Melatonin

Melatonin (N-acetyl-5-methoxytryptamine) is a neurohormone associated with sleep. Although the U. S. Agency for Healthcare Research and Quality (AHRQ) questions the evidence, the five sources that deal with melatonin all recommend it for:

• jet lag and 
• shift work adjustment,
• Melatonin is a promising treatment for other sleep disorders, especially:
• sleep latency (delay in falling asleep) in older people. 
• insomnia in the elderly, 
• sleep disturbances in children with neuro-psychiatric disorders, and 
• sleep enhancement in healthy people

However, some of the evidence is tentative, and much more study is needed. Uses of melatonin to treat insomnia and maintain cognitive capacity (neuroprotection) are particularly interesting but remain unresolved. Other suggested but unproven uses include:

• circadian sleep disorders [cyclical melatonin deficiency]
• dealing with the side effects of treatment for schizophrenia, particularly tardive dyskinesia and weight gain, 
• benzodiazepine withdrawal, 
• high-altitude adjustment, 
• insomnia in dementia,
• insomnia in people with autism, 
• "sundowning"/sleep pattern adjustment, 
• rapid eye movement behavior disorder, 
• seasonal affective disorder, 
• drug withdrawal syndrome, 
• major depression, and 
• adjunctive use.

Mental Health Implications

Melatonin is a promising treatment for jet lag and many mild to moderate sleep disorders. All other potential uses remain to be studied. Risks appear manageable, but caution is appropriate since melatonin is commonly over consumed, and, absent testing, people should "work up" to a therapeutic dose.

Drug Interactions

Drug interactions with melatonin have not been sufficiently studied, but appear manageable. Alcohol, caffeine and aspirin may affect melatonin levels. Psychotropic drugs that affect norepinephrine or serotonin levels might alter the pattern of melatonin production and that any drugs that might affect the metabolism of melatonin in the liver, such as valproic acid or methoxypsoralen, could affect blood serum levels of melatonin. Consultation with the prescribing physician is essential if any prescription drug is being taken with melatonin. Special care is appropriate for people taking:

• zolpidem (Ambien), 
• benzodiazepines such as lorazepam (Ativan), triazolam (Halcion), or diazepam (Valium), 
• barbiturates such as phenobarbital, 
• narcotics such as codeine, 
• antidepressants, 
• blood thinning medication such as warfarin (Coumadin), 
• methamphetamine,
• medication for glaucoma. 
• beta blockers, and 
• tranquilizers.  

Side Effects

Melatonin is classified by the FDA as "generally regarded as safe" in recommended doses for short-term use.

The most common side effect is gastric distress.

There is controversy about the effect of melatonin on seizure disorders. In the absence of better science, consultation with the health care professional providing care for an existing seizure disorder is essential if considering using melatonin.

Mood changes have been reported, both highs and lows, and even psychotic symptoms such as hallucinations and paranoia. Persons with major depression or psychotic disorders should consult with the health care professional providing care for the underlying disorder before using melatonin.

Given the lack of experimental data concerning melatonin supplementation in children, Mischoulon and Rosenbaum caution that melatonin treatment in children should be used only "very conservatively," when the benefits of melatonin treatment clearly outweigh any possible risks. There are no data concerning use during pregnancy or breastfeeding.

Overconsumption of melatonin can have significant risks. It has been suggested that millions of Americans currently consume melatonin in excessive quantities, elevating their melatonin levels many times over those that occur normally. The notion that uncontrolled use of melatonin is completely safe rests on little research and on the common public experience of lack of significant short-term toxic effects. However, disruption of the delicate mechanism of the circadian system is, in and of itself, a significant potential side effect.

Because individual rates of melatonin metabolism vary substantially, with older and smaller people disproportionately affected, adjustment of the dosage is essential to avoid decreased effects in the latter part of the night due to excessive use of "slow release" melatonin on the one hand or disturbance of circadian patterns by use of excessive amounts of "fast release" melatonin on the other.

Over-the-counter melatonin supplements typically contain 3-5 mg, but studies show that even a relatively low dose of 0.3 mg per day may induce circadian levels of the hormone well in excess of the normal level in people over 50 years old. Thus, before deciding on a therapeutic dose to deal with insomnia, people should consult with a physician to determine the precise amount of supplementation needed. Absent testing, leading researchers (Mischoulon and Rosenbaum) recommend that people "work up" to a therapeutic level, beginning with 0.1 to 0.2 mg per day.

Jet Lag

The sources differ in their prescription for jet lag, with Mischoulon and Rosenbaum's prescription the best reasoned: If melatonin is administered to contract the effect of eastward-travel jet lag, a dose of 0.1 to 0.3 mg at the local bedtime following the flight is recommended. Such treatment will restore the deficit in melatonin that the traveler will experience due to the advance of bedtime at the destination. Following a westward flight, when the day is extended rather than shortened, it would be advisable not to take melatonin at the local bedtime, when the endogenous level of the hormone is already increased.
However, it might be helpful to take a half dose (e.g., 0.1 mg) immediately following a night or early morning awakening, as is typically experienced in westward flights. In principle, this would facilitate resumption of sleep and its maintenance, plus delaying the circadian phase and adjusting to the new location.

Conclusion

Jet lag and sleep problems associated with shift work are the most promising uses, but many other suggested uses remain to be studied.

Melatonin does not have significant toxic effects, but it may interfere with sleep rhythms.

Risks appear manageable so long as drug interactions are avoided, but caution is appropriate since melatonin is commonly over consumed, and, absent testing, people should "work up" to a therapeutic dose.

For detailed information on Melatonin and other treatments, download the full review.