Agomelatine beyond Borders: Current Evidences of Its Efficacy in Disorders Other than Major Depression

Abstract

Agomelatine, a melatonergic antidepressant with a rapid onset of action, is one of the most recent drugs in the antidepressant category. Agomelatine’s antidepressant actions are attributed to its sleep-promoting and chronobiotic actions mediated by MT1 and MT2 receptors present in the suprachiasmatic nucleus, as well as to its effects on the blockade of 5-HT2c receptors. Blockade of 5-HT2c receptors causes release of both noradrenaline and dopamine at the fronto-cortical dopaminergic and noradrenergic pathways. The combined actions of agomelatine on MT1/MT2 and 5-HT2c receptors facilitate the resynchronization of altered circadian rhythms and abnormal sleep patterns. Agomelatine appeared to be effective in treating major depression. Moreover, evidence exists that points out a possible efficacy of such drug in the treatment of bipolar depression, anxiety disorders, alcohol dependence, migraines etc. Thus, the aim of this narrative review was to elucidate current evidences on the role of agomelatine in disorders other than major depression.

Effectiveness of agomelatine on anhedonia in depressed patients: an outpatient, open-label, real-world study

“…While various pharmacological treatment options are available, there are still unsatisfied needs, including the lack of consistent evidence of improvement in anhedonia, identified as a loss of interest and lack of reactivity to pleasurable stimuli in daily life, being one of the two core symptoms of depression (Treadway & Zald, ). Anhedonia has been considered crucial for the diagnosis of depression (Klein, ; Schrader, ), and is a transnosographic condition reported in several psychiatric disorders (Hatzigiakoumis, Martinotti, Di Giannantonio, & Janiri, ; Millan, Fone, Steckler, & Horan, ; De Berardis et al, ; Di Nicola et al, , Pettorruso et al, ), including alcohol, and substance abuse (Martinotti, Cloninger, & Janiri, ) and neurological disorders (Pettorruso et al, ). In major depression, anhedonia persistence is associated with the prediction of unsatisfactory outcomes in the treatment of depression, as patients do not achieve appropriate clinical remission, with functional and quality‐of‐life impairment (McMakin et al, ; Vrieze et al, ).…”

Personality traits, gender differences and symptoms of anhedonia: What does the Hospital Anxiety and Depression Scale (HADS) measure in nonclinical settings?

“…However, anhedonia is more than just the reduced experience of pleasure, and recent research on it has focused on the differentiation of the concept into impairments in wanting, liking, and learning (Rømer‐Thomsen et al ., ). In research on depression and its pharmacological treatment (anti‐depressants), there has been an emerging interest in anhedonia (De Berardis et al ., ; Di Giannantonio & Martinotti, ; Kennedy & Cyriac, ). The focus on different subtypes of depression, like anhedonic depression, has implications for treatment as well as for diagnoses as different antidepressants have unique effects on reward processes (McCabe, Mishor, Cowen & Harmer, ; Kennedy & Cyriac, ).…”

Clinical and Experimental Human Sleep-Wake Pharmacogenetics

“…Ramelteon received FDA-approval for treatment of insomnia in older adults, and the MT1/2 agonist/5-HT2C receptor antagonist, agomelatine, has EMA-and TGA (Therapeutic Goods Administration, Australia)-approval for major depressive disorder. Agomelatine phase shifts the circadian system and improves sleep in depressed patients, although its usefulness for primary sleep disorders is debated (De Berardis et al, 2015).…”