Summary

• Melatonin is a neurohormone produced in the brain. Levels of melatonin in the blood are highest prior to bedtime. Melatonin products have been used for a many medical conditions. It is most often used for people who have insomnia (trouble sleeping).

Uses 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.	Grade*
Jet lag	A
Delayed sleep phase syndrome (DSPS)	B
Insomnia (in the elderly)	B
Sleep disorders (children with behavioral, developmental, and intellectual disorders)	B
Sleep enhancement in healthy people	B
Age-related macular degeneration	C
Aging (changes in body temperature)	C
Anti-inflammatory	C
Anxiety (before surgery)	C
Benzodiazepine tapering	C
Cancer treatment	C
Chronic fatigue syndrome	C
Circadian rhythm entraining (in blind persons)	C
Cognitive disorders	C
Depression	C
Diabetes (adjunct therapy)	C
Exercise performance	C
Gastrointestinal disorders	C
Glaucoma	C
Headache (prevention)	C
High blood pressure	C
High cholesterol (diabetes-related complication, adjunct therapy)	C
HIV/AIDS	C
Insomnia (in children)	C
Memory	C
Menopause	C
Parkinson's disease	C
Periodic limb movement disorder	C
REM sleep behavior disorder	C
Restless leg syndrome	C
Rett's syndrome	C
Sarcoidosis	C
Seasonal affective disorder (SAD)	C
Seizure disorder (children)	C
Sleep disturbance	C
Sleep quality	C
Smoking cessation	C
Stroke	C
Tardive dyskinesia	C
Thrombocytopenia (low platelets)	C
Tinnitus (ringing in the ears)	C
Urination (nocturia)	C
UV-induced erythema prevention/sunburn (sunburn prevention)	C
Work shift sleep disorder	D

Safety

• Melatonin is generally considered safe in recommended doses for short-term use. Use cautiously with seizures, underlying major depression or psychotic disorders, high cholesterol, diabetes, blood sugar disorders, glaucoma, blood pressure disorders, bleeding disorders, or in patients using medications for any of these conditions. Use cautiously in patients using anesthetics, cytochrome P450 inhibitors, methamphetamine, nifedipine (a calcium channel blocker), or in children with a history of enuresis. Avoid in patients using CNS depressants, including benzodiazepines and alcohol. Avoid in women who are pregnant or are attempting to become pregnant. Avoid with known allergies to melatonin or related products.

Possible side effects

• Blood clotting abnormalities (particularly in patients taking blood thinners like warfarin) or increased risk of bleeding, increased risk of seizure, disorientation, fatigue, dizziness, headache, irritability, sleepiness, confusion, sleepwalking, vivid dreams and nightmares, nausea, vomiting, cramping, stomach pain, altered taste, abnormal feces, increased appetite, diarrhea, changes in blood pressure, increased cholesterol, increased blood sugar, increased urination, reduced glucose tolerance, reduced insulin sensitivity, hallucinations, paranoia, hormonal changes, increased breast size in men, reduced sperm motility, mood changes, abnormal heart rhythms, chest pain, liver inflammation (autoimmune hepatitis), increased intraocular (eye) pressure, rash, triggering of Crohn's disease symptoms.

Possible interactions

• Alcohol, Alzheimer's agents, analgesics, anesthetics, antianxiety drugs, antiasthma agents, anticancer agents, anticoagulants or drugs that increase the risk of bleeding (such as aspirin, heparin, and warfarin), antidepressants, antiglaucoma agents, anti-inflammatories, antiparasitics, antipsychotics, antiseizure drugs, antivirals, barbiturates, beta-blockers, caffeine, calcium channel blockers, central nervous system depressants and stimulants, chasteberry (Vitex agnus-castus), dextromethorphan, DHEA, diazepam, diuretics, drugs broken down by the liver, drugs used for osteoporosis, drugs that affect blood pressure (like atenolol), drugs that alter blood sugar levels (like insulin), drugs that lower cholesterol, drugs that affect GABA, echinacea, folate, flumazenil, gastrointestinal agents, haloperidol, hormonal agents, immune therapies, isoniazid, lithium, methamphetamine, methoxamine, muscle relaxants, naproxen (Naprosyn®, Aleve®), narcotics, nonsteroidal anti-inflammatories (like ibuprofen), radioprotective agents, remifentanil, sedatives (such as Ambien®), skin agents, somatostatin, stimulants, succinylcholine, tacrine, temazepam, valproic acid, vasodilators, verapamil, vitamin B12, weight loss agents, or herbs or supplements with similar effects.

Dosing

Adults (18 years and older)

• Studies have evaluated 0.1-80 milligrams of melatonin taken nightly by mouth for up to three years for a variety of conditions. Research suggests that quick-release melatonin may be more effective than sustained-release formulations for sleep-related conditions. Intramuscular injections of 20 milligrams of melatonin have also been studied.
• In studies of patients with melanoma, melatonin preparations have been applied to the skin. Patients are advised to discuss cancer treatment plans with an oncologist and pharmacist before considering use of melatonin either alone or with other therapies. For the prevention of sunburn, melatonin preparations, alone and in combination with ascorbic acid and vitamin E, in doses ranging from 20 to 100 milligrams in 70% ethanol, have been studied.
• Intranasal melatonin (1% solution in ethanol) at a dose of two milligrams daily for one week has also been studied for high blood pressure.
• A dose of 0.5 milligrams of transbuccal melatonin for two sessions on four consecutive nights, at least three days apart, has been studied for insomnia in the elderly.
• There are other uses with limited supportive study and unclear effectiveness or safety. Use of melatonin for any condition should be discussed with a primary healthcare provider, appropriate specialist, and pharmacist prior to starting, and it should not be substituted for more proven therapies.

Children (younger than 18 years)

• There is not enough scientific evidence to recommend melatonin supplements for children at this time. Doses of up to up to nine or 10 milligrams per kilogram of body weight, as a single dose or up to several months, have been studied. Use of melatonin should be discussed with the child's doctor and pharmacist before starting.