13 Oct Melatonin
Available dosage forms:
|Capsules||Up to 20mg|
|Capsules MR||Up to 10 mg|
|Mixture||1mg/ml – 2mg/ml – 5mg/ml|
|Troches||Up to 40 mg|
What is Melatonin and how does it work?
Melatonin is a hormone produced by the body that regulates sleep-wake cycles. Darkness causes the body to produce more melatonin, which signals the body to prepare for sleep, light decreases melatonin production and prepares the body to awaken. Melatonin as medication is used to adjust the body’s internal clock. It helps people with insomnia and jet lag to fall asleep and/or stay asleep. It has also been useful for adjusting sleep-wake cycles in people whose daily work schedules change (shift-work disorder), and for helping blind people establish a day and night cycle. Melatonin is most commonly available in capsule form, however other forms are troche (lozenge), mixture or drops.
Do not use Melatonin
If you are allergic to any of the ingredients, you have been drinking or intend to drink alcohol, and if you are pregnant or breastfeeding.
Tell your doctor
If you have liver or kidney problems, or suffer from an autoimmune disorder.
If you are taking any medications as some may interfere with Melatonin, especially hypnotics and tranquilizers (benzodiazepine), medicines used for depression (fluvoxamine, thioridazone and imipramine), contraceptives, hormone replacement therapy (oestrogen) or medication used to treat skin problems (cimetidine, psoralens).
Melatonin may cause drowsiness, therefore it is not recommended to drive or operate machinery for 8 hours after taking it. Melatonin does not impair morning alertness, but if you suffer from drowsiness during the day you should consult your doctor. Alcohol and caffeine can also affect Melatonin
Possible side effects of Melatonin: Irritability, restlessness, insomnia, anxiety, nightmares, migraine, lethargy, dizziness, somnolence, headache, high blood pressure, indigestion, upper abdominal pain, dry mouth and mouth ulcers, nausea, abnormal liver function with yellowing of the skin or eyes (jaundice), dry skin, rash, skin inflammation, menopausal symptoms, asthenia, chest pain, excretion of glucose in urine, and weight gain.
Rare side effects abnormal blood electrolytes and blood count, restless leg syndrome, visual impairment (blurred vision, watery eyes), hand dermatitis, shingles, increased thirst, increased liver enzymes.
Keep medication in a cool dry place. Do not leave medication in the car.
Melatonin or 5-methoxy-N-acetyltryptamine is a neurohormone used to regulate sleep-wake cycles in patients with sleep disorders. Endogenous melatonin is secreted by the pineal gland in all animals exhibiting circadian or circannual rhythms. Melatonin plays a proven role in maintaining sleep-wake rhythms, and supplementation may help to regulate sleep disturbances that occur with insomnia, jet lag, rotating shift-work, depression, chronic kidney disease, critical care unit stays, and various neurological disabilities.
Mechanism of Action
Melatonin is an endogenous hormone secreted by the pineal gland. The suprachiasmatic nuclei of the hypothalamus controls the numerous physiologic and endocrine circadian rhythms of the body, including that of rest and activity. The circadian clock is set via a process called entrainment, which is a response of the suprachiasmatic nuclei to photic input.
Melatonin has been administered orally and intravenously. Commercially available dietary supplement formulations of melatonin include oral and sublingual tablets, orally dissolving tablets, soft chews, capsules, teas, lozenges, and oral spray delivery systems. There have been reports of substantial variability in product purity and melatonin content of available products.
For the short-term treatment of insomnia†:
- for the self-treatment of mild insomnia†:
Adults: 0.3 to 10 mg PO before bedtime as needed. Doses usually should be taken 30 minutes to 1 hour before bedtime. Use as directed on individual product labels. Doses of 0.3 to 1 mg appear to produce physiological melatonin levels in the circulation; however, in most studies, higher doses (2 mg or more) are needed to obtain beneficial effects.4 Max: 10 mg/day PO. In a meta-analysis evaluating melatonin in primary sleep disorders, melatonin demonstrated a significant benefit in reducing sleep latency, increasing total sleep time, and improving sleep quality compared to placebo.
If melatonin is going to be used, a synthetic-source product is recommended. Consumers of melatonin should be informed that rigid quality control standards, as with other dietary supplements, are not required for melatonin and substantial variability can occur in both the potency and the purity of these products. Impurities have been found in many dietary supplement products.
Melatonin should be considered to be contraindicated in pregnancy at this time.1 In pregnant women, endogenous melatonin crosses the placenta and enters the fetal circulation, and appears to be responsible for setting circadian rhythm influences in utero. Melatonin receptors in the fetus are widespread in both central and peripheral tissues from the third week of fetal development. The administration of exogenous melatonin could potentially disrupt circadian entrainment and other pineal gland influences.21 Thus, fetal exposure to exogenous melatonin use in the mother may be of concern. Effects in non-clinical animal studies of melatonin were observed only at exposures considered sufficiently in excess of the maximum human exposure indicating little relevance to clinical use; however, the data are limited.2 In animal studies, ramelteon, a melatonin analog, produced evidence of developmental toxicity, including teratogenic effects, in rats at doses much greater than the recommended human dose.19 The potential effects of melatonin on the duration of labor and/or obstetric delivery, for either the mother or the fetus, have not been studied. Melatonin has no established use in labor and delivery.
Melatonin should generally be avoided in women who are breast-feeding their infants.2 1 Reports describing the use of melatonin dietary supplements in women who are breast-feeding are lacking; however, it is likely to be excreted in human milk. Endogenous melatonin passes into human milk and concentrations have been measured in the breast-milk of lactating women; the results coincided with the women’s daily circadian rhythm of melatonin with undetectable levels during the day and high levels at night.22
Most central nervous system (CNS) adverse effects of melatonin appear to be infrequent and mild in most patients with a few days of use. Much less is known regarding side effects occurring during the long term melatonin administration. Most clinical trials have involved <= 6 months of daily melatonin use. The most commonly reported adverse reactions are headache and somnolence.
1. Health Canada Drugs and Health Products and Natural Health Products Ingredients Database. Melatonin Monograph. First published 2012. Modified May 13, 2013. Web. Accessed August 4, 2015. Available at: webprod.hc-sc.gc.ca/nhpid-bdipsn.
2. Circadin (oral melatonin) European Medicines Agency official product label. Dublin 2, Republic of Ireland; Flynn Pharma Ltd: 2015 July.
3. Harpsoe NG, Andersen LP, Gogenur I, et a;. Clinical pharmacokinetics of melatonin: a systematic review. Eur J Clin Pharmacol. 2015;71:901-909.
4. Cardinali DP, Srinivasan V, Brzezinski A, et al. Melatonin and its analogs in insomnia and depression. J Pineal Res 2012;52:365-75.
5. Ferracioli-Oda E, Qawasmi A, Bloch MH. Meta-analysis: melatonin for the treatment of primary sleep disorders. 2013. PLoS ONE 8(5): e63773. doi:10.1371/journal.pone.0063773.
6. Wilson SJ, Nutt DJ, Alford C et al. British Association for Psychopharmacology consensus statement on evidence-based treatment of insomnia, parasomnias and circadian rhythm disorders. J Psychopharmacol 2010;24:1577–1601.
7. Quick Dissolve maximum strength 10 mg melatonin tablets. Nature’s Bounty. Bohemia, NY: 2014.
8. Dolberg OT, Hirschmann S, Grunhaus L. Melatonin for the treatment of sleep disturbances in major depressive disorder. Am J Psychiatry 1998;155:1119-21.
9. Chase JE, Gidal BE. Melatonin: therapeutic use in sleep disorders. Ann
10. Sack RL, Brandes RW, Kendall AR, et al. Entrainment of free-running circadian rhythms by melatonin in blind people. N Engl J Med 2000;343:1070-1077.