Suicidality Associated with Antidepressants inTennCare Children and Adolescents

描述（由申请人提供）：抑郁症是儿童和青少年的主要发病率和死亡率，最常用抗抑郁药治疗。近年来，人们越来越担心抗抑郁药本身可能会增加儿童和青少年自杀的风险。然而，由于临床试验的样本量较小（即使在荟萃分析中合并），导致评估自杀死亡风险和个体抗抑郁药自杀相关行为风险的把握度不足，因此有关儿童自杀倾向和抗抑郁药的可用证据有限。此外，临床试验持续时间短，无法评估治疗过程中严重自杀企图和自杀倾向的风险。了解儿童和青少年的抗抑郁治疗与自杀行为损伤之间的关系对临床实践至关重要。本提案中描述的研究将解决三个具体目标：1）检验氟西汀治疗后自杀未遂风险低于其他抗抑郁药的假设; 2）检验开始抗抑郁治疗后4周和12周内自杀未遂风险增加的假设;以及3）检验这样一个假设，即服用抗抑郁药的时间段比不服用抗抑郁药的时间段代表着更大的经药物治疗的自杀企图和自杀死亡的风险。为了实现这些目标，将从田纳西州医疗补助文件中收集一项回顾性研究队列，并将包括估计85，000名6-18岁的儿童，他们是抗抑郁药物的使用者，有证据表明可以治疗重度抑郁症。队列随访将从1995-2006年开始，将包括估计73，000人-年的随访。将按照研究药物暴露和潜在混杂因素对每个随访人-日进行分类。从医疗补助索赔、死亡证明中得出并通过病历审查确认的病例定义将定义队列中儿童经医学治疗的自杀企图和自杀死亡。将使用Poisson回归估计个体研究药物和研究药物暴露持续时间对研究终点的影响。病例交叉设计将比较服用抗抑郁药与停用抗抑郁药的风险。这项研究将解决具有重大公共卫生意义的问题。患者、家属和医生迫切需要知道，个别药物是否会对自杀风险产生不同的影响。在治疗过程的早期，风险是否增加将对监测这些药物的儿童产生影响。最后，了解在治疗期间和治疗期间的自杀风险将告知医生，患者和家庭面临治疗重要疾病。

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.