PURPOSE: This study was carried out to determine the effects of valproate (VPA), carbamazepine, and levetiracetam (LEV) on antioxidant and oxidant enzyme activities and the clinical importance of these effects. METHODS: We enrolled 32 patients receiving VPA, 17 receiving carbamazepine, 8 receiving LEV, 11 on multidrug therapy, and 30 sex- and age-matched healthy volunteers. We measured the serum activities of paraoxonase and arylesterase and the levels of 8-hydroxyguanine (8-OHG) and oxidized low-density lipoprotein in all the subjects. We also determined the clinical features of the patients. RESULTS: The serum paraoxonase and arylesterase activities were significantly lower (P = 0.003 and P = 0.0001, respectively), and the oxidized low-density lipoprotein and 8-OHG levels were higher (P = 0.029 and P = 0.0001, respectively) in the patients than in the controls. The serum antioxidant activity was low, and the oxidant activity was high in the monotherapy patients (P < 0.05). Comparing the monotherapy with the polytherapy, only the combination of VPA-LEV was associated with a high 8-OHG level (P = 0.04). The serum 8-OHG level was higher in the patients taking antiepileptic drugs (AEDs) for the first 2 months than in the controls (P = 0.0001) and positively correlated with the duration of epilepsy (r = 0.387, P < 0.01). CONCLUSIONS: Oxidative stress is seen in each of the AEDs after the first 2 months. There was no dominance of the monotherapy over the polytherapy, except for the VPA-LEV combination. None of the patients' characteristic features were related to oxidative damage, except for the duration of the epilepsy and the AED therapy. Copyright © 2010 by Lippincott Williams & Wilkins.