A randomized, double‐blind, placebo controlled trial of melatonin add‐on therapy in epileptic children on valproate monotherapy: effect on glutathione peroxidase and glutathione reductase enzymes

Aims To compare the effect of add‐on melatonin with placebo on the antioxidant enzymes (glutathione peroxidase and glutathione reductase) in epileptic children on valproate monotherapy. Methods In a double‐blind, randomized, placebo controlled trial, the effect of add‐on melatonin administration on the antioxidant enzymes in epileptic children on valproate (VPA) monotherapy was assessed. A total of 31 patients met the entry criteria. 16 patients were randomly allocated to receive add‐on melatonin, and 15 to receive add‐on placebo. Blood samples (5 ml) were collected just before the morning dose of valproate for baseline values of glutathione peroxidase and glutathione reductase enzymes, and then after 14 days of add‐on melatonin/placebo. Blood was then centrifuged at 3500 r.p.m., serum separated and stored in deep freezer at −20 °C until assay of glutathione reductase. Heparinized blood was collected and stored at −20 °C in eppendorfs in the deep freezer for assay of glutathione peroxidase. All activity assays were performed on the Ames (Technicon) RA 50 chemistry analyser. Results Fifteen patients in the add‐on melatonin group and 14 patients in the add‐on placebo group were finally assessed. There was an increase in the activity of antioxidant enzymes, glutathione peroxidase (GSH‐Px) and glutathione reductase (GSSG‐Rd), in the add‐on melatonin (MEL) group as compared with a reduction in the same in the add‐on placebo group (P). After the addition of melatonin/placebo in the respective groups, there was a 7.5% decrease in GSH‐Px in the valproate + placebo group, whereas a 11.9% increase in the valproate + melatonin group was observed, the difference between the groups being not statistically significant (P = 0.29). On administration of melatonin/placebo, the post‐treatment concentrations of GSSG‐Rd in the valproate + placebo group decreased from 92.0 U l−1 to 67.0 U l−1 and increased from 82.0 U l−1 to 113.0 U l−1, in the valproate + melatonin group, respectively, the difference between them being statistically significant (P = 0.05). The percentage change in the values of GSSG‐Rd in the two groups was statistically significant (P = 0.005). Conclusions Melatonin exerts neuroprotection due to its antioxidant, antiexcitotoxic and free radical scavenging properties within the central nervous system. Melatonin, thus, as an adjunct, can be a putative neuroprotector in conditions involving oxidative stress like epilepsies.