Soto M, Abushakra S, Cummings J, Siffert J, Robert P, Vellas B, Lyketsos C G
Gerontopole, INSERM U1027, Alzheimer's Disease Research and Clinical Center, Toulouse University Hospital, Toulouse, France.
Transition Therapeutics, San Matteo, California, USA.
J Prev Alzheimers Dis. 2015 Sep;2(3):184-188. doi: 10.14283/jpad.2015.77.
The management of neuropsychiatric symptoms (NPS) such as agitation and aggression is a major priority in caring for people with Alzheimer's disease (AD). Agitation and aggression (A/A) are among the most disruptive symptoms, and given their impact, they are increasingly an important target for development of effective treatments. Considerable progress has been made in the last years with a growing number of randomized controlled trials (RCTs) of drugs for NPS. The limited benefits reported in some RCTs may be accounted for by the absence of a biological link of the tested molecule to NPS and also by key methodological issues. In recent RCTs of A/A, a great heterogeneity design was found. Designing trials for dementia populations with NPS presents many challenges, including identification of appropriate participants for such trials, engagement and compliance of patients and caregivers in the trials and the choice of optimal outcome measures to demonstrate treatment effectiveness. The EU/US -CTAD Task Force, an international collaboration of investigators from academia, industry, non-profit foundations, and regulatory agencies met in Philadelphia on November 19, 2014 to address some of these challenges. Despite potential heterogeneity in clinical manifestations and neurobiology, agitation and aggression seems to be accepted as an entity for drug development. The field appears to be reaching a consensus in using both agitation and aggression (or other NPS)-specific quantitative measures plus a global rating of change for agitation outcomes based on clinician judgment as the main outcomes.
对诸如激越和攻击行为等神经精神症状（NPS）的管理是护理阿尔茨海默病（AD）患者的首要任务。激越和攻击行为（A/A）是最具破坏性的症状之一，鉴于其影响，它们日益成为有效治疗方法开发的重要目标。近年来，针对NPS药物的随机对照试验（RCT）数量不断增加，已取得了相当大的进展。一些RCT报告的益处有限，这可能是由于受试分子与NPS缺乏生物学联系，以及关键的方法学问题所致。在最近关于A/A的RCT中，发现设计存在很大异质性。为患有NPS的痴呆症患者设计试验面临许多挑战，包括确定此类试验的合适参与者、患者和护理人员参与试验并遵守试验要求，以及选择最佳结局指标以证明治疗效果。欧盟/美国CTAD特别工作组是一个由来自学术界、产业界、非营利基金会和监管机构的研究人员组成的国际合作组织，于2014年11月19日在费城开会，以应对其中一些挑战。尽管临床表现和神经生物学可能存在异质性，但激越和攻击行为似乎被视为药物开发的一个实体。该领域似乎正在达成共识，即使用激越和攻击行为（或其他NPS）特定的定量指标，以及基于临床医生判断的激越结局总体变化评分作为主要结局。
