Investigating the safety profiles of exogenous melatonin and associated adverse events: A pharmacovigilance study using WHO-VigiBase

IF 8.3 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM
Minyoung Ha, Dongwon Yoon, Chae-Young Lee, Mose Lee, Young-Wook Kim, Jung-Min Lee, Ju-Young Shin
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Abstract

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, x2 ≥ 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.

Abstract Image

调查外源性褪黑素的安全性概况及相关不良事件:利用 WHO-VigiBase 进行药物警戒研究。
褪黑素是一种松果体激素,可调节昼夜节律、睡眠和神经递质,被广泛用于治疗睡眠障碍。然而,有关褪黑素安全性的研究却很有限。因此,我们旨在介绍服用褪黑素后不良事件(AEs)的总体模式,并识别与褪黑素相关的潜在安全信号。我们利用世界卫生组织(WHO)管理的全球个体病例安全报告(ICSRs)数据库 VigiBase,对 1996 年 1 月至 2022 年 9 月期间的褪黑素进行了一项回顾性、观察性药物警戒研究。我们使用两种参照物进行了比例失调分析:所有其他药物和其他睡眠药物。我们使用多变量逻辑回归法估算了报告几率比(RORs)和 95% 置信区间(CIs),以比较褪黑素和每种参照物之间的 AE 报告频率。此外,我们还评估了可能与褪黑素有关的特殊利益不良事件(AESIs)。当符合以下标准时,我们将确定信号:病例数≥3、x2≥4、IC025≥0、ROR 的 95% CI 下限 > 2。然后将这些信号与监管机构提供的药物标签上的 AE 信息进行比较。共发现了 35 479 份与褪黑素相关的 AE 报告,其中女性(57.1%)和 45-64 岁人群(20.8%)的报告比例较高。在比例失调分析中,我们发现了 21 种作为安全信号的常见 AE,包括抽搐、教育问题、社交行为障碍、体温波动和生长迟缓。在AESI分析中,与所有其他药物相比,褪黑素可检测到意外伤害(调整后ROR为2.97;95% CI为2.80-3.16)、跌倒(2.24;2.12-2.37)、噩梦(4.90;4.37-5.49)和异常梦境(3.68;3.19-4.25)信号,而与其他睡眠药物相比,则未检测到这些信号。在这项药物警戒研究中,外源性褪黑素的安全性与其他睡眠药物相当。不过,也发现了几个意想不到的潜在安全信号,这表明有必要在人群层面开展进一步调查。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Pineal Research
Journal of Pineal Research 医学-内分泌学与代谢
CiteScore
17.70
自引率
4.90%
发文量
66
审稿时长
1 months
期刊介绍: The Journal of Pineal Research welcomes original scientific research on the pineal gland and melatonin in vertebrates, as well as the biological functions of melatonin in non-vertebrates, plants, and microorganisms. Criteria for publication include scientific importance, novelty, timeliness, and clarity of presentation. The journal considers experimental data that challenge current thinking and welcomes case reports contributing to understanding the pineal gland and melatonin research. Its aim is to serve researchers in all disciplines related to the pineal gland and melatonin.
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