The role of the melatoninergic system in epilepsy and comorbid psychiatric disorders

•Melatonin system has beneficial effect in anxiety, depression and epilepsy.•Melatonin system might be effective in treating comorbid behaviors in epilepsy.•Agomelatine is a promising therapeutic tool targeting comorbidities in epilepsy.

There is emerging evidence of the beneficial role of the melatonin system in a wide range of psychiatric and neurologic disorders, including anxiety, depression, and epilepsy. Although melatoninergic drugs have chronobiotic and antioxidant properties that positively influence circadian rhythm desynchronization and neuroprotection in neurodegenerative disorders, studies examining the use of melatonin for epilepsy's comorbid psychiatric and neurological symptomatology are still limited. Preclinical and clinical findings on the beneficial effects of the melatonin system on anxiety, depression, and epilepsy suggest that melatoninergic compounds might be effective in treating comorbid behavioral complications in epilepsy beyond regulation of a disturbed sleep–wake cycle.