Effects of Add‐on Melatonin Administration on Antioxidant Enzymes in Children with Epilepsy Taking Carbamazepine Monotherapy: A Randomized, Double‐blind, Placebo‐controlled Trial

Summary:  Purpose: Melatonin has been shown to exhibit antioxidant, antiexcitotoxic, and free radical–scavenging properties in various animal models. The study was designed to assess its effects on the blood levels of antioxidant enzymes in children with epilepsy receiving carbamazepine (CBZ). Methods: In a double‐blind, randomized, parallel‐group, placebo‐controlled trial, we assessed the effect of add‐on melatonin (6–9 mg/day for 14 days) on the antioxidant enzymes glutathione peroxidase (GPx) and glutathione reductase (GRd) in 31 children with epilepsy receiving CBZ monotherapy, who were seizure free at least for the last 6 months. The interaction of melatonin with CBZ and its active metabolite, carbamazepine‐10, 11‐epoxide (CBZ‐E), also was studied. Results: An increase in GRd activity was noted in the melatonin group as compared with a decrease of the same enzyme in the placebo group. Changes in GPx activity failed to reach statistical significance. No significant changes were found in the serum levels of CBZ and CBZ‐E in either group. Conclusions: The study suggests that melatonin exerts antioxidant activity in patients with epilepsy receiving CBZ therapy.