Gibbons Robert D, Coca Perraillon Marcelo, Hur Kwan, Conti Rena M, Valuck Robert J, Brent David A
Center for Health Statistics, Departments of Medicine and Health Studies, University of Chicago, Chicago, IL, USA.
Pharmacoepidemiol Drug Saf. 2015 Feb;24(2):208-14. doi: 10.1002/pds.3713. Epub 2014 Sep 29.
In the 2004, FDA placed a black box warning on antidepressants for risk of suicidal thoughts and behavior in children and adolescents. The purpose of this paper is to examine the risk of suicide attempt and self-inflicted injury in depressed children ages 5-17 treated with antidepressants in two large observational datasets taking account time-varying confounding.
We analyzed two large US medical claims databases (MarketScan and LifeLink) containing 221,028 youth (ages 5-17) with new episodes of depression, with and without antidepressant treatment during the period of 2004-2009. Subjects were followed for up to 180 days. Marginal structural models were used to adjust for time-dependent confounding.
For both datasets, significantly increased risk of suicide attempts and self-inflicted injury were seen during antidepressant treatment episodes in the unadjusted and simple covariate adjusted analyses. Marginal structural models revealed that the majority of the association is produced by dynamic confounding in the treatment selection process; estimated odds ratios were close to 1.0 consistent with the unadjusted and simple covariate adjusted association being a product of chance alone.
Our analysis suggests antidepressant treatment selection is a product of both static and dynamic patient characteristics. Lack of adjustment for treatment selection based on dynamic patient characteristics can lead to the appearance of an association between antidepressant treatment and suicide attempts and self-inflicted injury among youths in unadjusted and simple covariate adjusted analyses. Marginal structural models can be used to adjust for static and dynamic treatment selection processes such as that likely encountered in observational studies of associations between antidepressant treatment selection, suicide and related behaviors in youth.
2004年,美国食品药品监督管理局(FDA)针对抗抑郁药对儿童和青少年产生自杀念头及行为的风险发布了黑框警告。本文旨在通过两个大型观察数据集,在考虑随时间变化的混杂因素的情况下,研究5至17岁接受抗抑郁药治疗的抑郁儿童的自杀未遂及自我伤害风险。
我们分析了两个大型美国医疗索赔数据库(MarketScan和LifeLink),其中包含221,028名5至17岁有新发性抑郁症的青少年,这些青少年在2004年至2009年期间接受或未接受抗抑郁药治疗。对受试者进行了长达180天的随访。使用边际结构模型来调整随时间变化的混杂因素。
对于这两个数据集,在未经调整和简单协变量调整的分析中,抗抑郁药治疗期间自杀未遂及自我伤害风险显著增加。边际结构模型显示,大部分关联是由治疗选择过程中的动态混杂因素产生的;估计的优势比接近1.0,这与未经调整和简单协变量调整的关联仅是偶然结果一致。
我们的分析表明,抗抑郁药治疗的选择是静态和动态患者特征共同作用的结果。在未经调整和简单协变量调整的分析中,若未基于动态患者特征对治疗选择进行调整,可能会导致抗抑郁药治疗与青少年自杀未遂及自我伤害之间出现关联。边际结构模型可用于调整静态和动态治疗选择过程,比如在关于青少年抗抑郁药治疗选择、自杀及相关行为之间关联的观察性研究中可能遇到的情况。