多奈哌齐治疗轻中度阿尔茨海默病的效能及其安全性评估(英文)

Efficiency and safety assessment of donepezil for treating mild and moderate Alzheimer disease

背景:多奈哌齐(商品名安理申)作为FDA批准的第二个抗阿尔茨海默病药物在欧美等国已上市应用,卫生部规定,在中国上市前需做全国范围内多中心联合临床观察试验。目的:评价多奈哌齐治疗轻、中度阿尔茨海默病的有效性及安全性。设计:以患者为研究对象,随机、单盲、安慰剂对照的前瞻性研究。单位:北京医院的神经内科和解放军第三○一医院的神经内科。对象:1998/2000对北京、上海、广州15家大型综合医院的188例轻、中度阿尔茨海默病(简易智能状态量表10～24分)患者进行了12周临床试验,其中89例为单盲、安慰剂对照研究,99例为自身对照研究,所有阿尔茨海默病患者均符合国立神经病学、语言功能障碍和中风研究所(NINCDS-ADRDA)中的可能阿尔茨海默病标准及诊断与统计手册第4次修订版(DSM-IVR)中的阿尔茨海默病诊断标准。干预:给予多奈哌齐(口服,5mg/片,1次/d,5mg/次)或颜色、形状、味道、大小与多奈哌齐相同的安慰剂(口服,1次/d,1片/次),连续应用12周。主要观察指标:用药前和用药后每4周检查1次简易智能状态量表、临床痴呆程度量表、日常生活自理量表和实验室生化指标、心电图及胸片。结果:随机、单盲、安慰剂对照组研究结果表明,5mg/d多奈哌齐治疗12周时,多奈哌齐组较安慰剂组简易智能状态量表。

BACKGROUND:As the second anti Alzheimer disease drug approved by Food and Drug Administration(FDA),donepezil (Aricept) has been applied in European and American market.According to the regulation of Health Ministry of China,it needs conducting clinical trial of multiple center nationwide in order to come into Chinese market. OBJECTIVE:To evaluate the efficiency and safety of donepezil on treating mild and moderate Alzheimer disease(AD). DESIGN:Randomized,single blind and placebo control prospective study based on patients. SETTING:Neurological Department of Peking Hospital and Neurological Department of the 301 Hospital of Chinese PLA,and ect. PARTICIPANTS:Totally 188 patients with mild and moderate AD[with mini mental state examination(MMSE) score of 10 to 24 points] from 15 big hospitals of Beijng,Shanghai and Guangzhou were conducted 12 weeks' clinical trial,among which 89 cases were of single blind and placebo control study while 99 cases were of self controlled study.All the cases met the AD diagnostic standard of clinical neurology,linguistic dysfunction and stroke(NINCDS ADRDA) and the 4th edition of Statistic Manual (DSM IVR). INTERVENTIONS:Donepezil (5 mg/tablet,ip,5 mg/time) or placebo with same color,shape,flavor and size with donepezil (ip, 1 tablet/time) was taken orally for 12 consecutive weeks. MAIN OUTCOME MEASURES:MMSE,clinical dementia rating scale(CDR),activities of daily life scale(ADL),biochemical parameters,electrocardiograph(ECG) and chest x ray were conducted once every 4 weeks before and after treatment. RESULTS: The random,single blind and placebo control study showed that the score of MMSE,CDR and ADL was greatly improved in donepezil group after 12 weeks' treatment when comparing with placebo group(P< 0.01,0.05,0.01).Self controlled study showed that the score of MMSE,CRD and ADL in donepezil group after 12 weeks' treatment increased 3.5, 0.6 and 7.1 points respectively compared with those before treatment(P< 0.01,0.05,0.01).The score of MMSE was already improved in the 4th week of treatment. Among the 145 patients who took donepezil,7 cases(4.8%) experienced side effect of mild cholinergic excitability.In the placebo group,2 of the 43 cases appeared dizziness and nausea.There was no difference between two groups(P >0.05). CONCLUSION:Donepezil can effectively treat mild and moderate AD patients and improve their cognitive functions,dementia level and daily living abilities with good tolerance and high safety.