Abstract: This review included 10 RCTs (reported in 12 articles) consisting of 2326 participants The methodological quality of the studies varied. The type of intervention was separated into three categories; AED versus placebo or standard care, alternative neuroprotective agent versus placebo or standard care and AED versus other AED. Treatment with an AED (phenytoin or carbamazepine) decreased the risk of early seizure compared with placebo or standard care (RR 0.42, 95% CI 0.23 to 0.73; very low quality evidence). There was no evidence of a difference in the risk of late seizure occurrence between AEDs and placebo or standard care (RR 0.91, 95% CI 0.57 to 1.46; very low quality evidence). There was no evidence of a significant difference in all-cause mortality between AEDs and placebo or standard care (RR 1.08 95% CI 0.79 to 1.46,very low quality of evidence). Only one study looked at other potentially neuroprotective agents (magnesium sulfate) compared with placebo. The risk ratios were: late seizure 1.07 (95% CI 0.53 to 2.17) and all-cause mortality 1.20 (95% CI 0.80 to 1.81). The risk ratio for occurrence of early seizure was not estimable. Two studies looked at comparison of two AEDs (levetiracetam, valproate) with phenytoin used as the main comparator in each study. The risk ratio for all-cause mortality was 0.53 (95% CI 0.30 to 0.94). There was no evidence of treatment benefit of phenytoin compared with another AED for early seizures (RR 0.66, 95% 0.20 to 2.12) or late seizures(RR 0.77, 95% CI 0.46 to 1.30). Only two studies reported adverse events. The RR of any adverse event with AED compared with placebo was 1.65 (95% CI 0.73 to 3.66; low quality evidence). There were insufficient data on adverse events in the other treatment comparisons. This review found low-quality evidence that early treatment with an AED compared with placebo or standard care reduced the risk of early post-traumatic seizures. There was no evidence to support a reduction in the risk of late seizures or mortality. There was insufficient evidence to make any conclusions regarding the effectiveness or safety of other neuroprotective agents compared with placebo or for the comparison of phenytoin, a traditional AED, with another AED.

Plain-language summary: We searched for studies evaluating the effect of early administration of antiepileptic drugs or other potentially neuroprotective agents (which act by protecting the structure or function of nerves) on post-traumatic epilepsy. The primary outcomes of interest were early post-traumatic seizures (within one week of trauma) and late seizures (later than one week post-trauma). We also looked at death, time to late seizure and side effects. The evidence is current to January 2015. We found 10 clinical trials involving 2326 people reported in 12 published articles. The evidence available indicated that early treatment with a traditional antiepileptic drug (phenytoin or carbamazepine) may reduce the risk of early post-traumatic seizures. Traditional antiepileptic drugs are no more effective than placebo (a pretend pill) or standard care in reducing late seizures or mortality. Limited data were available for the comparison of an AED with another AED and for the comparison of other potentially neuroprotective agents with placebo. Most studies did not report serious side effects and other side effects. The overall quality of the evidence varied and findings should be interpreted with caution.