Safety and Efficacy of Melatonin in Children

A review of the studies on the many applications of melatonin in pediatrics

By Jaclyn Chasse, ND

About The Author

Jaclyn Chasse, ND is a medical educator at Emerson Ecologics, Manchester, New Hampshire, and a practicing naturopathic physician in New Hampshire. She also holds an adjunct faculty position at Bastyr University, Kenmore, Washington. Chasse is a graduate of Bastyr University and has an undergraduate degree in biochemistry and molecular biology. She has coauthored several scientific journal articles in the field of medical biophysics. Chasse has undergone extensive training in women’s health, pediatrics, and infertility, including an internship at the Jocelyn Centre for infertility in Sydney, Australia. Her clinical practice focuses on these specialties. Chasse has been very involved throughout her professional career in improving healthcare access and education. As a medical student, she cofounded the Naturopathic Medical Student Association, the only affiliate organization of the American Association of Naturopathic Physicians (AANP) representing medical students. She currently serves as the president of the New Hampshire Association of Naturopathic Doctors and has been an active member in the AANP since 2003.

Reference

Sanchez-Barcelo E, Mediavilla M, Reiter R. Clinical uses of melatonin in pediatrics. Int J Pediatrics. 2011; 892624. Epub ahead of print.
 

Design

This review article covers key studies on the use of melatonin in pediatrics, including its use for children’s sleep disorders, pediatric anesthesia, epilepsy and febrile seizures, adolescent idiopathic scoliosis, neonatal care, and the feeding of newborns.
 

Key Findings

Melatonin use in children has been well-studied to date, and research suggests efficacy for several conditions. Melatonin has been most studied for its chronobiotic (sleep modulation) effects in various pediatric populations. Experimental models have also demonstrated usefulness as an antioxidant. Inconsistent benefit has been found in studies on its analgesic/anxiolytic use in pediatric populations. No significant side effects of melatonin use in children have been reported.
 

Practice Implications

This review article provides very interesting information in support of melatonin’s use for several pediatric conditions.
 
Most interesting is the use of melatonin in children’s insomnia, a condition for which there are no approved pharmaceutical drugs. Most pediatricians and primary care physicians rely on behavioral treatments for insomnia, but a growing number of physicians are recommending melatonin, based on a 2003 survey in the journal Pediatrics.1 This review summarizes studies on general dyssomnias in addition to sleep disturbances associated with autism spectrum disorders (ASD), attention-deficit hyperactivity disorder (ADHD), and other mental or neurological disorders or disabilities. In general, these dyssomnias are associated with a difficult time initiating or maintaining sleep. Administration of melatonin has been associated with faster sleep onset, as well as increased sleep duration. The greatest effect is seen with advancing sleep onset, and the most benefit is achieved when melatonin is dosed approximately 30–60 minutes before desired bedtime. Doses used in the studies ranged from 0.5 to 9 mg, and positive effects were seen at all doses. The longest-term study evaluating melatonin use for insomnia was conducted in children with ADHD. This study surveyed parents whose children had been treated, on average, 3.7 years and demonstrated efficacy in 88% of cases and reported no serious adverse effects.2
 
Most importantly, the body of evidence reviewed highly suggests that melatonin administration is very safe, even in the youngest children.
 
 
In the area of pediatric anesthesia, melatonin has been studied as an alternative to general anesthesia for diagnostic procedures such as MRI or brainstem audiology. It has also been studied as a premedication to general anesthesia for surgical procedures. Study results conflict as to the efficacy of melatonin as an effective alternative.
 
Removal of the pineal gland has induced violent convulsions in animal models, as has intravenous injection of melatonin antibodies, suggesting a possible relationship between melatonin and epilepsy.3,4 Most studies conducted on melatonin use in epileptic children focus on the use of melatonin in addition to conventional antiepileptic drugs and report improved control in seizure activity with combined treatment over treatment with the conventional drug only. Researchers hypothesize that this may be due to the antioxidant and neuroprotective effects of melatonin in this population.
 
In neonates with sepsis, asphyxia, respiratory distress, or surgical stress, it has been theorized that associated oxidative stress may be one contributing factor to mortality. This review summarizes several studies in which high-dose (up to 80 mg) intravenous administration of melatonin was associated with a significant reduction in levels of malondialdehyde, nitrates/nitrites, and lipid peroxidation products, in addition to a significant reduction in mortality. While not directly applicable to primary care practice, these studies demonstrate an exciting use of melatonin in an acute setting, directly affecting patient outcomes in high-risk medical situations.
 
The final population reviewed in this paper is nursing infants. Melatonin levels change in breast milk according to the mother’s circadian rhythm.5 Given this information, the author suggests the importance of coordinating milk donation such that morning and evening milk is differentiated. In addition, the author suggests that it may be appropriate for synthetic milk formulations to consider differentiation of day and night products.
 
This review article presents several interesting uses for melatonin in clinical practice. Most importantly, the body of evidence reviewed highly suggests that melatonin administration is very safe, even in the youngest children.

References

1. Owens JA, Rosen CL, Mindell JA. Medication use in the treatment of pediatric insomnia: results of a survey of community-based pediatricians. Pediatrics. 2003;111(5):e628-635.
2. Hoebert M, van der Heijden KB, van Geijlswijk IM, Smits MG. Long-term follow-up of melatonin treatment in children with ADHD and chronic sleep-onset insomnia. J Pineal Research. 2009;47(1):1-7.
3. Reiter R, Blask DE, Talbot JA, Barnett MP. Nature and the time course of seizures associated with surgical removal of the pineal gland from parathyroidectomized rats. Exp Neurol. 1973;38:386-397.
4. Fariello R, Bubenik GA, Brown GM, Grota LJ. Epileptogenic action of intraventricularly injected antimelatonin antibody. Neurology. 1997;27(6):267-270.
5. Illerova H, Buresová M, Presl J. Melatonin rhythm in human milk. J Clin Endoc Metab. 1993;77(3):838-841.

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