title: The emerging role of melatonin agonists in the treatment of major depression: focus on agomelatine.
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.
authors.affiliation: National Health Service, Department of Mental Health, Psychiatric Service of Diagnosis and Treatment, "G. Mazzini" Hospital, Piazza Italia 1, 64100 Teramo, Italy. dodebera@aliceposta.it
authors.forename: Domenico
authors.initials: D
authors.lastname: De Berardis
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Di Iorio
authors.forename: Tiziano
authors.initials: T
authors.lastname: Acciavatti
authors.forename: Chiara
authors.initials: C
authors.lastname: Conti
authors.forename: Nicola
authors.initials: N
authors.lastname: Serroni
authors.forename: Luigi
authors.initials: L
authors.lastname: Olivieri
authors.forename: Marilde
authors.initials: M
authors.lastname: Cavuto
authors.forename: Giovanni
authors.initials: G
authors.lastname: Martinotti
authors.forename: Luigi
authors.initials: L
authors.lastname: Janiri
authors.forename: F S
authors.initials: FS
authors.lastname: Moschetta
authors.forename: P
authors.initials: P
authors.lastname: Conti
authors.forename: Massimo
authors.initials: M
authors.lastname: Di Giannantonio
mesh_terms: D000081:Acetamides / Q000009:adverse effects / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000928:Antidepressive Agents / Q000009:adverse effects / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000503:physiopathology; D006801:Humans; D008550:Melatonin / Q000819:agonists* / Q000378:metabolism / Q000494:pharmacology; D044122:Receptor, Melatonin, MT1 / Q000819:agonists* / Q000378:metabolism; D044123:Receptor, Melatonin, MT2 / Q000819:agonists*; D009281:Naphthalenes
chemical_list: D000081:Acetamides; D000928:Antidepressive Agents; D008550:Melatonin; D044122:Receptor, Melatonin, MT1; D044123:Receptor, Melatonin, MT2; C084711:agomelatine; D009281:Naphthalenes