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.

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调查外源性褪黑激素的安全性和相关不良事件：使用 WHO-VigiBase 进行的药物警戒研究

褪黑激素是一种调节昼夜节律、睡眠和神经递质的松果体激素，被广泛用于治疗睡眠障碍。然而，关于褪黑激素安全性的研究有限。因此，我们的目的是展示褪黑激素给药后不良事件 (AE) 的总体模式，并确定与褪黑激素相关的潜在安全信号。我们利用世界卫生组织 (WHO) 管理的全球个案安全报告 (ICSR) 数据库 VigiBase，在 1996 年 1 月至 2022 年 9 月期间对褪黑激素进行了一项回顾性观察性药物警戒研究。使用两种比较设置进行了不成比例分析：所有其他药物和其他睡眠药物。我们使用多变量逻辑回归来估计报告比值比 (ROR) 和 95% 置信区间 (CI)，以比较褪黑激素和每个比较器设置之间的 AE 报告频率。此外，我们评估了可能与褪黑激素相关的特殊利益不良事件 (AESI)。当满足以下标准时识别信号：病例≥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。总共发现了 35 479 起与褪黑激素相关的 AE 报告，其中女性 (57.1%) 和 45-64 岁人群 (20.8%) 的报告比例较高。我们确定了 21 种在不成比例分析中通常被检测为安全信号的 AE，包括抽动、教育问题、社会行为障碍、体温波动和生长迟缓。在 AESI 分析中，事故和伤害（调整后的 ROR 2.97；95% CI，2.80-3.16）、跌倒（2.24；2.12-2.37）、噩梦（4.90；4.37-5.49）和异常梦（3.68；3.19-4.25）分别为与所有其他药物相比，检测到褪黑激素信号，而与其他睡眠药物相比，未检测到这些信号。在这项药物警戒研究中，外源性褪黑激素的安全性与其他睡眠药物相当。然而，发现了一些意想不到的潜在安全信号，强调需要在人群层面进行进一步调查。