Citalopram Treatment for Agitation in Alzheimer Dementia

阿尔茨海默病(AD)中的激动症是一个严重的公共卫生问题，后果严重 为病人和照顾者服务。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。有几种药理选择是 进行了研究，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 或与可疑的风险：收益比率相关。需要更好的药理选择。有选择性的 5-羟色胺再摄取抑制剂(SSRIs)在这一领域研究不足，有望成为治疗躁动的药物。 在阿尔茨海默病中，基于激动症和阿尔茨海默病患者大脑5-羟色胺系统异常之间存在联系的证据 患者，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 其中西酞普兰优于奋乃静和安慰剂。现在有必要制定一个明确的随机对照试验 研究SSRI对AD患者激越的有效性和安全性。为了进行这样的研究， 建议在AD(Citad)中用于煽动的西妥普兰将汇集具有以下特征的调查人员 在正在进行的阿尔茨海默病抑郁症研究(DIADS-2)中成功合作 已完成的干预效果的临床抗精神病试验-阿尔茨海默病(CATIE- AD)。Citad将检查西酞普兰作为治疗有临床意义的 阿尔茨海默病患者的激越。它还将调查药物基因组学、遗传学和临床预测因素。 对西酞普兰治疗的反应。Citad将是一个安慰剂对照、面罩、为期9周、8个站点的RCT 涉及200名AD患者。它将招收来自真实世界的门诊、疗养院和 辅助生活环境。使用最先进的临床评分和新颖的每周护理员电话 Citad将检查西酞普兰对激越、其他神经精神症状的影响， 认知、生活质量和日常功能。Citad还将进行仔细的安全监测。这 研究是非常重要的，因为它将最终确定有希望的SSRI的有效性和安全性 作为治疗阿尔茨海默病中躁动的一种方法，这种情况没有得到证实的治疗选择，也没有 重大风险。如果西酞普兰被发现有效，它很可能成为一线疗法，考虑到 其他药物选择的局限性。Citad还将提供关于以下方面的重要知识 反应的预测因素，并为未来的研究奠定基础，以了解参与的机制 西酞普兰和其他SSRI对激越的影响。阿尔茨海默病(AD)中的激动症是一个严重的公共健康问题 对病人和照顾者的后果。管理骚动是#年的一个主要优先事项。 治疗阿尔茨海默病。建议在AD(Citad)中用于煽动的西妥普兰将带来 在持续的大萧条中成功合作的调查人员在 阿尔茨海默病研究(DIADS-2)和完成的抗精神病药物临床试验 干预效果-阿尔茨海默病(CATIE-AD)。

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).