Effect of Melatonin on Seizure Outcome, Neuronal Damage and Quality of Life in Patients With Generalized Epilepsy

Epilepsy is a chronic disabling neurologic condition which often leads to numerous adverse long-term neurologic complications, such as behavioural and cognitive deficits, increased susceptibility to recurrent seizures, and neuronal injury or death. Cognitive dysfunction, depression, anxiety and sleep disorders are some of the highly prevalent and most debilitating complications of epilepsy. Despite the abundance of antiepileptic drugs (AEDs), even after long-term treatment of 6-8 years, 30% of patients continue having seizures. This group of patients requires a more aggressive treatment, since monotherapy fails to control seizures, considering the fact that the number of seizures is the single most important predictive factor for both early and long-term remission of seizures. Nevertheless, polytherapy often results in a number of adverse effects. The need for better-tolerated add-on therapy is the need of the hour to overcome this therapeutic hurdle. Melatonin, an endogenous hormone, acting through MT1 and MT2 receptors exert a depressive effect on brain excitability and have been shown to exert an anticonvulsant activity in various animal models. In some clinical trials also it has been found that add-on melatonin therapy improves the clinical outcome. Uberoset al evaluated the sleep-wake pattern, plasma melatonin levels and the urinary excretion of its metabolite among children with severe epileptic disorders, before and after a therapeutic trial with melatonin. They found sleep efficiency was significantly higher and better controls of convulsive episodes were achieved with among patients who received melatonin. Goldberg-Stern et aland Elkhayat et al concluded that melatonin could be effective and safe for decreasing seizure frequency and severity in patients with intractable epilepsy. Gupta et al found that melatonin has the potential to improve quality of life in pediatric epilepsy because of its beneficial effects on sleep, its wide safety window, and its ability to cross the blood-brain barrier. In another study by Jain SV et al melatonin resulted in a statistically significant decrease in sleep onset latency and wakefulness after sleep onset. Guptaet al also concluded that add-on melatonin can be of promise in the pharmacotherapy of pediatric epilepsy and as an adjunct, can be a putative neuroprotector in conditions involving oxidative stress like epilepsies. Dabak et al and Brazil et measured melatonin in febrile seizure and temporal lobe epilepsy and found to be lower in epilepsy in comparison to the controls. Our literature review reveals that till date most of the clinical studies on the effect of melatonin in epilepsy have been conducted in the pediatric population and there is no clinical trial done on its effect on seizure outcome, neuroprotective effect, sleep and circadian rhythm and quality of life in adult patients with epilepsy. So the present randomized clinical trial has been designed to fill the knowledge gap and evaluate the effect of add-on melatonin on seizure severity, neuronal damage and sleep quality in adult patients suffering from a generalized seizure.