Neuroprotective agents in traumatic brain injury

The role of neuroprotection in traumatic brain injury (TBI) is reviewed. Ba sic research and experimental investigations have identified many different compounds with potential neuroprotective effect. However, none of the Phas e III trials performed in TBI have been successful in convincingly demonstr ating efficacy in the overall population. A common misconception is that co nsequently these agents are ineffective. The negative results as reported i n the overall population may in part be caused by specific aspects of the h ead injury population as well as by aspects of clinical trial design and an alysis. The heterogeneity of the TBI population causes specific problems, s uch as a risk of imbalances between placebo and treated groups but also cau ses problems m;hen a possible treatment effect is evaluated in relation to the prognostic effect present. Trials of neuroprotective agents should be t argeted first of all to a population in which the mechanism at which the ag ent is directed is likely to be present and secondly to a population in whi ch the chances of demonstrating efficacy are realistic, e.g., to patients w ith an intermediate prognosis. The possibilities for concomitant or sequent ial administration of different neuroprotective agents at different times d eserve consideration. The potential for neuroprotection in TBI remains high and we should not be discouraged by recent failures obtained up until now. Rather, prior to initiating new trials, careful consideration of experimen tal evidence is required in order to optimise chances for mechanistic targe ting and lessons learned from previous experience need to be taken to heart in the design of future studies.