Neurobehavioral effects of phenytoin prophylaxis of posttraumatic seizures

JAMA. 1991 Mar 13;265(10):1271-7.


In order to determine potential negative neurobehavioral effects of phenytoin given to prevent the development of posttraumatic seizures, 244 subjects were randomized to phenytoin or placebo. They received neurobehavioral assessments at 1 and 12 months postinjury while receiving their assigned drug and at 24 months while receiving no drugs. In the severely injured, phenytoin significantly impaired performance at 1 month. No significant differences were found as a function of phenytoin in the moderately injured patients at 1 month or in either severity group at 1 year. Patients who stopped receiving phenytoin according to protocol between 1 and 2 years improved more than corresponding placebo cases on several measures. We conclude that phenytoin has negative cognitive effects. This, combined with lack of evidence for its effectiveness in preventing posttraumatic seizures beyond the first week, raises questions regarding its use for long-term prophylaxis. Our findings do not negate phenytoin's proven efficacy in controlling established seizures nor do they indicate that its cognitive effects are worse than other anticonvulsant drugs.

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
  • Behavior / drug effects
  • Cognition / drug effects*
  • Craniocerebral Trauma / complications*
  • Craniocerebral Trauma / psychology
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Humans
  • Interpersonal Relations
  • Male
  • Neuropsychological Tests
  • Phenytoin / therapeutic use*
  • Psychomotor Performance / drug effects
  • Regression Analysis
  • Seizures / etiology
  • Seizures / prevention & control*


  • Phenytoin