QTc changes and early major adverse cardiovascular events associated with antidepressant treatment for major depressive disorder in adults: individual participant data network meta-regression of double blind randomised trials.

Methods

Individual participant data (IPD) network meta-regression and aggregate pairwise meta-analysis.

个体参与者数据(IPD)网络荟萃回归分析和聚合配对荟萃分析。

data_sources

Individual and aggregate level data from randomised controlled trials identified through Cochrane Central Register of Controlled Trials, CINAHL, Embase, LILACS, Medline, Medline In-Process, PsycINFO, the websites of regulatory agencies, and international registers.

通过Cochrane对照试验注册中心、CINAHL、Embase、LILACS、Medline、Medline In-Process、PsycINFO、监管机构网站以及国际注册处，识别出的随机对照试验的个体和聚合水平数据。

Methods

IPD were harmonised to enhance comparability and analysed using network meta-regressions to explore the interplay with baseline QTc, age, sex assigned at birth, body mass index, serum potassium level, and estimated glomerular filtration rate.

个体数据(IPD)被协调以增强可比性，并使用网络荟萃回归分析来探索基线QTc、年龄、出生时指定的性别、体重指数、血清钾水平和估算的肾小球滤过率之间的相互作用。

The primary outcome was changes in QTc Fridericia (QTcF) associated with specific antidepressants and placebo after taking into account modifiable and non-modifiable risk factors.

主要结果是考虑可修改和不可修改风险因素后，特定抗抑郁药物和安慰剂与QTc Fridericia (QTcF)变化的关联。

Aggregate data on early MACE were analysed using pairwise meta-analysiscomparing antidepressants with placebo.

使用配对荟萃分析比较抗抑郁药物与安慰剂，分析了早期MACE的聚合数据。

eligibility_criteria_for_selecti

Double blind randomised trials of adults (≥18 years) with major depressive disorder diagnosed according to standardised, operationalised criteria.

双盲随机试验的成人（≥18岁），根据标准化、操作化的标准诊断为重大抑郁症。

Results

Of 130 unique randomised controlled trials identified, 35 (27%) included individual level data (8679 participants) on QTc with placebo and 10 antidepressants (amitriptyline, bupropion, duloxetine, escitalopram, fluoxetine, mirtazapine, paroxetine, trazodone, venlafaxine, vortioxetine).

在识别出的130个独特的随机对照试验中，有35个（27%）包含了QTc与安慰剂和10种抗抑郁药物（阿米替林、安非他酮、度洛西汀、艾司西酞普兰、氟西汀、米氮平、帕罗西汀、曲唑酮、文拉法辛、沃替西汀）的个体水平数据（8679名参与者）。

Compared with placebo, escitalopram and amitriptyline were associated with increased QTc intervals (8.7 milliseconds (ms), 95% credibility interval (CrI) 1.6 to 15.8, and 5.3 ms, 0.8 to 9.8, respectively).

与安慰剂相比，艾司西酞普兰和阿米替林与QTc间期增加有关（分别为8.7毫秒（ms），95%可信区间（CrI）1.6至15.8，和5.3 ms，0.8至9.8）。

When risk factors were considered, amitriptyline and escitalopram were also associated with the highest QTc prolongations (58.8% and 21.3%, respectively), whereas venlafaxine and vortioxetine were often associated with the lowest QTc intervals (24.1% and 9.7%, respectively).

在考虑风险因素时，阿米替林和艾司西酞普兰也与最高的QTc延长相关（分别为58.8%和21.3%），而文拉法辛和伏硫西汀则通常与最低的QTc间期相关（分别为24.1%和9.7%）。

Important variability of effects was observed, especially for escitalopram, fluoxetine, and mirtazapine.

观察到效果的重要变异性，尤其是对于艾司西酞普兰、氟西汀和米氮平。

An aggregate analysis of 139 trials (52 398 participants) did not identify an association between antidepressant use and increased rates of early MACE and non-suicidal death compared with placebo (risk difference 0.01%, 95% CrI -0.01% to 0.02%).

对139项试验（52,398名参与者）的汇总分析未发现抗抑郁药使用与早期主要不良心血管事件（MACE）和非自杀性死亡率增加之间存在关联，与安慰剂相比（风险差异0.01%，95% CrI -0.01%至0.02%）。

Conclusions

The effect of specific antidepressants on QTc interval differed between adults with depression.

特定抗抑郁药对QTc间期的影响在成年抑郁症患者之间存在差异。

No evidence associated antidepressant use with early MACE and non-suicidal sudden death.

没有证据将抗抑郁药使用与早期MACE和非自杀性突然死亡相关联。

To support shared decision making and taking into account the trade-off between benefits and harms, individual modifiable and non-modifiable risk factors should be considered when choosing antidepressants.

为了支持共享决策并考虑到效益与危害之间的权衡，选择抗抑郁药时应考虑个体可修改和不可修改的风险因素。

systematic_review_registration

Open Science Framework https://osf.io/c8k65/.

开放科学框架 https://osf.io/c8k65/。