A randomized, double-blind study of phenytoin for the prevention of post-traumatic seizures

N Engl J Med. 1990 Aug 23;323(8):497-502. doi: 10.1056/NEJM199008233230801.


Background: Antiepileptic drugs are commonly used to prevent seizures that may follow head trauma. However, previous controlled studies of this practice have been inconclusive.

Methods: To study further the effectiveness of phenytoin (Dilantin) in preventing post-traumatic seizures, we randomly assigned 404 eligible patients with serious head trauma to treatment with phenytoin (n = 208) or placebo (n = 196) for one year in a double-blind fashion. An intravenous loading dose was given within 24 hours of injury. Serum levels of phenytoin were maintained in the high therapeutic range (3 to 6 mumol of free phenytoin per liter). Follow-up was continued for two years. The primary data analysis was performed according to the intention to treat.

Results: Between drug loading and day 7, 3.6 percent of the patients assigned to phenytoin had seizures, as compared with 14.2 percent of patients assigned to placebo (P less than 0.001; risk ratio, 0.27; 95 percent confidence interval, 0.12 to 0.62). Between day 8 and the end of year 1, 21.5 percent of the phenytoin group and 15.7 percent of the placebo group had seizures; at the end of year 2, the rates were 27.5 percent and 21.1 percent, respectively (P greater than 0.2 for each comparison; risk ratio, 1.20; 95 percent confidence interval, 0.71 to 2.02). This lack of a late effect could not be attributed to differential mortality, low phenytoin levels, or treatment of some early seizures in patients assigned to the placebo group.

Conclusions: Phenytoin exerts a beneficial effect by reducing seizures only during the first week after severe head injury.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Double-Blind Method
  • Epilepsy, Post-Traumatic / prevention & control*
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Phenytoin / blood
  • Phenytoin / therapeutic use*
  • Randomized Controlled Trials as Topic
  • Time Factors


  • Phenytoin