Homma Akira, Imai Yukimichi, Tago Hisao, Asada Takashi, Shigeta Masahiro, Iwamoto Toshihiko, Takita Masashi, Arimoto Itaru, Koma Hiroshi, Takase Takao, Ohbayashi Toshio
Dementia Interventional Research Group, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.
Dement Geriatr Cogn Disord. 2009;27(3):232-9. doi: 10.1159/000203887. Epub 2009 Feb 25.
BACKGROUND/AIMS: A 6-month, randomized, double-blind, placebo-controlled study was extended to evaluate long-term safety and efficacy of donepezil in community-dwelling Japanese patients with severe Alzheimer's disease (AD).
189 patients were enrolled from the double-blind study into a 52-week, open-label extension study. After a 2- to 8-week washout, donepezil was escalated within 6 weeks to 10 mg/day. Main outcomes were Severe Impairment Battery (SIB), Alzheimer's Disease Cooperative Study-Activities of Daily Living scale for severe AD (ADCS-ADL-sev) and Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD). Safety parameters were monitored throughout.
Overall, mean change from extension study baseline in SIB scores improved until week 24; however, scores were influenced by prior treatment during the double-blind study and by length of washout. Patients treated with donepezil retained some treatment benefits after a washout of 2-4 weeks but lost all treatment benefits after a washout of 4-8 weeks. There was no change in ADCS-ADL-sev or BEHAVE-AD scores. Adverse events were consistent with the known donepezil safety profile.
Donepezil is effective and safe for symptomatic treatment of severe AD for at least 1 year. Patients who receive donepezil 10 mg daily with little or no interruption achieve the best long-term outcome.
背景/目的：一项为期6个月的随机、双盲、安慰剂对照研究进行了扩展，以评估多奈哌齐对日本社区重度阿尔茨海默病（AD）患者的长期安全性和疗效。
189名患者从双盲研究进入为期52周的开放标签扩展研究。经过2至8周的洗脱期后，多奈哌齐在6周内逐渐增至10毫克/天。主要结局指标为严重损害量表（SIB）、阿尔茨海默病协作研究重度AD日常生活活动量表（ADCS-ADL-sev）和阿尔茨海默病行为病理评定量表（BEHAVE-AD）。全程监测安全参数。
总体而言，SIB评分从扩展研究基线的平均变化在第24周前有所改善；然而，评分受双盲研究期间的先前治疗以及洗脱期长度的影响。多奈哌齐治疗的患者在2至4周的洗脱期后仍保留一些治疗益处，但在4至8周的洗脱期后失去了所有治疗益处。ADCS-ADL-sev或BEHAVE-AD评分无变化。不良事件与已知的多奈哌齐安全性特征一致。
多奈哌齐对重度AD的对症治疗至少1年有效且安全。每日接受10毫克多奈哌齐且几乎无中断的患者可获得最佳长期疗效。
