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的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治疗相关的治疗紧急风险的了解大部分来自短期、随机、对照试验（RCTS）。由于测试主要疗效终点所需的参与者数量相对较少，这些试验在检测药物不良反应方面受到限制。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急性治疗中的相对安全性和耐受性来解决知识差距，该项目基于对所有可用随机对照试验（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对广泛性焦虑症、分离焦虑症和社交恐惧症的影响。结果将包括治疗中出现的不良事件（TEAE）以及治疗引起的生命体征、心血管影响、身高、体重和临床实验室参数的变化。该研究还旨在确定急性治疗期间出现不良后果风险最高的患者亚组。这项工作将建立在 PI 现有的针对儿童抑郁症、强迫症和非强迫症焦虑症的抗抑郁随机对照试验数据库的基础上。个体患者数据（MAP）的荟萃分析被认为是确定治疗相对疗效和安全性的最严格的经验方法。这项研究的新颖之处在于，MAP 可以进行统计上强大的事件发生时间分析，识别具有不同不良结果风险的患者亚组，并对可能混淆原始治疗比较的变量进行调整。因此，我们将能够检查安全性和耐受性问题，而这些问题是单次试验、多中心随机对照试验或传统研究级荟萃分析无法回答的。该项目的可行性得到了 PI 和行业赞助商现有承诺的支持，为我们的团队提供实现该应用目标所需的患者级数据。这些发现将对使用这些药物管理和治疗焦虑青少年的临床医生有益。这项初步研究还将为未来研究精神药物治疗其他精神疾病（包括重度抑郁症、强迫症和双相情感障碍）的紧急风险和副作用负担奠定基础。

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.