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(ADRD)患者生活在熟练的护理人员中 设施(SNF)。痴呆症的行为和心理症状(BPSD)发生在约80%的老年人中 ADRD住在SNF里。抗精神病药物是最常用的药物。 BPSD的治疗。由于急性呼吸暂停综合征与许多不良事件有关，临床指南 建议它们的使用应仅限于治疗急性发作，并尽快停用。 然而，研究表明，急性呼吸窘迫综合征患者经常持续使用APM(≥6 月)。用于BPSD的小规模随机对照试验(RCT)比较停用与继续使用的APM 产生了相互矛盾和令人困惑的结果，表明停用非处方药对以下方面几乎没有好处 不良事件。这些RCT显然力量不足，他们严重代表着脆弱和复杂。 患有ADRD的老年人在常规护理中。也缺乏针对这一关键问题的非随机研究。 知识鸿沟因为对行为障碍停药与症状严重程度高度相关， 除非有详细的临床信息，否则很难控制疾病严重程度的混淆 用于研究。我们的目标是评估不同的APM停药策略对健康的影响 SNF中的BPSD。为了提供确凿的证据指导停药过程，我们将评估 与不逐步减少剂量和不同剂量递减率相比，停止使用APM。我们将整合 Medicare报销数据包括电子健康记录(EHR)、最低数据集(MDS)、认证和 调查提供商增强型报告(Casper)，涵盖&>37万居住在SNF的ADRD老年人 从2013年到2026年。我们将使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，以最大限度地减少测量和 无法测量的混乱。我们将解决三个具体目标：1)评估处方和 在老年BPSD患者中停药模式和确定APM停药障碍 三井住友。2)确定不同停药策略与继续停药的比较健康结果 APMS用于居住在SNF中的老年人的BPSD。3)确定治疗效果异质性 按关键临床表型比较持续与不同停药策略使用的急性早幼粒细胞白血病 对于居住在SNF中的老年人的BPSD，以便可以根据 病人的特征。这项提议的影响很大，因为它将产生直接的证据来告知 生活在SNF的ADRD老年患者的精神药物的最佳管理。它还将产生一个 可扩展的分析框架，专门用于非处方药物的相对安全性和有效性分析 痴呆症行为和心理症状的精神药物治疗。

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.