Adverse Effects of Antidepressants in Pediatric Non-OCD Anxiety Disorders

描述（由申请人提供）：抗抑郁治疗与儿童和青少年自杀想法和行为之间的关联一直是最近争论的话题。我们对青少年抗抑郁药治疗相关的治疗后出现的风险的了解，大部分来自短期、随机、对照试验（RCTS）。这些试验在检测药物的不良反应方面受到限制，因为测试主要疗效终点所需的参与者数量相对较少。拟议的R03小额赠款项目将通过确定抗抑郁药物在儿童焦虑症急性治疗中的相对安全性和耐受性来解决知识差距，基于对所有可用的随机对照试验（RCT）的个体患者水平数据的二次分析，比较抗抑郁药和安慰剂治疗广泛性焦虑症，分离焦虑症和社交恐惧症。结局将包括治疗后出现的不良事件（TEAE）和治疗诱导的生命体征、心血管效应、身高、体重和临床实验室参数变化。该研究还旨在确定急性治疗期间不良结局风险最高的患者亚组。这项工作将建立在PI现有的儿童抑郁症、强迫症和非强迫症焦虑症抗抑郁药RCT数据库的基础上。个体患者数据的荟萃分析（MAP）已被提议为确定治疗相对疗效和安全性的最严格的经验方法。本研究的新颖之处在于，MAP允许进行统计学上强大的至事件发生时间分析，识别不良结局风险不同的患者亚组，并调整可能混淆原始治疗比较的变量。因此，我们将能够检查单一试验、多中心RCT或传统研究水平Meta分析无法回答的安全性和耐受性问题。该项目的可行性得到了PI和行业申办者的现有承诺的支持，这些承诺为我们的团队提供了实现该应用目标所需的患者水平数据。这些发现将有利于临床医生谁管理和治疗焦虑的青年与这些药物。这项初步研究也将为未来的工作奠定基础，研究精神药物在其他精神疾病（包括MDD，OCD和双相情感障碍）中的治疗紧急风险和副作用负担。

DESCRIPTION (provided by applicant): The association between antidepressant treatment and suicidal thoughts and behavior in children and adolescents has been the topic of recent debate. Much of our knowledge about treatment emergent risks associated with antidepressant treatment in youth derive from short-term, randomized, controlled trials (RCTS). These trials are limited in detecting adverse effects of medications due to the relatively small number of participants required to test primary efficacy end points. The proposed R03 small grant project will address gaps in knowledge by determining the relative safety and tolerability of antidepressant medications in the acute treatment of childhood anxiety, based on a secondary analysis of individual patient-level data of all available randomized controlled trials (RCTs) comparing antidepressants and placebo for generalized anxiety disorder, separation anxiety disorder, and social phobia. Outcomes will include treatment emergent adverse events (TEAEs) and treatment-induced changes in vital signs, cardiovascular effects, height, weight, and clinical laboratory parameters. The study also aims to identify patient subgroups at highest risk of adverse outcomes during acute treatment. This work will build on the PI's existing databases of antidepressant RCTs for pediatric depression, OCD, and non-OCD anxiety disorders. Meta-analysis of individual patient data (MAP) has been proposed as the most rigorous empirical method available to determine the relative efficacy and safety of treatments. This study is novel in that MAP allows for statistically powerful time-to-event analysis, identification of subgroups of patients at differential risk of adverse outcomes, and adjustment for variables that may have confounded the original treatment comparisons. We will therefore be able to examine questions of safety and tolerability otherwise unanswerable by a single trial, a multi-center RCT, or a traditional study-level meta- analysis. The feasibility of this project is supported by existing commitments from PIs and industry sponsors to provide our team with the patient-level data necessary to accomplish the goals of this application. These findings will be of benefit to clinicians who manage and treat anxious youth with these medications. This preliminary research will also build the foundation for future work examining the treatment emergent risks and side effects burden of psychotropic medications in other psychiatric disorders, including MDD, OCD, and bipolar disorder.