Review article

AGOMELATINE AS CHRONOPSYCHOPHARMACEUTICS RESTORING CIRCADIAN RHYTHMS AND ENHANCING RESILIENCE TO STRESS: A WISHFULL THINKING OR AN INNOVATIVE STRATEGY FOR SUPERIOR MANAGEMENT OF DEPRESSION?

Miro Jakovljević ; Department of Psychiatry, University Hospital Centre Zagreb, Croatia

Abstract

Background: While the research and treatment focus of biological aspects of depression has traditionally centered on
neutrotransmitters disturbances, there has been relatively little attention paid to the chronobiological aspects of depression that offer
rapid acting chronotherapeutis and from recently also an innovative circadian rhythms resynchronizing antidepressant.
Objective: This article discusses chronobiological aspects of psychiatric treatment, particularly related to depression. It is
concerned with chronotherapeutics and pharmacological interventions to resychronize circadian rhythms, particularly focused on
agomelatine, an innovative antidepressant targeting melatonergic M1/M2 and serotonergic 5-HT2c receptors.
Discussion: Depression can be explained as dysfunction at the nexus of the body, brain and mind, three mutually very dependent
components, associated through circadian pace makers at the molecular, cellular, physiological and behavioral levels. Mental
disorders, particularly depression, are common in people with circadian rest-activity cycle disturbances and sleep-wake problems.
The circadian rest-activity and sleep-wake cycle disturbances are risk factors for developing and recurrence of mental disorders as
well as, what is very important, they are associated with worse outcome. The interrelationships between circadian rhythm
disturbances and depression is very complex, and the fundamental question is whether they trigger depression or whether these
disturbances arise as a consequence of the disease. However, both depression and circadian rhythm disturbances may have a
common aetiology: a decreased cellurar resilience associated with lower resistance to stressful events. Treating depression
pharmacologicaly through the restoration of circadian rhythms may open a new era of superior management of depression and other
mental disorders.
Conclusion: Chronotherapeutic strategies that reset the internal clock may have specific advantage for the treatment of
depression and other mental disorders. There is still a lot of research to be done on utilising chronotherapeutic principles in clinical
practice, particularly regarding the specific indications. Agomelatine seems to be an promising resynchronizing agent expanding the
field of chronopharmacology and inducing new treatment strategy.

Keywords

agomelatine; chronotherapeutics; chronopsychopharmacology; allostatic regulation; resilience to stress and depression

Hrčak ID:

76421

URI

https://hrcak.srce.hr/76421

Publication date:

31.3.2011.

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