Agomelatine as chronopsychopharmaceutics restoring circadian rhythms and enhancing resilience to stress: a wishfull thinking or an innovative strategy for superior management of depression?

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.