Antidepressant chronotherapeutics for bipolar depression.

Chronotherapeutics refers to treatments based on the principles of circadian rhythm organization and sleep physiology, which control the exposure to environmental stimuli that act on biological rhythms, in order to achieve therapeutic effects in the treatment of psychiatric conditions. It includes manipulations of the sleep-wake cycle such as sleep deprivation and sleep phase advance, and controlled exposure to light and dark. The antidepressant effects of chronotherapeutics are evident in difficult-to-treat conditions such as bipolar depression, which has been associated with extremely low success rates of antidepressant drugs in naturalistic settings and with stable antidepressant response to chronotherapeutics in more than half of the patients. Recent advances in the study of the effects of chronotherapeutics on neurotransmitter systems, and on the biological clock machinery, allow us to pinpoint its mechanism of action and to transform it from a neglected or "orphan" treatment to a powerful clinical instrument in everyday psychiatric practice.