Melatonin and Sleep Disorders
By Marcus M. Reidenberg, MD, FACP
Weill Cornell CERT
Summary by Kathleen Mazor, EdD
HMO Research Network CERT
Recently, melatonin has been promoted in baked goods and drinks to help people get to sleep and relieve anxiety (1). It has been available as an over-the-counter nonprescription drug for many years to relieve jet lag and trouble falling asleep, also called “delayed sleep-phase syndrome” (2).
Melatonin is a part of the body’s clock system. This clock system regulates many functions of the body that appear to cycle every 24 hours. This is based on our night-day cycle. Decrease in the perception of light starts impulses from the brain to the pineal gland at the base of the brain to cause it to secrete melatonin. This melatonin acts to make one feel sleepy. Bright light decreases melatonin secretion helping us feel awake (3). This is one of the body’s biological clock mechanisms to have us asleep at night and awake in the daytime. Bright lights at night such as working late in front of a bright computer screen or on a night shift can disrupt this biological clock. Both melatonin and the similar prescription drug, ramelteon (Rozerem R), make people fall asleep faster than when they take inert placebos (4).
Melatonin is also made by many other cells in the body and does a variety of things. It is antioxidant (3). In animal experiments, it decreases seizures (3), has cardiovascular effects (5), and regulates parts of the inflammatory process (6).
It is subject to a drug interaction of real importance. This is the additive effect of taking several drugs, each of which causes sleepiness. Alcohol is the most common of these. Many over-the-counter as well as prescription medications also cause sleepiness. One must avoid taking alcohol and other drugs that cause sleepiness when alertness and accurate or prompt responses are needed.
Another type of drug interaction is due to drug metabolism. When melatonin is swallowed, only 15% of the dose is actually absorbed into the body. Most is metabolized during absorption into inactive compounds (7). Because much melatonin is metabolized during its path into the body, various other medicines can affect the rate of this metabolism and therefore, the amount of melatonin that actually enters the body. Caffeine slowed the metabolism increasing the amount of melatonin that got into the body (8). The antidepressant drug fluvoxamine did the same thing (9). Taking melatonin with another medicine may lead to more or less melatonin in the body with increased or decreased level of sleepiness.
Many studies have shown that melatonin, 5mg, taken 3 or 4 days at the intended bedtime after flying east speeded recovery from jet lag. It also has been effective in relieving anxiety when used as preoperative medication (10) but has not been adequately compared to other medicines used for this purpose to learn which is really best.Melatonin is regulated in a way that does not require FDA review and approval before marketing. Little is published about its safety when taken for more than a few days. As a medicine, the melatonin made chemically is identical to the natural product and is less likely to be contaminated by other substances.
- Saint Louis C. Dessert. Laid back and legal. New York Times 2011; May 14
- Srinivasan V, Singh J, Pandi-Perumal SR, Brown GM, Spence DW, Cardinali DP. Jet lag, circadian rhythm sleep disturbances, and depression: the role of melatonin and its analogs. Adv Ther. 2010 Nov;27(11):796-813.
- Rios ER, Venâncio ET, Rocha NF, Woods DJ, Vasconcelos S, Macedo D, Sousa FC, Fonteles MM. Melatonin: pharmacological aspects and clinical trends. Int J Neurosci. 2010 Sep;120(9):583-90.
- Wilson SJ, Nutt DJ, Alford C, Argyropoulos SV, Baldwin DS, Bateson AN, Britton TC, Crowe C, Dijk DJ, Espie CA, Gringras P, Hajak G, Idzikowski C, Krystal AD, Nash JR, Selsick H, Sharpley AL, Wade AG. British Association for Psychopharmacology consensus statement on evidence-based treatment of insomnia, parasomnias and circadian rhythm disorders. J Psychopharmacol. 2010 Nov;24(11):1577-601.
- Reiter RJ, Tan DX, Paredes SD, Fuentes-Broto L. Beneficial effects of melatonin in cardiovascular disease. Ann Med. 2010 May 6;42(4):276-85.
- Radogna F, Diederich M, Ghibelli L. Melatonin: a pleiotropic molecule regulating inflammation. Biochem Pharmacol. 2010 Dec 15;80(12):1844-52.
- DeMuro RL, Nafziger AN, Blask DE, Menhinick AM, Bertino JS Jr. The absolute bioavailability of oral melatonin. J Clin Pharmacol. 2000 Jul;40(7):781-4.
- Härtter S, Nordmark A, Rose DM, Bertilsson L, Tybring G, Laine K. Effects of caffeine intake on the pharmacokinetics of melatonin, a probe drug for CYP1A2 activity. Br J Clin Pharmacol. 2003 Dec;56(6):679-82.
- Härtter S, Grözinger M, Weigmann H, Röschke J, Hiemke C. Increased bioavailability of oral melatonin after fluvoxamine coadministration. Clin Pharmacol Ther. 2000 Jan;67(1):1-6.
- Yousaf F, Seet E, Venkatraghavan L, Abrishami A, Chung F. Efficacy and safety of melatonin as an anxiolytic and analgesic in the perioperative period: a qualitative systematic review of randomized trials. Anesthesiology. 2010 Oct;113(4):968-76.
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