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Agomelatine, Melatonin and Depression

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Melatonin, Neuroprotective Agents and Antidepressant Therapy

Abstract

While seasonal and circadian rhythm alterations in the condition of depression have been suggested since antiquity, only in recent times has the notion been tested with empirical data. Therapeutic approaches based on the manipulation of circadian rhythm are a later development, with the antidepressant medication, agomelatine, being approved for clinical use in many jurisdictions. Agomelatine is a multifunctional drug with agonist actions at melatonin-1 (MT1) and melatonin-2 (MT2) receptors. An additional antagonist action at the serotonin-2C (5HT2C) receptors also appears to be necessary for its antidepressant effect. Despite this, the potential role of both the endogenous agonist of melatonin receptors, melatonin, and other melatonin receptor agonists has been a renewed focus of attention as a potential source of additional antidepressant agents. A review of findings relating possible melatonin abnormalities in major depressive disorder as well as the action of melatonin and newer melatonin selective agonists as antidepressants is presented. Measurement of melatonin output in depression has not yielded consistent findings, and the suggestion of a ‘low melatonin syndrome’ in depression does not appear to be supported by the extant data. Furthermore, there is little evidence for melatonin or synthetic agonists as stand-alone antidepressant agents. On the other hand, adjunctive therapy with melatonin or other agonists has empirical evidence to support their use for benefiting sleep in depressed patients. This lack of efficacy of melatonin agonists for treatment of core depressive symptoms supports the notion that additional pharmacological actions of agomelatine are essential for its antidepressant effects. A brief review of the efficacy of agomelatine as an antidepressant is provided although this is not the major focus of this article. Normalisation of the circadian rhythm for antidepressant effects in patients may be a necessary but not sufficient condition for remission of symptoms. It would appear that additional pharmacological actions are an essential requirement for a molecule to demonstrate antidepressant effects in the clinic.

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Notes

  1. 1.

    Mesor is defined as the average of the rhythmic variable (melatonin concentration in this case) over a single cycle determined as the mean of a fitted cosine curve.

  2. 2.

    Acrophase: Time of maximum of a fitted cosine curve given as a delay from a given phase reference. The acrophase may also be specified with the phase reference being the point of an environmental cycle (e.g. mid-light time) or the acrophase of another rhythm in the same individual (e.g. mid-sleep time).

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Authors and Affiliations

  1. Department of Psychiatry, University of Melbourne, Austin Hospital, Heidelberg, 3084, Victoria, Australia

    Trevor R. Norman

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  1. Vice-Rectorate for Research and Sci, Camilo José Cela University Vice-Rectorate for Research and Sci, Madrid, Spain

    Francisco López-Muñoz

  2. International Medical Sciences Research Study Center, Sri Sathya Sai Medical Educational & Research Foundation, Coimbatore, India

    Venkataramanujam Srinivasan

  3. Department of Neurosciences and Ima, University of Chieti Department of Neurosciences and Ima, Italy, Italy

    Domenico de Berardis

  4. Department of Biomedical Sciences (Pharmacology Area), University of Alcalá, Madrid, Spain

    Cecilio Álamo

  5. Department of Neuropsychiatry, Kyushu University, Fukuoka, Japan

    Takahiro A. Kato

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Norman, T.R. (2016). Agomelatine, Melatonin and Depression. In: López-Muñoz, F., Srinivasan, V., de Berardis, D., Álamo, C., Kato, T. (eds) Melatonin, Neuroprotective Agents and Antidepressant Therapy. Springer, New Delhi. https://doi.org/10.1007/978-81-322-2803-5_18

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