The role of melatonin in sleep regulation

Abstract

Sleep, a state marked by lessened consciousness, lessened movement of the skeletal muscles, and slowed-down metabolism, has an essential restorative function and an important role in memory consolidation. Sleep is an orchestrated neurochemical process involving sleep promoting and arousal centers in the brain. Sleep propensity depends on the amount of sleep deprivation and on the circadian clock phase. Typically, humans sleep during the dark phase of the 24 h cycle. Insomnia is a symptom, resulting from insufficient sleep or sleep of poor quality. Insomnia is the most prevalent sleep complaint in the general population affecting about 27% of adults, and 10% in the general population reporting the symptoms as serious. The most commonly prescribed insomnia medications are the benzodiazepines and non-benzodiazepines GABA-A receptor modulators. These drugs typically shorten the latency to sleep, but are associated with sedation, anterograde amnesia, rebound, abuse potential, dependence, and tolerance, are indicated for short-term use and do not treat non-restorative sleep. Melatonin, the hormone secreted at night for the pineal gland, is a physiological sleep regulator in humans. Administration of melatonin to blind people who free run in the absence of the light cue and to subjects with delayed sleep phase syndrome is useful to attain synchronization of the sleep/wake cycle with the external night period. Aging is associated with increase in the prevalence of insomnia and decrease in melatonin production. Insomnia patients aged 55 years and older produce significantly less melatonin than younger adults and many of them produce lesser amounts than normal for their age. Administration of melatonin, in a prolonged release formulation to mimic the physiological release of the hormone, has proven effective in the improvement of sleep quality and daytime alertness in insomnia patients aged 55 years and over. Melatonin therapy may be less effective in patients producing timely and sufficient amounts of the hormone endogenously. Melatonin is not associated with the side effects of GABA-A modulators and thus represents a new paradigm is sleep medicine