Nine studies (n=1,936) were included in the review. Six were randomised controlled trials (n=1,532), two were quasi-randomised (n=237) and one study did not use randomisation (n=167).
Early post-traumatic seizures.
The risk of early seizure was significantly lower in patients receiving the AED phenytoin compared with controls; the RR was 0.37 (95% CI: 0.18, 0.74) based on 649 patients in two studies.
Few adverse effects were reported. In one study 5.2% of patients receiving phenytoin and 9.2% of patients receiving placebo discontinued use owing to personal request, idiosyncratic and other reactions. In an additional study, one patient receiving phenytoin reported a rash within the first week of treatment.
Late post-traumatic seizures.
There was no statistically-significant difference in the risk of late seizure in patients receiving an AED compared with controls; the RR was 1.05 (95% CI: 0.82, 1.35) based on 1,312 patients in five studies. Adverse effects were frequently reported, but were mild in severity. The development of a rash was the most prevalent adverse effect in patients receiving phenytoin, while fatigue and lethargy were prevalent in patients receiving valproate; these led to a change of medication or the discontinuation of treatment. No studies evaluating carbamazepine reported adverse effects.