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症患者死亡率的增加有关。此外，我们的团队最近证明，与通常用于治疗行为症状的其他精神药物相比，非典型和传统抗精神病药物与老年痴呆门诊患者的死亡风险更大。在新的抗精神病药物开始使用后，这些增加的风险可能会持续长达12个月。目前尚不清楚与非典型药物相关的死亡风险是总体的类别效应，还是与特定的药物有关。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和死亡率之间的潜在联系。最后，还没有研究能够检验认知障碍程度、行为障碍类型或痴呆症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非常重要，因为痴呆症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，以研究进一步的关键问题，包括：1)比较在新的抗精神病药物处方后12个月内，患有痴呆症和没有痴呆症的老年患者中个别抗精神病药物的死亡风险；2)检查在新的抗精神病药物处方后12个月内死亡的患者的死亡原因；以及3)调查认知障碍、痴呆症阶段和行为障碍对用药偏好和死亡率的影响。这将是一项回溯性的队列研究，使用2001-2004财政年度的国家退伍军人事务登记和国家死亡指数数据。样本将包括在02财年和03财年开始服用新的抗精神病药物的65岁门诊患者。在初步分析中，我们将使用多变量模型、倾向评分方法和工具变量方法来比较12个月的死亡率。二次分析将通过收集部分患者的详细病历数据，研究认知障碍程度、痴呆症阶段和神经精神症状对药物选择和死亡率的影响。这将是检查抗精神病药物和老年人死亡率之间关系的最大规模的研究，也是唯一一项研究：1)有足够的能力检查特定抗精神病药物和死亡率之间的关系；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.