Low risk of late post-traumatic seizures following severe head injury: implications for clinical trials of prophylaxis.

A randomised, controlled, double-blind clinical trial designed to determine the effectiveness of phenytoin in preventing epilepsy in patients who had suffered a serious head injury is reported. One hundred and sixty-four patients were randomly assigned to treatment with phenytoin or placebo capsules for one year. Patients who had a fit within one week of injury were excluded. Drug levels were monitored throughout with appropriate dosage adjustment; however only 48% of the phenytoin group had plasma levels greater than 40 mumol/l. There were seven deaths during the study. Only 11 patients (six in the phenytoin group and five in the placebo group) developed post-traumatic epilepsy within one year; a further four patients developed seizures between 1 and 2 years after injury. This low incidence of post-traumatic epilepsy (7% (SE 2%) at one year and 10 (SE 2%) at two years) means that future clinical trials of prophylaxis will have to be much larger (at least six fold).