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.

Authors' conclusions: 

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

Read the full abstract...

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.


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

Search strategy: 

We searched CENTRAL; MEDLINE; EMBASE; ISI Web of Science: Science Citation Index Expanded (SCI-EXPANDED) and Conference Proceedings Citation Index- Science (CPCI-S) and 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.