Suicidality Associated with Antidepressants inTennCare Children and Adolescents

描述(申请人提供)：抑郁障碍在儿童和青少年中占相当大的发病率和死亡率，最常见的治疗方法是抗抑郁药物。近年来，人们越来越担心抗抑郁药本身可能会增加自杀的风险，特别是在儿童和青少年中。然而，关于儿童自杀和抗抑郁药物的现有证据是有限的，因为临床试验的样本量很小(即使结合荟萃分析)，导致不足以评估单独使用抗抑郁药物的自杀死亡风险和自杀相关行为的风险。此外，由于临床试验持续时间较短，无法评估在治疗过程中严重自杀企图和自杀的风险。了解抗抑郁药物治疗与儿童和青少年自杀行为损伤之间的关系对于临床实践至关重要。这项建议中所描述的研究将解决三个具体目标：1)检验服用氟西汀的自杀企图的风险低于其他抗抑郁药的假设；2)检验在开始服用抗抑郁药物后的4周和12周内，服用抗抑郁药物的自杀企图的风险增加的假设；以及3)检验服用抗抑郁药的时间比停药的时间更大的自杀企图和自杀死亡风险的假设。为了达到这些目标，将从田纳西州的医疗补助文件中收集一个回溯性研究队列，其中将包括大约8.5万名6-18岁的儿童，他们使用抗抑郁药物，有证据表明他们可以治疗严重的抑郁症。队列后续行动将在1995-2006年期间进行，估计将包括73000人年的后续行动。每一次随访的人一天将根据暴露于研究药物和潜在的混杂因素进行分类。从医疗补助申请、死亡证明中得出的病例定义，并通过医疗记录审查确认，将定义队列中儿童中接受医疗治疗的自杀企图和自杀死亡。泊松回归将被用来估计个别研究药物和研究药物暴露时间对研究终点的影响。病例交叉设计将比较服用和停用抗抑郁药期间的风险。这项研究将解决对公共卫生具有巨大重要性的问题。患者、家属和医生迫切需要知道个别药物是否以不同方式影响自杀风险。在治疗早期风险是否增加，将对监测儿童服用这些药物产生影响。最后，了解在治疗期间和治疗期间自杀的风险将告知医生、患者和面临治疗的家庭一个重要的情况。

DESCRIPTION (provided by applicant): Depressive disorders account for substantial morbidity and mortality among children and adolescents and are most commonly treated with antidepressants. In recent years, increasing concerns have arisen that antidepressants in and of themselves might increase the risk of suicidality specifically among children and adolescents. However, the available evidence regarding suicidality and antidepressants in children is limited due to the small sample size of the clinical trials (even when combined in meta-analysis) resulting in insufficient power to assess the risk of suicide deaths and the risk of suicide-related behaviors for individual antidepressants. In addition, the short duration of clinical trials has precluded assessment of the risk of serious suicide attempts and suicidality over the course of treatment. Understanding the relationship between antidepressant treatment and injuries from suicidal behavior in children and adolescents is vital for clinical practice. The research described in this proposal will address three specific aims: 1) test the hypothesis that the risk of medically treated suicide attempts is lower for fluoxetine than for other antidepressants; 2) test the hypothesis that the risk of medically treated suicide attempts is increased in the time 4 and 12 weeks following initiation of antidepressant therapy; and, 3) test the hypothesis that periods on antidepressants represent greater risk for medically treated suicide attempts and suicide deaths than periods off antidepressants. To address these aims, a retrospective study cohort will be assembled from Tennessee Medicaid files and will include an estimated 85,000 6-18 year old children who are users of antidepressant medications with evidence suggesting treatment of major depression. Cohort follow up will be from 1995-2006 and will include an estimated 73,000 person-years of follow-up. Every person-day of follow-up will be classified by exposure to study medications and potential confounding factors. A case definition drawn from Medicaid claims, death certificates, and confirmed through medical record review will define medically treated suicide attempts and suicide deaths among children in the cohort. Poisson regression will be used to estimate the effects of the individual study drugs and the duration of study drug exposure on study endpoints. A case-crossover design will compare risk for periods on vs. off antidepressants. This research will address questions of enormous public health importance. Patients, families, and physicians urgently need to know whether or not individual drugs affect the risk of suicidality differently. Whether or not risk is increased early in the course of treatment will have implications for monitoring of children on these medications. Finally, understanding the risk of suicidality for periods off and on treatment will inform practitioners, patients, and families faced with treating an important condition.