Differences between paediatric and adult suspected neuropsychiatric adverse drug reactions of Melatonin reported to the European Medicines Agency

Abstract

Melatonin has been approved as a sleep medication in Europe since 2007. The pharmacological dosages of this substance are much higher than the physiological ones, so it is no surprise that it has potential for many adverse effects. In children melatonin has been used for many years off-label, but in 2018 the Committee for Medicinal Products for Human Use (CHMP) granted paediatric-use marketing authorization for melatonin. We used the European Medicines Agency (EMA) database to compare the distribution of melatonin adverse drug reaction (ADRs) between the pediatric and the adult population. The results will serve as a basis for future research involving melatonin use in specific populations. All ADR reports received in EMA up to 23.03.2019 were analyzed for overall numbers, age and gender. The nature of the ADRs and the most frequently reported drug substances and drug event combinations were evaluated using MedDRA 21.0. As of 27th March 2019, EudraVigilance contained 1061 spontaneous reports. After excluding all the cases with other suspected or concomitant drugs, we are left with 177 cases. In children ADRs were generally associated with central nervous system (CNS) excitability, whereas in adults there was mainly inhibition. The present study focused on the ADR reports of melatonin in one of the largest databases. Future research of melatonin in the pediatric population is needed, because the current SmPCs lack such information, and in the cases of melatonin use in children are increasing in recent years.