The Therapeutic Potential of Melatonin: A Review of the Science

Samir Malhotra, MD; Girish Sawhney, MD; Promila Pandhi, MD

Disclosures
In This Article

Sleep Disturbances

Studies[10,11,12,13] have suggested that a relationship exists among sleep, pineal function, and melatonin levels. Nocturnal melatonin levels and the quality of sleep both decline at puberty;[10] in elderly populations, periods of sleep tend to become shorter and the quality of sleep poorer. Controlled clinical trials have shown that melatonin is effective as a chronobiotic in a number of circadian rhythm sleep disorders.

Jet Lag

When melatonin is taken at the destination, between 10 pm and midnight, it can correct the sleep disturbances, mental inefficiency, and daytime fatigue (cumulatively known as "jet lag") that occur after flights across several time zones.[11,12,13] The biological rhythm disorganization caused by the rapid change of environment (and associated light/dark cues) apparently can be corrected by melatonin. The benefit is likely to be greater as more time zones are crossed and less for westward flights.[12] However, melatonin taken before travel can actually worsen symptoms as opposed to the benefit of melatonin initiated immediately upon arrival.[13] Parry[14] has reviewed the use and effectiveness of melatonin as a 'dark pulse' at night, with appropriately timed bright light to reduce symptoms of jet lag.

Insomnia

Nocturnal melatonin levels are reduced in primary insomnia.[15] Supplemental melatonin has been used successfully as a hypnotic for delayed sleep-phase syndrome, a type of insomnia characterized by wakefulness and the inability to fall asleep before 2:00 to 3:00 am. In several small studies, 5-mg doses of melatonin given at 10 pm resulted in an advance of the sleep phase (shortening of time to sleep) by about 1.5 hours[16,17] and reduced sleep duration by about 30 minutes,[16] suggesting a lowered sleep requirement as a consequence of improved sleep quality.[18]

Narcolepsy

Melatonin has also been used to alter sleep architecture in narcolepsy, a disorder of disturbed circadian sleep/wake rhythm and rapid-eye-movement (REM) sleep deficit. Changes in REM sleep patterns similar to those of narcolepsy also occur in animals and humans after removal of the pineal gland.[19] Pharmacologic doses of melatonin (50 mg) dramatically increased REM sleep time in both narcoleptics and normals and greatly intensified subjective dream phenomena.[19]

Several studies using varying doses of melatonin (2-20 mg/daily) have reported improved sleep quality, accelerated sleep initiation, and improved sleep maintenance without significantly altering memory, in contrast to benzodiazepines.[20,21]

Sleep Disorders in Children

Melatonin has also been used successfully to treat serious sleep disorders in hyperactive and neurologically compromised children, such as those with attention-deficit/hyperactivity disorder. In 1 study, doses of 2.5-5 mg nightly provided prompt sedation and improved sleep quality, noted in almost all the 15 subjects, with no side effects.[22] Irritability has been reduced, children have tended to become more alert and sociable, and developmental gains have been reported in children treated with melatonin.[22]

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