Bidirectional communication between sleep and circadian rhythms and its implications for depression: lessons from agomelatine

Depression is a family of complex and multifactorial illnesses that are characterized by disruptions in the functioning of a number of physiological, neuroendocrine and behavioral processes. Of these, sleep disturbance and circadian rhythm abnormalities constitute the most prevalent signs of depressive illness. Difficulty in falling asleep, decreases in total sleep time and sleep efficiency, early morning awakenings, and rapid eye movement sleep alterations are all commonly seen in depressed patients. Advances or delays in the phase of circadian rhythms have been documented in patients with major depressive disorder (MDD), bipolar disorder and patients with seasonal affective disorder (SAD). The disturbances in the amplitude and rhythm of melatonin secretion that occur in patients with depression resemble those seen in subjects with chronobiological disorders. The finding that insomnia and circadian rhythm abnormalities are prominent features in depression suggests that a close link exists between melatonin secretion disturbance and depressed mood. This inference has been further strengthened by the finding that agomelatine, a recently introduced melatonergic agent with a novel mechanism of action, has beneficial effects in patients with MDD, bipolar disorder or SAD. Among agomelatine's characteristics are a rapid onset of action and a pronounced effectiveness for improving sleep efficiency and correcting circadian rhythm abnormalities. Disruptions in melatonin secretion or availability may be the common factor, which underlies depressive disorder and its prominent signs and symptoms such as sleep and circadian rhythm abnormalities.