The Affiliated Brain Hospital, Guangzhou Medical University, 36 Mingxin Road, Guangzhou 510370, China; Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou Medical University, Guangzhou 510370, China.
The Affiliated Brain Hospital, Guangzhou Medical University, 36 Mingxin Road, Guangzhou 510370, China.
J Affect Disord. 2024 Dec 15;367:96-108. doi: 10.1016/j.jad.2024.08.161. Epub 2024 Aug 30.
The high comorbidity and mutually reinforcing relation between depression and cardiovascular disease have raised concerns about the cardiovascular risk of antidepressants. To gain a better understanding of this correlation, we performed a comprehensive evaluation regarding the types and degrees of cardiovascular adverse events (AEs) associated with 37 commonly prescribed antidepressants.
AE reports from January 2004 to December 2023 were retrieved from the FDA Adverse Event Reporting System (FAERS) database. Disproportionality analysis was performed to identify antidepressant-related cardiovascular signals using the reporting odds ratio, proportional reporting ratio, and information component. Influencing factors of cardiovascular death, including age, sex, antidepressant choice, and concomitant medication, were explored. The underlying mechanisms of antidepressant-associated cardiovascular risk related to neurotransmitter transporters/receptors were further explored.
The use of antidepressants was associated with eight categories of Standardized MedDRA Queries of cardiovascular events. Different antidepressants exerted varying types and degrees of cardiovascular risks along with contributions to death in reports with cardiovascular AEs. Among them, monoamine oxidase inhibitors had the highest risk of developing six cardiovascular event categories: torsades de pointes (TdP)/QT prolongation, hypertension, cardiac arrhythmias, cardiomyopathy, pulmonary hypertension, and ischaemic heart disease. Age, male and the use of 24 types of antidepressants and concomitant medications were positively correlated with death in cardiovascular AEs. The highest risk associated with antidepressants was found in amoxapine (OR = 5.00 [2.13, 11.75], P < 0.001), followed by moclobemide (OR = 3.66 [1.85, 7.24], P < 0.001). Correlation analysis indicated the occurrence of antidepressant-related TdP/QT prolongation, hypertension and cardiomyopathy was associated with the binding and uptake inhibition of dopamine and norepinephrine transporters as well as their selectivity over serotonin transporters.
The retrospective analysis revealed that cardiovascular AEs were connected with antidepressant use, and the binding/uptake inhibitory potency and selectivity of neurotransmitters of antidepressants played an important role, providing a preliminary basis for further in-depth study of antidepressant-related cardiovascular toxicity. However, as an exploratory study, prospective studies are needed to validate our findings in the future.
抑郁症和心血管疾病之间的高共病性和相互加强的关系引起了人们对抗抑郁药心血管风险的关注。为了更好地理解这种相关性，我们对 37 种常用抗抑郁药相关的心血管不良事件（AE）的类型和程度进行了全面评估。
从 FDA 不良事件报告系统（FAERS）数据库中检索了 2004 年 1 月至 2023 年 12 月的 AE 报告。使用报告比值比、比例报告比和信息成分进行了不相称性分析，以识别与抗抑郁药相关的心血管信号。探讨了影响心血管死亡的因素，包括年龄、性别、抗抑郁药的选择和伴随用药。进一步探讨了与神经递质转运体/受体相关的抗抑郁药相关心血管风险的潜在机制。
抗抑郁药的使用与心血管事件的八项标准 MedDRA 查询类别相关。不同的抗抑郁药在报告心血管 AE 时表现出不同类型和程度的心血管风险，并导致死亡。其中，单胺氧化酶抑制剂发生 6 类心血管事件的风险最高：尖端扭转型室性心动过速（TdP）/QT 延长、高血压、心律失常、心肌病、肺动脉高压和缺血性心脏病。年龄、男性和 24 种抗抑郁药和伴随药物的使用与心血管 AE 中的死亡呈正相关。在心血管 AE 中，与抗抑郁药相关的最高风险发生在阿莫沙平（OR=5.00[2.13，11.75]，P<0.001），其次是吗氯贝胺（OR=3.66[1.85，7.24]，P<0.001）。相关性分析表明，抗抑郁药相关的 TdP/QT 延长、高血压和心肌病的发生与多巴胺和去甲肾上腺素转运体的结合和摄取抑制以及它们对 5-羟色胺转运体的选择性有关。
回顾性分析显示，心血管 AE 与抗抑郁药的使用有关，抗抑郁药的神经递质结合/摄取抑制能力和选择性起着重要作用，为进一步深入研究抗抑郁药相关的心血管毒性提供了初步依据。然而，作为一项探索性研究，未来需要进行前瞻性研究来验证我们的发现。
