A systemic review of levetiracetam versus phenytoin in the prevention of late post-traumatic seizures and survey of UK neurosurgical prescribing practice of antiepileptic medication in acute traumatic brain injury

Background: Guidelines recommend 1 week of prophylactic phenytoin for post-traumatic seizures (PTS). Levetiracetam is gaining popularity as an alternative with a superior side-effect profile and may be suitable for extended use. We performed a systematic review comparing the efficacy of levetiracetam and phenytoin in reducing the incidence of late PTS. The secondary objectives were to compare their effects on the Extended Glasgow Outcome Scale (GOS-E) and length of stay. We also aimed to survey current prophylaxis prescribing practices. 

Methods: A systematic review was performed using Medline, Pubmed, Embase and Cochrane. Trials and observational studies comparing the efficacy of phenytoin and levetiracetam in the prevention of late PTS were included. A survey assessing prescribing practices was e-mailed to all consultant members of the Society of British Neurological Surgeons (n = 249) in March 2013. 

Results: One randomised controlled trial (RCT) (52 patients) and a cohort study (19 patients) met our criteria. Neither found a significant difference in the incidence of late PTS or length of hospital stay, although the RCT showed an improvement in the GOS-E with levetiracetam. Of the 249 consultants included in the survey, 55 responded (22.1%). Prophylaxis was prescribed by 32 consultants (58%), of whom 21 (65.6%) chose phenytoin, 7 (21.9%) chose levetiracetam, 3 (9.4%) chose valproate and 1 (3%) chose ‘other’. Half indicated they would prescribe prophylaxis for 1 week, the remainder opting for extended use. 

Conclusion: While our review found no evidence of a difference in late seizure incidence, there is evidence of improved long-term outcomes with levetiracetam. Neither study used an extended course of levetiracetam or continuous electroencephalography. Further research which accounts for these factors is required for the development of guidelines which take levetiracetam into account. Our survey showed a lack of awareness of the potential harms of extended phenytoin use and a move towards levetiracetam.