Agomelatine and the sleep-wake-rhythm in depression

Agomelatine and the sleep-wake-rhythm in depression The clinical finding that depression and related symptoms such as sleep-wake disorders, loss of appetite and diurnal changes of mood are often associated with altered circadian biological rhythms has encouraged the idea that resetting normal circadian rhythms may have antidepressant potential. The dual acting antidepressant agomelatine functions as agonist at melatonergic MT1 und MT2 receptors in the central nervous circadian system and as antagonist at postsynaptic, serotonergic 5-HT2C receptors. Agomelatine thereby combines chronobiotic activity (resetting and synchronizing circadian rhythms such as the sleep-wake-rhythm) and sleep promoting properties (enhancing slow wave sleep activity) with neurotransmitter augmentation properties (enhancing levels of dopamine and norepinephine in the frontal cortex). In contrast to other sleep inducing antidepressants, sedative effects with agomelatine are not prominent. The efficacy of agomelatine affecting sleep-wake-functions and other circadian parameters has been well investigated in animal models of depression and in healthy human subjects. Sleep recording in humans has shown that agomelatine improves sleep efficiency and enhances deep sleep. In controlled treatment studies for depression, depressive patients showed improved sleep initiation, sleep maintenance and sleep quality, in particular when compared with selective serotonin reuptake inhibitors. These effects of agomelatine on sleep represent a novel contributing property in the class of antidepressant agents.