Piracetam for dementia or cognitive impairment

 

Abstract

Background

Piracetam is a drug that may enhance memory and other intellectual functions, but its usefulness in treating dementia is uncertain. It is, however, commonly prescribed for cognitive impairment and dementia in several countries of continental Europe.

Objectives

To determine the clinical efficacy of piracetam for features of dementia (classified into the major subtypes: vascular, Alzheimer's disease or mixed vascular and Alzheimer's disease, or unclassified dementia) or cognitive impairment not fulfilling diagnostic criteria for dementia.

Search methods

The Specialized Register of the Cochrane Dementia and Cognitive Improvement Group (CDCIG), The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL and LILACS were searched on 17 December 2007 using the terms piracetam, nootropic and 2-Oxo-1-pyrrolidine. A review by employees and consultants of the manufacturing company, UCB Pharma (Waegemans 2002) included data from unpublished studies not made available to Cochrane reviewers.

Selection criteria

All unconfounded, randomized, double-blind in which treatment with piracetam was administered for more than a day and compared with placebo in people with dementia of Alzheimer type, vascular dementia, or mixed vascular and Alzheimer's disease, or unclassified dementia, or cognitive impairment not fulfilling diagnostic criteria for dementia.

Data collection and analysis

Two reviewers independently extracted data from studies fulfilling inclusion criteria. Intention-to-treat analysis was used where feasible and studies were pooled if appropriate. Sensitivity analyses were to be performed to determine if studies performing poorly on quality criteria affected results. The pharmaceutical company marketing piracetam did not release the results of several unpublished trials.

Main results

Many studies were of cross-over design and first-phase data were unavailable, or could not be extracted. Global Impression of Change (GIC) was the only outcome for which pooling of data was possible, involving only four studies. There was evidence of heterogeneity in the results, chi-square test = 19.17 (df = 3, P < 0.001). The OR for improvement in the piracetam group compared with placebo was 3.43 (95% CI 2.32 to 5.07). Using a fixed-effects model the OR for improvement with piracetam compared with placebo was 3.55 (95% CI 2.45 to 5.16). This estimate was derived from completers rather than from an intention-to-treat analysis as relevant data could not be extracted from the reports.

In the limited data available no significant differences were found between treatment and placebo groups for cognition (immediate memory, visuospatial, MMSE, delayed memory or speech) for dependency, or for depression.

The large volume of unpublished and untraceable data not available to the reviewers raises the possibility of publication bias.

Authors' conclusions

Published evidence does not support the use of piracetam in the treatment of people with dementia or cognitive impairment. Although effects were found on global impression of change, no benefit was shown by any of the more specific measures of cognitive function.

The evidence indicates a need for further evaluation of piracetam.

 

Plain language summary

Evidence for the efficacy of piracetam for dementia or cognitive impairment is inadequate for clinical use but sufficient to justify further research

Piracetam was one of the first drugs used for dementia and comes from the class of drugs called nootropics, whose putative actions are still poorly defined. Most of the trials of piracetam were undertaken many years ago and did not use methods which would be currently considered standard. Some of the studies suggested there may be some benefit from piracetam but overall the evidence is not consistent or positive enough to support its use for dementia or cognitive impairment.

 

摘要

背景

Piracetam用於癡呆症或認知障礙

Piracetam是一種可增強記憶及其他智力的藥物，但是本藥物對於治療癡呆症的療效還不明確。然而，在數個歐陸國家，本藥物常被處方以處置認知障礙及癡呆症。

目標

確認piracetam對於癡呆症(區分其主要亞型為:血管型、阿茲海默症或混合了血管及阿茲海默症、或是尚未分類的癡呆症)，或未能符合癡呆症診斷標準的認知障礙的療效。

搜尋策略

於2005年5月11日以piracetam、nootropic及2Oxo1pyrrolidine搜尋Specialized Register of the Cochrane Dementia and Cognitive Improvement Group。 該登錄中心的內容來自於定期更新重要健康照護資料庫及許多試驗資料庫。 此外並由藥廠、UCB Pharma(Waegemans 2002)的職員及顧問再次進行複查，以納入Cochrane回顧作者無法取得的未發表研究的數據。

選擇標準

所納入的研究條件如下： 1.未受干擾、隨機、雙盲； 2.進行piracetam與安慰劑用於阿茲海默症、血管型失智症、或是混合阿茲海默症與血管型失智，或是不符合癡呆症診斷標準的認知障礙患者身上之比較，治療時間需超過1天。

資料收集與分析

2位作者單獨從合乎納入標準的試驗摘錄數據，如果適合的話則會進行治療意向分析(Intentiontotreat analysis)或是合併研究，此外並進行敏感度分析，以確定是否研究執行品質不佳以至於影響結果。而銷售piracetam的藥廠並未提供一些未發表的研究結果。

主要結論

許多研究是交叉設計，而且無法取得第一階段數據或是摘錄數據。臨床總體改變(GIC) 是惟一個適於合併的結果，共包含了4個研究。 證據顯示各個結果之間具有異質性，卡方檢定 = 19.17 (df = 3, P < 0.001)。相較於安慰劑組，piracetam組改善的OR = 3.43 (95% CI 2.32 to 5.07)。 若採用固定效果模式，相較於安慰劑組，piracetam組改善的OR = 3.55 (95% CI 2.45 to 5.16)。 不過由於無法取得某些數據，因此上述的結果是以完成治療者為基礎，而非來自治療意向分析。 有限的證據顯示治療組與安慰劑之間，在認知(立即記憶、空間感、MMSE、 延遲記憶或口語能力)、 依賴或是憂鬱方面沒有差異。 由於回顧作者沒辦法取得大量未發表或無法追蹤的數據，因此可能會有發表偏誤。

作者結論

已公布的證據並不能支持使用piracetam治療患有癡呆症或認知受損傷者。 雖然經由臨床整體變化診斷可發現藥物效用，但是對於認知功能的評量，沒有更多專一性的測量可以展現出其效益。證據指出，有必要進一步評估piracetam功效。

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

Piracetam對於癡呆症或認知障礙的療效，證據尚不足以使其於臨床上應用，但足以證明深入研究的必要性。 Pracetam是首批應用於癡呆症的藥物之一，且是來自稱為nootropics的某類藥物，目前仍不確定該類藥物的作用。 Piracetam的試驗大都是多年前所進行的，而且未使用目前認定的標準測試方式。某些研究認為piracetam具有效益，不過整體來說證據並不一致，而且並不夠好到支持使用於失智症或是認知障礙患者。