Melatonin
(N-acetyl-5-methoxytryptamine) is a neurohormone associated with sleep.
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.
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.
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.
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.
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