Unit of Clinical Pharmacology, Department of Experimental Medicine, Campania Regional Center of Pharmacovigilance and Pharmacoepidemiology, University of Campania "Luigi Vanvitelli", via de Crecchio 7, 80138, Naples, Italy.
Department of Medical Informatics, Erasmus MC University, Rotterdam, The Netherlands.
Drug Saf. 2018 Jan;41(1):95-102. doi: 10.1007/s40264-017-0583-5.
Pre-marketing clinical trials show that antidepressant-induced liver injury seems to be a rare adverse event. Because of short follow-up trial duration, the incidence of liver injury due to antidepressant use could be underestimated.
We aimed to quantify the risk of acute liver injury associated with antidepressant use through a case-control analysis among an inpatient population.
A multicenter study was carried out in nine Italian hospitals from October 2010 to January 2014, within the DILI-IT (Drug-Induced Liver Injury in Italy) study project. After exclusion of all patients with a clear competing cause of liver injury, cases were defined as adults admitted to the hospital with a diagnosis of acute liver injury, while controls had any other acute clinical condition not related to the liver. Antidepressant exposure was evaluated within 90 days prior to the date of the first sign/symptom of liver injury. Odds ratio (OR) with 95% confidence interval (95% CI) was calculated as a measure of risk estimates for liver injury.
We included 17 cases exposed to antidepressants matched to 99 controls. According to the features of liver injury, all cases showed symptomatic liver function test abnormalities at hospital admission, with the main signs/symptoms represented by fatigue, nausea, asthenia, or dark urine. Citalopram was the antidepressant mostly involved in the increase of liver enzymes, mainly alanine aminotransferase. Compared with non-use, current use of antidepressants was associated with a significantly increased risk of liver injury (adjusted OR, OR, 1.84; 95% CI 1.02-3.32). Specifically, an increased, but not significant, risk of developing liver injury was observed for citalopram, a selective serotonin-reuptake inhibitor (OR 1.82; 95% CI 0.60-5.53).
The use of antidepressants is not as safe in terms of liver injury as expected; instead, the risk of antidepressant-induced liver injury is likely underestimated. The lack of significance does not reflect the absence of risk, but rather suggests the need to evaluate it in a wider setting of antidepressant users.
上市前临床试验表明，抗抑郁药引起的肝损伤似乎是一种罕见的不良反应。由于随访试验时间短，抗抑郁药引起肝损伤的发生率可能被低估。
我们旨在通过对住院患者进行病例对照分析，量化抗抑郁药使用相关急性肝损伤的风险。
本研究于 2010 年 10 月至 2014 年 1 月在意大利 9 家医院进行，属于 DILI-IT（意大利药物性肝损伤）研究项目的一部分。排除所有具有明确肝损伤竞争原因的患者后，将入院诊断为急性肝损伤的成年患者定义为病例，而其他任何与肝脏无关的急性临床状况的患者则为对照。在肝损伤的第一个症状/体征出现前 90 天内评估抗抑郁药暴露情况。比值比（OR）及其 95%置信区间（95%CI）用于计算肝损伤风险的估计值。
我们纳入了 17 例暴露于抗抑郁药的病例，匹配了 99 例对照。根据肝损伤的特征，所有病例在入院时均出现有症状的肝功能试验异常，主要症状/体征为疲劳、恶心、乏力或尿液深黄。西酞普兰是引起肝酶升高的主要抗抑郁药，主要为丙氨酸氨基转移酶。与未使用相比，当前使用抗抑郁药与肝损伤风险显著增加相关（调整后 OR，OR，1.84；95%CI，1.02-3.32）。具体而言，西酞普兰（一种选择性 5-羟色胺再摄取抑制剂）肝损伤风险增加，但无统计学意义（OR 1.82；95%CI，0.60-5.53）。
抗抑郁药在肝损伤方面的安全性并不像预期的那样高；相反，抗抑郁药引起的肝损伤风险可能被低估。缺乏显著性并不能反映不存在风险，而是表明需要在更广泛的抗抑郁药使用者群体中评估这种风险。
