Antipsychotics and Mortality in Older Patients

描述（由申请人提供）：最近的荟萃分析表明，非典型抗精神病药物与痴呆患者死亡率增加相关。此外，我们的小组最近已经证明，非典型和传统的抗精神病药物与老年痴呆症门诊患者的死亡风险比其他精神药物通常用于行为症状。这些增加的风险可能会持续长达12个月后，新的抗精神病药物开始。目前尚不清楚与药物相关的死亡风险是总体类效应还是与特定药物相关。目前也没有关于服用这些药物时死亡的患者的死亡原因的信息;这些信息将有助于研究人员和临床医生更好地了解抗精神病药物与死亡率之间的潜在联系。最后，没有研究能够检查认知障碍程度、行为障碍类型或痴呆阶段等因素对这种关系的影响。了解抗精神病药物与老年人死亡率之间的关系对老年患者具有深远的重要性，因为痴呆和其他晚年精神病综合征的神经精神症状在这些患者中非常常见和有问题。在这项研究中，我们将扩展我们以前的工作，以检查进一步的关键问题，包括：1）比较单独的抗精神病药物在老年患者中的死亡风险，无论是否有痴呆诊断，在12个月后，新的抗精神病药物处方; 2）检查死亡的患者在12个月后，新的抗精神病药物处方的死亡原因;（3）探讨认知功能障碍、痴呆分期和行为障碍对药物偏好和死亡率的影响。这将是一项回顾性队列研究，使用2001-2004财政年度的国家退伍军人事务登记处和国家死亡指数数据。样本将由2002和2003财年开始使用新抗精神病药物的> 65岁的门诊患者组成。在主要分析中，我们将使用多变量模型、倾向评分法和工具变量法比较12个月的死亡率。次要分析将通过收集患者子集的详细病历数据，检查认知障碍程度、痴呆分期和神经精神症状对药物选择和死亡率的影响。这将是研究抗精神病药物与老年人死亡率之间关系的最大规模研究，也是唯一一项：1）有足够的把握度来研究特定抗精神病药物与死亡率之间的关系; 2）解决死亡原因; 3）明确考虑认知和行为严重程度对抗精神病药物死亡风险的影响。这项研究的结果将与临床医生和政策制定者直接相关。

DESCRIPTION (provided by applicant): Recent meta-analyses indicate that atypical antipsychotic medications are associated with increased mortality among patients with dementia. Moreover, our group has recently demonstrated that both atypical and conventional antipsychotic medications are associated with a greater mortality risk for elderly outpatients with dementia than other psychotropic medications often used for behavioral symptoms. These increased risks may persist for as long as 12 months following new antipsychotic starts. It is not yet known whether the mortality risk associated with the atypicals is an overall class effect, or associated with particular agents. There is also currently no information on causes of death from patients who die while taking these agents; this information would help researchers and clinicians to understand better the potential link between antipsychotics and mortality. Finally, no studies have been able to examine the impact of factors such as degree of cognitive impairment, type of behavior disorder or dementia stage on this relationship. Understanding the relationship between antipsychotics and mortality in the elderly is of profound importance to older patients as neuropsychiatric symptoms of dementia and other late-life psychotic syndromes are extremely common and problematic in these patients. In this study, we will extend our prior work to examine further critical questions including: 1) comparing mortality risks for individual antipsychotic agents in older patients both with and without dementia diagnoses in the 12 months following a new antipsychotic prescription; 2) examining cause of death in patients who die in the 12 months following a new prescription for antipsychotic medications; and 3) investigating the impact of cognitive impairment, dementia stage and behavioral disturbance on medication preference and mortality. This will be a retrospective, cohort study using national Veterans Affairs registry and National Death Index data from fiscal years 2001-2004. The sample will be comprised of outpatients > 65 years with new antipsychotic medication starts in FY 02 and 03. In the primary analysis, we will compare 12-month mortality rates using multivariate models, propensity- scoring methods, and instrumental variable methods. Secondary analyses will examine the impact of degree of cognitive impairment, dementia stage and neuropsychiatric symptoms on medication choice and mortality by collecting detailed medical chart data from a subset of patients. This will be the largest study to examine the relationship between antipsychotic agents and mortality in the elderly, and the only study to: 1) be sufficiently powered to examine the association between specific antipsychotic agents and mortality; 2) address causes of death; and 3) consider explicitly the implications of cognitive and behavioral severity on risk of mortality with antipsychotics. The results of this study will be of immediate relevance to clinicians and policymakers.