Bartorelli L, Giraldi C, Saccardo M, Cammarata S, Bottini G, Fasanaro A M, Trequattrini A
Geriatrics Unit, S. Eugenio Hospital, Rome, Italy.
Curr Med Res Opin. 2005 Nov;21(11):1809-18. doi: 10.1185/030079905X65655.
Cholinesterase (ChE) inhibitors are the only medications approved for the treatment of Alzheimer's disease (AD). The features of ChE inhibitors differ considerably. In addition to acetylcholinesterase (AChE) inhibition, rivastigmine also inhibits butrylcholinesterase (BuChE), providing dual AChE and BuChE inhibition. An observational study was performed to determine the response in routine clinical practice to switching AD patients to rivastigmine from a selective AChE inhibitor when that treatment no longer delivered a satisfactory clinical response.
A prospective, multicentre, 3-month observational trial in patients with mild to moderately severe AD (adjusted Mini Mental State Examination [MMSE] score 10-26) deteriorating (at least 2 adjusted MMSE points in last 6 months) on selective AChE inhibitor treatment. Adjusted MMSE, activities of daily living (ADL) and instrumental activities of daily living (IADL), the Zarit caregiver burden and global function (short Clinical Global Impression of Change, CGIC) scores were noted before the switch and 3 months after the switch.
225 patients entered the study. The switches made were from donepezil to rivastigmine in (D-R) in 188 patients, galantamine to rivastigmine (G-R) in 33 patients and donepezil to galantamine (D-G) in four patients. Ten patients discontinued due to adverse events and eight for other reasons. More than half of the switches were within 36 hours of a patient's first treatment visit. In the D-R and G-R groups, 67.7% and 66.7% of patients responded (CGIC score < or = 4), respectively. In non-responders, worsening (CGIC score 5-7) was mild in approximately 80% or more of patients. Adjusted MMSE improved after the switch from both donepezil and galantamine to rivastigmine (+0.69 +/- 3.2, p = 0.008 and +0.6 +/- 1.6, p = 0.05, respectively). Mean ADL, IADL, and Zarit scores remained stable. The proportion of patients on concomitant antipsychotic therapy diminished by 30.5% and benzodiazepines were discontinued in all patients, except one.
AD patients deteriorating on selective AChE inhibitor treatment can benefit from switching to a dual AChE-BuChE inhibitor, such as rivastigmine, in terms of stabilization of disease, improvement in cognitive function and reduction in the burden of concomitant psychoactive treatment. The switch was well tolerated. Confirmation of these results is required in a controlled study.
胆碱酯酶（ChE）抑制剂是唯一被批准用于治疗阿尔茨海默病（AD）的药物。ChE抑制剂的特性差异很大。除抑制乙酰胆碱酯酶（AChE）外，卡巴拉汀还抑制丁酰胆碱酯酶（BuChE），实现对AChE和BuChE的双重抑制。本观察性研究旨在确定在常规临床实践中，当选择性AChE抑制剂治疗不再产生令人满意的临床反应时，将AD患者换用卡巴拉汀后的反应情况。
一项针对轻度至中度重度AD患者（简易精神状态检查表[MMSE]校正评分10 - 26）的前瞻性、多中心、为期3个月的观察性试验，这些患者在接受选择性AChE抑制剂治疗时病情恶化（过去6个月内MMSE校正评分至少下降2分）。记录换药前及换药后3个月时的MMSE校正评分、日常生活活动能力（ADL）和工具性日常生活活动能力（IADL）、扎里特照料者负担以及整体功能（临床总体印象变化量表简表，CGIC）评分。
225例患者进入研究。其中188例患者从多奈哌齐换用卡巴拉汀（D - R），33例患者从加兰他敏换用卡巴拉汀（G - R），4例患者从多奈哌齐换用加兰他敏（D - G）。10例患者因不良事件停药，8例因其他原因停药。超过半数患者在首次就诊治疗的36小时内完成换药。在D - R组和G - R组中，分别有67.7%和66.7%的患者有反应（CGIC评分≤4）。在无反应者中，约80%或更多患者病情恶化程度较轻（CGIC评分5 - 7）。从多奈哌齐和加兰他敏换用卡巴拉汀后，MMSE校正评分均有所改善（分别为+0.69±3.2，p = 0.008和+0.6±1.6，p = 0.05）。ADL、IADL及扎里特评分的均值保持稳定。接受联合抗精神病药物治疗的患者比例减少了30.5%，除1例患者外，所有患者均停用了苯二氮䓬类药物。
在选择性AChE抑制剂治疗中病情恶化的AD患者，换用如卡巴拉汀这种双重AChE - BuChE抑制剂，在疾病稳定、认知功能改善及减轻联合精神活性药物治疗负担方面可能有益。换药耐受性良好。这些结果需要在对照研究中得到证实。
