Melatonin

by MedlinePlus

Melatonin is a neurohormone produced in the brain by the pineal gland, from the amino acid tryptophan. The synthesis and release of melatonin are stimulated by darkness and suppressed by light, suggesting the involvement of melatonin in circadian rhythm and regulation of diverse body functions. Levels of melatonin in the blood are highest prior to bedtime.

Synthetic melatonin supplements have been used for a variety of medical conditions, most notably for disorders related to sleep.

Melatonin possesses antioxidant activity, and many of its proposed therapeutic or preventive uses are based on this property.

New drugs that block the effects of melatonin are in development, such as BMS-214778 or luzindole, and may have uses in various disorders.

Synonyms

5-Methoxy-N-acetyltryptamine, acetamide, beta-methyl-6-chloromelatonin, BMS-214778, luzindole, mel, MEL, melatonine, MLT, N-acetyl-5-methoxytryptamine, N-2-(5-methoxyindol-3-ethyl)-acetamide.

Evidence

These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.

Uses based on scientific evidence

Jet lag

Several randomized, placebo controlled human trials suggest that melatonin taken by mouth, started on the day of travel (close to the target bedtime at the destination) and continued for several days, reduces the number of days required to establish a normal sleep pattern, diminishes the time it takes to fall asleep ("sleep latency"), improves alertness, and reduces daytime fatigue. Effects may be greatest when traveling eastward, and when crossing more than four time zones (results may be less impressive for westward travel or crossing of fewer time zones). Combination with prescription sleep aids such as zolpidem (Ambien®) may add to these effects, although side effects such as morning sleepiness may occur.Although these results are compelling, the majority of studies have had methodological problems with their designs and reporting, and some trials have not found benefits. Overall, the scientific evidence does suggest benefits of melatonin in up to half of people who take it for jet-lag (number needed to treat = 2, meaning that for every two people treated, one will experience benefits). Further well-designed trials are necessary to confirm these findings, to determine optimal dosing, and to evaluate use in combination with prescription sleep aids.Preliminary research reports that started melatonin on the day of travel, rather than prior to travel, may yield superior results. Higher doses (such as 5 milligrams nightly) may be slightly more effective than lower doses (for example, 0.1 to 0.5 milligrams nightly) for improvement of sleep quality and latency, although this area remains controversial with some studies suggesting no differences. Slow-release melatonin may not be as effective as standard (quick release) formulations. If the dose is taken too early in the day, it may actually result in excessive daytime sleepiness and greater difficulty adapting to the destination time zone.

Delayed sleep phase syndrome (DSPS)

Delayed sleep phase syndrome is a condition that results in delayed sleep onset, despite normal sleep architecture and sleep duration. Several small controlled studies and case series in healthy volunteers and in patients with delayed sleep phase syndrome have used 5 to 6 milligrams of melatonin, with reported improvements in sleep latency. Although these results are promising, additional research with large, well-designed controlled studies is needed before a stronger recommendation can be made.

Sleep disturbances in children with neuro-psychiatric disorders

There are multiple controlled trials and several case reports of melatonin use in children with various neuro-psychiatric disorders, including mental retardation, autism, psychiatric disorders, visual impairment, or epilepsy. Studies have demonstrated reduced time to fall asleep (sleep latency) and increased sleep duration. Oral doses of melatonin have ranged between 2.5 and 10 milligrams administered at the desired bedtime. Well-designed controlled trials in select patient populations are needed before a stronger or more specific recommendation can be made.

Insomnia in the elderly

Several human studies report that melatonin taken by mouth 30 to 120 minutes prior to bedtime decreases the amount of time it takes to fall asleep ("sleep latency") in elderly individuals with insomnia. It is not clear if melatonin increases the length of time that people are able to stay asleep. Low doses (0.1 to 0.3 milligrams taken nightly) appear to be equally effective as higher doses (3 to 5 milligrams nightly). However, most studies have not been high quality in their designs and some research has found limited or no benefits. The majority of trials have been brief in duration (several days long), and long-term effects are not known.Although the evidence overall does suggest short-term benefits, additional study is needed before a strong recommendation can be made. It is not known how melatonin compares to standard therapies used for insomnia, such as benzodiazepines like diazepam (Valium®) and lorazepam (Ativan®), or other sleep aids such as zolpidem (Ambien®).

Sleep enhancement in healthy people

Multiple human studies have measured the effects of melatonin supplements on sleep in healthy individuals. A wide range of doses has been used, including "low-dose" melatonin (0.1 to 1.0 milligrams), or doses between 5 and 10 milligrams, often taken by mouth 30 to 60 minutes prior to sleep time. Most trials have been small, brief in duration (often single-dose studies), and have not been rigorously designed or reported (inadequate blinding and randomization). However, the weight of scientific evidence does suggest that melatonin decreases the time it takes to fall asleep ("sleep latency"), increases the feeling of "sleepiness," and may increase the duration of sleep. Better quality research is needed in this area. It is not known how melatonin compares to standard therapies used for insomnia, such as benzodiazepines like diazepam (Valium®) and lorazepam (Ativan®), or other sleep aids such as zolpidem (Ambien®).

Alzheimer's disease (sleep disorders)

There is limited study of melatonin for improving sleep disorders associated with Alzheimer's disease (including nighttime agitation or poor sleep quality in patients with dementia). It has been reported that natural melatonin levels are altered in people with Alzheimer's disease, although it remains unclear if supplementation with melatonin is beneficial. Further research is needed in this area before a firm conclusion can be reached.

Antioxidant (free radical scavenging)

There are well over 100 laboratory and animal studies of the antioxidant (free radical scavenging) properties of melatonin. As a result, melatonin has been proposed as a supplement to prevent or treat many conditions that are associated with oxidative damage. However, there are no well-designed trials in humans that have demonstrated benefits of melatonin as an antioxidant for any health problem.

Attention deficit hyperactivity disorder (ADHD)

There is limited research of the use of melatonin in children with ADHD. A clear conclusion cannot be made at this time.

Benzodiazepine tapering

A small amount of research has examined the use of melatonin to assist with tapering or cessation of benzodiazepines such as diazepam (Valium®) or lorazepam (Ativan®). Although preliminary results are promising, due to weaknesses in the design and reporting of this research, further study is necessary before a firm conclusion can be reached.

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