Galantamine for Alzheimer's disease and mild cognitive impairment

  • Review
  • Intervention




Galantamine is a specific, competitive, and reversible acetylcholinesterase inhibitor.


To assess the clinical effects of galantamine in patients with mild cognitive impairment (MCI), probable or possible Alzheimer's disease (AD), and potential moderators of effect.

Search methods

The trials were identified from a search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group, last updated on 25 April 2005 using the terms galanthamin*, galantamin* and Reminyl. Published reviews were inspected for further sources. Additional information was collected from unpublished clinical research reports for galantamine obtained from Janssen and from

Selection criteria

Trials selected were randomised, double-blind, parallel-group comparisons of galantamine with placebo for a treatment duration of greater than 4 weeks in subjects with MCI or AD.

Data collection and analysis

Data were extracted independently by the reviewers and pooled where appropriate and possible. Outcomes of interest include the clinical global impression of change (CIBIC-plus or CGIC), Alzheimer's Disease Assessment Scale-cognitive sub scale (ADAS-cog), Alzheimer's Disease Cooperative Study/Activities of Daily Living (ADCS-ADL), Disability Assessment for Dementia scale (DAD) and Neuropsychiatric Inventory (NPI). Potential moderating variables of treatment effect assessed included trial duration, dose, and diagnosis of possible versus probable Alzheimer's disease.

Main results

Ten trials with a total 6805 subjects were included in the analysis.
Treatment with galantamine led to a significantly greater proportion of subjects with improved or unchanged global rating scale rating (k = 8 studies), at all dosing levels except for 8 mg/d . Confidence intervals for the ORs overlapped across the dose range of 16 mg to 36 mg per day, with point estimates of 1.6 - 1.8 when analysed with the intention-to-treat sample.
Treatment with galantamine also led to significantly greater reduction in ADAS-cog score at all dosing levels (k = 8), with greater effect over six months compared to three months. Confidence intervals again overlapped. Point estimate of effect was lower for 8 mg/d but similar for 16 mg to 36 mg per day. For example, treatment effect for 24 mg/d over six months was 3.1 point reduction in ADAS-cog (95%CI 2.6-3.7, k = 4, ITT).
ADCS-ADL, DAD and NPI were reported only in a small proportion of trials: all showed significant treatment effect in some individual trials at least. Confidence interval of treatment effect for the one trial recruiting patients with possible AD overlapped with the other seven recruiting patients with probable AD. Galantamine's adverse effects appeared similar to those of other cholinesterase inhibitors and to be dose related.
Prolong release / once daily formulation of galantamine at 16 - 24mg/d was found to have similar efficacy and side-effect profile as the equivalent twice-daily regime.
Data from the two MCI trials suggest marginal clinical benefit, but a yet unexplained excess in death rate.

Authors' conclusions

Subjects in these trials were similar to those seen in earlier anti dementia AD trials, consisting primarily of mildly to moderately impaired outpatients. Galantamine's effect on more severely impaired subjects has not yet been assessed.
Nevertheless, this review shows consistent positive effects for galantamine for trials of three to six months' duration. Although there was not a statistically significant dose-response effect, doses above 8 mg/d were, for the most part, consistently statistically significant.
Galantamine's safety profile in AD is similar to that of other cholinesterase inhibitors with respect to cholinergically mediated gastrointestinal symptoms. It appears that doses of 16 mg/d were best tolerated in the single trial where medication was titrated over a four week period, and because this dose showed statistically indistinguishable efficacy with higher doses, it is probably most preferable initially. Longer term use of galantamine has not been assessed in a controlled fashion.
Galantamine use in MCI is not recommended due to its association with an excess death rate.








在2005年4月25日搜尋最新更新的Specialized Register of the Cochrane Dementia and Cognitive Improvement Group資料庫,利用「galanthamin*, galantamin* 和 Reminyl」關鍵字進行檢索,已發表的評論性文章也進行審視。未公開的臨床研究報告則從Janssen和獲得。




數據由審查者獨立進行擷取並盡可能將其彙整。有興趣的治療結果包含clinical global impression of change (CIBICplus 或 CGIC), Alzheimer's Disease Assessment Scalecognitive sub scale (ADAScog), Alzheimer's Disease Cooperative Study/Activities of Daily Living (ADCSADL), Disability Assessment for Dementia scale (DAD) and Neuropsychiatric Inventory (NPI)。並且評估治療效果的變異因素包括試驗的長短、劑量和阿茲海默症possible或probable的診斷。


10個試驗包含有6805位受試者被納入分析。除了每日服用8毫克的組別之外,接受galantamine治療的患者,對於global rating scale rating是有改善或不變的(k = 8 組)。ORs的信心區間與服藥劑量範圍介於每日使用16 毫克到36毫克一致,當分析以意圖分析時其值在1.61.8。不管任何劑量(k = 8),使用galantamine治療對於ADAScog評量結果會產生明顯的下降,治療6個月比三個月有更好的結果。 信心區間也是重疊的。使用8 mg galantamine的患者效果較差但是每日使用16 mg到36 mg galantamine的患者效果相同。例如,每日以24 mg治療超過六個月ADAScog結果會下降3.1點(95%信心區間 2.63.7, k = 4, ITT)。只有少數試驗提出關於ADCSADL, DAD 和 NPI的結果,但至少這些試驗都顯是有治療的效果。有1個試驗納入possible AD患者進行研究,治療效果的信心區間與其他7個納入proableAD患者的試驗是相近的。使用Galantamine所引發的不良事件與其他膽鹼酯?抑制劑相似而且也與劑量有關。每天一次、緩釋型的16 – 24mg/d Galantamine與每日二次的劑型有相同的療效及副作用。2個有關MCI的試驗顯示galantamine一些療效,但確有較高的死亡率。


這些試驗的受試者類似其他針對早期失智阿茲海默症治療的試驗,納入輕度到中度的門診病人。有關Galantamine使用在更嚴重的病患上的療效還未被評估。不過,從三到六個月的試驗顯示galantamine是有療效的。在統計上劑量對治療並沒有差別,只要Galantamine每天劑量大於8mg在統計上都有療效。Galantamine的安全性與其他膽鹼酯?抑制劑藥物類似,大多是有關於膽鹼引起的胃腸症狀。在單一試驗中顯示在四個星期中緩慢增加劑量至每日16 mg有較好的耐受性,而且這個劑量與高劑量在統計上療效是相同的。長期使用galantamine的療效還未被評估。Galantamine使用於MCI並不被推薦因為有較高的死亡率。


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


每天16 mg或更高劑量的Galantamine可以改善輕度到中度的阿茲海默氏症的整體症狀和認知功能達六個月。阿茲海默氏症是漸進性神經退化疾病,他會影響思想跟記性。Galantamine是個可逆的膽鹼酯?抑制劑,其會減少神經傳導物質乙醯膽鹼的分解,另外他也會作用在菸鹼接受器。此回顧發現與安慰劑相比galantamine可以改善認知功能。在三個月到六個月之後,患者使用galntamine比起安慰劑有高比例改善或維持目前的認知功能。也有證據顯示可以改善measures of activities of daily living and behavioral symptoms。長期controlled的試驗還沒完成或公開。從兩個MCI試驗顯示galantamine有些許療效但會增加死亡率。








galanthamin*、galantamin*およびレミニルを検索用語に用いて、2005年4月25日に最終更新を行ったCochrane Dementia and Cognitive Improvement Groupの Specialized Registerを検索し、試験を同定した。さらに情報源を得るため、過去に発表されたレビューを調査した。Janssen社およびから入手したガランタミンに関する未発表の臨床研究報告から、追加情報を収集した。






総数6805名の被験者を対象とした10件の試験を解析に含めた。8 mg/日以外のすべての用量レベルにおいて、ガランタミンによる治療を受けた被験者では、全般的評点尺度が改善した、または変化しなかった人の割合が有意に高かった(k=試験8件)。ORsの信頼区間は16~36 mg/日の用量範囲で重なり合っており、ITT対象の解析による点推定値は1.6~1.8であった。いずれの用量レベルでもガランタミンによる治療を受けた被験者は、ADAS-cogスコアの減少が有意に大きく(k=8)、3ヵ月後よりも6カ月後に効果が大きかった。この場合も、信頼区間が重なり合っていた。8 mg/日では効果の点推定値が低かったが、16~36 mg/日では同程度であった。たとえば、24 mg/日を6カ月間投与した場合では、ADAS-cogスコアが3.1ポイント減少するという治療効果が認められた(95%CI 2.6~3.7、k=4、ITT)。ADCS-ADL、DADおよびNPIが報告されていた試験は少数であり、少なくとも一部の試験では、これらの指標にはいずれも有意な治療効果が認められた。ADの可能性が考えられる患者を採用した1件の試験に観察された治療効果の信頼区間は、ADの可能性が高い患者を採用した7件の試験と重なり合っていた。ガランタミンの有害作用は他のコリンエステラーゼ阻害薬と近く、用量に関連するようであった。ガランタミンの徐放性/1日1回投与製剤は、16~24 mg/日の用量範囲では、有効性および副作用プロファイルが1日2回投与レジメンと類似していることが見い出された。2件のMCI試験からのデータは、臨床的利益はわずかにあるが、死亡率の原因の説明できない上昇も示唆している。


これらの試験の被験者は、主に軽症から中等症の外来患者を対象とした初期の抗痴呆AD試験の被験者と類似していた。重症度の高い被験者に対するガランタミンの効果は未だ評価されていない。しかし、本レビューにより、試験期間が3~6カ月間の試験ではガランタミンに肯定的効果があることが一貫して示された。統計的に有意な用量反応効果は認められなかったが、8 mg/日を超える用量では、試験期間の大半の部分で一貫して統計的に有意であった。


監  訳: 2006.6.23

実施組織: 厚生労働省委託事業によりMindsが実施した。

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Plain language summary

Galantamine improves global and cognitive symptoms at doses of 16 mg/day or greater, in people with mild to moderate Alzheimer's disease, for at least 6 months

Alzheimer's disease is a progressive neurodegenerative illness, affecting thinking and memory. Galantamine is a reversible cholinesterase inhibitor that inhibits the degradation of the neurotransmitter acetylcholine, and may have other actions on nicotinic receptors as well. The review finds that galantamine was more effective than placebo in improving cognitive function. A greater proportion of people taking galantamine than of those taking placebo was rated as improved or not changed after three to six months. There was evidence of improvement on measures of activities of daily living and behavioral symptoms. Longer-term controlled studies have yet to be performed or published.

Data from the two MCI trials suggest marginal clinical benefit, but a yet unexplained excess in death rate.

Laički sažetak

Galantamin poboljšava opće i kognitivne simptome u osoba s blagom do umjerenom Alzheimerovom bolesti, u dozama od 16 mg/dan ili višima tijekom najmanje 6 mjeseci

Alzheimerova bolest je progresivna neurodegenerativna bolest koja pogađa razmišljanje i pamćenje. Galantamin je reverzibilni inhibitor kolinesteraze koji inhibira razgradnju neurotransmitera acetilkolina, a može imati i druga djelovanja na nikotinskim receptorima. Zaključaj je ovog Cochrane sustavnog pregleda da je galantamin bio učinkovitiji od placeba u poboljšanju kognitivne funkcije. Veći udio osoba koje su uzimale galantamin od onih koje su uzimale placebo je ocijenjen kao poboljšan ili nepromijenjen nakon tri do šest mjeseci. Bilo je dokaza poboljšanja u mjerama aktivnosti u svakodnevnom životu i simptomima ponašanja. Dugoročnije kontrolirane studije tek trebaju biti provedene ili objavljene.

Podaci iz dva istraživanja blagog kognitivnog oštećenja ukazuju na graničnu kliničku korist, ali ipak i neobjašnjenu veću stopu smrti.

Bilješke prijevoda

Cochrane Hrvatska
Prevela: Katarina Vučić
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