Background:Oxidative stress has been a frequent finding in epileptic patients receiving antiepileptic drugs (AEDs). In this study, the influence of Vitamin E on the antiseizure activity and redox state of patients treated with carbamazepine, sodium valproate, and levetiracetam has been investigated.Materials and Methods:This double-blind, placebo-controlled trial was carried out on 65 epileptic patients with chronic antiepileptic intake. The subjects received 400 IU/day of Vitamin E or placebo for 6 months. Seizure frequency, electroencephalogram (EEG), and redox state markers were measured monthly through the study.Results:Total antioxidant capacity, catalase and glutathione were significantly higher in Vitamin E received group compared with controls (P < 0.05) whereas malodialdehyde levels did not differ between two groups (P < 0.07). Vitamin E administration also caused a significant decrease in the frequency of seizures (P < 0.001) and improved EEG findings (P = 0.001). Of 32 patients in case group, the positive EEG decreased in 16 patients (50%) whereas among 33 patients in control group only 4 patients (12.1%) showed decreased positive EEG.Conclusion:The results of this preliminary study indicate that coadministration of antioxidant Vitamin E with AEDs improves seizure control and reduces oxidative stress.