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The use of Levetiracetam and Phenytoin for Seizure Prophylaxis in the Setting of Severe Traumatic Brain Injury

11 August 2012


Background: Each year in the United States an estimated 1.7 million people suffer a traumatic brain injury (TBI). Current standard of care for these patients is seven days of phenytoin (PHT) for seizure prophylaxis. Given the known side effect profile and drug interactions associated with the use of PHT, levetiracetam (LEV) has been proposed as an alternative for seizure prophylaxis. This systematic review examined available literature to determine whether or not there is sufficient evidence to recommend the use of LEV in lieu of PHT.

Method: A highly sensitive search of Medline, CINAHL, and EBMRMultifile was conducted looking for studies comparing the efficacy of phenytoin vs. levetiracetam in the setting of severe TBI (sTBI) using the terms phenytoin and either levetiracetam or piracetam. In an effort to ensure that no articles that met inclusion criteria were missed, additional searches were conducted using Google Scholar and Web of Science. A manual search of the bibliographies of the articles to be reviewed as well as the bibliographies of background articles was conducted.

Results: Two articles comparing LEV and PHT in the setting of sTBI were found. Neither article was able to show a difference in the rate of seizure between patients treated with PHT and LEV. An increase in seizure tendency on EEG for patients taking PHT was reported, as was an increase in gastrointestinal upset and worsening of neurologic status. A modest improvement in some long term outcome measures was reported in patients treated with LEV. Both of the studies that were found were hampered by a small n (52 and 73), which was further limited by the studies’ methodology.

Conclusion: There is insufficient evidence to recommend the use of LEV instead of PHT for seizure prophylaxis in the setting of sTBI. Further studies, with larger patient populations and more sound methodology, are needed to continue to examine this issue.


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