PMID- 38528668
OWN - NLM
STAT- MEDLINE
DCOM- 20240327
LR  - 20240328
IS  - 1600-079X (Electronic)
IS  - 0742-3098 (Linking)
VI  - 76
IP  - 2
DP  - 2024 Mar
TI  - Investigating the safety profiles of exogenous melatonin and associated adverse 
      events: A pharmacovigilance study using WHO-VigiBase.
PG  - e12949
LID - 10.1111/jpi.12949 [doi]
AB  - Melatonin, a pineal hormone that modulates circadian rhythms, sleep, and 
      neurotransmitters, is widely used to treat sleep disorders. However, there are 
      limited studies on the safety of melatonin. Therefore, we aimed to present the 
      overall patterns of adverse events (AEs) following melatonin administration and 
      identify potential safety signals associated with melatonin. Using VigiBase, a 
      global individual case safety report (ICSRs) database managed by the World Health 
      Organization (WHO), we conducted a retrospective, observational, 
      pharmacovigilance study of melatonin between January 1996 and September 2022. 
      Disproportionality analysis was conducted using two comparator settings: all 
      other drugs and other sleep medications. We used multivariable logistic 
      regression to estimate reporting odds ratios (RORs) with 95% confidence intervals 
      (CIs) to compare the frequencies of AEs reporting between melatonin and each 
      comparator setting. Furthermore, we assessed adverse events of special interests 
      (AESIs) that could potentially be associated with melatonin. Signals were 
      identified when the following criteria were met: cases >/=3, x(2) >/= 4, IC025 >/= 0, 
      and the lower end of the 95% CI of ROR > 2. These signals were then compared with 
      the AE information on the drug labels provided by regulatory bodies. A total of 
      35 479 AE reports associated with melatonin were identified, with a higher 
      proportion of reports from females (57.1%) and individuals aged 45-64 years 
      (20.8%). We identified 21 AEs that were commonly detected as safety signals in 
      the disproportionality analyses, including tic, educational problems, disturbance 
      in social behavior, body temperature fluctuation, and growth retardation. In AESI 
      analyses, accidents and injuries (adjusted ROR 2.97; 95% CI, 2.80-3.16), fall 
      (2.24; 2.12-2.37), nightmare (4.90; 4.37-5.49), and abnormal dreams (3.68; 
      3.19-4.25) were detected as a signal of melatonin when compared to all other 
      drugs, whereas those signals were not detected when compared to other sleep 
      medications. In this pharmacovigilance study, exogenous melatonin showed safety 
      profiles comparable to other sleep medications. However, several unexpected 
      potential safety signals were identified, underscoring the need for further 
      investigation at the population level.
CI  - (c) 2024 The Authors. Journal of Pineal Research published by John Wiley & Sons 
      Ltd.
FAU - Ha, Minyoung
AU  - Ha M
AD  - School of Pharmacy, Sungkyunkwan University, Suwon, South Korea.
FAU - Yoon, Dongwon
AU  - Yoon D
AD  - School of Pharmacy, Sungkyunkwan University, Suwon, South Korea.
FAU - Lee, Chae-Young
AU  - Lee CY
AD  - School of Pharmacy, Sungkyunkwan University, Suwon, South Korea.
FAU - Lee, Mose
AU  - Lee M
AD  - Regional Pharmacovigilance Center, Korean Pharmaceutical Association, Seoul, 
      Republic of Korea.
FAU - Kim, Young-Wook
AU  - Kim YW
AD  - Regional Pharmacovigilance Center, Korean Pharmaceutical Association, Seoul, 
      Republic of Korea.
FAU - Lee, Jung-Min
AU  - Lee JM
AD  - Regional Pharmacovigilance Center, Korean Pharmaceutical Association, Seoul, 
      Republic of Korea.
FAU - Shin, Ju-Young
AU  - Shin JY
AUID- ORCID: 0000-0003-1010-7525
AD  - School of Pharmacy, Sungkyunkwan University, Suwon, South Korea.
AD  - Department of Biohealth Regulatory Science, Sungkyunkwan University, Suwon, South 
      Korea.
LA  - eng
PT  - Journal Article
PT  - Observational Study
PL  - England
TA  - J Pineal Res
JT  - Journal of pineal research
JID - 8504412
RN  - JL5DK93RCL (Melatonin)
SB  - IM
MH  - Female
MH  - Humans
MH  - Adverse Drug Reaction Reporting Systems
MH  - *Melatonin/adverse effects
MH  - *Pharmacovigilance
MH  - Retrospective Studies
MH  - World Health Organization
OTO - NOTNLM
OT  - Adverse event (AE)
OT  - Adverse event of special interest (AESI)
OT  - VigiBase
OT  - melatonin
OT  - pharmacovigilance study
OT  - signal detection
OT  - sleep disorder
EDAT- 2024/03/26 06:44
MHDA- 2024/03/27 06:43
CRDT- 2024/03/26 01:26
PHST- 2023/12/21 00:00 [revised]
PHST- 2023/09/19 00:00 [received]
PHST- 2024/03/04 00:00 [accepted]
PHST- 2024/03/27 06:43 [medline]
PHST- 2024/03/26 06:44 [pubmed]
PHST- 2024/03/26 01:26 [entrez]
AID - 10.1111/jpi.12949 [doi]
PST - ppublish
SO  - J Pineal Res. 2024 Mar;76(2):e12949. doi: 10.1111/jpi.12949.