Melatonin is a dietary supplement and medication as well as naturally occurring hormone. As a hormone, melatonin is released by the pineal gland and is involved in sleep–wake cycles. As a supplement, it is often used for the attempted short-term treatment of disrupted sleep patterns, such as from jet lag or shift work, and is typically taken orally. Evidence of its benefit for this use, however, is not strong. A 2017 review found that sleep onset occurred six minutes faster with use, but found no change in total time asleep.
Side effects from melatonin supplements are minimal at low doses for short durations (in the studies reported about equally for both melatonin and placebo). Side effects of melatonin are rare but may occur in 1 to 10 patients in 1,000. They may include somnolence (sleepiness), headaches, nausea, diarrhea, abnormal dreams, irritability, nervousness, restlessness, insomnia, anxiety, migraine, lethargy, psychomotor hyperactivity, dizziness, hypertension, abdominal pain, heartburn, mouth ulcers, dry mouth, hyperbilirubinaemia, dermatitis, night sweats, pruritus, rash, dry skin, pain in the extremities, symptoms of menopause, chest pain, glycosuria (sugar in the urine), proteinuria (protein in the urine), abnormal liver function tests, increased weight, tiredness, mood swings, aggression and feeling hungover. Its use is not recommended during pregnancy or breastfeeding or for those with liver disease.
Melatonin acts as an agonist of the melatonin MT1 and MT2 receptors, the biological targets of endogenous melatonin. It is thought to activate these receptors in the suprachiasmatic nucleus of the hypothalamus in the brain to regulate the circadian clock and sleep–wake cycles. Immediate-release melatonin has a short elimination half-life of about 20 to 50minutes. Prolonged-release melatonin used as a medication has a half-life of 3.5 to 4hours.
Melatonin was discovered in 1958. It is sold over the counter in Canada and the United States; in the United Kingdom, it is a prescription-only medication. In Australia and the European Union, it is indicated for difficulty sleeping in people over the age of 54. In the European Union, it is indicated for the treatment of insomnia in children and adolescents. The US Food and Drug Administration (FDA) treats melatonin as a dietary supplement and as such has not approved it for any medical uses. It was approved for medical use in the European Union in 2007. Besides melatonin, certain synthetic melatonin receptor agonists like ramelteon, tasimelteon, and agomelatine are also used in medicine. In 2020, it was the 298th most commonly prescribed medication in the United States, with more than 1million prescriptions.
Medical uses
Insomnia
There is no good evidence that melatonin helps treat insomnia and its attempted use for this purpose is recommended against by the American Academy of Sleep Medicine.
A prolonged-release form of melatonin is also approved for use as a medication in Europe for the treatment of insomnia in certain people.
Circadian rhythm sleep disorders
Melatonin may be useful in the treatment of delayed sleep phase syndrome.
Melatonin is known to reduce jet lag, especially in eastward travel. However, if it is not taken at the correct time, it can instead delay adaptation.
Melatonin appears to have limited use against the sleep problems of people who work shift work. Tentative evidence suggests that it increases the length of time people are able to sleep.
REM sleep behavior disorder
Melatonin is a safer alternative than clonazepam in the treatment of REM sleep behavior disorder – a condition associated with the synucleinopathies like Parkinson's disease and dementia with Lewy bodies. However, clonazepam may be more effective. In any case, the quality of evidence for both treatments is very low and it is unclear whether either is definitely effective.
Dementia
A 2020 Cochrane review found no evidence that melatonin helped sleep problems in people with moderate to severe dementia due to Alzheimer's disease. A 2019 review found that while melatonin may improve sleep in minimal cognitive impairment, after the onset of Alzheimer's disease it has little to no effect. Melatonin may, however, help with sundowning (increased confusion and restlessness at night) in people with dementia.
Available forms
A prolonged-release 2mg oral formulation of melatonin sold under the brand name Circadin is approved for use in the European Union in the short-term treatment of insomnia in people age 55 and older.