Citalopram Treatment for Agitation in Alzheimer Dementia

描述（由申请人提供）：阿尔茨海默氏痴呆症（AD）的躁动是一个重大的公共卫生问题，对患者和护理人员造成严重后果。躁动的管理是治疗AD患者的主要优先事项。非药物治疗的效果有限。已经探索了几种药物选择，但抗惊厥药，抗精神病药和胆碱酯酶抑制剂的发现令人失望或与可疑的风险：效益比相关。需要更好的药物选择。选择性5 -羟色胺再摄取抑制剂（SSRIs）在这一领域的研究尚不充分，基于AD患者躁动与脑5 -羟色胺系统异常之间的联系的证据，以及来自单点、随机、安慰剂对照试验（RCT）的初步临床数据，西酞普兰优于奋那嗪和安慰剂，显示出治疗AD患者躁动的希望。现在需要一项明确的随机对照试验来调查SSRI治疗AD躁动的有效性和安全性。为了开展这样一项研究，拟议的西酞普兰躁动在阿尔茨海默病（CITAD）中将汇集已经成功合作正在进行的阿尔茨海默病抑郁症研究（DIADS-2）和已完成的阿尔茨海默病（CATIE- AD）临床抗精神病药物干预有效性试验的研究人员。CITAD将检查西酞普兰作为阿尔茨海默病患者临床显著躁动的治疗的有效性和安全性。它还将研究药物基因组学、遗传学和对西酞普兰治疗反应的临床预测因素。CITAD将是一项安慰剂对照、蒙面、9周、8点随机对照试验，涉及200名AD患者。它将招募来自现实世界门诊、养老院和辅助生活环境的患者。使用最先进的临床评分和新颖的每周护理人员电话评分，CITAD将检查西酞普兰对躁动、其他神经精神症状、认知、生活质量和日常功能的影响。CITAD还将进行仔细的安全监测。这项研究非常重要，因为它将明确确定一种有前景的SSRI作为AD躁动症治疗的有效性和安全性，AD是一种没有治疗选择的疾病，既没有证明也没有显著风险。如果发现西酞普兰有效，考虑到其他药物选择的局限性，它很可能成为一线治疗。CITAD还将提供有关反应预测因子的重要知识，并为未来研究了解西酞普兰和其他SSRIs对躁动的影响机制奠定基础。阿尔茨海默氏痴呆症（AD）的躁动是一个重大的公共卫生问题，对患者和护理人员造成严重后果。躁动的管理是治疗AD患者的主要优先事项。拟议的西酞普兰用于阿尔茨海默病的躁动（CITAD）将汇集在正在进行的阿尔茨海默病抑郁症研究（DIADS-2）和已完成的阿尔茨海默病干预有效性临床抗精神病药物试验（CATIE-AD）中成功合作的研究人员。

DESCRIPTION (provided by applicant): Agitation in Alzheimer's dementia (AD) is a significant public health problem with serious consequences for patients and caregivers. The management of agitation is a major priority in treating patients with AD. Non-pharmacologic options have limited effectiveness. Several pharmacologic options have been explored, but findings for anticonvulsants, antipsychotics, and cholinesterase inhibitors are disappointing or associated with questionable risk: benefit ratio. Better pharmacologic options are needed. Selective serotonin reuptake inhibitors (SSRIs), understudied in this area, show promise as a treatment for agitation in AD, based on evidence of a link between agitation and brain serotonin system abnormalities in AD patients, and on preliminary clinical data from a single-site, randomized, placebo-controlled trial (RCT) in which citalopram was superior to perphenazine and placebo. A definitive RCT is now warranted investigating the efficacy and safety of an SSRI for agitation in AD. To carry out such a study, the proposed Citalopram for Agitation in AD (CITAD) will bring together investigators who have collaborated successfully in the ongoing Depression in Alzheimer's Disease Study (DIADS-2) and the completed Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease (CATIE- AD). CITAD will examine the efficacy and safety of citalopram as treatment for clinically significant agitation in AD patients. It will also investigate pharmacogenomic, genetic, and clinical predictors of response to citalopram therapy. CITAD will be a placebo-controlled, masked, 9-week, 8-site RCT involving 200 patients with AD. It will enroll patients from real world outpatient, nursing home and assisted living settings. Using state of the art clinical ratings and novel weekly caregiver telephone ratings, CITAD will examine the effects of citalopram on agitation, other neuropsychiatric symptoms, cognition, quality of life, and daily functioning. CITAD will also conduct careful safety monitoring. This study is of great importance, as it will determine definitively the efficacy and safety of a promising SSRI as a treatment for agitation in AD, a condition with no treatment options that are both proven and without significant risk. Should citalopram be found effective, it will likely become a first line therapy, given the limitations of other pharmacologic options. CITAD will also provide significant knowledge about predictors of response, and lay the foundation for future studies to understand mechanisms involved in the effects of citalopram and other SSRIs on agitation. Agitation in Alzheimer's dementia (AD) is a significant public health problem with serious consequences for patients and caregivers. The management of agitation is a major priority in treating patients with AD. The proposed Citalopram for Agitation in AD (CITAD) will bring together investigators who have collaborated successfully in the ongoing Depression in Alzheimer's disease study (DIADS-2) and the completed Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease (CATIE-AD).