Marco Canevelli, MD, PhD, Department of Human Neuroscience, "Sapienza" University of Rome, Viale dell'Università 30, 00185 Rome, Italy, Tel/fax +39 (0)6 49914604; Email:
J Frailty Aging. 2021;10(1):22-30. doi: 10.14283/jfa.2020.36.
The implementation of effective interventions for neuropsychiatric symptoms (NPS) is perceived as one of the most pressing research priorities in the field of dementia and one of the main unmet needs from the perspective of affected individuals and their caregivers and relatives. Nevertheless, to date, only a relatively marginal part of dementia research has focused on NPS. This study aimed to describe and discuss the state of the art concerning the identification and development of new pharmacological treatments for NPS in dementia. A review of 320 ongoing phase 1, 2, 3, and 4 protocols registered in the clinicaltrials.gov database was performed. All the trials enrolling patients with dementia were selected. Only studies adopting clinical measures of NPS frequency and/or severity as primary outcome were retained and analyzed. Overall, only a minority of ongoing phase 1, 2, 3 and 4 protocols on dementia (i.e., 9.0%) is primarily targeting NPS. Most of these studies are adopting a placebo-controlled parallel assignment design, testing oral compounds, and targeting specific NPS (mostly agitation and/or aggression). A total of 3,445 subjects with dementia will tentatively be recruited in these trials. The methodologies adopted in these studies, the characteristics of the tested interventions, the eligibility criteria, and the operational definitions of NPS are presented and discussed. The relevance of NPS is not yet matched by an adequate research effort. The current tendency at privileging disease-modifying approaches and other symptoms of dementia and the methodological complexity of studying NPS are still substantially contributing to the gap between research activities and clinical needs.
神经精神症状（NPS）的有效干预措施的实施被认为是痴呆症领域最紧迫的研究重点之一，也是受影响个体及其护理人员和亲属的主要未满足需求之一。尽管如此，迄今为止，只有相对较少的痴呆症研究关注 NPS。本研究旨在描述和讨论痴呆症中 NPS 的新药物治疗的识别和开发的最新进展。对 clinicaltrials.gov 数据库中注册的 320 项正在进行的 1 期、2 期、3 期和 4 期方案进行了审查。所有招募痴呆症患者的试验均被选中。仅保留并分析了采用 NPS 频率和/或严重程度的临床测量作为主要结局的研究。总体而言，只有少数正在进行的 1 期、2 期、3 期和 4 期痴呆症（即 9.0%）方案主要针对 NPS。这些研究大多采用安慰剂对照平行分配设计，测试口服化合物，并针对特定的 NPS（主要是激越和/或攻击）。这些试验预计将有 3445 名痴呆症患者参与。本文介绍并讨论了这些研究中采用的方法学、测试干预措施的特征、纳入标准和 NPS 的操作定义。NPS 的相关性尚未得到足够的研究努力的支持。目前，优先考虑疾病修饰方法和其他痴呆症症状的趋势以及研究 NPS 的方法学复杂性仍然在很大程度上导致了研究活动与临床需求之间的差距。
