Citalopram Treatment for Agitation in Alzheimer Dementia

描述(由申请人提供)：阿尔茨海默氏症(AD)中的激动症是一个严重的公共卫生问题，对患者和照顾者造成严重后果。激越的管理是治疗AD患者的主要优先事项。非药物选择的效果有限。已经探索了几种药理选择，但抗惊厥药、抗精神病药物和胆碱酯酶抑制剂的发现令人失望，或者与可疑的风险：收益比有关。需要更好的药理选择。选择性5-羟色胺再摄取抑制剂(SSRIs)在这一领域研究不足，基于AD患者激动症与脑5-羟色胺系统异常之间存在联系的证据，以及来自单一地点、随机、安慰剂对照试验(RCT)的初步临床数据，表明选择性5-羟色胺再摄取抑制剂(SSRIs)有望成为治疗AD躁动的方法。在RCT中，西酞普兰优于奋乃静和安慰剂。现在有必要进行一项明确的随机对照试验，调查SSRI对AD激动剂的有效性和安全性。为了进行这样的研究，拟议的阿尔茨海默病激动剂西妥普兰(Citad)将汇集在正在进行的阿尔茨海默病抑郁研究(DIADS-2)和已完成的干预有效性的临床抗精神病试验-阿尔茨海默病(CATIE-AD)中成功合作的研究人员。Citad将检查西酞普兰作为治疗AD患者临床显著激越的有效性和安全性。它还将调查西酞普兰治疗反应的药物基因组学、遗传学和临床预测因素。Citad将是一项安慰剂对照、面罩、为期9周、8个部位的RCT，涉及200名AD患者。它将从现实世界的门诊、疗养院和辅助生活环境中招募患者。Citad将使用最先进的临床评级和新颖的每周照顾者电话评级，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，因为它将最终确定一种有前景的SSRI作为治疗AD躁动的有效性和安全性，AD是一种没有经过证实且没有重大风险的治疗方案。如果西酞普兰被发现有效，考虑到其他药物选择的局限性，它很可能成为一线治疗方法。Citad还将提供有关反应预测因素的重要知识，并为未来的研究奠定基础，以了解西酞普兰和其他SSRI对激越的影响所涉及的机制。阿尔茨海默病(AD)中的激动症是一个严重的公共卫生问题，给患者和照顾者带来严重后果。激越的管理是治疗AD患者的主要优先事项。拟议的阿尔茨海默病激动剂西妥普兰(Citad)将汇集在正在进行的阿尔茨海默病抑郁研究(DIADS-2)和已完成的干预有效性的临床抗精神病试验-阿尔茨海默病(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).