The Emerging Role of Melatonin Agonists in the Treatment of Major Depression: Focus on Agomelatine

Domenico      De Berardis; Giuseppe      Di Iorio; Tiziano      Acciavatti; Chiara      Conti; Nicola      Serroni; Luigi      Olivieri; Marilde      Cavuto; Giovanni      Martinotti; Luigi      Janiri; Francesco      Saverio Moschetta; Pio      Conti; Massimo      Di Giannantonio

Abstract

Major Depressive Disorder (MDD) is an extremely disabling, chronic and recurrent disease. Moreover, subthreshold depressive symptoms often persist during periods of apparent remission. Such symptoms include sleep disturbances, sexual dysfunction, weight gain, fatigue, disinterest, anxiety, and/or emotional blunting, which do not often respond to available antidepressant treatments. Agomelatine is a melatonergic agonist (at both MT1 and MT2 receptors) and serotonin 2C (5-HT2C) receptor antagonist. Agomelatine should be particularly useful in the treatment of MDD because of its unique pharmacological profile, accounting for its effective antidepressant action with a relative lack of serious adverse effects. Several clinical trials confirmed the antidepressant efficacy of agomelatine in patients with MDD, with significant efficacy even in severe manifestations of disease and on residual subtreshold symptoms. This compound showed a relative early onset of action as well as an excellent safety and tolerability profile linked to a low discontinuation rate in MDD patients. Moreover, some data suggest that agomelatine has not only antidepressant effects but also anxiolytic effects, with a potential benefit both on anxiety symptoms associated with MDD and in the treatment of generalised anxiety disorder. This review will summarise the role of the melatonergic system in MDD and will describe the characteristics of agomelatine, focusing on its efficacy and safety in the treatment of MDD.

Keywords: Agomelatine, circadian rhythms, efficacy, melatonin, major depressive disorder, tolerability, treatment, NCS-R, STAR D, Circadian Timing System, SCN, N-acetyl-5-methoxytryptamine, Zeitgeber, SPZ, norepinephrine, MDD, DMV, adrenocorticotropin, fluoxetine, duloxetine, hypericum perforatum, low melatonin syndrome, 5-HT2C, 5-HT1A, selective serotonin, SSRI, slow wave sleep, NREM, HAM-D, CYP1A, CYP2C9, CYP2C19, lorazepam, fluconazole, paroxetine, mirtazapine, sleep-phase syndrome, imipramine, Montgomery-Åsberg Depression Rating Scale, CGI, REM, electroconvulsive therapy