Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil - A randomized controlled trial
Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil - A randomized controlled trial
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DOI：
10.1001/jama.291.3.317
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发表时间：
2004-01-21
影响因子：
120.7
通讯作者：
Gergel, I
中科院分区：
文献类型：
--
作者：
Tariot, PN;Farlow, MR;Gergel, I
上下文美金刚是一种低亲和力到中等亲和力的非竞争性N-甲基-D-天冬氨酸受体拮抗剂。对照试验已经证明了美金刚单一治疗中重度阿尔茨海默病(AD)患者的安全性和有效性，但还没有对接受胆碱酯酶抑制剂治疗的患者进行美金刚对照试验。目的比较美金刚和安慰剂在已经接受多奈哌齐稳定治疗的中重度AD患者中的疗效和安全性。设计、设置和参与者2001年6月11日至2002年6月3日，在美国37个地点进行了一项随机、双盲、安慰剂对照临床试验，404名中到重度AD患者接受了稳定剂量的多奈哌齐治疗。共有322名患者(80%)完成了试验。干预参与者被随机分成两组，分别接受美金刚(开始剂量为5 mg/d，增加到20 mg/d，n=203)或安慰剂(n=201)治疗24周。主要结果指标在严重损害成套测验(SIB)和改良的19项AD合作研究-日常生活活动量表(ADCS-ADL(19))上与基线相比发生了变化。次要结果包括临床医生对改变的印象加上照顾者的投入(Cibic-Plus)、神经精神病学问卷和老年患者行为评定量表(BGP关怀依赖子量表)。结果总平均分(SE)的改变分别有利于美金刚和安慰剂治疗SIB(可能的分数范围为0-100)，0.9(0.67)比-2.5(0.69)(P
Context Memantine is a low- to moderate-affinity, uncompetitive N-methyl-D-aspartate receptor antagonist. Controlled trials have demonstrated the safety and efficacy of memantine monotherapy for patients with moderate to severe Alzheimer disease (AD) but no controlled trials of memantine in patients receiving a cholinesterase inhibitor have been performed.Objective To compare the efficacy and safety of memantine vs placebo in patients with moderate to severe AD already receiving stable treatment with donepezil.Design, Setting, and Participants A randomized, double-blind, placebo-controlled clinical trial of 404 patients with moderate to severe AD and Mini-Mental State Examination scores of 5 to 14, who received stable doses of donepezil, conducted at 37 US sites between June 11, 2001, and June 3, 2002. A total of 322 patients (80%) completed the trial.Interventions Participants were randomized to receive memantine (starting dose 5 mg/d, increased to 20 mg/d, n =203) or placebo (n =201) for 24 weeks.Main Outcome Measures Change from baseline on the Severe Impairment Battery (SIB), a measure of cognition, and on a modified 19-item AD Cooperative Study-Activities of Daily Living Inventory (ADCS-ADL(19)). Secondary outcomes included a Clinician's Interview-Based Impression of Change Plus Caregiver Input (CIBIC-Plus), the Neuropsychiatric Inventory, and the Behavioral Rating Scale for Geriatric Patients (BGP Care Dependency Subscale).Results The change in total mean (SE) scores favored memantine vs placebo treatment for SIB (possible score range, 0-100), 0.9 (0.67) vs -2.5 (0.69), respectively (P