Melatonin: What Do We Really Know?

It is probably safe to say that melatonin has become the go-to agent for the treatment of children who struggle to fall asleep. According to a recent article in the Wall Street Journal, melatonin is now a 260 million dollar market in this country where it is sold over the counter, unlike some European countries where a prescription is still required.

Melatonin is a hormone that is synthesized from the amino acid tryptophan in the pineal gland. Its release is controlled by the suprachiasmic nucleus of the hypothalamus with the level peaking in the evening.  The fact that our body makes melatonin naturally has  been one factor related to many primary care physicians and psychiatrists alike giving the hormone a “pass” when it comes to

Image by phanlop88 and freedigitalphotos.net

Image by phanlop88 and freedigitalphotos.net

scrutiny, but questions about both is efficacy and safety remain.

Recently, a selective review (which reads more like a commentary) about melatonin use in youth was published in the Journal of Paediatrics and Child Health.  While the article certainly seems to be trying to persuade as much as inform, the author makes some important and surprising points.  One is that animal studies have shown a range of effects on the reproductive system for melatonin that have not been well understood. Indeed, there still exists a registered use for melatonin in animals to increase fertility.  These effects on reproduction or puberty in humans have yet to be demonstrated, although the few studies that have examined this issue have been small and contain significant limitations.  It is also worth noting that melatonin is metabolized in the liver by the enzymes CYP1A2 and CYP2C19 which can be inhibited by antidepressants such as fluvoxamine and citalopram, respectively.  As melatonin is often used in conjunction with psychiatric medications, these potential interactions need to be considered.

With regard to efficacy, studies seem to support its usefulness, although perhaps not to the extent one might expect.  Two recent controlled trials in children found that melatonin increased sleep onset by about 30 to 45 minutes but it does not generally increase total amount of sleep.

The author concluded that the research on melatonin in children is inadequate, especially given the effects on the reproductive system documented in animal studies. He urged much more research before governing bodies decree melatonin as safe and effective.

The review was later criticized in a letter to the editor for omitting studies from melatonin prescription products such as Circadin which is approved in Europe (although not for kids).  In the USA, there is also the melatonin receptor agonist remelton (Rozerum) which also has some data but, again, is not approved for pediatric ages.

Counter-balancing the concern of melatonin is the large body of literature that demonstrates the negative effects of poor and inadequate sleep.   In trying to balance these concerns, I’m not sure I’m ready to take melatonin out of my bag (particularly in comparison to other sleep medications that are used).  At the same time, however, it is important not to use melatonin or any other sleep-aid as a shortcut to addressing behavioral measures.   Many children benefit from consistent routines that gradually wind down stimulation and prepare a child to settle down for the night, and families that try to circumvent this process often run into problems.  Exercise (or lack thereof) can also be a major player in why some kids just don’t feel tired at night.  Nevertheless, it is also certainly true that many children will struggle with sleep no matter how good the bedtime routine is.

Reference

Kennaway D.  Potential safety issues in the use of the hormone melatonin in paediatrics.  J Paediatrics Child Health.  2015: 51(6):584-589.

 

 

Comments are closed.