Intervention Review

Memantine for dementia

  1. Rupert McShane1,*,
  2. Almudena Areosa Sastre2,
  3. Neda Minakaran3

Editorial Group: Cochrane Dementia and Cognitive Improvement Group

Published Online: 19 APR 2006

Assessed as up-to-date: 21 FEB 2006

DOI: 10.1002/14651858.CD003154.pub5

How to Cite

McShane R, Areosa Sastre A, Minakaran N. Memantine for dementia. Cochrane Database of Systematic Reviews 2006, Issue 2. Art. No.: CD003154. DOI: 10.1002/14651858.CD003154.pub5.

Author Information

  1. 1

    University of Oxford, Department of Psychiatry, Oxford, Oxfordshire, UK

  2. 2

    Madrid, Spain

  3. 3

    University of Oxford, Clinical Medical School, Oxford, Oxon, UK

*Rupert McShane, Department of Psychiatry, University of Oxford, John Radcliffe Hospital, Room 7611, Oxford, Oxfordshire, OX3 9DU, UK. rupert.mcshane@obmh.nhs.uk. Rupert.McShane@obmh.nhs.uk.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 19 APR 2006

SEARCH

 

Abstract

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

Background

Memantine, a low affinity antagonist to glutamate NMDA receptors, may prevent excitatory neurotoxicity in dementia.

Objectives

To determine efficacy and safety of memantine for people with Alzheimer's disease (AD), vascular (VD) and mixed dementia.

Search methods

The Specialized Register of the Cochrane Dementia and Cognitive Improvement Group was searched on 8 February 2006. This register contains references from all major healthcare databases and many ongoing trial databases and is updated regularly. In addition, the search engines Copernic and Google were used to identify unpublished trials through inspection of the websites of licensing bodies like the FDA , EMEA and NICE and of companies' websites (Lundbeck, Merz, Forest, Suntori etc) and clinical trials registries.

Selection criteria

Double-blind, parallel group, placebo-controlled, randomized trials of memantine in people with dementia.

Data collection and analysis

Data were pooled where possible. Intention-to-treat (ITT) and observed case (OC) analyses are reported.

Main results

1. Moderate to severe AD. Two out of three six month studies show a small beneficial effect of memantine. Pooled data indicate a beneficial effect at six months on cognition (2.97 points on the 100 point SIB, 95% CI 1.68 to 4.26, P < 0.00001), activities of daily living (1.27 points on the 54 point ADCS-ADLsev, 95% CI 0.44 to 2.09, P = 0.003) and behaviour (2.76 points on the 144 point NPI, 95% CI 0.88 to 4.63, P=0.004), supported by clinical impression of change (0.28 points on the 7 point CIBIC+, 95% CI 0.15 to 0.41, P < 0.0001).
2. Mild to moderate AD. Pooled data from three unpublished studies indicate a marginal benefical effect at six months on ITT cognition (0.99 points on the 70 point ADAS-Cog, 95% CI 0.21 to 1.78, P = 0.01) which was barely detectable clinically (0.13 CIBIC+ points, 95% CI 0.01 to 0.25, P = 0.03) but no effect on behaviour, activities of daily living or OC analysis of cognition.
3. Mild to moderate vascular dementia. Pooled data from two six month studies indicated a small beneficial effect of memantine on cognition (1.85 ADAS-Cog points, 95% CI 0.88 to 2.83, P = 0.0002), and behaviour (0.84 95% CI 0.06 to 0.91, P = 0.03) but this was not supported by clinical global measures.
4. Patients taking memantine were slightly less likely to develop agitation (134/1739, 7.7% versus 175/1873, 9.3% OR 0.78, 95% CI 0.61 to 0.99, P = 0.04). This effect was slightly larger, but still small, in moderate to severe AD (58/506 [12%] vs 88/499 [18%]; OR = 0.6, 95% CI 0.42 to 0.86, P = 0.005). There is no evidence either way about whether it has an effect on agitation which is already present.
5. Memantine is well tolerated.

Authors' conclusions

Memantine has a small beneficial effect at six months in moderate to severe AD. In patients with mild to moderate dementia, the small beneficial effect on cognition was not clinically detectable in those with vascular dementia and was detectable in those with AD. Memantine is well tolerated.

 

Plain language summary

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

Some evidence of efficacy of memantine for dementia

Memantine has a small beneficial, clinically detectable effect on cognitive function and functional decline measured at 6 months in patients with moderate to severe Alzheimer's Disease (AD). In patients with mild to moderate dementia, the small beneficial effect on cognition was not clinically detectable in those with vascular dementia and barely detectable in those with AD. It is well tolerated. Slightly fewer patients with moderate to severe AD taking memantine develop agitation, but there is no evidence either way about whether it has an effect on agitation which is already present.

 

摘要

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

背景

Memantine用於失智症

Memantine是一種對於麩胺酸NMDA受體(glutamate NMDA receptor)親和力低的拮抗劑,可能可以阻止失智症中刺激性神經毒害的現象。

目標

確認memantine對於患有阿茲海默症(Alzheimer disease; AD),血管型失智症(vascular; VD)及綜合型失智症的人們的效力及安全性。

搜尋策略

於2006年的2月8日搜尋The Specialized Register of the Cochrane Dementia and Cognitive Improvement Group。 這個文獻登錄處(register)包含了全部主要健康照護的資料庫以及許多建立中的試驗資料庫並且規律地更新。此外,使用搜尋引擎Copernic及Google,經由檢視頒發證明的機構,如美國食品及藥物管理局(FDA),歐洲醫藥品管理局(EMEA)及國際傳統藥物學大會(NICE)的網址以及公司的網址(如Lundbeck,Merz,Forest,Suntori等等)以及臨床試驗註冊平台以鑑別出未發表的試驗。

選擇標準

將memantine以雙盲、平行群組、安慰劑作對照,以及隨機方式對失智症人們進行的試驗。

資料收集與分析

儘我們所能將可蒐集到的資料彙整。分析其治療意向(intentiontotreat, ITT)及觀察病例(observed case, OC)並加以報告。

主要結論

1.中重度的患者,3個持續6個月的研究中,有2個顯示出memantine發揮小幅度的有益的療效。合併後的資料指出6個月時,對於以下項目具有效益: 認知(100 SIB點值上有2.97點,95% CI為1.68到4.26,P值小於0.00001)、日常生活活動功能(54點ADCSADLsev上有1.27點進步,95% CI 0.442.09,P = 0.003)及行為(144點NPI上有2.76點,95% CI 0.88到4.63,P = 0.004),這些是由臨床診斷加以支持(7點CIBIC+上有0.28點,95% CI 0.15到0.41,P <0.0001)。 2.輕至重度阿茲海默症的病患(Mild to moderate AD)。由三項未公布的研究匯聚的資料指出六個月時,在治療意向認知上的邊際利益效果(在70點ADASCog,95% CI 0.21到1.78,P值 = 0.01),幾乎無法在臨床上探測得到(0.13 CIBIC+點,95% CI 0.01到0.25,P值為0.03),但在日常生活或認知行為觀察病例的分析中,未獲得該治療在行為及活動上產生的效果。 3.輕至重度血管型失智症。兩項為期六個月的研究結果匯總後,指出在認知上(1.85 ADASCog點數,95% CI 0.88到2.83,P值為0.0002),以及在行為上(0.84 ADASCog點數,95% CI 0.06到0.91,P值為0.03)memantine有小量有益的影響,但這並未受到各臨床整體測量的支持。 4..使用memantine的病患較不會發生躁動(134/1739, 7.7%相對於175/1873, 9.3% 或是 0.78, 95% CI 0.61 到 0.99, P = 0.04)。這效果在中度到重度阿茲海默症病患較大一些,但總體來說,其效益仍算小(58/506 [12%] 相對於 88/499 [18%]; OR = 0.6, 95% CI 0.42 到 0.86, P = 0.005)。 兩者中並無證據顯示其中任一者是否在已出現的躁動中產生效果。 5. Memantine耐受性良好。

作者結論

對於中度到重度阿茲海默病患,Memantine於6個月時的效益小。輕至中度阿茲海默病患,該藥物在改善病患認知上的效益,於血管型失智症者臨床上無法偵測得到,而只能在阿茲海默症患者身上可以探得,而Memantine耐受性良好。

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

有一些證據證明Memantine對於失智症具有效益。Memantine對於失智症的小量效益,是臨床上可在認知功能偵測得到該效益的影響,並且在中度至重度阿茲海默症病患施用達6個月時,其影響力漸漸衰減。 對於輕至中度失智病患在血管型失智症患者身上無法探測到對於認知的療效;而在阿茲海默症患者身上則很少探測得到效益。 Memantine具有良好的耐受力。使用memntine的中度至重度阿茲海默症病患較少會發展成出現躁動的症狀,但對於已經出現躁動的病患,無證據顯示其具有影響的能力。