Practice parameter: antiepileptic drug prophylaxis in severe traumatic brain injury: report of the Quality Standards Subcommittee of the American Academy of Neurology

Neurology. 2003 Jan 14;60(1):10-6. doi: 10.1212/01.wnl.0000031432.05543.14.


Objective: To review the evidence regarding antiepileptic drug (AED) prophylaxis in patients with severe traumatic brain injury (TBI) in order to make practice recommendations.

Methods: The authors identified relevant studies by searching multiple databases and reviewing reference lists of other sources. They included studies that prospectively compared post-traumatic seizure rates in patients given AED prophylaxis vs controls. Each study was graded (class I to IV) according to a standard classification-of-evidence scheme and results were analyzed and pooled.

Results: Pooled class I studies demonstrated a significantly lower risk of early post-traumatic seizures (those occurring within 7 days after injury) in patients given phenytoin prophylaxis compared to controls (relative risk 0.37, 95% CI 0.18 to 0.74). Pooled class I and class II studies demonstrated no significant difference in the risk of late post-traumatic seizures (those occurring beyond 7 days after injury) in patients given AED prophylaxis compared to controls (relative risk 1.05, 95% CI 0.82 to 1.35). Serum AED levels were suboptimal in these studies and adverse effects were mild but frequent.

Conclusions: For adult patients with severe TBI, prophylaxis with phenytoin is effective in decreasing the risk of early post-traumatic seizures. AED prophylaxis is probably not effective in decreasing the risk of late post-traumatic seizures. Further studies addressing milder forms of TBI, the use of newer AEDs, the utility of EEG, and the applicability of these findings to children are recommended.

Publication types

  • Guideline
  • Practice Guideline
  • Review

MeSH terms

  • Acute Disease
  • Adult
  • Animals
  • Anticonvulsants / adverse effects
  • Anticonvulsants / blood
  • Anticonvulsants / therapeutic use*
  • Brain Injuries / classification
  • Brain Injuries / complications
  • Brain Injuries / drug therapy*
  • Carbamazepine / adverse effects
  • Carbamazepine / blood
  • Carbamazepine / therapeutic use
  • Child
  • Controlled Clinical Trials as Topic / statistics & numerical data
  • Dose-Response Relationship, Drug
  • Electroencephalography
  • Epilepsy, Post-Traumatic / etiology
  • Epilepsy, Post-Traumatic / prevention & control*
  • Humans
  • Models, Animal
  • Phenytoin / adverse effects
  • Phenytoin / blood
  • Phenytoin / therapeutic use
  • Prospective Studies
  • Risk
  • Risk Assessment
  • Time Factors
  • Treatment Outcome


  • Anticonvulsants
  • Carbamazepine
  • Phenytoin