Table 1_Arrhythmic events pertinent with antidepressants: a Bayesian disproportional analysis mining the FDA Adverse Event Reporting System database.pdf

ObjectiveThe aim of this study was to investigate pharmacovigilance (PV) and make pairwise comparisons on arrhythmic events among antidepressants from the US Food and Drug Administration Adverse Event Reporting System (FAERS).
MethodsRecords regarding antidepressants treating depression and major depression from the first quarter of 2015 to the third quarter of 2023 documented in the FAERS database were harvested. The primary endpoint of this study was PV for arrhythmic events, including QT prolongation/Torsades de Pointes (TdP), atrial fibrillation (AF), heart block, and ventricular arrhythmia. The secondary endpoints comprised the pairwise comparisons on constituent ratio and severity of outcomes of drugs of interest on the above four diseases.
ResultUltimately, 746,507 records were eligible for analysis. PV for QT interval prolongation/TdP was identified for citalopram [proportional reporting ratio (PRR) = 2.13, 95% confidence interval (CI): 1.89 to 2.40, reporting odds ratio (ROR) = 2.14, 95% CI: 1.90 to 2.40, IC = 0.98, 95% CI: 0.80 to 1.12], escitalopram (ROR = 1.72, 95% CI: 1.52 to 1.96, IC = 0.71, 95% CI: 0.51 to 0.86), fluoxetine (ROR = 1.39, 95% CI: 1.21 to 1.60, IC = 0.43, 95% CI: 0.21 to 0.60), and quetiapine (ROR = 1.58, 95% CI: 1.30 to 1.91, IC = 0.63, 95% CI: 0.31 to 0.85). In terms of AF, PV was detected in citalopram (ROR = 1.82, 95% CI: 1.44 to 2.30, IC = 0.78, 95% CI: 0.41 to 1.05), escitalopram (ROR = 1.34, 95% CI: 1.03 to 1.74), sertraline (ROR = 1.32, 95% CI: 1.07 to 1.64, IC = 0.35, 95% CI: 0.01 to 0.59), and fluoxetine (ROR = 1.68, 95% CI: 1.32 to 2.13, IC = 0.68, 95% CI: 0.29 to 0.95). With regard to heart block, PV was detected in citalopram (ROR = 1.37, 95% CI: 1.05 to 1.80) and mirtazapine (ROR = 1.40, 95% CI: 1.03 to 1.90). Regarding ventricular arrhythmia, PV was detected in citalopram (ROR = 1.55, 95% CI: 1.19 to 2.02, IC = 0.58, 95% CI: 0.15 to 0.88), escitalopram (ROR = 1.51,95% CI: 1.16 to 1.97, IC = 0.54, 95% CI: 0.12 to 0.85), and quetiapine (PRR = 2.39, 95% CI: 1.75 to 3.25, ROR = 2.39, 95% CI: 1.75 to 3.26, IC = 1.17, 95% CI: 0.67 to 1.54).
ConclusionCitalopram and escitalopram [classified as selective serotonin reuptake inhibitors (SSRIs)] exhibited the strongest correlations with arrhythmic occurrences. Quetiapine [classified as a second-generation antipsychotic (SGA)] demonstrated higher risk and worse prognosis on QT prolongation/TdP and ventricular arrhythmic events. Venlafaxine and duloxetine [classified as serotonin-norepinephrine reuptake inhibitors (SNRIs)] did not show any PV of any arrhythmia and had lower risks and a lower degree of adverse events compared with the rest. Certainly, more head-to-head related studies are merited.

**研究目的** 本研究旨在开展药物警戒（pharmacovigilance, PV）研究，并基于美国食品药品监督管理局不良事件报告系统（US Food and Drug Administration Adverse Event Reporting System, FAERS）数据，对抗抑郁药相关心律失常不良事件进行两两比较分析。
**研究方法** 本研究提取了FAERS数据库中2015年第一季度至2023年第三季度收录的、用于治疗抑郁症及重度抑郁症的抗抑郁药相关记录。本研究的主要终点为针对以下四类心律失常不良事件的药物警戒评估：QT间期延长/尖端扭转型室速（QT prolongation/Torsades de Pointes, TdP）、心房颤动（atrial fibrillation, AF）、心脏传导阻滞及室性心律失常。次要终点为针对上述四类疾病，对目标药物的不良事件构成比与结局严重程度开展两两比较分析。
**研究结果** 最终共有746507条记录符合分析纳入标准。针对QT间期延长/尖端扭转型室速的药物警戒分析显示，西酞普兰[比例报告比（proportional reporting ratio, PRR）=2.13，95%置信区间（confidence interval, CI）：1.89至2.40，报告比值比（reporting odds ratio, ROR）=2.14，95%CI：1.90至2.40，信息成分（IC）=0.98，95%CI：0.80至1.12]、艾司西酞普兰（ROR=1.72，95%CI：1.52至1.96，IC=0.71，95%CI：0.51至0.86）、氟西汀（ROR=1.39，95%CI：1.21至1.60，IC=0.43，95%CI：0.21至0.60）及喹硫平（ROR=1.58，95%CI：1.30至1.91，IC=0.63，95%CI：0.31至0.85）均存在显著信号。针对心房颤动的药物警戒分析显示，西酞普兰（ROR=1.82，95%CI：1.44至2.30，IC=0.78，95%CI：0.41至1.05）、艾司西酞普兰（ROR=1.34，95%CI：1.03至1.74）、舍曲林（ROR=1.32，95%CI：1.07至1.64，IC=0.35，95%CI：0.01至0.59）及氟西汀（ROR=1.68，95%CI：1.32至2.13，IC=0.68，95%CI：0.29至0.95）均存在显著信号。针对心脏传导阻滞的药物警戒分析显示，西酞普兰（ROR=1.37，95%CI：1.05至1.80）及米氮平（ROR=1.40，95%CI：1.03至1.90）存在显著信号。针对室性心律失常的药物警戒分析显示，西酞普兰（ROR=1.55，95%CI：1.19至2.02，IC=0.58，95%CI：0.15至0.88）、艾司西酞普兰（ROR=1.51，95%CI：1.16至1.97，IC=0.54，95%CI：0.12至0.85）及喹硫平（PRR=2.39，95%CI：1.75至3.25，ROR=2.39，95%CI：1.75至3.26，IC=1.17，95%CI：0.67至1.54）均存在显著信号。
**研究结论** 西酞普兰与艾司西酞普兰[属于选择性5-羟色胺再摄取抑制剂（selective serotonin reuptake inhibitors, SSRIs）]与心律失常发生的相关性最强。喹硫平[属于第二代抗精神病药（second-generation antipsychotic, SGA）]在QT间期延长/TdP及室性心律失常事件中展现出更高的风险与更差的预后。文拉法辛与度洛西汀[属于5-羟色胺-去甲肾上腺素再摄取抑制剂（serotonin-norepinephrine reuptake inhibitors, SNRIs）]未检测到任何类型心律失常的药物警戒信号，且与其他受试药物相比，其不良事件风险与严重程度均更低。本研究结果仍需更多头对头相关研究进一步验证。