Pain and Rehabilitation Centre, Department of Medicine and Health Sciences, Linköping University, Linköping, Sweden.
Department of Hygiene and Epidemiology, School of Medicine, University of Ioannina, University Campus, Ioannina, Greece.
JAMA Psychiatry. 2019 Dec 1;76(12):1241-1255. doi: 10.1001/jamapsychiatry.2019.2859.
Antidepressant use is increasing worldwide. Yet, contrasting evidence on the safety of antidepressants is available from meta-analyses, and the credibility of these findings has not been quantified.
To grade the evidence from published meta-analyses of observational studies that assessed the association between antidepressant use or exposure and adverse health outcomes.
PubMed, Scopus, and PsycINFO were searched from database inception to April 5, 2019.
Only meta-analyses of observational studies with a cohort or case-control study design were eligible. Two independent reviewers recorded the data and assessed the methodological quality of the included meta-analyses. Evidence of association was ranked according to established criteria as follows: convincing, highly suggestive, suggestive, weak, or not significant.
Forty-five meta-analyses (17.9%) from 4471 studies identified and 252 full-text articles scrutinized were selected that described 120 associations, including data from 1012 individual effect size estimates. Seventy-four (61.7%) of the 120 associations were nominally statistically significant at P ≤ .05 using random-effects models. Fifty-two associations (43.4%) had large heterogeneity (I2 > 50%), whereas small-study effects were found for 17 associations (14.2%) and excess significance bias was found for 9 associations (7.5%). Convincing evidence emerged from both main and sensitivity analyses for the association between antidepressant use and risk of suicide attempt or completion among children and adolescents, autism spectrum disorders with antidepressant exposure before and during pregnancy, preterm birth, and low Apgar scores. None of these associations remained supported by convincing evidence after sensitivity analysis, which adjusted for confounding by indication.
This study's findings suggest that most putative adverse health outcomes associated with antidepressant use may not be supported by convincing evidence, and confounding by indication may alter the few associations with convincing evidence. Antidepressant use appears to be safe for the treatment of psychiatric disorders, but more studies matching for underlying disease are needed to clarify the degree of confounding by indication and other biases. No absolute contraindication to antidepressants emerged from this umbrella review.
抗抑郁药的使用在全球范围内不断增加。然而，荟萃分析提供了关于抗抑郁药安全性的相互矛盾的证据，这些发现的可信度尚未得到量化。
对评估抗抑郁药使用或暴露与不良健康结果之间关联的观察性研究的已发表荟萃分析进行分级，以评估其证据质量。
从数据库建立到 2019 年 4 月 5 日，在 PubMed、Scopus 和 PsycINFO 上进行了检索。
只有队列或病例对照研究设计的观察性研究荟萃分析符合条件。两名独立的审查员记录数据并评估纳入荟萃分析的方法学质量。根据既定标准对关联证据进行分级，如下所示：有说服力、高度提示、提示、微弱或无显著性。
从 4471 项研究中确定了 45 项荟萃分析（17.9%），并对 252 篇全文文章进行了仔细审查，这些文章描述了 120 项关联，包括来自 1012 个个体效应量估计的研究数据。74 项（61.7%）关联使用随机效应模型在 P≤0.05 时具有统计学意义。52 项关联（43.4%）存在较大异质性（I2＞50%），而 17 项关联（14.2%）存在小样本效应，9 项关联（7.5%）存在过度显著偏差。主要分析和敏感性分析都为抗抑郁药使用与儿童和青少年自杀企图或完成、自闭症谱系障碍在妊娠前和妊娠期间暴露于抗抑郁药、早产和低阿普加评分之间的风险之间的关联提供了令人信服的证据。在调整混杂因素后，没有一项关联仍然支持有说服力的证据。
本研究结果表明，大多数与抗抑郁药使用相关的潜在不良健康结果可能没有令人信服的证据支持，而混杂因素可能改变了少数有说服力的关联。抗抑郁药治疗精神疾病似乎是安全的，但需要更多针对潜在疾病的匹配研究来阐明混杂因素和其他偏倚的程度。本综述没有发现抗抑郁药的绝对禁忌症。
