Deprescribing antipsychotics in patients with Alzheimers disease and related dementias and behavioral disturbance in skilled nursing facilities

项目摘要 大约40-45%的阿尔茨海默病和相关痴呆症（ADRD）患者居住在熟练的护理机构， 设施（SNF）。痴呆的行为和心理症状（BPSD）发生在约80%的老年人中， ADRD生活在SNF中。抗精神病药物（APM）是最常用的药理学 治疗BPSD。由于APM与许多不良事件相关，临床指南 建议其使用应限于管理急性发作，并尽快停止使用。 然而，研究表明，APM通常用于ADRD患者持续时间（≥6 月）。比较停药与继续使用APM治疗BPSD的小型随机对照试验（RCT） 得出了相互矛盾和令人困惑的结果，这些结果表明，取消杀伤人员地雷的处方对 不良事件。这些随机对照试验显然不够有力，严重低估了虚弱和复杂的患者 在常规护理中患有ADRD的老年人。也缺乏针对这一关键问题的非随机研究。 知识差距，因为对行为障碍停用APM在很大程度上取决于症状的严重程度， 除非有详细的临床信息，否则很难控制疾病严重程度的混杂 用于研究我们的目标是评估不同的APM处方策略对健康的影响， SNF中的BPSD。为了提供可靠的证据，指导取消处方的过程，我们将评估 停止杀伤人员地雷，同时逐渐减少剂量和以不同的速度逐渐减少剂量。我们将整合 医疗保险索赔数据，包括电子健康记录（EHR）、最小数据集（MDS）和认证， 调查提供者增强报告（CASPER），覆盖超过370，000名生活在SNF的ADRD老年人 从2013年到2026年。我们将采用克隆审查权重方法，高维机器学习辅助 代理调整方法，外部调整和工具变量分析，以尽量减少测量和 不可测量的混杂。我们将解决三个具体目标：1）评价处方和 停药模式，并确定老年BPSD患者停用APM的障碍， SNF。2)确定不同停药策略与继续治疗的比较健康结局 用于居住在SNF的老年人BPSD的APM。3)确定治疗效果异质性 当比较所用APM的继续与不同停药策略时，按关键临床表型 对于居住在SNF的老年人中的BPSD，这样可以根据以下情况定制这种取消处方的决定： 患者特征。这一提议的影响很大，因为它将产生直接证据， 生活在SNF的ADRD老年人的精神药物治疗的最佳管理。它还将产生一个 可扩展的分析框架，专门用于比较安全性和有效性分析， 治疗痴呆症的行为和心理症状。

Project Summary About 40-45% of people living with Alzheimer’s disease and related dementias (ADRD) reside in a skilled nursing facility (SNF). Behavioral and psychological symptoms of dementia (BPSD) occur in ~80% of older adults with ADRD living in an SNF. Antipsychotic medications (APMs) are the most commonly used pharmacological treatment for BPSD. Because APMs are associated with numerous adverse events, clinical guidelines recommend that their use should be limited to managing acute episodes and discontinued as soon as possible. However, studies have shown that APMs are often used in individuals with ADRD for sustained periods (≥6 months). Small randomized controlled trials (RCTs) comparing withdrawing vs. continuing APMs used for BPSD have yielded conflicting and confusing results that suggested deprescribing APMs had little or no benefits for adverse events. These RCTs were clearly underpowered, and they severely underrepresented frail and complex older adults with ADRD in routine care. There was also a lack of non-randomized studies addressing this critical knowledge gap because deprescribing APMs for behavior disturbance is highly informed by symptom severity, and confounding by disease severity can be very difficult to control unless detailed clinical information is available for research. Our objective is to assess the health effects of different APM deprescribing strategies for managing BPSD in an SNF. To provide solid evidence guiding the deprescribing process, we will assess the effects of discontinuing APMs with vs. without gradual dose reduction and different rates of dose tapering. We will integrate Medicare claims data with electronic health records (EHR), Minimum Data Set (MDS), and Certification and Survey Provider Enhanced Reporting (CASPER), covering >370,000 older adults with ADRD living in an SNF from 2013 to 2026. We will employ the clone-censor-weight approach, high-dimensional machine-learning-aided proxy adjustment methods, external adjustment, and instrumental variable analysis to minimize measured and unmeasured confounding. We will address three specific aims: 1) To evaluate the prescribing and discontinuation patterns and determine the barriers to APMs deprescribing among older adults with BPSD in an SNF. 2) To determine comparative health outcomes of different discontinuation strategies vs. continuation of APMs used for BPSD in older adults who reside in an SNF. 3) To determine the treatment effect heterogeneity by key clinical phenotypes when comparing continuation vs. different discontinuation strategies of APMs used for BPSD in older adults who reside in an SNF so that such deprescribing decisions can be tailored according to patient characteristics. The impact of this proposal is high because it will generate direct evidence to inform optimal management of psychotropic medications in older adults with ADRD living in an SNF. It will also yield a scalable analytical framework specializing in comparative safety and effectiveness analyses of deprescribing psychotropic treatments for behavioral and psychological symptoms of dementia.