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

描述（由申请人提供）：虽然抗抑郁药物对减轻成人抑郁症状有效，但最近再次出现的担忧是，这些药物在开始治疗或改变剂量时可能增加自杀风险。美国食品药品监督管理局发布了儿童和青少年使用抗抑郁药的“黑箱”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分类，可能不会与自杀完全连续。社区治疗的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严格限制。我们将使用退伍军人管理局国家抑郁症登记处（NARDEP）、医疗保险和国家死亡指数数据来检验抗抑郁药、伴随治疗和自杀之间的关系。NARDEP包括自1997财政年度（财政年度）以来诊断为抑郁症的150多万名患者的纵向数据，包括人口统计、卫生服务使用（从1997财政年度起）和药物使用（从99财政年度起）的数据。大约994,000人将符合拟议研究的纳入标准，数据超过280万人年。我们将评估接受以下治疗的患者自杀率和自杀未遂率的潜在差异：a)接受不同抗抑郁药物组的治疗，b)接受四种最常用的SSRI类药物和三种最常用的SSRI药物替代品的治疗，c)与抗抑郁药物一起使用辅助药物以增强治疗效果，d)与抗抑郁药物一起使用补充催眠药物以解决失眠问题。研究分析将首先使用随时间变化的治疗暴露和协变量的cox比例风险模型。我们还将使用具有治疗加权逆概率（IPTW）和工具变量的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，我们还将使用医疗记录数据进行两项嵌套病例对照研究，以对行政数据中未观察到的潜在选择偏差进行详细评估。这些次级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更多的信息，了解替代性抑郁症治疗在减少自杀方面的相对有效性。我们预计，拟议的项目将推进这一关键领域的知识，并为未来使用组织数据集检查哨兵事件（如自杀）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.