Monoaminergic agonists for acute traumatic brain injury

 

Abstract

Background

Although there have been considerable gains in understanding the cascade of events that lead to secondary injury after traumatic brain injury (TBI), efforts to translate this understanding into new therapeutic, so-called neuroprotective approaches, have so far proved disappointing. As an alternative, there is growing interest in approaches to enhance brain repair after injury. Animal models suggest that agents enhancing monoaminergic transmission (monoaminergic agonists, or MAs) particularly amphetamines, promote motor recovery from focal brain injury and it is proposed that this might represent a complementary means of therapeutic intervention in the later post-injury phase.

Objectives

To evaluate the evidence that MAs improve final outcome after TBI.

Search methods

We searched CENTRAL; MEDLINE; EMBASE; ISI Web of Science: Science Citation Index Expanded (SCI-EXPANDED) and Conference Proceedings Citation Index- Science (CPCI-S) and www.controlled-trials.com to March 2009. We contacted authors of known unpublished trials in progress.

Selection criteria

Randomised controlled trials comparing the use of a MA (together with conventional non-pharmacological rehabilitative therapy) versus conventional non-pharmacological rehabilitative therapy alone.

Data collection and analysis

Two authors independently screened records, extracted data and assessed trial quality.

Main results

Although there is limited clinical literature addressing this topic, none of the studies identified fully met inclusion criteria for this review.

Authors' conclusions

At present there is insufficient evidence to support the routine use of MAs to promote recovery after TBI.

 

Plain language summary

Do a group of drugs known as monoaminergic agonists help the brain recovery after a severe injury?

Not all of the brain damage sustained after a traumatic brain injury (TBI) is due to the direct injury that occurs at the moment of impact. Severe injury can initiate a sequence of events over several hours that can lead to secondary damage or death of brain tissue. However, the effectiveness of so-called "neuroprotective" interventions aimed at preventing this sequence of events or minimising its harm have so far been disappointing.

An alternative approach might be to use drugs known as monoaminergic agonists (MAs), which attempt to enhance brain repair after an injury. Animal studies have suggested that such drugs promote brain reorganisation and functional recovery after injury. The effectiveness of MAs in humans on recovery after brain injury has yet to be ascertained.

The authors of this review searched for all high quality trials investigating the effectiveness of MAs on the recovery of severely brain-injured patients of all ages. None of the published studies identified addressed the reseach question directly and thus they were not eligible for inclusion in the review. The authors therefore concluded that there are to date no satisfactory studies of the effectiveness of MAs for people who have experienced a severe TBI. Consequently, there is, at present, insufficient evidence to support the routine use of MAs to promote recovery from TBI.

The authors state that there is an urgent need to explore the effectiveness of interventions, such as MAs, for the enhancement of brain repair after a severe injury. The findings from existing trials of MAs require replication in larger studies, to involve other groups including more severely injured patients, and children.

 

摘要

背景

Monoaminergic agonists對急性腦部外傷之作用

雖然在了解一連串的事件導致急性腦部外傷(traumatic brain injury, TBI)的續發性傷害上已經有相當多的收穫，但是將此了解轉化為新的治療所做的努力，即所謂的神經保護性方式，迄今仍令人失望。為了另闢蹊徑，近來對於受傷後增進腦部修復的相關方法有愈來愈多的興趣。動物模式顯示能夠增加monoaminergic (MA)傳遞的藥物，尤其是amphetamines類，可以促進局部腦部損傷的運動功能恢復，有人並且提出這可能代表一種受傷後晚期的治療性介入的互補性療法。

目標

評估以MAs提昇急性腦部外傷最後結果的證據。

搜尋策略

我們搜尋了CENTRAL (The Cochrane Library, Issue 2, 2005), the Cochrane Injuries Group's Specialised Register (to May 2005), MEDLINE (1966 to May 2005), EMBASE (1980 to May 2005) and the Science Citation Index (1992 to June 2005)。我們連絡了已發表與未發表的研究者與作者。搜尋的最後更新是在2005年5月。

選擇標準

比較使用MA(合併常見的非藥理學修復治療)與僅以傳統非藥物的復健治療的隨機臨床對照試驗。

資料收集與分析

兩作者分別篩檢記錄、擷取資料並評估試驗的品質。

主要結論

雖然有少數的臨床文獻論及本主題，但是所能找到的這些研究中沒有一篇符合本回顧的納入條件。

作者結論

目前沒有足夠的證據支持常規使用MAs來促進急性腦部外傷後的修復。

翻譯人

本摘要由高雄榮民總醫院徐圭璋翻譯。

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

總結

monoaminergic agonists這類的藥物能夠幫助嚴重受傷後的腦部修復嗎?並非所有急性腦部外傷的腦部傷害都肇因於事件發生時的直接傷害。嚴重受傷幾個小時後可引發一連串的事件造成續發性傷害或腦部組織的壞死。為預防這類一連串的事件或減少它的傷害而使用的介入性治療的效果目前仍另人失望。另一種替代的方法便是使用monoaminergic agonists (MAAs)這類的藥物以增加受傷後腦部的修復。儘管其作用方式仍然不明，動物研究認為這類藥物可能可以增進受傷後的腦部修復。MAA用於人類腦部受傷後的修復效果尚未確定。本篇回顧的作者們搜尋了所有有關MAAs對於各年齡層嚴重腦傷患者療效的高品質臨床試驗。作者們找到3篇研究，但是沒有一篇專門著重於嚴重腦受傷的病人，所以不合納入本篇回顧的條件。作者因此總結沒有滿意的研究足以證實有關MAs作用在經歷嚴重TBI患者的效果。所以目前沒有足夠的證據支持常規使用MAAs來促進TBI的修復。作者提出有迫切需要去探求對於增進嚴重傷後腦部修復的介入性治療如MAAs等的療效。現存MAAs的試驗結果需要大型研究以印證之，並納入更為嚴重的受傷患者和兒童等其他群體。