Antiepileptic drugs as prophylaxis for post-craniotomy seizures

The incidence of seizures following supratentorial craniotomy for non-traumatic pathology has been estimated to be 15% to 20%; however, the risk of experiencing a seizure may vary from 3% to 92% over a five-year period. Postoperative seizures can precipitate the development of epilepsy; seizures are most likely to occur within the first month of cranial surgery. The use of antiepileptic drugs (AEDs) administered pre- or postoperatively to prevent seizures following cranial surgery has been investigated in a number of randomised controlled trials. To determine the efficacy and safety of AEDs when used prophylactically in people undergoing craniotomy and to examine which AEDs are most effective. We searched the Cochrane Epilepsy Group's Specialized Register (September 2012), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library Issue 9, 2012), and MEDLINE (1946 to September 2012). No language restrictions were imposed. Randomised controlled trials of people with no history of epilepsy who were undergoing craniotomy for either therapeutic or diagnostic reasons were included. Trials with adequate randomisation methods and concealment were included; these could either be blinded or unblinded parallel trials. No minimum treatment period was stipulated, trials using active drugs or placebo as a control group were included. Two review authors (JP and JG) independently selected trials for inclusion and carried out data extraction and risk of bias assessments. Any disagreements were resolved through discussion. Outcomes investigated included the number of patients experiencing seizures (early - occurring within first week following craniotomy and late - occurring after first week following craniotomy), the number of deaths and the number of people experiencing disability and adverse effects. Due to the heterogeneous nature of the trials, data from the trials were not combined in a meta-analysis; the findings of the review are presented in narrative format. Six RCTs (N = 1398) were eligible for inclusion within the review with publication dates ranging between 1983 and 1999. Two trials compared a single AED (phenytoin) with a placebo. One three-arm trial compared two AEDs (carbamazepine, phenytoin) with no treatment. A second three-arm trial compared phenytoin, phenobarbital and no treatment. Two other trials were head-to-head trials of AEDs (phenytoin vs. valproate and zonisamide vs. phenobarbital). Of the four trials comparing AEDs with