Melatonin in Mood Disorders and Agomelatine’s Antidepressant Efficacy

Abstract

Numerous clinical studies have shown that melatonin is involved in the pathogenesis of mood disorders like major depressive disorder, bipolar disorder, and seasonal affective disorder or winter depression. Many clinical symptoms seen in depressive patients suggest that disturbances of sleep and circadian rhythms play an important role in the pathophysiology of mood disorders. Disturbances of sleep-wake rhythms and circadian rhythms are linked to malfunctioning of SCN-pineal-melatonin axis. As a rhythm regulating factor and as a hormone involved in the physiological regulation of sleep-wake rhythm, melatonin plays an important role in regulating sleep and circadian rhythm disturbances of mood disorders. Melatonin receptors, namely, MT1 and MT2, are found expressed in the suprachiasmatic nucleus of the hypothalamic region, an area concerned with the regulation of various circadian rhythms and sleep-wake rhythm. Although pharmacotherapy of mood disorders has long been associated with the modulation of monoaminergic systems of neuronal circuits in different regions of the brain that are involved in the regulation of mood, attention has been paid in recent years for the development of drugs that can shift, reset, and stabilize the circadian rhythms and improve the quality of sleep. In this context agomelatine, a novel antidepressant with MT1/MT2 agonistic and 5-HT2c antagonistic properties, has been introduced. Having proved its efficacy as an effective antidepressant in various animal models of depression, agomelatine has been introduced as an antidepressant for treating patients with major depressive disorders in many European countries and also in the USA. Agomelatine has also been used for treating patients with bipolar disorder, winter depression, and anxiety disorder and has demonstrated its clinical efficacy with rapid onset of action, comparable to other antidepressants like SSRIs and SNRIs. But unlike these drugs, agomelatine does not exhibit adverse side effects like worsening of insomnia or sexual problems, and hence, it is considered as an antidepressant of choice for effective treatment of mood disorders.