Memantine in patients with Parkinson's disease dementia or dementia with Lewy bodies: a double-blind, placebo-controlled, multicentre trial
Memantine in patients with Parkinson's disease dementia or dementia with Lewy bodies: a double-blind, placebo-controlled, multicentre trial
复制标题
DOI：
10.1016/s1474-4422(09)70146-2
复制
发表时间：
2009-07-01
期刊：
影响因子：
48
通讯作者：
Londos, Elisabet
中科院分区：
文献类型：
--
作者：
Aarsland, Dag;Ballard, Clive;Londos, Elisabet
研究背景路易体痴呆(DLB)和帕金森氏病痴呆(PDD)是严重影响生活质量的常见痴呆类型。目前，唯一获得许可的治疗PDD的药物是利瓦斯明，而目前还没有获得许可的治疗DLB的方法。我们的目的是测试N-甲基-D-天冬氨酸(NMDA)受体拮抗剂美金刚治疗PDD或DLB患者的安全性和有效性。方法2005-08年间，我们在挪威、瑞典和英国的四家精神科和神经科门诊诊所进行了一项平行分组、为期24周的随机对照研究，研究对象是美金刚(每天20 mg)和安慰剂。如果患者符合英国帕金森氏病协会脑库对帕金森氏病(PD)的临床诊断标准，并在出现运动症状(PDD)至少一年后根据精神疾病诊断和统计手册第四版(DSM IV)标准发展为痴呆症，或符合修订后的DLB共识操作标准，则纳入患者。患者被分配到计算机生成的随机名单中。所有与患者有过接触的医生都被蒙面接受治疗分配。主要的预后指标是临床总体变化印象(CGIC)，范围为1~7分，得分越低，预后越好。分析是基于最后一次观察结果的意向处理。这项试验是注册的，编号为ISRCTN89624516。结果72名PDD或DLB患者被随机分配并开始治疗：34名服用美金刚，38名服用安慰剂。56人(78%)完成了研究。所有的撤资都是由于不良事件，但两组撤资的比例相似。24周时，美金刚组患者的CGIC评分好于服用安慰剂的患者(平均差异0。7，95%可信区间0.04-1-39；P=0.03)。除美金刚组在注意任务上的速度提高外(认知快速测试表：差异12.4，95%可信区间6.0-30.9；p=0.004)，两组在次要结果测量方面无显著差异。现在需要进行大规模研究来证实我们的初步发现。
Background Dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) are common forms of dementia that substantially affect quality of life. Currently, the only treatment licensed for PDD is rivastigmine, and there are no licensed treatments for DLB. We aimed to test the safety and efficacy of the N-methyl D-aspartate (NMDA) receptor antagonist memantine in patients with PDD or DLB.Methods We did a parallel-group, 24-week, randomised controlled study of memantine (20 mg per day) versus placebo at four psychiatric and neurological outpatient clinics in Norway, Sweden, and the UK during 2005-08. Patients were included if they fulfilled the UK Parkinson's Disease Society Brain Bank clinical diagnostic criteria for Parkinson's disease (PD) and developed dementia according to the Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM IV) criteria at least 1 year after the onset of motor symptoms (PDD) or met the revised consensus operationalised criteria for DLB. Patients were assigned to a computer-generated randomisation list. All physicians who had contact with patients were masked to treatment allocation. The primary outcome measure was clinical global impression of change (CGIC), which ranged from 1 to 7 points, and a low score means a better outcome. Analysis was by intention to treat based on the last observation carried forward. This trial is registered, number ISRCTN89624516.Findings 72 patients with PDD or DLB were randomly assigned and started treatment: 34 with memantine and 38 with placebo. 56 (78%) completed the study. All withdrawals were owing to adverse events, but the proportion of withdrawals was similar in both groups. At week 24 the patients in the memantine group had better CGIC scores than those taking placebo (mean difference 0 . 7, 95% CI 0.04-1-39; p=0.03). With the exception of improved speed on attentional tasks in the memantine group (a quick test of cognition [AQT] form: difference 12.4, 95% CI 6.0-30.9; p=0.004), there were no significant differences between the groups in secondary outcome measures.Interpretation Patients with DLB or PDD might benefit from treatment with memantine, which was well tolerated. Large-scale studies are now required to confirm our preliminary findings.