Han Jungmin, Kim Minsung, Kim Yujin, Lee Soo Hyeon, Shin Sooyoung, Choi Yeo Jin
Department of Pharmacy, School of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea.
Department of Pharmacy, School of Pharmacy, Sookmyung Women's University, Seoul 02447, Republic of Korea.
Medicina (Kaunas). 2025 Jun 17;61(6):1103. doi: 10.3390/medicina61061103.
This study aims to characterize the prevalence and severity of antidepressant-associated adverse drug events (ADEs) and to identify predictors strongly associated with serious adverse events (SAEs). Disproportionality analysis on antidepressant-related ADEs spontaneously reported to the Korea Adverse event Reporting System (KIDS KAERS DB) from 2014 to 2023 was performed. Multiple logistic regression was conducted to identify predictors associated with SAEs. Sensitivity analysis was performed to validate the overall findings and assess the robustness of associations across subgroups defined by completeness of demographic data (age and sex), elderly age-stratification, and causality assessment. The study protocol was approved by the Kyung Hee University institutional review board. Among 21,103 antidepressant-related ADEs, duloxetine was the most etiologic medication, followed by amitriptyline and escitalopram. Fluoxetine is the only agent with a high likelihood of reporting SAEs. ADEs involving vascular (extracardiac) disorders (ROR 42.42, 95% CI 13.19-136.42) and liver and biliary system disorders (ROR 7.84, 95% CI 3.77-16.29) were most likely to be SAEs. The predictors associated with substantial increased SAE risk were fluoxetine use (OR 2.71, 95% CI 1.68-4.39), male sex (OR 1.48, 95% CI 1.11-1.98), and concomitant administration of antiparkinsonian treatment (OR 8.29, 95% CI 3.61-19.06) and antidementia treatment (OR 2.94, 95% CI 1.34-6.05). Sensitivity analyses demonstrated similar and consistent findings. However, reversed trends in the association between SOC-based ADEs and sex were observed in the sensitivity analysis restricted to cases with "certain" and "probable" causality. The type of antidepressant, concomitant medications, and sex are major predictors for SAE risk. Further controlled studies on the impact of comorbidities and polypharmacy on antidepressant-related SAEs are warranted.
本研究旨在描述抗抑郁药相关不良药物事件（ADEs）的发生率和严重程度，并确定与严重不良事件（SAEs）密切相关的预测因素。对2014年至2023年自发报告至韩国不良事件报告系统（KIDS KAERS数据库）的抗抑郁药相关ADEs进行不成比例分析。进行多因素逻辑回归以确定与SAEs相关的预测因素。进行敏感性分析以验证总体研究结果，并评估由人口统计学数据（年龄和性别）完整性、老年年龄分层和因果关系评估所定义的亚组间关联的稳健性。本研究方案已获庆熙大学机构审查委员会批准。在21,103例抗抑郁药相关ADEs中，度洛西汀是最主要的致病药物，其次是阿米替林和艾司西酞普兰。氟西汀是唯一一种报告SAEs可能性较高的药物。涉及血管（心脏外）疾病（报告比值比42.42，95%置信区间13.19 - 136.42）和肝脏及胆道系统疾病（报告比值比7.84，95%置信区间3.77 - 16.29）的ADEs最有可能是SAEs。与SAE风险显著增加相关的预测因素包括使用氟西汀（比值比2.71，95%置信区间1.68 - 4.39）、男性（比值比1.48，95%置信区间1.11 - 1.98）以及同时使用抗帕金森治疗（比值比8.29，95%置信区间3.61 - 19.06）和抗痴呆治疗（比值比2.94，95%置信区间1.34 - 6.05）。敏感性分析显示了相似且一致的结果。然而，在仅限于“肯定”和“很可能”因果关系病例的敏感性分析中，观察到基于系统器官分类的ADEs与性别之间的关联出现了相反的趋势。抗抑郁药类型、合并用药和性别是SAE风险的主要预测因素。有必要进一步开展关于合并症和联合用药对抗抑郁药相关SAEs影响的对照研究。
