Adverse Effects of Melatonin Use in Pediatric Populations
In this podcast, Henriette Edemann-Callesen, MsC, PhD, discusses the safety of melatonin use in children and adolescents with chronic insomnia, including both short-term and long-term serious and non-serious adverse events.
Additional Resource:
- Handel MN, Andersen HK, Ussing A, et al. The short-term and long-term adverse effects of melatonin treatment in children and adolescents: a systematic review and GRADE assessment. eClinicalMedicine. 2023;61:102083. doi:110.1016/j.eclinm.2023.102083.
TRANSCRIPTION:
Leigh Precopio: Hello everyone and welcome to another installment of Podcasts360, your go-to resource for medical education and clinical updates. I'm your moderator, Leigh Precopio, with Consultant360, a multidisciplinary medical information network.
The use of melatonin supplementation in the treatment of sleep disorders is on the rise worldwide, but despite its popularity, questions remain on the associated adverse effects of melatonin use.
These knowledge gaps persist among children and adolescents, a patient population in which melatonin is commonly used to treat insomnia. In effort to better understand the short-term and long-term adverse events associated with melatonin use in this patient population, researchers conducted a systematic review of both serious and non-serious adverse events.
Here to discuss these study results is lead study author Henriette Edemann-Callesen, MsC, PhD, who is a consultant at the Danish Health Authority and a researcher for the Center for Evidence-Based Psychiatry.
Thank you for taking the time to join us today. To begin, what was the impetus for this study?
Henriette Edemann-Callesen, MsC, PhD: The incentive to initiate this study was driven by data showing that within the last decade there has been a substantial increase in the number of children and adolescents who are using melatonin as a treatment for insomnia. So we have registry data from Denmark showing that from 2011 to 2021, the number of users below the age of 17 more than tripled. And for those between 18 and 24 years of age, there was a sevenfold increase in the number of users. So it was really quite a drastic increase in the number of users in melatonin.
And when looking beyond our own borders, you also saw the same rise in the other countries. So Sweden and Norway, for example, had the same increase in number of users. And also there was a publication showing that in Australia, in particular, the prescription of melatonin increased by just over 600% from 2011 to 2018, and this was in children below 19 years of age. So what we took from that was that melatonin has become a popular drug worldwide to treat insomnia, and therefore we thought it was important to systematically evaluate the safety of using this particular drug in the young population.
Leigh Precopio: What is the current standard of care for managing insomnia in children and adolescents?
Dr Edemann-Callesen: It depends on which country you're looking at, but at least in Denmark, the treatment of insomnia in children and adolescents should ideally be provided in steps. So the first line of treatment would include an improvement of so-called sleep hygiene practices. So this basically entails counseling the families on specific habits and behaviors before bedtime. So for example, making sure that there is a regular bedtime routine, that the room is calm, dark, not too warm, the child doesn't look at screens just before going to bed, etc. So essentially making sure that you enhance practices which are known to facilitate and improve sleep in general. So that would be the first step.
If that is not enough, then in Denmark it's recommended that the next step would be to try out different non-pharmacological interventions, such as weighted blankets, light therapy, cognitive behavioral therapy. And then finally, if this is not enough, so there's still a problem with the child who has problems with functioning during the daytime due to constant or chronic insomnia, well then the next step would be to consider treating with melatonin and this for a short period of time.
So that is the ideal way to do it, to take these steps. So starting out very carefully, slowly. We're looking at what are the habits at home. If that is not enough, then non-pharmacological intervention, and then essentially melatonin as one of the last steps. However, the everyday practice may vary a lot, and it also depends on the patient, of course, but also what kind of interventions are available to you in your clinic. So not everyone has access to non-pharmacological interventions, for example.
Leigh Precopio: The results of your study revealed that melatonin use in pediatric populations was not associated with serious adverse events, such as death or hospitalization, but was associated with non-serious adverse events, such as headache, fatigue and drowsiness, and more. How should this finding impact how clinicians approach the use of melatonin to manage insomnia in this population?
Dr Edemann-Callesen: Yes. So we found that patients are likely, as you said, to experience various non-serious adverse events when being treated with melatonin. And I don't think it comes as a surprise that being treated with a drug also means the potential of experiencing adverse events. However, what kind of striked us the most when going through the literature was the major gap of knowledge when it comes to the safety of using melatonin in children and adolescents.
So what we could see was that the reporting of adverse events in the current evidence is inadequate. What we could see in the identified studies was that they only rarely performed a systematic evaluation of the adverse events, and even fewer studies provided a full report on the frequency and type of adverse events that occurred throughout that specific trial. So collectively, this means that we do not actually know the extent to which melatonin leads to non-serious adverse events. There is a risk that it is actually under-reported, and also what we could see was that the long-term consequences remain uncertain. This has been a topic for quite some time. What are the long-term consequences of providing melatonin to the young population? And while still we don't actually have a clear answer on that. So that is definitely still uncertain. So we hope that our findings will introduce a level of caution in the clinical practice with the clinician bearing in mind that there is an uncertainty when it comes to safety data and through this, by being mindful about it, tries to avoid a complacent use of melatonin in children and adolescents.
Leigh Precopio: Do you believe there is a need for clinical practice guidelines or formal recommendations on the use of melatonin in children and adolescents with insomnia in countries where there is no formal guidance? Why or why not?
Dr Edemann-Callesen: Yes. I think there is a need for formal recommendations within this field. And the major search in the use of melatonin within the last decade definitely also highlights that. And actually this paper is based on a national clinical guideline published last year by the Danish Health Authorities on the use of melatonin in the young population. So at least in Denmark, we now have formal recommendations, and these have actually also been published in English in eClinicalMedicine for those who may be interested.
So there might be some who say that clinical recommendations should not be made if the evidence is uncertain. And we obviously found that this is the case when it comes to melatonin, at least in terms of safety. However, I like to argue that it is, especially when the evidence is uncertain, that we as clinicians need guidance. So having formal recommendations helps us when we are consulting patients on this topic, and it enables us to make an informed decision together with our patients when it comes to deciding on a treatment.
Leigh Precopio: What are the next steps for research in this area?
Dr Edemann-Callesen: We definitely need to know more about the consequences of providing this drug to children and adolescents. So what are the short-term consequences and what are the long-term consequences? So the next step for research would be to provide a systematic evaluation of the safety. Simply being completely clear about what kind of adverse events are happening, how frequent are they, so stuff like this. But what we also need to look more into is not only the safety, but also the use of non-pharmacological interventions for this age group because there are also some major gaps there. So different things to be mindful about the short and long-term consequences, but also what other options may there be that we could try prior to going into melatonin treatment.
Leigh Precopio: Is there anything else you would like to add?
Dr Edemann-Callesen: I think more of a general comment, I hope that our research reaches those who on a daily basis are working with children and adolescents who are experiencing insomnia. And I'm always open to discuss our findings because it is an important topic. I think we can all agree that insomnia in children and adolescents is serious. It may have huge consequences for the individual and therefore we definitely need to help them. But we need to keep in mind that treating with melatonin does not come for free and that there are some non-pharmacological steps that we ideally should take into consideration prior to administering melatonin.
Leigh Precopio: Great. Thank you so much again for taking the time to speak with me today.
Dr Edemann-Callesen: Thank you for having me.