Melatonin use in pediatric practice: multidisciplinary approach

Objective. To analyse the results of studies of the use of melatonin preparations in pediatric practice and to identify the main possible directions for the use of melatonin based on nosological and syndromic indications.

Materials and methods. We have analyzed 21 scientific publications in MEDLINE, PubMed, Google Scholar, eLIBRARY database (using keywords «melatonin», «children», «epilepsy», «neuroprotection»): clinical trials, randomized controlled trials, systematic reviews, clinical cases from 1997 to 2024. The article reviews the main clinical directions on the use of melatonin in pediatric practice: epilepsy, headaches, sleep disorders, sepsis, neuroprotection.

Results. Taking into account the experience of foreign colleagues, we consider that the use of melatonin as an adjunctive therapy in pediatrics is acceptable in the absence or insufficient effectiveness of other methods of treatment, in case of the insufficient theoretical and practical basis (because of the possibility of aggravation of symptoms). It should also be noted that the use of this hormone should be carried out under control of its concentration in blood plasma and dynamic monitoring by an endocrinologist. In this case, treatment can be started from 6 months, but preference is given to the age range from 7 years because of the gradual reduction of nocturnal concentration peaks. It should also be noted that the dosage should be increased gradually: 0.2 – 0.5 mg per week to 3 – 9 mg per day.

Conclusion. Melatonin plays a key role in modulation of various physiological processes of the organism and is successfully used in pediatric practice for treatment of epilepsy, primary headaches, sleep disorders, sepsis, as analgesic therapy during invasive manipulations, and as a neuroprotector. Melatonin is a promising therapy in a number of nosologies associated with sleep-wake cycle disorders. However, for justified and relevant prescription it is necessary to conduct complex multivectoral studies, including, in particular, daily monitoring of melatonin concentrations taking into account age and gender aspects.

1. Brzezinski, A. Melatonin in humans / A. Brzezinski // The New England Journal of Medicine. — 1997. — Vol. 336, № 3. — P. 186—195.

2. Melatonin as an antiepileptic molecule: therapeutic implications via neuroprotective and inflammatory mechanisms / E. Akyuz, I. Kullu, A. Arulsamy, M. F. Shaikh // ACS Chemical Neuroscience. — 2021. — Vol. 12, iss. 8. — P. 1281—1292.

3. Kennaway, D. J. Measuring melatonin by immunoassay / D. J. Kennaway // Journal of Pineal Research. — 2020. — Vol. 69, iss. 1. — DOI: 10.1111/jpi.12657.

4. Melatonin: a potential candidate for the treatment of experimental and clinical perinatal asphyxia / R. Pluta, W. Furmaga-Jabłońska, S. Januszewski, A. Tarkowska // Molecules. — 2023. — Vol. 28, iss. 3. — DOI: 10.3390/molecules28031105.

5. Melatonin: from neurobiology to treatment / G. Biggio, F. Biggio, G. Talani [et al.] // Brain Sciences. — 2021. — Vol. 11, iss. 9. — DOI: 10.3390/brainsci11091121.

6. Melatonin in experimental seizures and epilepsy / M. Banach, E. Gurdziel, M. Jędrych, K. K. Borowicz // Pharmacological Reports. — 2011. — Vol. 63, iss. 1. — Р. 1—11.

7. Efficacy of melatonin for prolonged disorders of consciousness : a double-blind, randomized clinical trial / X. Wen, J. Yu, G. Zhu [et al.] // BMC Medicine. — 2024. — Vol. 22. — DOI: 10.1186/s12916-024-03793-2.

8. Melatonin as an add-on anti-seizure medication in children with epilepsy : аn open-label randomized controlled trial / V. Muppa, S. Mahapatro, S. Bhoi [et al.] // Journal of Neurosciences in Rural Practice. — 2024. — Vol. 15, iss. 3. — P. 455—460.

9. Current role of melatonin in pediatric neurology : clinical recommendations / O. Bruni, D. Alonso-Alconada, F. Besag [et al.] // European Journal of Paediatric Neurology. — 2015. — Vol. 19, iss. 2. — P. 122—133.

10. Melatonin for sleep problems in children with neurodevelopmental disorders: randomised double masked placebo controlled trial / P. Gringras, C. Gamble, A. P. Jones [et al.] // BMJ. — 2012. — Vol. 345. — DOI: 10.1136/bmj.e6664.

11. Schwichtenberg, A. J. Melatonin treatment in children with developmental disabilities / A. J. Schwichtenberg, B. A. Malow // Sleep Medicine Clinics. — 2015. — Vol. 10, iss. 2. — P. 181—187.

12. Paprocka, J. Melatonin in childhood epilepsy and in child neurology / J. Paprocka, M. Kijonka, M. Sokol // Melatonin — Molecular Biology, Clinical and Pharmaceutical Approaches / eds.: C. M. Dragoi, A. C. Nicolae. — London, 2018. — Ch. 6. — P. 123—141.

13. Melatonin as an adjuvant therapy in preterm infants with neonatal sepsis, randomized trial / Z. A. El-Kabbany, O. G. El-Farghali, S. M. Khafagy [et al.] // Egyptian Pediatric Association Gazette. — 2020. — Vol. 68. — DOI: org/10.1186/s43054-019-0013-7.

14. Henderson, R. Use of melatonin as adjunctive therapy in neonatal sepsis : a systematic review and meta-analysis / R. Henderson, S. Kim, E. Lee // Complementary Therapies in Medicine. — 2018. — Vol. 39. — P. 131—136.

15. Effects of melatonin treatment in septic newborns / E. Gitto, M. Karbownik, R. J. Reiter [et al.] // Pediatric Research. — 2001. — Vol. 50, № 6. — P. 756—760.

16. Efficacy of magnesium sulfate in addition to melatonin therapy in neonates with hypoxic-ischemic encephalopathy / M. H. Khan, Q.-U. Ann, M. S. Khan [et al.] // Cureus. — 2022. — Vol. 14, № 1. — DOI: 10.7759/cureus.21163.

17. Melatonin augments hypothermic neuroprotection in a perinatal asphyxia model / N. J. Robertson, S. Faulkner, B. Fleiss [et al.] // Brain. — 2013. — Vol. 136. — P. 90—105.

18. The use of melatonin in hypoxic-ischemic brain damage : an experimental study / W. Balduini, S. Carloni, S. Perrone [et al.] // The Journal of Maternal-Fetal and Neonatal Medicine. — 2012. — Vol. 25, iss. 1. — P. 119—124.

19. Pang, R. Efficacy of melatonin in term neonatal models of perinatal hypoxia-ischaemia / R. Pang, H. J. Han, Ch. Meehan [et al.] // Annals of Clinical and Translational Neurology. — 2022. — Vol. 9, iss. 6. — P. 795—809.

20. Measuring melatonin in humans / S. Benloucif, H. J. Burgess, E. B. Klerman [et al.] // Journal of Clinical Sleep Medicine. — 2008. — Vol. 4, iss. 1. — P. 66—69.

21. Clinical Practice Guideline for the Treatment of Intrinsic Circadian Rhythm Sleep-Wake Disorders: Advanced Sleep Wake Phase Disorder (ASWPD), Delayed Sleep-Wake Phase Disorder (DSWPD), Non- 24-Hour Sleep-Wake Rhythm Disorder (N24SWD), and Irregular Sleep-Wake Rhythm Disorder (ISWRD). An Update for 2015 : an American Academy of Sleep Medicine Clinical Practice Guideline / R. R. Auger, H. J. Burgess, J. S. Emens [et al.] // Journal of Clinical Sleep Medicine. — 2015. — Vol. 11, iss. 10. — P. 1199—1236.