Sleep aids have become big business for the pharmaceutical industry. In 2006 alone, prescription drug sales for somnolence agents in the United States topped $3.6 billion.1 Unfortunately, the majority of the most popular prescription sleep aids are in the benzodiazepine class and carry the potential for addiction and abuse. Amidst these manufactured drugs, simple melatonin is a modestly effective alternative.

Studies show that the average American gets 6.9 hours of sleep per night, shy of the seven to nine hours recommended by the National Sleep Foundation.2 According to NIH, at least 70 million Americans suffer from some sort of sleep disorder.3

Melatonin is a naturally occurring hormone found in the human body. Chemically known as 5-methoxy-N-acetyltryptamine, melatonin is produced by the pineal gland. Melatonin’s release, which is stimulated by darkness and suppressed by light,3 is the result of a chain of events that link the pineal gland and the retina of the eye. Physiologically, this chain begins with tryptophan, which is enzymatically converted to serotonin, with a final transition to melatonin in the pineal gland itself.4

Serum melatonin levels correspond to sleep periods. Levels are low during the daylight hours and spike with nightfall. Because melatonin is considered the chief hormone of the circadian rhythm, supplementation can alter the sleep-wake cycle.4

Current studies

Melatonin was released in the U.S. marketplace in 1993.3 A large number of the clinical trials on melatonin have focused on the prevention and/or management of the problems associated with jet lag. The inability to sleep at appropriate times after traversing multiple time zones is both frustrating and debilitating for business travelers, military personnel, and tourists. Multiple reviews have awarded the data supporting melatonin’s use for jet lag an evidence level of “A.”5

A Cochrane review discovered nine melatonin trials that met the criteria for meta-analysis. All nine trials found that melatonin taken close to the target bedtime at the destination decreased jet lag resulting from crossing five or more time zones.6

For chronic insomnia, or the more common delayed sleep phase syndrome in which it is simply difficult to fall asleep, nightly dosing of a small amount (0.3 mg) of melatonin has been shown to effectively hasten sleep onset and reduce awakenings during the sleep cycle.7 This condition, while common in all ages, becomes more prevalent as patients get older. A supportive evidence level of “B” has been assigned to melatonin’s safety and efficacy for this condition.5

The explanation for the age differential is found in studies that defined the negative association of age with intrinsic melatonin production. Apparently, melatonin production is yet one more process that slows with aging. The delayed sleep phase syndrome is more prevalent in people older than 50, as is the efficacy of maintenance melatonin usage.8

Dosage and cost

For chronic insomnia, melatonin may be used nightly one or two hours before sleep at a dose of 2-3 mg. For difficulty falling asleep or delayed sleep phase syndrome, 3-5 mg before bedtime is recommended.2 Daily doses of 0.5-5 mg of melatonin taken at the target bedtime two days before departure and at the destination for two to five days after arrival will lessen the effects of jet lag.6 The timing of the use of melatonin is crucial. Obviously, as with any other sleep aid, taking it too early before the intended time of sleep can cause significant drowsiness and might pose a safety hazard.

In the sometimes dizzying array of products available in stores, one specific type of melatonin to avoid is the long- or sustained-action version. Dose-range trials verify that the maximum sleep benefit is gained from a rapid onset and peaking concentration and that serum concentrations lasting beyond that have a higher chance of causing sedation the following day.7

Melatonin is most commonly found in tablet form. As previously noted, the extended- or long-acting formulations should be avoided because of poor efficacy and higher incidence of day-after somnolence. Melatonin is very affordable. Depending on the source, a bottle of 30-100 tablets, 1.5-3 mg each, costs less than $10.7

Safety and side effects

Very few significant side effects of melatonin have been identified. Persons with seizure disorders and those taking warfarin should discuss the use of melatonin with their health-care provider before using.6 Because of its sedativelike action, melatonin should be used with caution if patients are also on sedative drugs, such as beta blockers or benzodiazepines.2

The most commonly reported side effects are altered sleep patterns, confusion, headache, pruritus, sedation, and occasionally tachycardia.4

Summary

Melatonin appears to be a relatively safe and moderately effective alternative to prescription sleep aids. Its low side-effect profile and lack of addiction potential, combined with its inexpensive price tag, makes melatonin an attractive alternative for individuals with uncomplicated sleep disorders.

References

1. USA Today. We should be feeling very sleepy, considering flood of sleep aids. Available at www.usatoday.com/money. Accessed November 7, 2007.

2. Skidmore RL. Mosby’s Handbook of Herbs & Natural Supplements. 3rd ed. St. Louis, Mo.: Elsevier Mosby; 2006:713.

3. Wikipedia. Melatonin. Available at http://en.wikipedia.org/wiki. Accessed November 7, 2007.

4. Fetrow CW, Avila JR. Professional’s Handbook of Complementary & Alternative Medicines. Springhouse, Pa.: Springhouse Corp; 1999:426.

5. MedlinePlus. Melatonin. Available at www.nlm.nih.gov/medlineplus. Accessed November 7, 2007.

6. Smucny J. Can melatonin prevent or treat jet lag? Am Fam Physician. 2002;66:2087-2088.

7. Massachusetts Institute of Technology. Scientists pinpoint dosage of melatonin for insomnia. Available at http://web.mit.edu/newsoffice. Accessed November 7, 2007.

8. Ben Best. Melatonin. Available at www.benbest.com/nutrceut. Accessed November 7, 2007.

Ms. Sego is a staff clinician at the Veterans Administration Hospital in Kansas City, Mo., where she practices adult medicine and women’s health. She also teaches at the nursing schools of the University of Missouri and the University of Kansas.