In all life forms, circadian rhythms are defined by a period of approximately 24 hours. The daily light/dark cycle governs rhythmic changes in behavior and physiological and mental functions, ie, in activity, core body temperature, hormones, sleep-wake cycle. All circadian rhythms are driven and controlled by the biological clock, which in mammals is located in the suprachiasmatic nucleus (SCN) of the anterior hypothalamus.

Disruption of circadian organization is a characteristic of a variety of affective disorders, especially major depression, and, circadian abnormalities may constitute a core component of the pathophysiology of depression and may also determine the treatment response.

Depressed patients have documented abnormalities in mood, body-temperature, neuroendocrine secretion, and, most importantly and disabling, in sleep (approximately 90% of patients complain about their sleep). The sleep alterations are mainly related to poor sleep quality and maintenance and to difficulties in maintaining alertness during the day. Polysomnographic recordings show disruption of sleep continuity with prolonged sleep latency, increased wake time during the night, increased early morning wake time, decreased slow-wave sleep, and disinhibition of REM sleep. Most antidepressants can influence the architecture of sleep: SSRIs, SNRIs, and some TCAs (clomipramine) have "alerting" effects whereas others, among them, mirtazapine or trazodone, are sleep promoting often also causing sedation and daytime sleepiness. An important clinical goal in the treatment of major depression would therefore include antidepressants that improve both mood and quality of sleep without impairing daytime alertness.