Peters Oliver, Fuentes Manuel, Joachim Lisa Katharina, Jessen Frank, Luckhaus Christian, Kornhuber Johannes, Pantel Johannes, Hüll Michael, Schmidtke Klaus, Rüther Eckart, Möller Hans-Jürgen, Kurz Alexander, Wiltfang Jens, Maier Wolfgang, Wiese Birgitt, Frölich Lutz, Heuser Isabella
Department of Psychiatry, Charité - Campus Benjamin Franklin and German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany.
Department of Psychiatry and German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
Alzheimers Dement (N Y). 2015 Oct 19;1(3):198-204. doi: 10.1016/j.trci.2015.10.001. eCollection 2015 Nov.
Several studies have tested the N-methyl-D-aspartate-receptor antagonist memantine as an add-on to pre-existing treatment with acetylcholinesterase inhibitors. The objective of this study was to evaluate the efficacy and safety of a combined memantine and galantamine-CR de novo regimen compared with galantamine-CR only treatment in never treated patients with mild-to-moderate Alzheimer's disease (AD).
Antidementia drug-naïve participants (n = 232) with probable, mild-to-moderate AD, and mini-mental state examination scores between 15 and 26 (inclusive) were randomized to receive either 20 mg/day memantine plus 24 mg/day galantamine-CR or 24 mg/day galantamine-CR plus placebo in a 52-week, prospective, double-blind, controlled trial. The primary outcome measurement was the change on the Alzheimer's disease assessment scale-cognition score. Secondary measures comprised the Alzheimer's Disease Cooperative Study-activities of daily living inventory and the clinical dementia rating.
At the end of the trial, there were no statistically significant differences between the galantamine-CR/memantine combination and galantamine-CR only group in primary and secondary outcome measurements. The incidence and the severity of adverse events were similar between the groups.
In this trial, memantine in combination with galantamine-CR did not show an advantage with respect to cognition, function, and behavior in previously never treated patients with mild-to-moderate AD. There were no significant differences in tolerability and safety between the groups. Thus, a de novo combination treatment results in no significant improvement in disease progression (current controlled trials number: NCT01921972).
多项研究已对N-甲基-D-天冬氨酸受体拮抗剂美金刚作为乙酰胆碱酯酶抑制剂现有治疗的附加用药进行了测试。本研究的目的是评估在从未接受过治疗的轻度至中度阿尔茨海默病（AD）患者中，美金刚与缓释加兰他敏联合起始治疗方案相较于仅使用缓释加兰他敏治疗的疗效和安全性。
在一项为期52周的前瞻性双盲对照试验中，将232名未使用过抗痴呆药物、可能患有轻度至中度AD且简易精神状态检查得分在15至26分（含）之间的参与者随机分为两组，分别接受每日20毫克美金刚加每日24毫克缓释加兰他敏治疗或每日24毫克缓释加兰他敏加安慰剂治疗。主要结局指标是阿尔茨海默病评估量表-认知得分的变化。次要指标包括阿尔茨海默病协作研究日常生活活动量表和临床痴呆评定量表。
在试验结束时，缓释加兰他敏/美金刚联合治疗组与仅使用缓释加兰他敏治疗组在主要和次要结局指标方面均无统计学上的显著差异。两组不良事件的发生率和严重程度相似。
在本试验中，对于之前从未接受过治疗的轻度至中度AD患者，美金刚与缓释加兰他敏联合使用在认知、功能和行为方面未显示出优势。两组在耐受性和安全性方面无显著差异。因此，起始联合治疗在疾病进展方面未带来显著改善（当前对照试验编号：NCT01921972）。
