Wabont Guillaume, Ferret Laurie, Houdre Nicolas, Lepied Antoine, Bene Johana, Cousein Etienne
Department of Pharmacy, Valenciennes Hospital, Valenciennes 59300, France.
Department of Emergency Medicine, Valenciennes Hospital, Valenciennes 59300, France.
World J Clin Cases. 2022 Mar 16;10(8):2468-2473. doi: 10.12998/wjcc.v10.i8.2468.
The antidepressant escitalopram is widely prescribed for the treatment of depression. It is generally well-tolerated, and cholestasis is not mentioned in its summary of product characteristics (SmPC). We present a case of cholestatic and cytolysis liver injury due to escitalopram and a VigiBase study.
A 68-year-old man was admitted to our emergency unit due to clinical jaundice associated with hepatitis, pruritus and dark urine. We tested the patient for the most common etiologies of jaundice, including hemolysis, viral hepatitis, cirrhosis, carcinoma, cholangitis, cholelithiasis and intrahepatic or extrahepatic obstruction. The etiological study was negative, and an adverse drug reaction was the sole possible explanation. The patient was receiving treatment with escitalopram. Two days after its withdrawal, pruritus was resolved. Ten days after withdrawal, clinical jaundice disappeared. It took a month and three weeks after withdrawal for the patient to have normalized liver function tests. To our knowledge, this is the first reported case of cholestasis where treatment with escitalopram was the only possible cause, with a highly probable causality. In addition, we determined whether escitalopram is associated with hepatotoxicity and cholestasis by performing a disproportionality analysis. All cases of hepatobiliary disorders induced by escitalopram and reported in the World Health Organization pharmacovigilance database (VigiBase) were analyzed to characterize this toxicity. We found that patients treated with escitalopram had an increased risk of hepatitis [odds ratio (OR) = 1.938] and cholestasis [OR = 1.866] [OR (95% confidence interval)]. The median duration between the introduction of escitalopram and the occurrence of acute hepatitis and/or cholestasis was ten days +/- seven days.
Although extremely rare, this case report, the review of the literature and the pharmacovigilance update confirm that escitalopram can cause drug-induced hepatotoxicity and cholestasis, generally within a week after initiation. Thus, escitalopram should be withdrawn immediately if an iatrogenic cause cannot be excluded. If its responsibility is ascertained, escitalopram should be consequently contraindicated. In addition, serotoninergic antidepressants in patients with non-severe depression are ineffective and harmful. Finally, the SmPC of escitalopram should be updated to alert for this risk and give clear clinical guidelines.
抗抑郁药艾司西酞普兰被广泛用于治疗抑郁症。它通常耐受性良好，其产品特性摘要（SmPC）中未提及胆汁淤积。我们报告一例因艾司西酞普兰导致胆汁淤积和细胞溶解型肝损伤的病例以及一项VigiBase研究。
一名68岁男性因临床黄疸伴肝炎、瘙痒和深色尿入住我们的急诊科。我们对患者进行了黄疸最常见病因的检测，包括溶血、病毒性肝炎、肝硬化、癌、胆管炎、胆石症以及肝内或肝外梗阻。病因学研究结果为阴性，药物不良反应是唯一可能的解释。该患者正在接受艾司西酞普兰治疗。停药两天后，瘙痒症状缓解。停药十天后，临床黄疸消失。停药一个月零三周后患者肝功能检查恢复正常。据我们所知，这是首例报告的以艾司西酞普兰治疗为唯一可能病因且因果关系高度可能的胆汁淤积病例。此外，我们通过进行不成比例分析来确定艾司西酞普兰是否与肝毒性和胆汁淤积有关。对世界卫生组织药物警戒数据库（VigiBase）中报告的所有由艾司西酞普兰引起的肝胆疾病病例进行分析以描述这种毒性特征。我们发现接受艾司西酞普兰治疗的患者患肝炎的风险增加[比值比（OR）=1.938]以及患胆汁淤积的风险增加[OR =1.866][OR（95%置信区间）]。开始使用艾司西酞普兰至发生急性肝炎和/或胆汁淤积的中位时间为十天±七天。
尽管极为罕见，但本病例报告、文献回顾以及药物警戒更新证实艾司西酞普兰可导致药物性肝毒性和胆汁淤积，通常在开始用药一周内发生。因此，如果不能排除医源性病因，应立即停用艾司西酞普兰。如果确定其责任，则应禁用艾司西酞普兰。此外，5-羟色胺能抗抑郁药对非重度抑郁症患者无效且有害。最后，艾司西酞普兰的SmPC应更新以警示这种风险并给出明确的临床指南。
