Agomelatine, a novel intriguing antidepressant option enhancing neuroplasticity: A critical review

Abstract

Objectives. The treatment of major affective disorders, commonly associated with high disability and elevated social costs may be still considered unsatisfactory. Among all antidepressant drugs, predominantly acting through monoaminergic mechanisms, agomelatine is of particular interest due to another alternative mechanism of action. Targeting melatonergic receptors, agomelatine play a crucial role in synchronizing circadian rhythms, known to be altered in depressed subjects. Methods. A critical review of the literature focusing on efficacy, safety and tolerability of agomelatine in major affective disorders was performed. Additionally, we focused on the potential of agomelatine in enhancing neuroplasticity mechanisms and promote neurogenesis. A total of 136 articles from peer-reviewed journals were identified, of which 50 were assessed for eligibility and 21 were included. Results. Agomelatine, a melatonergic analogue drug acting as MT₁/MT₂ agonist and 5-HT_2C antagonist, has been reported to be effective as antidepressant drug. Studies confirmed not only clinical efficacy but also safety and tolerability of agomelatine. Also, it enhances neuroplasticity mechanisms and adult neurogenesis in brain areas such as hippocampus and prefrontal cortex. Conclusions. Agomelatine actually represents an intriguing option in the treatment of affective disorders.

Key words::

• Agomelatine
• antidepressant drugs
• efficacy
• tolerability
• neuroplasticity

Acknowledgements

Dr Pompili and Dr Serafini contributed equally in reviewing the literature and in drafting the paper. Dr Girardi provided the intellectual impetuous and supervised the search strategy. Drs Innamorati, Sher, Amore, Fusar-Poli and Venturini provided help in selecting papers and drafting the papers. This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Statement of Interest

The authors declare no competing interests for this paper. No financial support was provided for this paper.

Dr Pompili has served as a consultant with ScheringPlough Corporation Italy, or has engaged in research collaborations with AstraZeneca and received travel support from Servier and Stroder. Dr Serafini has served as a consultant to, or engaged in research collaborations with Bristol-Myers Squibb, Janssen, Eli Lilly, Glaxo Smith Kline and AstraZeneca and received travel support from Servier and Lundbeck. Dr Girardi has served as a consultant to, or has engaged in research collaborations with Organon, Eli Lilly, Janssen, Merck, Bristol-Myers Squibb, Pfizer, and AstraZeneca Corporations.