Lee Daniel, Clark Emily D, Antonsdottir Inga M, Porsteinsson Anton P
Alzheimer's Disease Care, Research and Education (AD-CARE), Department of Psychiatry, University of Rochester School of Medicine and Dentistry, Rochester, NY.
Johns Hopkins School of Nursing, Baltimore, MD, USA.
Expert Opin Pharmacother. 2023 Apr;24(6):691-703. doi: 10.1080/14656566.2023.2195539. Epub 2023 Mar 28.
Neuropsychiatric symptoms (NPS) in Alzheimer's Disease (AD) are associated with negative outcomes for patients and their care partners. Agitation is a common and distressing NPS, without safe and effective treatments. Nonpharmacological interventions are first line treatment, but not effective or appropriate for every patient. Current pharmacological treatments of agitation in AD include off-label use of antipsychotics, sedative/hypnotics, anxiolytics, mood-stabilizing anticonvulsants, acetylcholinesterase inhibitors, NMDA receptor antagonists, and antidepressants. Despite prevalent use, efficacy and safety concerns remain.
Better understanding of neurobiological mechanisms of agitation have fueled recent clinical trials. This article is an update to our 2017 review. Comprehensive search of ClinicalTrials.gov was completed from January 2017 to February 2023 using the search terms "Alzheimer's Disease" and "Agitation". Subsequent scoping review was completed in PubMed and Google Scholar. Several agents were identified, including: brexpiprazole, cannabinoids, dexmedetomidine, dextromethorphan, escitalopram, masupirdine, and prazosin.
Clinical trials utilize both novel and repurposed agents for agitation in AD. With increasing understanding of the neurobiological mechanisms that fuel development of agitation in AD, use of enahanced trial design and conduct, advanced statistical approaches, and accelerated pathways for regulatory approval, we advance closer to safe and efficacious treatment options for agitation in AD.
阿尔茨海默病（AD）中的神经精神症状（NPS）与患者及其护理伙伴的不良结局相关。激越（agitation）是一种常见且令人痛苦的NPS，目前尚无安全有效的治疗方法。非药物干预是一线治疗方法，但并非对每个患者都有效或适用。目前AD激越的药物治疗包括抗精神病药物、镇静/催眠药、抗焦虑药、心境稳定抗惊厥药、乙酰胆碱酯酶抑制剂、NMDA受体拮抗剂和抗抑郁药的非标签使用。尽管广泛使用，但疗效和安全性问题仍然存在。
对激越神经生物学机制的更好理解推动了近期的临床试验。本文是我们2017年综述的更新。2017年1月至2023年2月，使用搜索词“阿尔茨海默病”和“激越”在ClinicalTrials.gov上完成了全面搜索。随后在PubMed和谷歌学术上完成了范围综述。确定了几种药物，包括：布瑞哌唑、大麻素、右美托咪定、右美沙芬、艾司西酞普兰、马苏必利和哌唑嗪。
临床试验使用新型和重新利用的药物治疗AD激越。随着对引发AD激越的神经生物学机制的理解不断增加，采用改进的试验设计和实施、先进的统计方法以及加速的监管批准途径，我们正在更接近为AD激越找到安全有效的治疗选择。
