Efficacy of rivastigmine in dementia with Lewy bodies: a randomised, double-blind, placebo-controlled international study
Efficacy of rivastigmine in dementia with Lewy bodies: a randomised, double-blind, placebo-controlled international study
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DOI：
10.1016/s0140-6736(00)03399-7
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发表时间：
2000-12-16
期刊：
影响因子：
168.9
通讯作者：
Spiegel, R
中科院分区：
文献类型：
--
作者：
McKeith, I;Del Ser, T;Spiegel, R
研究背景路易体痴呆（Dementia with Lewy bodies）是一种常见的老年痴呆，临床表现为波动性认知障碍、注意力缺陷、视幻觉、帕金森综合征等神经精神症状。抗精神病药物可引起这类痴呆患者的严重敏感反应。路易体痴呆患者的大脑中存在许多胆碱能神经传递缺陷，因此，增强中枢胆碱能功能的药物是治疗这种疾病的合理方法。卡巴拉汀，胆碱酯酶抑制剂，进行了测试，在一组临床特征的患者与路易体dementia.Methods安慰剂对照，双盲，多中心研究，在120例路易体痴呆症从英国，西班牙，和意大利。受试者每天给予12 mg rivastigmine或安慰剂，持续20周，随后休息3周。通过神经精神量表在基线时进行评估，并在第12、20和23周再次进行评估。一个计算机化的认知评估系统和神经心理学测试也被使用，患者进行了密切的医疗和实验室的安全性analysis.Findings服用卡巴拉汀的患者显着减少冷漠和焦虑，并有较少的妄想和幻觉，而在治疗比对照。rivastigmine组（37，63%）显示较基线至少改善30%的患者几乎是安慰剂组（18，30%）的两倍。在计算机认知评估系统和神经心理学测试中，患者明显比安慰剂组更快更好，特别是在具有大量注意力成分的任务中。rivastigmine和安慰剂之间的两个预定义的主要疗效指标均存在显著差异。停药后，rivastigmine和安慰剂之间的差异趋于消失。与安慰剂相比，卡巴拉汀组胆碱酯酶抑制剂的已知不良事件（恶心、呕吐、厌食）发生率更高，但在这些多病患者中，该药的安全性和耐受性被判定为可接受。解读卡巴拉汀6-12 mg每日给药对路易体痴呆患者产生统计学和临床显著的行为影响，如果单独滴定，似乎安全且耐受性良好。
Background Dementia with Lewy bodies is a common form of dementia in the elderly, characterised clinically by fluctuating cognitive impairment, attention deficits, Visual hallucinations, parkinsonism, and other neuropsychiatric features. Neuroleptic medication can provoke severe sensitivity reactions in patients with dementia of this type. Many deficits in cholinergic neurotransmission are seen in the brain of patients with Lewy-body dementia; therefore, drugs enhancing central cholinergic function represent a rationally-based therapeutic approach to this disorder. Rivastigmine, a cholinesterase inhibitor, was tested in a group of clinically characterised patients with Lewy-body dementia.Methods A placebo-controlled, double-blind, multicentre study was done in 120 patients with Lewy-body dementia from the UK, Spain, and Italy. Individuals were given up to 12 mg rivastigmine daily or placebo for 20 weeks, followed by 3 weeks rest. Assessment by means of the neuropsychiatric inventory was made at baseline, and again at weeks 12, 20, and 23. A computerised cognitive assessment system and neuropsychological tests were also used, and patients underwent close medical and laboratory safety analysis.Findings Patients taking rivastigmine were significantly less apathetic and anxious, and had fewer delusions and hallucinations while on treatment than controls. Almost twice as many patients on rivastigmine (37, 63%), than on placebo (18, 30%), showed at least a 30% improvement from baseline. In the computerised cognitive assessment system and the neuropsychological tests, patients were significantly faster and better than those oh placebo, particularly on tasks with a substantial attentional component. Both predefined primary efficacy measures differed significantly between rivastigmine and placebo. After drug discontinuation differences between rivastigmine and placebo tended to disappear. Known adverse events of cholinesterase inhibitors (nausea, vomiting, anorexia) were seen more frequently with rivastigmine than with placebo, but safety and tolerability of the drug in these mostly multimorbid patients were judged acceptable.Interpretation Rivastigmine 6-12 mg daily produces statistically and clinically significant behavioural effects in patients with Lewy-body dementia, and seems safe and well tolerated if titrated individually.