Suicidality Associated with Antidepressants inTennCare Children and Adolescents

描述（由申请人提供）：抑郁症在儿童和青少年中占很大的发病率和死亡率，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小（即使在荟萃分析中结合），导致不足以评估个体抗抑郁药物的自杀死亡风险和自杀相关行为风险。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的风险。了解抗抑郁药物治疗与儿童和青少年自杀行为伤害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)验证氟西汀治疗后自杀未遂风险低于其他抗抑郁药的假设；2)在开始抗抑郁药物治疗后的4周和12周内，检验药物治疗自杀企图的风险增加的假设；并且，3)验证一个假设，即服用抗抑郁药的时期比不服用抗抑郁药的时期有更大的医学治疗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档案中收集一项回顾性研究队列，其中包括估计85,000名使用抗抑郁药物的6-18岁儿童，这些儿童有证据表明可以治疗重度抑郁症。队列随访将从1995年至2006年进行，估计包括73,000人年的随访。每个人/天的随访将根据暴露于研究药物和潜在混杂因素进行分类。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经医学治疗的自杀企图和自杀死亡。泊松回归将用于估计单个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。这项研究将解决具有巨大公共卫生重要性的问题。患者、家属和医生迫切需要知道，个别药物对自杀风险的影响是否不同。在治疗过程的早期，风险是否会增加，这将对使用这些药物的儿童的监测产生影响。最后，了解治疗期间和治疗期间的自杀风险将告知从业者、患者和面临治疗重要疾病的家庭。

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.