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D-cycloserine for Alzheimer's disease

  • Review
  • Intervention

Authors


Abstract

Background

Evidence supports a role for NMDA receptors in learning and memory. These can be modulated by the antibiotic D-cycloserine in such a way that the effect of the excitatory transmitter substance glutamate is enhanced. A study on healthy subjects pretreated with scopolamine to mimic Alzheimer's disease showed a positive effect of D-cycloserine at low doses.

Objectives

To assess the efficacy and safety of D-cycloserine in patients with Alzheimer's disease.

Search methods

The trials were identified from a search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 2 January 2004 using the terms: cycloserine, D-cycloserine. The Register contains records from all major health care databases and is updated regularly.

Selection criteria

Randomized, double-blinded and unconfounded trials comparing D-cycloserine with a control treatment.

Data collection and analysis

Two larger and two smaller randomized controlled trials were identified. The Clinical Global Impression scale was used in all studies and was a primary outcome measure.

Main results

It was not possible to extract the results from the first phases of the two crossover studies and therefore the meta-analyses are based on the two parallel group 6-month studies. There was no indication of a positive effect favouring D-cycloserine for the numbers showing improvement at 6 months as assessed by the Clinical Global Impression for any dose. The number of withdrawals for any reason before end of treatment at 6 months was significantly in favour of placebo (fewer withdrawals) compared with D-cycloserine for dose levels of 30 mg/day (OR 2.94, 95% CI 1.52, 5.70) and 100 mg/day (OR 3.23, 95% CI 1.67, 6.25). There was no significant difference between treatment, (2, 10, 30, 100, or 200 mg/day) and placebo for the number of withdrawals due to adverse events by six months.

Authors' conclusions

The lack of a positive effect of D-cycloserine on cognitive outcomes in controlled clinical trials with statistical power high enough to detect a clinically meaningful effect means that D-cycloserine has no place in the treatment of patients with Alzheimer's disease.

摘要

背景

蘭絲菌素(Dcycloserine)使用於阿茲海默症

證據證實NMDA受體對學習跟記憶扮演一些角色。這些NMDA受體可以被抗菌的蘭絲菌素調節經由此過程可以增加刺激性傳遞物質麩胺酸的功效。一個針對健康受試者使用scopolamine用以模擬阿茲海默症的試驗中顯示Dcycloserine在低劑量是有療效的。

目標

本研究的主要目的在於評估使用蘭絲菌素對阿茲海默症病人進行治療的功效性和安全性。

搜尋策略

在2004年1月2號針對Specialized Register of the Cochrane Dementia and Cognitive Improvement Grou資料庫進行檢索以確認可以納入本研究的試驗,檢索關鍵字包括:cycloserine, Dcycloserin。這個資料庫包含記錄所有主要健康保健資料庫和並且有進行定期的更新。

選擇標準

比較蘭絲菌素和控制組的隨機,雙盲和無干擾試驗都可以被納入本研究中。

資料收集與分析

有2個大型跟2個小型隨機對照組試驗被確認,所有試驗都使用臨床整體印象評量表(Clinical Global Impression scale)作為主要治療成果的判斷依據。

主要結論

目前不太能由2個交叉試驗的第一階段獲得結果,因此必須根據兩個平行組的六個月試驗進行統合分析,這裡沒有正向的暗示說明使用任何劑量蘭絲菌素對於臨床整體印象評估在六個月可以出現改進。因為任何原因在進行治療6個月結束前停藥的人數顯示安慰劑與蘭絲菌素組相比有較好的耐受性(因為較少患者停藥),其中包含劑量濃度每日30 mg(OR 2.94, 95% 信心區間 1.52, 5.70)和每日100 mg(OR 3.23, 95% 信心區間 1.67, 6.25)。在6個月試驗中,使用安慰劑和治療組(2, 10, 30, 100, 或200 mg/day)相比,因為不良試驗所引發的停藥現象並沒有顯著差異。

作者結論

由具有的高統計效力足以檢測臨床上重要意義的對照性臨床試驗中,並沒有獲得蘭絲菌素對於認知治療結果的正面影響數據,意味著蘭絲菌素在任何方面都不能去治療阿茲海默症的病人。

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

蘭絲菌素在治療阿茲海默症病人沒有功效性和安全性的證據,蘭絲菌素是一個用途廣泛的抗菌素,以前都使用高劑量(5001000 mg / day)在治療結核病(TB),曾經被認為蘭絲菌素可能可以改善記憶力和其他認知功能,而這可能透過NmethylDaspartate (NMDA)受體達成想要的功效。從蘭絲菌素使用在阿茲海默症的兩個納入交叉試驗的第一階段不可能去摘取結果因此分析方法需根據納入的兩個平行組的六個月試驗進行統合分析,由具有的高統計效力足以檢測臨床上重要意義的對照性臨床試驗中,並沒有獲得蘭絲菌素對於認知治療結果的正面影響數據,意味著蘭絲菌素在任何方面都無法治療阿茲海默症的病人。

Plain language summary

No evidence of the efficacy and safety of D-cycloserine in the treatment of patients with Alzheimer's disease

D-cycloserine is a broad-spectrum antibiotic formerly used at high doses (500-1000 mg/day) for the treatment of tuberculosis (TB). It has been suggested that D-cycloserine might improve memory and other cognitive processes through its desired effects on N-methyl-D-aspartate (NMDA) receptor function. It was not possible to extract the results from the first phases of two included crossover studies of D-cycloserine for Alzheimer's disease and therefore the meta-analyses are based on the included two parallel group 6-month studies. The lack of a positive effect of D-cycloserine on cognitive outcomes in controlled clinical trials with statistical power high enough to detect a clinically meaningful effect means that D-cycloserine has no place in the treatment of patients with Alzheimer's disease.

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