Agomelatine for the treatment of generalized anxiety disorder: focus on its distinctive mechanism of action

Millan, M. J. (2022) Agomelatine for the treatment of generalized anxiety disorder: focus on its distinctive mechanism of action. Therapeutic Advances in Psychopharmacology, 12, p. 20451253221105128. (doi: 10.1177/20451253221105128)

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Abstract

Generalized anxiety disorder (GAD), the most frequently diagnosed form of anxiety, is usually treated by cognitive-behavioural approaches or medication; in particular, benzodiazepines (acutely) and serotonin or serotonin/noradrenaline reuptake inhibitors (long term). Efficacy, compliance, and acceptability are, however, far from ideal, reinforcing interest in alternative options. Agomelatine, clinically employed in the treatment of major depression, expresses anxiolytic properties in rodents and was effective in the treatment of GAD (including severely ill patients) in several double-blind, short-term (12 weeks) and relapse-prevention (6 months) studies. At active doses, the incidence of adverse effects was no higher than for placebo. Agomelatine possesses a unique binding profile, behaving as a melatonin (MT1/MT2) receptor agonist and 5-HT2C receptor antagonist, yet recognizing neither monoamine transporters nor GABAA receptors. Extensive evidence supports a role for 5-HT2C receptors in the induction of anxious states, and their blockade likely plays a primary role in mediating the anxiolytic actions of agomelatine, including populations in the amygdala and bed nucleus of stria terminalis, as well as the hippocampus. Recruitment of MT receptors in the suprachiasmatic nucleus, thalamic reticular nucleus, and hippocampus appears to fulfil a complimentary role. Downstream of 5-HT2C and MT receptors, modulation of stress-sensitive glutamatergic circuits and altered release of the anxiogenic neuropeptides, corticotrophin-releasing factor, and vasopressin, may be implicated in the actions of agomelatine. To summarize, agomelatine exerts its anxiolytic actions by mechanisms clearly distinct from those of other agents currently employed for the management of GAD.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Millan, Dr Mark
Creator Roles:
Millan, M. J.Conceptualization, Formal analysis, Investigation, Writing – original draft, Writing – review and editing
Authors: Millan, M. J.
College/School:College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
Journal Name:Therapeutic Advances in Psychopharmacology
Publisher:SAGE Publications
ISSN:2045-1253
ISSN (Online):2045-1261
Published Online:30 June 2022
Copyright Holders:Copyright © 2022 The Author
First Published:First published in Therapeutic Advances in Psychopharmacology 12: 20451253221105128
Publisher Policy:Reproduced under a Creative Commons License

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