Antidepressant-Induced Acute Liver Injury: A Case-Control Study in an Italian Inpatient Population
Antidepressant-Induced Acute Liver Injury: A Case-Control Study in an Italian Inpatient Population
复制标题
DOI：
10.1007/s40264-017-0583-5
复制
发表时间：
2018-01-01
期刊：
影响因子：
4.2
通讯作者：
Capuano, Annalisa
中科院分区：
文献类型：
--
作者：
Ferrajolo, Carmen;Scavone, Cristina;Capuano, Annalisa
导言上市前的临床试验表明，抗抑郁药所致的肝损伤似乎是一种罕见的不良事件。目的通过在住院人群中进行病例对照分析，量化抗抑郁药使用所致急性肝损伤的风险。方法2010年10月至2014年1月，在DILI-IT(DILI-IT)研究项目范围内，在9家意大利医院开展了一项多中心研究。在排除了所有有明显相互竞争的肝损伤原因的患者后，病例被定义为入院诊断为急性肝损伤的成年人，而对照组有任何其他与肝脏无关的急性临床症状。在出现肝损伤的第一个体征/症状之前的90天内评估抗抑郁药的暴露情况。计算优势比(OR)，95%可信区间(95%CI)作为评估肝损伤风险的指标。结果17名服用抗抑郁药物的患者与99名对照组相匹配。根据肝损伤的特点，所有病例入院时均有症状性肝功能异常，主要体征/症状为乏力、恶心、乏力或尿色变暗。西酞普兰是主要参与肝酶升高的抗抑郁药，主要是丙氨酸氨基转移酶。与不使用抗抑郁药相比，当前使用抗抑郁药与肝损伤风险显著增加相关(调整后的OR，ORADJ，1.84；95%CI 1.02-3.32)。具体地说，选择性5-羟色胺再摄取抑制剂西酞普兰发生肝损伤的风险增加，但并不显著。结论抗抑郁药的使用并不像预期的那样安全；相反，抗抑郁药导致肝损伤的风险可能被低估。缺乏重要性并不反映没有风险，而是表明有必要在更广泛的抗抑郁药物使用者环境中对其进行评估。
Introduction 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.Objectives We aimed to quantify the risk of acute liver injury associated with antidepressant use through a case-control analysis among an inpatient population.Methods 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.Results 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, ORADJ, 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 (ORADJ 1.82; 95% CI 0.60-5.53).Conclusion 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.