Ballard Clive, Thomas Alan, Gerry Stephen, Yu Ly-Mee, Aarsland Dag, Merritt Claire, Corbett Anne, Davison Christopher, Sharma Narenda, Khan Zunera, Creese Byron, Loughlin Paul, Bannister Carol, Burns Alistair, Win Soe Nyunt, Walker Zuzana
Wolfson Centre for Age-Related Diseases, King's College London, London, UK.
Institute for Ageing, University of Newcastle, Newcastle Upon Tyne, UK.
J Am Med Dir Assoc. 2015 Apr;16(4):316-22. doi: 10.1016/j.jamda.2014.11.002. Epub 2014 Dec 15.
Neuropsychiatric symptoms in Alzheimer disease (AD) cause significant distress and present a complex clinical challenge for treatment. Pharmacological treatment options are limited to antipsychotics, which carry extensive safety issues. There is emerging evidence to support the potential benefits of memantine, currently licensed for moderate to severe AD, in the prophylaxis of neuropsychiatric symptoms.
The MAIN-AD study is a double-blind randomized placebo-controlled withdrawal trial comparing memantine with antipsychotics for the treatment of neuropsychiatric symptoms over 24 weeks. A total of 199 people with probable AD living in care homes already receiving an antipsychotic were randomized to receive either memantine or to continue an antipsychotic. The primary outcomes were function (Bristol Activities of Daily Living Scale [BADLS]) and agitation (Cohen-Mansfield Agitation Inventory [CMAI]). Secondary outcomes were Neuropsychiatric Inventory (NPI), Mini-Mental State Examination (MMSE), and mortality.
There was no significant difference between groups on the BADLS or CMAI. At 24 weeks, there was a nonsignificant adjusted difference in favor of memantine on the BADLS of 0.23 (95% CI -1.80-2.27; P = .82) and in favor of antipsychotic on the CMAI of 0.09 (95% CI -0.35-8.53; P = .07). Although there were no significant differences in total NPI, there were 5.01 (95% CI -1.68-11.70; P = .05) and 3.63 (95% CI -1.40-8.67; P = .16) point advantages favoring antipsychotics at weeks 12 and 24, respectively. In addition, in an exploratory analysis, individuals allocated to antipsychotics were significantly less likely to experience relapse of neuropsychiatric symptoms at all time points. The group receiving memantine had a nonsignificant 1.3-point advantage on the MMSE at 24 weeks.
This study indicates no benefits for memantine in the long-term treatment and prophylaxis of clinically significant neuropsychiatric symptoms. The results did indicate some benefits for antipsychotic medications in reducing the relapse of neuropsychiatric symptoms, but this must be balanced against increased mortality risk.
阿尔茨海默病（AD）中的神经精神症状会造成严重困扰，给治疗带来复杂的临床挑战。药物治疗选择仅限于抗精神病药物，但这类药物存在诸多安全问题。有新证据支持美金刚（目前已获批用于中重度AD）在预防神经精神症状方面的潜在益处。
MAIN-AD研究是一项双盲随机安慰剂对照撤药试验，比较美金刚与抗精神病药物在24周内治疗神经精神症状的效果。共有199名居住在养老院且已在服用抗精神病药物的可能患有AD的患者被随机分组，分别接受美金刚治疗或继续服用抗精神病药物。主要结局指标为功能（布里斯托尔日常生活活动量表[BADLS]）和激越（科恩-曼斯菲尔德激越量表[CMAI]）。次要结局指标为神经精神科问卷（NPI）、简易精神状态检查表（MMSE）和死亡率。
两组在BADLS或CMAI上无显著差异。在24周时，美金刚在BADLS上有0.23的非显著调整优势（95%可信区间-1.80至2.27；P = 0.82），抗精神病药物在CMAI上有0.09的优势（95%可信区间-0.35至8.53；P = 0.07）。虽然在NPI总分上无显著差异，但在第12周和第24周时，抗精神病药物分别有5.01（95%可信区间-1.68至11.70；P = 0.05）和3.63（95%可信区间-1.40至8.67；P = 0.16）分的优势。此外，在一项探索性分析中，被分配接受抗精神病药物治疗的个体在所有时间点出现神经精神症状复发的可能性显著更低。接受美金刚治疗的组在24周时MMSE有1.3分的非显著优势。
本研究表明美金刚在长期治疗和预防具有临床意义的神经精神症状方面并无益处。结果确实表明抗精神病药物在减少神经精神症状复发方面有一些益处，但这必须与增加的死亡风险相权衡。
