Gauthier Serge, Juby Angela, Morelli Lidia, Rehel Bonita, Schecter Robyn
McGill Centre for Studies in Aging, Douglas Hospital, Montreal, Quebec, Canada.
Curr Med Res Opin. 2006 Nov;22(11):2251-65. doi: 10.1185/030079906X132749.
Previous studies in Alzheimer's Disease (AD) suggest a benefit from switching from one cholinesterase (ChE) inhibitor to another in the event of treatment failure on the index agent. This observational, open-label study sought to evaluate the efficacy of the ChE inhibitor rivastigmine on cognition, functional autonomy and behavior in patients with mild-to-moderate AD previously treated with other ChE inhibitors (switched patients) as well as in those previously ChE-inhibitor-naive (de novo users).
Patients were eligible for a switch if they experienced a lack or loss of efficacy or had experienced intolerance to prior ChE inhibitor therapy. Rivastigmine was initiated at a dose of 1.5 mg b.i.d. and titration was done as per standard medical practice. Efficacy was assessed using the mini-mental state examination (MMSE) and an abbreviated version of the Clinician's Global Impression of Change (CGI-C) at Month 3 and Month 6. Caregiver burden was also assessed at Month 6 using a self-rated scale.
Overall, 2633 subjects were enrolled in this study. The mean MMSE improved from 20.6 at baseline to 21.5 at Month 6. More patients improved than deteriorated on every domain of the CGI-C. Caregivers felt less burdened after the 6 month evaluation period. Efficacy parameters demonstrated favorable results for both de novo and switched patients, but more so in the first group.
Open-label studies have an inherent potential for bias by both the caregiver and the physician. In this study, there was also a large percentage of missing patient records for each of the follow-up visits (Months 3 and 6).
Patients with mild-to-moderate AD switched from previous ChE inhibitor therapy to rivastigmine can obtain measurable benefits, although the treatment effect may be less than in de novo patients. Further research into switching cholinesterase inhibitors is warranted.
先前关于阿尔茨海默病（AD）的研究表明，在使用初始药物治疗失败的情况下，从一种胆碱酯酶（ChE）抑制剂换用另一种可能有益。这项观察性、开放标签研究旨在评估ChE抑制剂卡巴拉汀对先前接受过其他ChE抑制剂治疗的轻至中度AD患者（换药患者）以及先前未使用过ChE抑制剂的患者（初治患者）的认知、功能自主性和行为的疗效。
如果患者出现疗效不足或丧失，或对先前的ChE抑制剂治疗不耐受，则符合换药条件。卡巴拉汀起始剂量为1.5毫克，每日两次，并按照标准医疗实践进行滴定。在第3个月和第6个月使用简易精神状态检查表（MMSE）和临床医师总体印象变化量表（CGI-C）的简化版评估疗效。在第6个月还使用自评量表评估照顾者负担。
总体而言，本研究共纳入2633名受试者。MMSE平均分从基线时的20.6提高到第6个月时的21.5。在CGI-C的各个领域，病情改善的患者多于病情恶化的患者。经过6个月的评估期后，照顾者感觉负担减轻。疗效参数在初治患者和换药患者中均显示出良好结果，但在第一组中更为明显。
开放标签研究存在照顾者和医生双方固有的偏倚可能性。在本研究中，每次随访（第3个月和第6个月）时患者记录缺失的比例也很高。
从先前的ChE抑制剂治疗换用卡巴拉汀的轻至中度AD患者可获得可衡量的益处，尽管治疗效果可能低于初治患者。有必要对胆碱酯酶抑制剂的换药进行进一步研究。
