Skip to main content
×
×
Home

Drug information update: agomelatine

  • Daniel Whiting (a1) and Philip J. Cowen (a1)
Summary

Agomelatine is a new antidepressant, licensed for the treatment of unipolar major depression, with a mode of action that combines activation of melatonin receptors with blockade of 5-HT2C receptors. Agomelatine is notable for its short duration of action in the body and modest side-effect burden; however, a number of theoretical and practical challenges have limited its adoption into mainstream treatment in the UK. Current meta-analyses show marginal clinical benefits of agomelatine relative to placebo and an association with occasional increases in liver transaminases. Theoretically it is not clear whether agomelatine does block brain 5-HT2C receptors in humans at therapeutic doses and the optimum daily timing of administration in depression has not been clearly established. However, agomelatine's novel mode of action justifies further study, perhaps with the eventual aim of matching its use in depression to patients with specific disturbances in circadian rhythm.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Drug information update: agomelatine
      Available formats
      ×
      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Drug information update: agomelatine
      Available formats
      ×
      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Drug information update: agomelatine
      Available formats
      ×
Copyright
This is an Open Access article, distributed under the terms of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
Corresponding author
Philip Cowen (phil.cowen@psych.ox.ac.uk)
Footnotes
Hide All

Declaration of interest

P.J.C. has been a paid member of advisory boards for Eli Lilly, Lundbeck and Servier.

Footnotes
References
Hide All
1 Boivin, DB. Influence of sleep-wake and circadian rhythm disturbances in psychiatric disorders. J Psychiatry Neurosci 2000; 25: 446–58.
2 Germain, A, Kupfer, DJ. Circadian rhythm disturbance in depression. Human Psychopharmacol 2008; 23: 571–85.
3 Pandi-Perumal, SR, Trakht, I, Spence, DW, Srinivasan, V, Dagan, Y, Cardinali, DP. The roles of melatonin and light in the pathophysiology and treatment of circadian rhythm sleep disorders. Nat Clin Pract Neurol 2008; 4: 436–47.
4 Millan, MJ, Gobert, A, Lejeune, F, Dekeyne, A, Newman-Tancredi, A, Pasteau, V, et al. The novel melatonin agonist agomelatine (S20098) is an antagonist at 5-hydroxytryptamine2C receptors, blockade of which enhances the activity of frontocortical dopaminergic and adrenergic pathways. J Pharmacol Exp Ther 2003; 306: 954–64.
5 Pandi-Perumal, SR, Trakht, I, Srinivasan, V, Spence, DW, Masetroni, GJM, Zisapel, N, et al. Physiological effects of melatonin: role of melatonin receptors and signal transduction pathways. Prog Neurobiol 2008; 85: 335–53.
6 San, L, Arranz, B. Agomelatine: a novel mechanism of antidepressant action involving the melatonergic and the serotonergic system. Eur Psychiatry 2008; 23: 396402.
7 Tardito, D, Molteni, R, Popoli, M, Racagni, G. Synergistic mechanisms involved in the antidepressant effects of agomelatine. Eur Neuropsychopharmacol 2012; 22 (suppl 3): S4826.
8 Molteni, R, Calabrese, F, Pisoni, S, Gabriel, C, Racagni, G, Riva, MA. Synergistic mechanisms in the modulation of the neurotrophin BDNF in the rat prefrontal cortex following acute agomelatine administration. World J Biol Psychiatry 2010; 11: 148–53.
9 Sen, S, Duman, R, Sanacora, G. Serum brain-derived neurotrophic factor, depression, and antidepressant medications: meta-analyses and implications. Biol Psychiatry 2008; 64: 527–32.
10 Sharpley, AL, Rawlings, NB, Brain, S, McTavish, SFB, Cowen, PJ. Does agomelatine block 5-HT2c receptors in humans? Psychopharmacology 2011; 213: 653–5.
11 Krauchi, K, Cajochen, C, Mori, D, Graw, P, Wirz-Justice, A. Early evening melatonin and S-20098 advance circadian phase and nocturnal regulation of core body temperature. Am J Physiol 1997; 272: R117888.
12 Leproult, G, Van Onderbergen, A, L'hermite-Balériaux, M, Van Cauter, E, Copinschi, G. Phase-shifts of 24-h rhythms of hormonal release and body temperature following early evening administration of the melatonin agonist agomelatine in healthy older men. Clin Endocrinol 2005; 63: 298304.
13 British Medical Association, Royal Pharmaceutical Society. British National Formulary (64th edn, September 2012). BMJ Group & Pharmaceutical Press, 2012.
14 Hickie, IB, Rogers, N. Novel melatonin-based therapies: potential advances in the treatment of major depression. Lancet 2011; 378: 621–31.
15 Singh, SP, Singh, V, Kar, N. Efficacy of agomelatine in major depressive disorder: meta-analysis and appraisal. Int J Neuropsychopharmacol 2012; 15: 417–28.
16 Barbui, C, Cipriani, A. Agomelatine and the brave old world of narrative-based medicine. Evid Based Ment Health 2012; 15: 23.
17 Rihmer, Z, Dome, P, Baldwin, DS, Gonda, X. Psychiatry should not become hostage to placebo: an alternative interpretation of antidepressant-placebo differences in the treatment response in depression. Eur Neuropsychopharmacol 2012; 22: 782–6.
18 Zajecka, J, Schatzberg, A, Stahl, S, Caputo, A, Post, A. Efficacy and safety of agomelatine in the treatment of major depressive disorder: a multicentre, randomized, double-blind, placebo-controlled trial. J Clin Psychopharmacol 2010; 30: 135–44.
19 Montejo, A, Majadas, S, Rizvi, SJ, Kennedy, SH. The effects of agomelatine on sexual function in depressed patients and healthy volunteers. Hum Psychopharmacol 2011; 26: 537–42.
20 Sparshatt, A, McAllister-Williams, RH, Baldwin, DS, Haddad, PM, Bazire, S, Weston, S, et al. A naturalistic evaluation and audit database of agomelatine: clinical outcome at 12 weeks. Acta Psychiatr Scand 2013; 128: 203–11.
21 Lewy, AJ. Circadian misalignment in mood disturbances. Curr Psychiatry Rep 2009; 11: 459–65.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

BJPsych Bulletin
  • ISSN: 1758-3209
  • EISSN: 1758-3217
  • URL: /core/journals/bjpsych-bulletin
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
×

Metrics

Full text views

Total number of HTML views: 0
Total number of PDF views: 4 *
Loading metrics...

Abstract views

Total abstract views: 54 *
Loading metrics...

* Views captured on Cambridge Core between 2nd January 2018 - 16th July 2018. This data will be updated every 24 hours.

Drug information update: agomelatine

  • Daniel Whiting (a1) and Philip J. Cowen (a1)
Submit a response

eLetters

No eLetters have been published for this article.

×

Reply to: Submit a response


Your details


Conflicting interests

Do you have any conflicting interests? *