University of Rochester School of Medicine and Dentistry, Rochester, New York.
Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
JAMA. 2014 Feb 19;311(7):682-91. doi: 10.1001/jama.2014.93.
Agitation is common, persistent, and associated with adverse consequences for patients with Alzheimer disease. Pharmacological treatment options, including antipsychotics are not satisfactory.
The primary objective was to evaluate the efficacy of citalopram for agitation in patients with Alzheimer disease. Key secondary objectives examined effects of citalopram on function, caregiver distress, safety, cognitive safety, and tolerability.
DESIGN, SETTING, AND PARTICIPANTS: The Citalopram for Agitation in Alzheimer Disease Study (CitAD) was a randomized, placebo-controlled, double-blind, parallel group trial that enrolled 186 patients with probable Alzheimer disease and clinically significant agitation from 8 academic centers in the United States and Canada from August 2009 to January 2013.
Participants (n = 186) were randomized to receive a psychosocial intervention plus either citalopram (n = 94) or placebo (n = 92) for 9 weeks. Dosage began at 10 mg per day with planned titration to 30 mg per day over 3 weeks based on response and tolerability.
Primary outcome measures were based on scores from the 18-point Neurobehavioral Rating Scale agitation subscale (NBRS-A) and the modified Alzheimer Disease Cooperative Study-Clinical Global Impression of Change (mADCS-CGIC). Other outcomes were based on scores from the Cohen-Mansfield Agitation Inventory (CMAI) and the Neuropsychiatric Inventory (NPI), ability to complete activities of daily living (ADLs), caregiver distress, cognitive safety (based on scores from the 30-point Mini Mental State Examination [MMSE]), and adverse events.
Participants who received citalopram showed significant improvement compared with those who received placebo on both primary outcome measures. The NBRS-A estimated treatment difference at week 9 (citalopram minus placebo) was -0.93 (95% CI, -1.80 to -0.06), P = .04. Results from the mADCS-CGIC showed 40% of citalopram participants having moderate or marked improvement from baseline compared with 26% of placebo recipients, with estimated treatment effect (odds ratio [OR] of being at or better than a given CGIC category) of 2.13 (95% CI, 1.23-3.69), P = .01. Participants who received citalopram showed significant improvement on the CMAI, total NPI, and caregiver distress scores but not on the NPI agitation subscale, ADLs, or in less use of rescue lorazepam. Worsening of cognition (-1.05 points; 95% CI, -1.97 to -0.13; P = .03) and QT interval prolongation (18.1 ms; 95% CI, 6.1-30.1; P = .01) were seen in the citalopram group.
Among patients with probable Alzheimer disease and agitation who were receiving psychosocial intervention, the addition of citalopram compared with placebo significantly reduced agitation and caregiver distress; however, cognitive and cardiac adverse effects of citalopram may limit its practical application at the dosage of 30 mg per day.
clinicaltrials.gov Identifier: NCT00898807.
躁动是常见的、持续的，并与阿尔茨海默病患者的不良后果相关。药物治疗选择，包括抗精神病药，并不令人满意。
主要目的是评估西酞普兰治疗阿尔茨海默病患者躁动的疗效。主要次要目标考察了西酞普兰对功能、照料者痛苦、安全性、认知安全性和耐受性的影响。
设计、地点和参与者：西酞普兰治疗阿尔茨海默病躁动研究（CitAD）是一项随机、安慰剂对照、双盲、平行组试验，在美国和加拿大的 8 个学术中心招募了 186 名患有可能的阿尔茨海默病和临床显著躁动的患者，从 2009 年 8 月至 2013 年 1 月入组。
参与者（n=186）被随机分配接受心理社会干预加西酞普兰（n=94）或安慰剂（n=92）治疗 9 周。起始剂量为 10mg/天，根据反应和耐受性计划在 3 周内滴定至 30mg/天。
主要结局指标基于 18 点神经行为评定量表（NBRS-A）和改良阿尔茨海默病合作研究-临床总体印象变化（mADCS-CGIC）的激动亚量表评分。其他结局指标基于 Cohen-Mansfield 激动量表（CMAI）和神经精神病学问卷（NPI）评分、完成日常生活活动（ADLs）的能力、照料者痛苦、认知安全性（基于 30 分简易精神状态检查[MMSE]评分）和不良事件。
与接受安慰剂的患者相比，接受西酞普兰治疗的患者在两项主要结局指标上均有显著改善。第 9 周时 NBRS-A 估计的治疗差异（西酞普兰减去安慰剂）为-0.93（95%CI，-1.80 至 -0.06），P=0.04。mADCS-CGIC 的结果显示，40%的西酞普兰治疗患者从基线开始有中度或明显改善，而安慰剂组为 26%，治疗效果估计（优势比[OR]处于或优于特定 CGIC 类别）为 2.13（95%CI，1.23-3.69），P=0.01。接受西酞普兰治疗的患者在 CMAI、总 NPI 和照料者痛苦评分上有显著改善，但在 NPI 激动亚量表、ADLs 或更少使用劳拉西泮解救方面没有改善。认知恶化（-1.05 分；95%CI，-1.97 至 -0.13；P=0.03）和 QT 间期延长（18.1ms；95%CI，6.1-30.1；P=0.01）在西酞普兰组中观察到。
在接受心理社会干预的可能患有阿尔茨海默病和躁动的患者中，与安慰剂相比，西酞普兰的添加可显著减少躁动和照料者痛苦；然而，西酞普兰的认知和心脏不良反应可能限制其在 30mg/天的剂量下的实际应用。
clinicaltrials.gov 标识符：NCT00898807。
