Effect of Dextromethorphan-Quinidine on Agitation in Patients With Alzheimer Disease Dementia A Randomized Clinical Trial
Effect of Dextromethorphan-Quinidine on Agitation in Patients With Alzheimer Disease Dementia A Randomized Clinical Trial
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DOI：
10.1001/jama.2015.10214
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发表时间：
2015-09-22
影响因子：
120.7
通讯作者：
Siffert, Joao
中科院分区：
文献类型：
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作者：
Cummings, Jeffrey L.;Lyketsos, Constantine G.;Siffert, Joao
重要性 阿尔茨海默病患者的躁动很常见。缺乏安全、有效的治疗方法。 目的 评估氢溴酸右美沙芬-硫酸奎尼丁治疗阿尔茨海默病相关躁动的疗效、安全性和耐受性。 设计、设置和参与者 2012 年 8 月至 2014 年 8 月进行的 2 期随机、多中心、双盲、安慰剂对照试验，采用序贯平行比较设计，进行 2 个连续 5 周的治疗阶段。阿尔茨海默病、临床显着的躁动（临床总体印象-严重性躁动评分 >= 4）以及 8 至 28 分的简易精神状态检查分数参与了 42 个美国研究中心的研究。允许使用稳定剂量的抗抑郁药、抗精神病药、安眠药和抗痴呆药物。 干预措施 在第一阶段，220 名患者按 3:4 的比例随机分配接受右美沙芬奎尼丁 (n = 93) 或安慰剂 (n = 127)。在第2阶段，患者继续接受右美沙芬-奎尼丁治疗；接受安慰剂的患者按反应进行分层，并以 1:1 的比例重新随机分配至右美沙芬-奎尼丁 (n = 59) 或安慰剂 (n = 60)。 主要结果和测量 主要终点是神经精神量表 (NPI) 激越/攻击领域相对于基线的变化（量表范围，0 [无症状] 至 12 [症状每天出现，并且伴有症状）结果 共有 194 名患者 (88.2%) 完成了研究。通过序贯平行比较设计，研究期间 152 名患者接受右美沙芬奎尼丁治疗，127 名患者接受安慰剂。结合第 1 阶段（所有患者）和第 2 阶段（重新随机安慰剂无反应者）的分析显示，与安慰剂相比，右美沙芬-奎尼丁的 NPI 激动/攻击性评分显着降低（普通最小二乘统计，-3.95；P < .001）。在第一阶段，右美沙芬-奎尼丁组的平均 NPI 激动/攻击性评分从 7.1 降低至 3.8，安慰剂组从 7.0 降低至 5.3。第 1 阶段组间治疗差异显着（最小均值，-1.5；95% CI，-2.3 至 -0.7；P
IMPORTANCE Agitation is common among patients with Alzheimer disease; safe, effective treatments are lacking.OBJECTIVE To assess the efficacy, safety, and tolerability of dextromethorphan hydrobromide-quinidine sulfate for Alzheimer disease-related agitation.DESIGN, SETTING, AND PARTICIPANTS Phase 2 randomized, multicenter, double-blind, placebo-controlled trial using a sequential parallel comparison design with 2 consecutive 5-week treatment stages conducted August 2012-August 2014. Patients with probable Alzheimer disease, clinically significant agitation (Clinical Global Impressions-Severity agitation score >= 4), and a Mini-Mental State Examination score of 8 to 28 participated at 42 US study sites. Stable dosages of antidepressants, antipsychotics, hypnotics, and antidementia medications were allowed.INTERVENTIONS In stage 1, 220 patients were randomized in a 3: 4 ratio to receive dextromethorphan-quinidine (n = 93) or placebo (n = 127). In stage 2, patients receiving dextromethorphan-quinidine continued; those receiving placebo were stratified by response and rerandomized in a 1: 1 ratio to dextromethorphan-quinidine (n = 59) or placebo (n = 60).MAIN OUTCOMES AND MEASURES The primary end point was change from baseline on the Neuropsychiatric Inventory (NPI) Agitation/Aggression domain (scale range, 0 [absence of symptoms] to 12 [symptoms occur daily and with marked severity]).RESULTS A total of 194 patients (88.2%) completed the study. With the sequential parallel comparison design, 152 patients received dextromethorphan-quinidine and 127 received placebo during the study. Analysis combining stages 1 (all patients) and 2 (rerandomized placebo nonresponders) showed significantly reduced NPI Agitation/Aggression scores for dextromethorphan-quinidine vs placebo( ordinaryleastsquareszstatistic,-3.95; P < .001). In stage 1, mean NPI Agitation/Aggression scores were reduced from 7.1 to 3.8 with dextromethorphan-quinidine and from 7.0 to 5.3 with placebo. Between-groupt reatment differences were significantin stage 1(leasts quaresmean, -1.5; 95% CI, -2.3 to -0.7; P