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Agomelatine: A novel mechanism of antidepressant action involving the melatonergic and the serotonergic system

Published online by Cambridge University Press:  16 April 2020

Luis San  and
Belen Arranz
Luis San
Affiliation:
Department of Psychiatry, Hospital San Rafael, Barcelona, Spain
Belen Arranz*
Affiliation:
Sant Joan de Déu, Serveis de Salut Mental, Antoni Pujades, 42, 08830, Sant Boi de Llobregat, Barcelona, Spain
*
*Corresponding author. E-mail address: [email protected] (B. Arranz).
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Abstract

The clinical finding that depressive disorders are often associated with desynchronization of internal rhythms has encouraged the idea that resetting normal circadian rhythms may have antidepressant potential. Agomelatine, a naphthalene analog of melatonin, is both an agonist of human cloned melatonergic MT1 and MT2 receptors and a serotonin 5-HT2C receptor antagonist. Agomelatine combines zeitgeber (synchroniser of the circadian system) activity with neurotransmitter augmentation properties (enhances the levels of dopamine and noradrenaline in frontal cortex). The efficacy of agomelatine in treating depression has been shown in three short-term, pivotal, randomized, placebo–controlled studies. These studies have demonstrated agomelatine to be efficacious in Major Depressive Disorder at the standard dose of 25 mg/day, with the possibility of increasing doses to 50 mg/day in those patients with insufficient improvement. The number of adverse events during the treatment period was comparable to placebo. Four studies have shown the positive effect of agomelatine on sleep continuity and quality and shortening of sleep latency. Despite these promising data, further studies are needed to examine agomelatine's efficacy over a longer treatment period.

Keywords

Circadian rhythmsDepressionSleep disordersMelatoninAgomelatine
Type
Review
Information
European Psychiatry , Volume 23 , Issue 6 , September 2008 , pp. 396 - 402
Copyright
Copyright © Elsevier Masson SAS 2008

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