Skip to main content
SpringerLink
Log in

Agomelatine: an agent against anhedonia and abulia?

  • Psychiatry and Preclinical Psychiatric Studies - Review article
  • Published:
Journal of Neural Transmission Aims and scope Submit manuscript

Abstract

Anhedonia and abulia are syndromes often presented as components of various psychiatric and neurological disorders, including depression, schizophrenia, stroke, multiple sclerosis and brain injury. On the basis of the hypothesis that alterations in the dopaminergic motivational system might be involved in the etiopathogenesis of these clinical phenomena, the antidepressant agomelatine is a highly interesting candidate substance for their treatment because of its indirect dopaminergic effects resulting from its melatoninergic and partial anti-serotoninergic properties. Systematic clinical studies are urgently needed to test the hypothesis that agomelatine might be a clinically useful and versatile anti-anhedonic and/or anti-abulic substance.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  • Bakheit AM, Fletcher K, Brennan A (2011) Successful treatment of severe abulia with co-beneldopa. NeuroRehabilitation 29:347–351

    CAS  PubMed  Google Scholar 

  • Barrett K (1991) Treating organic abulia with bromocriptine and lisuride: four case studies. J Neurol Neurosurg Psychiatry 54:718–721

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Berrios GE, Gili M (1995) Will and its disorders: a conceptual history. Hist Psychiatry 6:87–104

    Article  Google Scholar 

  • Blier P, El Monsari M (2013) Serotonin and beyond: therapeutics for major depression. Phil Trans R Soc B 368:20120536

    Article  PubMed Central  PubMed  Google Scholar 

  • Chenu F, El Mansari M, Blier P (2013) Electrophysiological effects of repeated administration of agomelatine on the dopamine, norepinephrine, and serotonin systems in the rat brain. Neuropsychopharmacology 38:275–284

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Corruble E, de Bodinat C, Belaïdi C, Goodwin GM (2013) Efficacy of agomelatine and escitalopram on depression, subjective sleep and emotional experiences in patients with major depressive disorder: a 24-wk randomized, controlled, double-blind trial. Int J Neuropsychopharmacol 16:2219–2234

    Article  CAS  PubMed  Google Scholar 

  • Dahale AB, Narayanaswamy JC, Venkatasubramanian G, Bagewadi VI (2013) Successful use of agomelatine and venlafaxine combination in major depression. Gen Hosp Psychiatry. doi:10.1016/j.genhosppsych.2013.09.001 (in press)

  • De Berardis D, Valchera A, Fornaro M, Serroni N, Marini S, Moschetta FS, Martinotti G, Di Giannantonio M (2013a) Agomelatine reversal of escitalopram-induced apathy: a case report. Psychiatry Clin Neurosci 67:190–191

    Article  PubMed  Google Scholar 

  • De Berardis D, Marini S, Fornaro M, Srinivasan V, Iasevoli F, Tomasetti C, Valchera A, Perna G, Quera-Salva M-A, Martinotti G, di Giannantonio M (2013b) the melatonergic system in mood and anxiety disorders and the role of agomelatine: implications for clinical practice. Int J Mol Sci 14:12458–12483

    Article  PubMed Central  PubMed  Google Scholar 

  • De Berardis D, Conti CM, Marini S, Ferri F, Iasevoli F, Valchera A, Fornaro M, Cavuto M, Srinivasan V, Perna G, Carano A, Piersanti M, Martinotti G, Di Giannantonio M (2013c) Is there a role for agomelatine in the treatment of anxiety disorders?a review of published data. Int J Immunopathol Pharmacol 26:299–304

    PubMed  Google Scholar 

  • Demyttenaere K, Corruble E, Hale A, Quera-Salva MA, Picarel-Blanchot F, Kasper S (2013) A pooled analysis of six month comparative efficacy and tolerability in four randomized clinical trials: agomelatine versus escitalopram, fluoxetine, and sertraline. CNS Spectr 18:163–170

    Article  PubMed  Google Scholar 

  • Di Giannantonio M, Martinotti G (2012) Anhedonia and major depression: the role of agomelatine. Eur Neuropsychopharmacol 22(Suppl 3):S505–S510

    Article  PubMed  Google Scholar 

  • Di Giannantonio M, Di Iorio G, Guglielmo R, De Berardis D, Conti CM, Acciavatti T, Cornelio M, Martinotti G (2011) Major depressive disorder, anhedonia and agomelatine: an open-label study. J Biol Regul Homeost Agents 25:109–114

    PubMed  Google Scholar 

  • Fonken LK, Nelson RJ (2013) Dim light at night increases depressive-like responses in male C3H/HeNHsd mice. Behav Brain Res 243:74–78

    Article  PubMed  Google Scholar 

  • Fornaro M, McCarthy MJ, De Berardis D, De Pasquale C, Tabaton M, Martino M, Colicchio S, Cattaneo CI, D’Angelo E, Fornaro P (2013) Adjunctive agomelatine therapy in the treatment of acute bipolar II depression: a preliminary open-label study. Neuropsychiat Dis Treatment 9:243–251

    Article  CAS  Google Scholar 

  • Förstl H, Sahakian B (1991) A psychiatric presentation of abulia—three cases of left frontal lobe ischaemia and atrophy. J R Soc Med 84:89–91

    PubMed Central  PubMed  Google Scholar 

  • Fuchs E, Simon M, Schmelting B (2006) Pharmacology of a new antidepressant: benefits of the implications of the melatonergic system. Int J Clin Psychopharmacol 2006(Suppl 1):S17–S20

    Article  Google Scholar 

  • Ghoshal S, Gokhale S, Rebovich G, Caplan LR (2011) The neurology of decreased activity: abulia. Rev Neurol Dis 8:55–67

    Google Scholar 

  • Heun R, Ahokas A, Boyer P, Giménez-Montesinos N, Pontes-Soares F, Olivier V (2013) Agomelatine Study Group The efficacy of agomelatine in elderly patients with recurrent major depressive disorder: a placebo-controlled study. J Clin Psychiatry 74:587–594

    Article  CAS  PubMed  Google Scholar 

  • Howland RH (2009) Critical appraisal and update on the clinical utility of agomelatine, a melatonergic agonist, for the treatment of major depressive disease in adults. Neuropsychiatr Dis Treat 5:563–576

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kasper S, Hajak G (2013) The efficacy of agomelatine in previously-treated depressed patients. Eur Neuropsychopharmacol 23:814–821

    Article  CAS  PubMed  Google Scholar 

  • Kennedy SH (2009) Agomelatine: efficacy at each phase of antidepressant treatment. CNS Drugs 23(Suppl 2):41–47

    Article  CAS  PubMed  Google Scholar 

  • Kennedy SH, Rizvi SJ (2010) Agomelatine in the treatment of major depressive disorder: potential for clinical effectiveness. CNS Drugs 24:479–499

    Article  CAS  PubMed  Google Scholar 

  • Koesters M, Guaiana G, Cipriani A, Becker T, Barbui C (2013) Agomelatine efficacy and acceptability revisited: systematic review and meta-analysis of published and unpublished randomised trials. Br J Psychiatry 203:179–187

    Article  PubMed  Google Scholar 

  • Lanfumey L, Mongeau R, Hamon M (2013) Biological rhythms and melatonin in mood disorders and their treatments. Pharmacol Ther 138:176–184

    Article  CAS  PubMed  Google Scholar 

  • Mairesse J, Silletti V, Laloux C, Zuena AR, Giovine A, Consolazione M, van Camp G, Malagodi M, Gaetani S, Cianci S, Catalani A, Mennuni G, Mazzetta A, van Reeth O, Gabriel C, Mocaër E, Nicoletti F, Morley-Fletcher S, Maccari S (2012) Chronic agomelatine treatment corrects the abnormalities in the circadian rhythm of motor activity and sleep/wake cycle induced by prenatal restraint stress in adult rats. Int J Neuropsychopharmacol 6:1–16

    Google Scholar 

  • Marin RS, Wilkosz PA (2005) Disorders of diminished motivation. J Head Trauma Rehabil 20:377–388

    Article  PubMed  Google Scholar 

  • Martinotti G, Sepede G, Gambi F, Di Iorio G, De Berardis D, Di Nicola M, Onofrj M, Janiri L, Di Giannantonio M (2012) Agomelatine versus venlafaxine XR in the treatment of anhedonia in major depressive disorder: a pilot study. J Clin Psychopharmacol 32:487–491

    Article  CAS  PubMed  Google Scholar 

  • Milano W, De Rosa M, Milano L, Riccio A, Sanseverino B, Capasso A (2013) Successful treatment with agomelatine in NES: a series of five cases. Open Neurol J. 7:32–37

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Millan MJ, Gobert A, Lejeune F, Dekeyne A, Newman-Tancredi A, Pasteau V, Rivet JM, Cussac D (2003) 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 306:954–964

    Article  CAS  PubMed  Google Scholar 

  • Miller DB, O’Callaghan JP (2013) Personalized medicine in major depressive disorder – opportunities and pitfalls. Metabolism 62(Suppl 1):S34–S39

    Article  CAS  PubMed  Google Scholar 

  • O’Brien EM, Chelminski I, Young D, Dalrymple K, Hrabosky J, Zimmerman M (2011) Severe insomnia is associated with more severe presentation and greater functional deficits in depression. J Psychiatr Res 45:1101–1105

    Article  PubMed  Google Scholar 

  • Pecenak J, Novotny V (2013) Agomelatine as monotherapy for major depression: an outpatient, open-label study. Neuropsychiatr Dis Treat 9:1595–1604

    Article  PubMed Central  PubMed  Google Scholar 

  • Rainer Q, Xia L, Guilloux JP, Gabriel C, Mocaër E, Hen R, Enhamre E, Gardier AM, David DJ (2011) Beneficial behavioural and neurogenic effects of agomelatine in a model of depression/anxiety. Int J Neuropsychopharmacol 2011:1–15

    Google Scholar 

  • Redman JR, Guardiola-Lemaitre B, Brown M, Delagrange P, Armstrong SM (1995) Dose dependent effects of S-20098, a melatonin agonist on a direction of re-entrainment of rat circadian activity rhythms. Psychopharmacol (Berlin) 118:385–390

    Article  CAS  Google Scholar 

  • Ribot TA (1896) La psychologie des sentiments. Felix Alcan, Paris

    Google Scholar 

  • Sansone RA, Sansone LA (2011) Agomelatine: a novel antidepressant. Innov Clin Neurosci 8:10–14

    Google Scholar 

  • Sinnott C, Morris M (2013) Agomelatine: clinical experience and adherence to EMA recommendations for a novel antidepressant. Ir Med J 106:52–54

    CAS  PubMed  Google Scholar 

  • Souery D, Papakostas GI, Trivedi MH (2006) Treatment-resistant depression. J Clin Psychiatry 67(Suppl 6):16–22

    PubMed  Google Scholar 

  • Stahl SM (2007) Novel mechanism of antidepressant action: norepinephrine and dopamine disinhibition (NDDI) plus melatonergic agonism. Int J Neuropsychopharmacol 10:575–578

    Article  CAS  PubMed  Google Scholar 

  • Stahl SM, Fava M, Trivedi MH, Caputo A, Shah A, Post A (2010) Agomelatine in the treatment of major depressive disorder: an 8-week, multicenter, randomized, placebo-controlled trial. J Clin Psychiatry 71:616–626

    Article  CAS  PubMed  Google Scholar 

  • Stein DJ, Picarel-Blanchot F, Kennedy SH (2013) Efficacy of the novel antidepressant agomelatine for anxiety symptoms in major depression. Hum Psychopharmacol 28:151–159

    Article  CAS  PubMed  Google Scholar 

  • Štuhec M (2013) Agomelatine-induced hepatotoxicity. Wien Klin Wochenschr 125:225–226

    Article  PubMed  Google Scholar 

  • Sunderajan P, Gaynes BN, Wisniewski SR, Miyahara S, Fava M, Akingbala F, DeVeaugh-Geiss J, Rush AJ, Trivedi MH (2010) Insomnia in patients with depression: a STAR*D report. CNS Spectr 15:394–404

    PubMed  Google Scholar 

  • Tapia-Osorio A, Salgado-Delgado R, Angeles-Castellanos M, Escobar C (2013) Disruption of circadian rhythms due to chronic constant light leads to depressive and anxiety-like behaviors in the rat. Behav Brain Res 252:1–9

    Article  PubMed  Google Scholar 

  • Treadway MT, Zald DH (2011) Reconsidering anhedonia in depression: lessons from translational neuroscience. Neurosci Biobehav Rev 35:537–555

    Article  PubMed Central  PubMed  Google Scholar 

  • Vijayaraghavan L, Krishnamoorthy ES, Brown RG, Trimble MR (2002) Abulia: a Delphi survey of British neurologists and psychiatrists. Mov Disord 17:1052–1057

    Article  PubMed  Google Scholar 

  • Warden D, Trivedi MH, Fava M, Wisniewski SR (2007) The STAR*D project results: a comprehensive review of findings. Curr Psychiatry Rep 9:449–459

    Article  PubMed  Google Scholar 

  • Weizman S, Gonda X, Dome P, Faludi G (2012) Pharmacogenetics of antidepressive drugs: a way towards personalized treatment of major depressive disorder. Neuropsychopharmacol Hung 14:87–101

    PubMed  Google Scholar 

  • Zajecka J, Schatzberg A, Stahl S, Shah A, Caputo A, Post A (2010) Efficacy and safety of agomelatine in the treatment of major depressive disorder: a multicenter, randomized, double-blind, placebo-controlled trial. J Clin Psychopharmacol 30:135–144

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

J.T. has received financial support from Servier, the manufacturer of agomelatine (as a member of the German advisory board, for organising and attending conferences and for conducting a survey). He has also received financial support from the following companies, some of which are manufacturers of other antidepressants: Actelion, Ever, Lilly, Lundbeck, Medice, Merz, Novartis, Pfizer, Roche, Trommsdorff.

Author information

Authors and Affiliations

  1. Department of Psychiatry, University of Rostock, Rostock, Germany

    J. Thome & P. Foley

Authors
  1. J. Thome
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. P. Foley
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J. Thome.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Thome, J., Foley, P. Agomelatine: an agent against anhedonia and abulia?. J Neural Transm 122 (Suppl 1), 3–7 (2015). https://doi.org/10.1007/s00702-013-1126-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00702-013-1126-6

Keywords

Search

Navigation