reporting odds ratio (ROR) and information component (IC) identified signals of disproportionate reporting (SDRs) for depressive disorders. Time-to-onset analysis, stratified analyses, active comparator assessments, and co-medication evaluations were conducted to characterize these associations.</p><p><strong>Findings: </strong>Only semaglutide demonstrated statistically significant SDRs for depressive disorders in both databases (FAERS: ROR 1.26, 95% confidence interval (CI) 1.15-1.37; IC 0.33, 95% CI 0.20-0.45; VigiBase: ROR 1.38, 95% CI 1.27-1.49; IC 0.46, 95% CI 0.34-0.57), while liraglutide and tirzepatide showed no SDRs. Stratified analyses revealed increased disproportionality in females and healthcare professional reports. WSP analysis showed semaglutide-associated depression followed an early failure pattern, with no significant drug interactions identified with psychotropic medications.</p><p><strong>Interpretation: </strong>This pharmacovigilance investigation identified a semaglutide-specific SDR for depressive disorders across both databases, while liraglutide and tirzepatide showed no SDRs. Although inconsistent with reported protective effects in existing studies of GLP-1RAs, these findings suggest drug-specific rather than class-wide safety monitoring is warranted.</p><p><strong>Funding: </strong>This work was supported by grants from the Foshan \\\"Fourteen Five\\\" Key Medical Specialty Construction Project (grant number FSZD145035) and Natural Science Foundation of Hunan Province (grant number 2023JJ60520).</p>\",\"PeriodicalId\":11393,\"journal\":{\"name\":\"EClinicalMedicine\",\"volume\":\"86 \",\"pages\":\"103385\"},\"PeriodicalIF\":10.0000,\"publicationDate\":\"2025-07-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12329256/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"EClinicalMedicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.eclinm.2025.103385\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/8/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICINE, GENERAL & INTERNAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"EClinicalMedicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.eclinm.2025.103385","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/8/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"MEDICINE, GENERAL & INTERNAL","Score":null,"Total":0}
引用次数: 0
摘要
背景：GLP-1受体激动剂（GLP-1RAs）越来越多地被用于糖尿病和肥胖治疗。最近的药物警戒报告引起了对潜在的神经精神不良事件的关注，然而针对抑郁症的综合安全性评估仍然有限。本研究利用真实世界的上市后监测数据调查了特定GLP-1RAs与抑郁症之间的关系。方法：我们分析了截至2024年12月FDA不良事件报告系统（FAERS）和WHO VigiBase数据库中利拉鲁肽、西玛鲁肽和替西帕肽的个案安全报告（ICSRs）。使用报告优势比（ROR）和信息成分（IC）识别抑郁症不成比例报告（SDRs）信号的不成比例分析。进行发病时间分析、分层分析、主动比较者评估和联合用药评估来表征这些关联。结果：在两个数据库中，只有西马鲁肽显示出具有统计学意义的抑郁障碍特别推荐率(FAERS: ROR 1.26, 95%可信区间（CI） 1.15-1.37；IC 0.33, 95% ci 0.20-0.45；VigiBase: ROR 1.38, 95% CI 1.27-1.49；IC 0.46, 95% CI 0.34-0.57)，而利拉鲁肽和替西帕肽无特别反应。分层分析显示，在女性和医疗保健专业报告中，这一比例增加。WSP分析显示，semaglutide相关的抑郁症遵循早期失败模式，与精神药物没有明显的药物相互作用。解释：这项药物警戒调查在两个数据库中都发现了西格鲁肽对抑郁症的特异性SDR，而利拉鲁肽和替西帕肽没有显示出SDR。尽管与现有研究中报道的GLP-1RAs的保护作用不一致，但这些发现表明有必要进行药物特异性而不是整个类别的安全性监测。本工作得到佛山市“十四五”重点医学专业建设项目（批准号FSZD145035）和湖南省自然科学基金（批准号2023JJ60520）的资助。
Exploring potential associations between GLP-1RAs and depressive disorders: a pharmacovigilance study based on FAERS and VigiBase data.
Background: GLP-1 receptor agonists (GLP-1RAs) are increasingly prescribed for diabetes and obesity management. Recent pharmacovigilance reports have raised concerns about potential neuropsychiatric adverse events, yet comprehensive safety assessments focusing on depressive disorders remain limited. This study investigated associations between specific GLP-1RAs and depressive disorders using real-world post-marketing surveillance data.
Methods: We analyzed individual case safety reports (ICSRs) for liraglutide, semaglutide, and tirzepatide from the FDA Adverse Event Reporting System (FAERS) and WHO VigiBase databases through December 2024. Disproportionality analysis using reporting odds ratio (ROR) and information component (IC) identified signals of disproportionate reporting (SDRs) for depressive disorders. Time-to-onset analysis, stratified analyses, active comparator assessments, and co-medication evaluations were conducted to characterize these associations.
Findings: Only semaglutide demonstrated statistically significant SDRs for depressive disorders in both databases (FAERS: ROR 1.26, 95% confidence interval (CI) 1.15-1.37; IC 0.33, 95% CI 0.20-0.45; VigiBase: ROR 1.38, 95% CI 1.27-1.49; IC 0.46, 95% CI 0.34-0.57), while liraglutide and tirzepatide showed no SDRs. Stratified analyses revealed increased disproportionality in females and healthcare professional reports. WSP analysis showed semaglutide-associated depression followed an early failure pattern, with no significant drug interactions identified with psychotropic medications.
Interpretation: This pharmacovigilance investigation identified a semaglutide-specific SDR for depressive disorders across both databases, while liraglutide and tirzepatide showed no SDRs. Although inconsistent with reported protective effects in existing studies of GLP-1RAs, these findings suggest drug-specific rather than class-wide safety monitoring is warranted.
Funding: This work was supported by grants from the Foshan "Fourteen Five" Key Medical Specialty Construction Project (grant number FSZD145035) and Natural Science Foundation of Hunan Province (grant number 2023JJ60520).
期刊介绍：
eClinicalMedicine is a gold open-access clinical journal designed to support frontline health professionals in addressing the complex and rapid health transitions affecting societies globally. The journal aims to assist practitioners in overcoming healthcare challenges across diverse communities, spanning diagnosis, treatment, prevention, and health promotion. Integrating disciplines from various specialties and life stages, it seeks to enhance health systems as fundamental institutions within societies. With a forward-thinking approach, eClinicalMedicine aims to redefine the future of healthcare.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
