Auriacombe S, Pere J J, Loria-Kanza Y, Vellas B
Clinique St. Augustin, Bordeaux, France.
Curr Med Res Opin. 2002;18(3):129-38. doi: 10.1185/030079902125000471.
Selective acetylcholinesterase (AChE) and dual acetyl- and butyrylcholinesterase inhibitors constitute the only approved agents for the symptomatic treatment of Alzheimer's disease (AD). Donepezil is a specific, reversible inhibitor of AChE, while rivastigmine is a slowly reversible (pseudoirreversible) dual cholinesterase (ChE) inhibitor, with brain-regional specificity for the cerebral cortex and hippocampus. According to the European Marketing Authorisations, the clinical benefit of ChE inhibitors should be reassessed on a regular basis and discontinuation should be considered when evidence of a therapeutic effect is no longer present. However, substantial differences in the pharmacological and pharmacokinetic profiles of the available ChE inhibitors suggest that it may be desirable to switch between ChE inhibitors if patients fail to show efficacy, deteriorate or are unable to tolerate their initially prescribed medication.
This open-label, six-month study evaluated the efficacy and safety of rivastigmine in 382 AD patients who had previously failed to benefit from treatment with donepezil (80% due to lack of efficacy, 11% due to tolerability problems, 9% both reasons).
At the end of the study, 56.2% of patients were responders to rivastigmine, as assessed using a global function scale (the Clinicians' Global Impression of Change). Cognitive performance (measured by the Mini-Mental State Examination) and the ability to perform activities of daily living (measured by the Instrumental Activities of Daily Living scale) were improved/stabilised in 48.9% and 57.0% of patients, respectively. Rivastigmine was generally well tolerated, the most common adverse events being nausea and vomiting, consistent with reports from previous clinical studies. The occurrence of side-effects or lack of efficacy with donepezil treatment was not a predictor of similar problems when treated with rivastigmine.
Rivastigmine treatment appears to be beneficial in AD patients who have previously failed to benefit from, or were unable to tolerate treatment with, donepezil.
选择性乙酰胆碱酯酶（AChE）抑制剂和双重乙酰胆碱酯酶及丁酰胆碱酯酶抑制剂是目前唯一获批用于阿尔茨海默病（AD）症状性治疗的药物。多奈哌齐是一种特异性、可逆性AChE抑制剂，而卡巴拉汀是一种缓慢可逆（假不可逆）的双重胆碱酯酶（ChE）抑制剂，对大脑皮质和海马体具有脑区特异性。根据欧洲药品上市许可，应定期重新评估ChE抑制剂的临床获益，当不再有治疗效果证据时应考虑停药。然而，现有ChE抑制剂在药理和药代动力学特征上存在显著差异，这表明如果患者治疗无效、病情恶化或无法耐受最初开具的药物，在ChE抑制剂之间进行转换可能是可取的。
这项开放标签、为期6个月的研究评估了卡巴拉汀对382例先前使用多奈哌齐治疗无效的AD患者的疗效和安全性（80%是由于缺乏疗效，11%是由于耐受性问题，9%是由于这两个原因）。
在研究结束时，使用整体功能量表（临床医师总体印象变化量表）评估，56.2%的患者对卡巴拉汀有反应。分别有48.9%和57.0%的患者认知功能（通过简易精神状态检查表测量）和日常生活活动能力（通过日常生活活动工具性量表测量）得到改善/稳定。卡巴拉汀总体耐受性良好，最常见的不良事件是恶心和呕吐，与先前临床研究报告一致。多奈哌齐治疗出现副作用或缺乏疗效并不是使用卡巴拉汀治疗时出现类似问题的预测因素。
对于先前使用多奈哌齐治疗无效或无法耐受的AD患者，卡巴拉汀治疗似乎有益。
