Antidepressants, Concurrent Treatments, and Completed Suicide in VA Registry Data

描述(申请人提供)：虽然抗抑郁药物在减轻成人抑郁症状方面是有效的，但最近又出现了一些担忧，即这些药物在治疗开始或剂量改变期间可能会增加自杀风险。FDA对儿童和青少年使用抗抑郁药发出了黑匣子警告，并建议在开始或改变剂量时密切监测所有年龄段的患者。目前FDA的警告是基于自杀行为，而不是完全自杀。然而，这些中间结果通常很难归类，并且可能与完全自杀不是一个完整的连续体。社区的治疗结果也可能与对照试验的结果不同，在对照试验中，辅助药物的使用受到了极大的限制。我们将使用退伍军人事务部全国抑郁症登记处(NARDEP)、医疗保险和全国死亡指数数据来检查抗抑郁药物、伴随治疗和完全自杀之间的关系。NARDEP包括1997财年(FY)以来超过1500,000名被诊断为抑郁症的患者的纵向数据，包括人口统计数据、卫生服务使用数据(从1997财年开始)和药房使用数据(从1999财年开始)。大约99.4万人将符合拟议研究的纳入标准，拥有超过280万人年的数据。我们将评估接受以下治疗的患者自杀和自杀企图的潜在差异：a)使用不同的抗抑郁药物组进行治疗，b)使用SSRI类别中四种最常用的处方药物和三种最常用的SSRI药物替代品进行治疗，c)与抗抑郁药物一起使用以增强治疗反应的辅助药物，以及d)与抗抑郁药物一起使用以解决失眠问题的补充催眠剂。研究分析将首先使用具有时变治疗暴露和协变量的COX比例风险模型。我们还将使用具有逆治疗概率加权(IPTW)和辅助变量的COX模型来解决潜在的治疗选择偏差。除了主要的队列分析外，我们还将利用病历数据进行两项嵌套病例对照研究，以对管理数据中无法观察到的潜在选择偏向进行详细评估。这些子研究将为队列分析提供信息，并使我们能够适当地解释研究结果。临床医生、政策制定者和患者迫切需要关于替代抑郁症治疗在减少自杀方面的相对有效性的更多信息。我们预计，拟议的项目将促进这一关键领域的知识，并为未来利用组织数据集检查自杀等哨兵事件的努力提供信息。

DESCRIPTION (provided by applicant): Although antidepressant medications are effective in reducing depressive symptoms among adults, concerns recently have re-emerged that these medications may increase suicide risks during times of treatment initiation or dosage change. The FDA has issued a "black box" warning for antidepressants when used by children and adolescents and advised close monitoring of patients of all ages when beginning or changing doses. Current FDA warnings are based on suicidal behaviors rather than completed suicide. However, these intermediate outcomes are often difficult to categorize and may not be on a complete continuum with completed suicide. Outcomes of treatment in the community may also differ from outcomes in controlled trials in which the use of adjunctive medications are sharply limited. We will use the VA National Registry for Depression (NARDEP), Medicare, and National Death Index data to examine the relationships between antidepressants, concomitant treatments, and completed suicide. NARDEP includes longitudinal data for over 1,500,000 patients diagnosed with depression from fiscal year (FY) 1997 forward, including data on demographics, health services use (from FY97 forward), and pharmacy use (from FY99 forward). Approximately 994,000 individuals will meet inclusion criteria for the proposed study, with over 2,800,000 person-years of data. We will evaluate potential differences in rates of suicide and suicide attempts among patients receiving: a) treatment with different antidepressant medication groups, b) treatment with four most commonly prescribed agents within the SSRI class and the three most commonly prescribed alternatives to SSRI agents, c) adjunctive agents used with antidepressants to augment treatment response, and d) supplemental hypnotic agents used with antidepressants to address insomnia. Study analyses will first use Cox-proportional hazards models with time-varying treatment exposures and covariates. We will also use Cox models with inverse probability of treatment weighting (IPTW) and instrumental variables to address potential treatment selection biases. In addition to the primary cohort analyses, we will conduct two nested case-control studies, using medical record data, to conduct a detailed assessment of potential selection biases that are not observable in the administrative data. These sub- studies will inform the cohort analyses and allow us to appropriately interpret study results. Clinicians, policymakers, and patients urgently need additional information about relative effectiveness of alternative depression treatments in reducing suicide. We anticipate that the proposed project will advance knowledge in this critical area and inform future efforts to use organizational datasets to examine sentinel events, such as suicide.