Pathophysiology of depression: Role of sleep and the melatonergic system
by
Srinivasan V, Pandi-Perumal SR, Trakht I, Spence DW,
Hardeland R, Poeggeler B, Cardinali DP.
Department of Physiology, School of Medical Sciences,
University Sains Malaysia,
Kubang Kerian, Kota Bharu, Kelantan, Malaysia.
Psychiatry Res. 2009 Feb 28;165(3):201-14.


ABSTRACT

Profound disturbances in sleep architecture occur in major depressive disorders (MDD) and in bipolar affective disorders. Reduction in slow wave sleep, decreased latency of rapid eye movement (REM) sleep and abnormalities in the timing of REM/non-REM sleep cycles have all been documented in patients with MDD. It is thus evident that an understanding of the basic mechanisms of sleep regulation is essential for an analysis of the pathophysiology of depressive disorders. The suprachiasmatic nucleus (SCN), which functions as the body's master circadian clock, plays a major role in the regulation of the sleep/wakefulness rhythm and interacts actively with the homeostatic processes that regulate sleep. The control of melatonin secretion by the SCN, the occurrence of high concentrations of melatonin receptors in the SCN, and the suppression of electrical activity in the SCN by melatonin all underscore the major influence which this neurohormone has in regulating the sleep/wake cycle. The transition from wakefulness to high sleep propensity is associated with the nocturnal rise of endogenous melatonin secretion. Various lines of evidence show that depressed patients exhibit disturbances in both the amplitude and shape of the melatonin secretion rhythm and that melatonin can improve the quality of sleep in these patients. The choice of a suitable antidepressant that improves sleep quality is thus important while treating a depressive disorder. The novel antidepressant agomelatine, which combines the properties of a 5-HT(2C) antagonist and a melatonergic MT(1)/MT(2) receptor agonist, has been found very effective for resetting the disturbed sleep/wake cycle and in improving the clinical status of MDD. Agomelatine has also been found useful in treating sleep problems and improving the clinical status of patients suffering from seasonal affective disorder.
5-HT2c
Valdoxan
Serotonin
Melatonin
Agomelatine
Agomelatine trials
Agomelatine: structure
Serotonin 5-HT2c receptors
Agomelatine (Valdoxan): review
Agomelatine, stress and memory
New antidepressants: agomelatine
Agomelatine (Valdoxan) and melatonergic drugs
Agomelatine (Valdoxan): efficacy and tolerance profile
Agomelatine, 5-HT2c antagonist and melatonin agonist
Agomelatine, circadian rhythms and antidepresant efficacy
Agomelatine (Valdoxan, Melitor, Thymanax) to treat major depression
Agomelatine (Valdoxan) and the serotonin 5-HT2b and 5-HT2c receptors
Jet lag: therapeutic use of melatonin and possible application of melatonin analogs


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