Agomelatine: An astounding sui-generis antidepressant?

Abstract

: Major depressive disorder (MDD) is one of the foremost causes of disability and premature death worldwide. Although the available antidepressants are effective and well tolerated, they also have many limitations. Therapeutic advances in developing a new drug's ultimate relation between MDD and chronobiology, which targets the circadian rhythm, have led to a renewed focus on psychiatric disorders. In order to provide a critical analysis about antidepressant properties of agomelatine, a detailed PubMed (Medline), Scopus (Embase), Web of Science (Web of Knowledge), Cochrane Library, Google Scholar, and PsycInfo search was performed using the following keywords: melatonin analog, agomelatine, safety, efficacy, adverse effects, pharmacokinetics, pharmacodynamics, circadian rhythm, sleep disorders, neuroplasticity, MDD, bipolar disorder, anhedonia, anxiety, generalized anxiety disorder (GAD), and mood disorders. Agomelatine is a unique melatonin analog with antidepressant properties and a large therapeutic index that improves clinical safety. It is a melatonin receptor agonist (MT1 and MT2) and a 5-HT2C receptor antagonist. The effects on melatonin receptors enable the resynchronization of irregular circadian rhythms with beneficial effects on sleep architectures. In this way, agomelatine is accredited for its unique mode of action, which helps to exert antidepressant effects and resynchronize the sleep-wake cycle. To sum up, an agomelatine has not only antidepressant properties but also has anxiolytic effects.