Freiesleben Silka Dawn, Furczyk Karolina
Department of Psychiatry, University of Rostock, Gehlsheimerstraße 20, 18147 Rostock, Germany.
J Mol Psychiatry. 2015 Apr 21;3(1):4. doi: 10.1186/s40303-015-0011-7. eCollection 2015.
Agomelatine is an antidepressant with a unique mechanism of action. Since its marketing in 2009, concerns have been raised regarding its potential to induce liver injury. The authors therefore address the need to comprehensively evaluate the potential risk posed by agomelatine of inducing liver injury by reviewing data from published and unpublished clinical trials in both the pre- and postmarketing settings, as well as data from non-interventional studies, pharmacovigilance database reviews and one case report. Recommendations for clinicians are also provided. In this review, agomelatine was found to be associated with higher rates of liver injury than both placebo and the four active comparator antidepressants used in the clinical trials for agomelatine, with rates as high as 4.6% for agomelatine compared to 2.1% for placebo, 1.4% for escitalopram, 0.6% for paroxetine, 0.4% for fluoxetine, and 0% for sertraline. The review also provides evidence for the existence of a positive relationship between agomelatine dose and liver injury. Furthermore, rates of liver injury were found to be lower in non-interventional studies. Findings from pharmacovigilance database reviews and one case report also highlight the risk of agomelatine-induced liver injury. As agomelatine does pose a risk of liver injury, clinicians must carefully monitor liver function throughout treatment. However, agomelatine's unique mechanism of action and favourable safety profile render it a valuable treatment option. A quantitative analysis of agomelatine-induced liver injury is lacking in the literature and would be welcomed.
阿戈美拉汀是一种作用机制独特的抗抑郁药。自2009年上市以来,人们对其诱发肝损伤的可能性表示担忧。因此,作者通过回顾上市前和上市后已发表及未发表的临床试验数据、非干预性研究数据、药物警戒数据库审查数据以及一份病例报告,来全面评估阿戈美拉汀诱发肝损伤的潜在风险。文中还为临床医生提供了相关建议。在本次综述中,发现阿戈美拉汀诱发肝损伤的发生率高于安慰剂以及阿戈美拉汀临床试验中使用的四种活性对照抗抑郁药,阿戈美拉汀诱发肝损伤的发生率高达4.6%,而安慰剂为2.1%,艾司西酞普兰为1.4%,帕罗西汀为0.6%,氟西汀为0.4%,舍曲林为0%。该综述还为阿戈美拉汀剂量与肝损伤之间存在正相关关系提供了证据。此外,在非干预性研究中肝损伤发生率较低。药物警戒数据库审查结果和一份病例报告也突出了阿戈美拉汀诱发肝损伤的风险。由于阿戈美拉汀确实存在肝损伤风险,临床医生在整个治疗过程中必须仔细监测肝功能。然而,阿戈美拉汀独特的作用机制和良好的安全性使其成为一种有价值的治疗选择。目前文献中缺乏对阿戈美拉汀诱发肝损伤的定量分析,这方面的研究将受到欢迎。