Therapeutics for Circadian Rhythm Sleep Disorders

The sleep-wake cycle is regulated by the interaction of endogenous circadian and homeostatic processes. The circadian system provides timing information for most physiologic rhythms, including the sleep and wake cycle. In addition, the central circadian clock located in the suprachiasmatic nucleus of the hypothalamus has been shown to promote alertness during the day. Circadian rhythm sleep disorders arise when there is a misalignment between the timing of the endogenous circadian rhythms and the external environment, or when there is dysfunction of the circadian clock or its entrainment pathways. The primary synchronizing agents of the circadian system are light and melatonin. Light is the strongest entraining agent of circadian rhythms, and timed exposure to bright light is often used in the treatment of circadian rhythm sleep disorders. In addition, timed administration of melatonin, either alone or in combination with light therapy, has been shown to be useful in the treatment of the following circadian rhythm sleep disorders: delayed sleep phase, advanced sleep phase, free-running, irregular sleep-wake, jet lag, and shift work.