Abstract: We included 10 RCTs (N = 1815), which were published between 1983 and 2015. Three trials compared a single AED (phenytoin) with placebo or no treatment. One three-armed trial compared two AEDs (phenytoin, carbamazepine) with no treatment. A second three-armed trial compared phenytoin, phenobarbital with no treatment. Of these five trials comparing AEDs with placebo or no treatment, two trials reported a statistically significant advantage for AED treatment compared to controls for early seizure occurrence; all other comparisons showed no clear or statistically significant differences between AEDs and control treatment. None of the trials that were head-to-head comparisons of AEDs (phenytoin versus sodium valproate, phenytoin versus phenobarbital, levetiracetam versus phenytoin, zonisamide versus phenobarbital) reported any statistically significant differences between treatments for either early or late seizure occurrence. Incidences of death were reported in only five trials. One trial reported statistically significantly fewer deaths in the carbamazepine and no-treatment groups compared with the phenytoin group after 24 months of treatment, but not after six months of treatment. Incidences of adverse effects of treatment were poorly reported; however, three trials did show that significantly more adverse events occurred on phenytoin compared to valproate, placebo, or no treatment. No trials reported any results relating to functional outcomes such as disability. We considered the evidence to be of low quality for all reported outcomes due to methodological issues and variability of comparisons made in the trials. There is limited, low-quality evidence to suggest that AED treatment administered prophylactically is either effective or not effective in the prevention of postcraniotomy (early or late) seizures. The current evidence base is limited due to the different methodologies employed in the trials and inconsistencies in the reporting of outcomes including deaths and adverse events. Further evidence from good-quality, contemporary trials is required in order to assess the clinical effectiveness of prophylactic AED treatment compared to placebo or no treatment, or other AEDs in preventing postcraniotomy seizures in this select group of patients.

Plain-language summary: The evidence is current to June 2017. Ten trials met our inclusion criteria, and included 1815 people. Three trials compared phenytoin (an AED) with a placebo or no treatment. One trial compared the AEDs phenytoin or carbamazepine with no treatment. One trial compared the AEDs phenytoin or phenobarbital with no treatment. Five other trials were head-to-head trials (where one drug is directly compared against another drug) of AEDs (phenytoin versus valproate; zonisamide versus phenobarbital and levetiracetam versus phenytoin). We did not find any consistent evidence to suggest that preventative AED treatments are effective in reducing the number of seizures that occurred postsurgery, deaths or adverse effects. Taking all the trials together, we considered that the quality of the evidence was low due to potential problems with the designs of the trials. Also the differences in the designs of the trials relating to the treatments examined and the results reported meant that it was difficult to compare results across trials. Further good-quality studies are needed to validate the findings mentioned above.