Kitamura Shin, Nakamura Yu, Homma Akira, Kimura Noriyuki, Asami Yumiko
Department of Internal Medicine, Nippon Medical School Musashikosugi Hospital.
Nihon Ronen Igakkai Zasshi. 2014;51(1):74-84. doi: 10.3143/geriatrics.51.74.
Memantine hydrochloride (Memary®), launched in June 2011 in Japan, is used in patients with moderate to severe Alzheimer's disease. We performed an integrated analysis of data obtained from different clinical studies of memantine hydrochloride conducted between 2002 and 2011 in Japan in order to examine the long-term tolerability and efficacy of this drug at a dose of 20 mg/day.
Using clinical studies of memantine hydrochloride performed in Japan between 2002 and 2011, the therapeutic safety and the time course of MMSE scores in 702 subjects who had received memantine hydrochloride were examined.
The mean duration of memantine treatment was 798.1 days, with the longest duration of 3,373 days (approximately nine years and two months). The incidence of adverse events every 52 weeks of treatment ranged from 71.0% to 88.9%, and the incidence of adverse drug reactions ranged from 5.6% to 32.1%, with no associations between the incidence of adverse events and the treatment duration. There were no adverse drug reactions specific to the long-term administration of this drug. The occurrence of "adverse events" was the primary reason for drug discontinuation. During the long-term study observation period, there were many cases of adverse events and treatment discontinuation due to the background factors of the subjects, including adverse events associated with aging and progression of the underlying conditions. In addition, treatment discontinuation was also associated with admission to a nursing home or facility due to changes in home nursing care. The degree of MMSE score reduction over time was lower in the patients treated with memantine than the expected MMSE score reduction observed in the untreated patients.
Based on these findings, there are no issues regarding the tolerability of memantine hydrochloride administered at a dose of 20 mg/day over the long term. Considering changes in the MMSE score, the results indicated that memantine hydrochloride may inhibit worsening of the cognitive function for long periods of time in patients with Alzheimer's disease.
盐酸美金刚（Memary®）于2011年6月在日本上市，用于中重度阿尔茨海默病患者。我们对2002年至2011年期间在日本进行的不同盐酸美金刚临床研究获得的数据进行了综合分析，以研究该药物20mg/天剂量的长期耐受性和疗效。
利用2002年至2011年在日本进行的盐酸美金刚临床研究，对702例接受盐酸美金刚治疗的受试者的治疗安全性和MMSE评分的时间进程进行了检查。
美金刚治疗的平均持续时间为798.1天，最长持续时间为3373天（约九年零两个月）。每52周治疗的不良事件发生率在71.0%至88.9%之间，药物不良反应发生率在5.6%至32.1%之间，不良事件发生率与治疗持续时间之间无关联。该药物长期给药无特定的药物不良反应。“不良事件”的发生是停药的主要原因。在长期研究观察期内，由于受试者的背景因素，包括与衰老和基础疾病进展相关的不良事件，有许多不良事件和停药病例。此外，由于家庭护理的变化，停药也与入住养老院或护理机构有关。美金刚治疗患者随时间的MMSE评分降低程度低于未治疗患者观察到的预期MMSE评分降低程度。
基于这些发现，长期服用20mg/天剂量的盐酸美金刚耐受性方面没有问题。考虑到MMSE评分的变化，结果表明盐酸美金刚可能在很长一段时间内抑制阿尔茨海默病患者认知功能的恶化。
