Intervention Review

Indomethacin for Alzheimer's disease

  1. Naji Tabet1,*,
  2. Howard Feldman2

Editorial Group: Cochrane Dementia and Cognitive Improvement Group

Published Online: 22 APR 2002

Assessed as up-to-date: 5 MAY 2008

DOI: 10.1002/14651858.CD003673


How to Cite

Tabet N, Feldman H. Indomethacin for Alzheimer's disease. Cochrane Database of Systematic Reviews 2002, Issue 2. Art. No.: CD003673. DOI: 10.1002/14651858.CD003673.

Author Information

  1. 1

    University of Brighton, Postgraduate Medical School, Brighton, UK

  2. 2

    Vancouver Hospital and Health Sciences Center, UBC Division of Neurology, Vancouver, British Columbia, Canada

*Naji Tabet, Postgraduate Medical School, University of Brighton, Falmer, Brighton, BN1 9PH, UK. N.T.Tabet@bton.ac.uk.

Publication History

  1. Publication Status: Stable (no update expected for reasons given in 'What's new')
  2. Published Online: 22 APR 2002

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Abstract

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要
  5. Laički sažetak

Background

Inflammatory processes involving cytokines, prostaglandins, free radicals and glial cells have been implicated in the pathogenesis of Alzheimer's disease. Non-steroidal anti-inflammatory drugs such as indomethacin attenuate inflammatory reactions. Hence, there may be a role for some of these drugs in the treatment of Alzheimer's disease.

Objectives

To examine the efficacy of indomethacin in the treatment of patients suffering from Alzheimer's disease.

Search methods

The trials were identified from a search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group (which contains records from many different medical and trials databases) on 14 April 2004 using the terms "indomethacin", "indome*" and "NSAIDS". In addition two independent reviewers systematically searched relevant computerized databases and Internet sites. This was supplemented by hand searching and additional references sought from selected papers.

Selection criteria

Single or multi-centre placebo-controlled randomized trials examining the efficacy of indomethacin in patients diagnosed with Alzheimer's disease were eligible for selection for this review. Using a standard extraction form, inclusion/exclusion criteria were set to ensure design quality and lack of bias of all trials included.

Data collection and analysis

Data were collected independently by two reviewers and any discrepancies were subject to discussion. Corresponding authors were contacted for any missing data needed for statistical analysis.

Main results

Only one study was selected for this review (Rogers 1993). We detected no statistically significant difference between indomethacin treatment and placebo for the individual cognitive tests: Mini Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale ( ADAS), Boston Naming Test (BNT) and Token Test (TK). Dropouts and death rate were the only reported results that were amenable to evaluation. The dropout rate was higher in the indomethacin group (10/24) than in the control group (6/20). Gastrointestinal adverse events were more prevalent in the treatment group (5/24 compared with 1/20 in control group). There was no statistically significant difference in death rate between the two groups (p=0.9).

Authors' conclusions

On the basis of this one trial and subsequent analysis of data as reported by the authors, indomethacin cannot be recommended for the treatment of mild to moderate severity Alzheimer's disease. At doses of 100-150 mg daily, serious side effects will limit its use.

 

Plain language summary

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要
  5. Laički sažetak

No evidence for efficacy and safety of indomethacin for treatment of mild to moderate Alzheimer's disease

Extensive evidence implicates inflammatory processes in the pathogenesis of Alzheimer's disease. Non-steroidal anti-inflammatory drugs such as indomethacin have been proposed for the treatment of patients with Alzheimer's disease. Only one study met criteria for inclusion. In this one selected trial, authors did not carry out statistical analyses on the absolute change from baseline, but on the percentage change from the baseline score. Taking into account the difficulties in evaluating a single trial, at present there is no indication for treatment of mild to moderate Alzheimer's disease with indomethacin.

 

摘要

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要
  5. Laički sažetak

背景

Indomethacin用於阿茲海默症

阿茲海默症可能的發病原因包含由遺傳細胞質分裂、前列腺素,自由基和細胞神經膠質引起的發炎反應。 非類固醇的抗發炎藥如indomethacin可使發炎反應減弱。因此,這些藥對於阿茲海默症可能具有療效。

目標

本研究的主要目的在於評估使用indomethacin治療阿茲海默症引起疼痛的功效。

搜尋策略

於2004年8月14日,以"indomethacin"、"indome*" 及"NSAIDS"關鍵字搜尋Specialized Register of the Cochrane Dementia and Cognitive Improvement Group (which contains records from many different medical and trials databases)以找出試驗。 此外,2位獨立作者系統性的搜尋相關的電子資料庫以及網站。此外並進行人工搜尋以及所找到的文章的參考文獻加以補充。

選擇標準

以下試驗合乎本文獻回顧的選擇標準: 採用單中心或是多中心的安慰劑對照隨機試驗,驗證indomethacin用於診斷為阿茲海默症病患的療效。 採用標準的摘錄表格、並設置納入及排除標準,以確保所納入試驗的研究設計品質以及減少偏誤。

資料收集與分析

由兩位研究者各別收集數據,若有任何不同即進行的討論;此外並與通訊作者連絡,以取得進行統計分析所需的遺漏數據。

主要結論

只有1個試驗符合本回顧的納入標準(Rogers 1993),我們發現以indomethancin和安慰劑進行個別認知試驗中:小型精神狀態測驗 (MMSE)、阿茲海默症評估等級(ADAS)、波士頓命名試驗(BNT) 和東京試驗 (TK)兩者之間沒有顯著差異。 退出比率與死亡率是報告的數據中惟一可以進行分析的。indomethacin(10/24)組相較於安慰劑組(6/20)具有很高的退出率。而治療組出現腸胃道不良反應的情形也高於對照組(5/24 v.s 1/20)。而這兩組間的死亡率則沒有顯著差異(p = 0.9)。

作者結論

作者認為根據這一個試驗及其後續數據分析,不建議以indomethacin治療輕度∼重度阿茲海默症患者。若劑量達到每天100 – 150 mg,則indomethacin嚴重的副作用將會限制它的使用。

翻譯人

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

沒有證據証明indomethacin 治療由輕度∼重度的阿茲海默氏症患者的功效跟安全性。 許多證據顯示發炎反應為阿茲海默症致病機轉,非類固醇抗發炎藥物如indomethacin以被建議用於治療阿茲海默症患者。 在本回顧當中只有一個研究符合納入標準,在該研究當中作者並未進行臨床重要結果的統計分析,只有計算臨床重要結果變化的百分比。由於只分析一個試驗會有些困難,因此目前並沒有輕度∼中度阿茲海默症病患使用indomethacin的指示。

 

Laički sažetak

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要
  5. Laički sažetak

Nema dokaza o djelotvornosti i sigurnosti indometacina u liječenju blage do umjerene Alzheimerove bolesti

Opsežni dokazi ukazuju da u razvoju Alzheimerove bolesti imaju ulogu upalni procesi. Za liječenje bolesnika s Alzheimerovom bolešću predloženi su nesteroidni protuupalni lijekovi kao što je indometacin. Samo je jedna studija ispunila kriterije za uključivanje u ovaj Cochrane sustavni pregled. U tom jednom istraživanju autori nisu proveli statističke analize za apsolutnu promjenu od početne vrijednosti, nego za postotak promjene od početnog rezultata. Uzimajući u obzir poteškoće pri procjeni jednog istraživanja, trenutno nema indikacije za liječenje blage do umjerene Alzheimerove bolesti indometacinom.

Bilješke prijevoda

Cochrane Hrvatska
Prevela: Katarina Vučić
Ovaj sažetak preveden je u okviru volonterskog projekta prevođenja Cochrane sažetaka. Uključite se u projekt i pomozite nam u prevođenju brojnih preostalih Cochrane sažetaka koji su još uvijek dostupni samo na engleskom jeziku. Kontakt: cochrane_croatia@mefst.hr