以統合分析法比較治療阿茲海默症藥物Donepezil、Rivastigmine之成效與副作用

研究背景：由於醫療水準的提高，人類平均壽命延長許多；老化幾乎是每個人無法避免的事實。目前人口老化亦是全球化的現象，隨之而來的是慢性疾病的增加。目前治療阿茲海默症的認知缺損方面的藥物包括了Donepezil（Aricept®愛憶欣膜衣錠）、Rivastigmine（Exelon®憶思能膠囊）、Galantamine（Reminyl®利憶靈持續藥效膠囊）等。我國老年人口已從 2016年9月65歲以上老人約305萬人持續增加中，其中輕微認知障礙(Mild cognitive impairment, MCI)有563,147人，佔18.45%；失智症人口有243,430 人，佔7.98% (包括極輕度失智症98,747人，佔3.24%，輕度以上失智症有144,683人，佔4.74%)。也就是說65歲以上的老人每13人即有1位失智者，而80歲以上的老人則每5人即有1位失智者，預估於2060年將增加失智人口327萬人。目前全球有約1500萬人罹患阿茲海默症，預估至2030年，患者人數將暴增至7500萬人。研究目的：探討治療阿茲海默症藥物Donepezil（Aricept®愛憶欣膜衣錠）、Rivastigmine（Exelon®憶思能膠囊）此兩種對於病患減緩病情之成效及患者對藥物所產生的副作用，以提供臨床人員於用藥前參考。本研究未放入galantamine（Reminyl®利憶靈持續藥效膠囊），因此種藥物的學術研究及臨床實驗數據不足，固未放入。研究方法：本研究採用實證醫學的文獻搜尋法，利用線上的實證醫學資料庫 The Cochrane Library、PubMed、Medline等搜尋，經過文獻評讀後，篩選適當的文獻資料，以統合分析軟體RevMan5.3加以分析並得出結果。本篇所納入的範圍在年齡65歲以上(包含65歲)的老人，並單獨使用Donepezil或Rivastigmine兩種藥物，於服用藥物30週後使用MMSE問卷作測驗之老人。研究結果：本研究最後共納入7個隨機對照試驗之個別研究提供的結果，為病患使用藥物後所產生的副作用分析；並在7文獻中找出4篇與成效相關的臨床研究做為病患使用藥物後是否有減緩病情之成效(另外3篇不符合納入標準)。運用統合分析軟體RevMan5.3軟體得出統計結果。病患使用藥物後所產生的副作用分析，由收錄的7篇文獻樣本總計，Donepezil共納入940個研究，Rivastigmine共納入433個研究；病患使用藥物後是否有減緩病情之成效，在符合研究中的4篇文獻總計，Donepezil共納入734個研究，Rivastigmine共納入466個研究。使用統計軟體分析Rivastigmine及Donepezil的成效，得出森林圖結果(見圖4.1.1)。文獻結果以異質性檢定分析，顯示無異質性(p=0.17)，I2=40%，所得出的固定模式結果為0.32(95%CI -0.43,-0.20)，森林圖分析結果顯示，菱形圖並未跨過無效中線1。藥物組別上顯示在單獨使用Rivastigmine，成效上優於Donepezil。副作用之比較上，兩種藥物比較也是有差異性的，文獻中找出使用藥物後有副作用之患者Donepezil人數為940人有297人有副作用產生，Rivastigmine人數為433人有87人有副作用產生，兩種藥物共計1,383人納入研究)，結果顯示在異質性檢定方面P=0.02，I2=62%，具有異質性，所以採用隨機模式，P=0.79，I2=29%，結果為(RD,0.79；95%CI,0.41,1.27)，森林圖分析後最終結果顯示Rivastigmine藥物的平均值大於Donepezil藥物0.03標準差，Rivastigmine藥物對於阿茲海默症患者於副作用上較顯著性的影響，所以Donepezil副作用小於Rivastigmine。統合分析發現，Donepezil 10mg 的NNT為11，Rivastigmine 6mg的NNT為5；由高劑量的NNT可看出Rivastigmine 6mg 對於治療阿茲海默症(Alzheimer’s Disease)患者所產生的成效高於Donepezil 10mg；Rivastigmine 6mg 對於治療阿茲海默症(Alzheimer’s Disease)患者所產生的副作用高於Donepezil 10mg。結論：本研究顯示在治療阿茲海默症用藥時，發現Donepezil的成效低於Rivastigmine，Rivastigmine的副作用高於Donepezil；本研究建議治療阿茲海默症患者時，可優先使用Rivastigmine治療，以提供患者較佳的療效，由於Rivastigmine的副作用高，請臨床醫護人員對於病患及病患家屬多加衛教。

關鍵字

統合分析；阿茲海默症； Mata Analysis ； Donepezil ； Rivastigmine ； Alzheimer's disease

並列摘要

Research background: due to the improvement of medical standards, the average life expectancy of many people; aging is almost everyone can not avoid the fact. The current population aging is also a phenomenon of globalization, followed by the increase in chronic diseases. Drugs for cognitive deficits in the treatment of Alzheimer's disease include Donepezil, Rivastigmine, Galantamine, and the like (Reminyl®). There were 563,147 persons (18.45%) of the Mild cognitive impairment (MCI) in the elderly population aged over 65 in September 2016, and there were 243,430 people, accounting for 7.98 % (Including 98,747 persons with mild disability, accounting for 3.24%, and 144,683 or 4.74% of patients with mild orphrodisiac disorder). That is more than 65 years old for every 13 people that have a deaf who, while the elderly over the age of 80 every 5 people that there is a dementia, estimated in 2060 will increase the mentally handicapped population of 3.27 million people. At present, about 15 million people worldwide suffer from Alzheimer's disease, estimated to 2030, the number of patients will surge to 75 million people. Objective: To investigate the effects of these two drugs on the side effects of patients treated with Donepezil and Rivastigmine inorder to provide clinical reference before treatment. Methods: This study was used Evidence-based medicine. The literature search method, the use of online empirical medicine database The Cochrane Library, PubMed, Medline search, after the literature review, the appropriate screening of the literature to analyze the software RevMan5.3 to be analyzed and the results. This article is included in the elderly over 65 years of age (including 65 years old), and the use of Donepezil or Rivastigmine alone drugs, 30 weeks after taking the use of MMSE questionnaire for the elderly. Results: At the end of this study, a total of seven randomized controlled trials were included in the results of individual studies, and the side effects were analyzed for the use of the drug in the patient. Four clinical trials related to efficacy were identified in the literature as patient use Whether the slowness of the disease after the results (the other three do not meet the inclusion criteria). use Meta-analysis software RevMan5.3 software to obtain statistical results. The results of the side effects of the drug after the use of the drug were analyzed by a total of 940 samples from Donepezil, 433 studies of Rivastigmine, and whether the patient had slowed the disease after using the drug. Of the total of four literatures, Donepezil were included in 734 studies, Rivastigmine included a total of 466 studies. Using the statistical software to analyze the results of Rivastigmine and Donepezil, the results of the forest map are obtained (Figure 4.1.1). The results of the literature showed heterogeneity (p = 0.17), I2 = 40%, and the result of the fixed pattern was 0.32 (95% CI -0.43, -0.20). The results of the forest map showed that the diamond Does not cross invalid midline 1. The drug group was shown to be superior to Donepezil alone in the use of Rivastigmine. Side effects of the comparison, the two drugs are also different, the literature to find the side effects of patients with drugs Donepezil number 940 people have 297 people have side effects, Rivastigmine number of 433 people have 87 side effects, the results showed that P = 0.02, I2 = 62%, heterogeneity in heterogeneity test, so the random pattern was P = 0.79, I2 = 29%, and the result was (RD, 0.79; 95% CI, 0.41, 1.27). The final result of the forest map analysis showed that the mean value of Rivastigmine was greater than the standard deviation of Donepezil drug 0.03, and Rivastigmine had a significant effect on side effects in patients with Alzheimer's disease, so Donepezil side effects Less than Rivastigmine. The analysis showed that Donepezil 10mg NNT was 11, Rivastigmine 6mg NNT was 5; from high dose of NNT can be seen Rivastigmine 6mg for the treatment of Alzheimer's disease (Alzheimer's Disease) patients produced more than Donepezil 10mg; Rivastigmine 6mg for the treatment of Alzheimer's disease (Alzheimer's Disease) patients produced side effects than Donepezil 10mg. Conclusions: This study showed that Donepezil had lower efficacy than Rivastigmine and Rivastigmine than Donepezil in the treatment of Alzheimer's disease. This study suggests that patients with Alzheimer's disease can be treated with Rivastigmine in order to provide patients with more Good efficacy, due to the high side effects of Rivastigmine, please clinical staff for patients and patients with family members more health education.