Department of Molecular Biology and Endocrinology, "Vinča" Institute of Nuclear Sciences, National Institute of the Republic of Serbia, University of Belgrade, 12-14 Mike Petrovića Alasa, P.O. Box 522-090, 11000, Belgrade, Serbia.
Institute of Physiology and Biochemistry "Ivan Đaja", Faculty of Biology, University of Belgrade, 16 Studentski Trg, 11000, Belgrade, Serbia.
Arch Toxicol. 2021 Mar;95(3):767-789. doi: 10.1007/s00204-020-02963-4. Epub 2021 Jan 5.
Drug-induced liver injury (DILI) is a serious health burden. It has diverse clinical presentations that can escalate to acute liver failure. The worldwide increase in the use of psychotropic drugs, their long-term use on a daily basis, common comorbidities of psychiatric and metabolic disorders, and polypharmacy in psychiatric patients increase the incidence of psychotropics-induced DILI. During the last 2 decades, hepatotoxicity of various antidepressants (ADs) and antipsychotics (APs) received much attention. Comprehensive review and discussion of accumulated literature data concerning this issue are performed in this study, as hepatotoxic effects of most commonly prescribed ADs and APs are classified, described, and discussed. The review focuses on ADs and APs characterized by the risk of causing liver damage and highlights the ones found to cause life-threatening or severe DILI cases. In parallel, an overview of hepatic oxidative stress, inflammation, and steatosis underlying DILI is provided, followed by extensive review and discussion of the pathophysiology of AD- and AP-induced DILI revealed in case reports, and animal and in vitro studies. The consequences of some ADs and APs ability to affect drug-metabolizing enzymes and therefore provoke drug-drug interactions are also addressed. Continuous collecting of data on drugs, mechanisms, and risk factors for DILI, as well as critical data reviewing, is crucial for easier DILI diagnosis and more efficient risk assessment of AD- and AP-induced DILI. Higher awareness of ADs and APs hepatotoxicity is the prerequisite for their safe use and optimal dosing.
药物性肝损伤(DILI)是一种严重的健康负担。它具有多种临床表现,可能恶化为急性肝衰竭。全球范围内精神药物的使用增加、长期每日使用、精神和代谢疾病的常见合并症以及精神科患者的多药治疗增加了精神药物引起的 DILI 的发病率。在过去的 20 年中,各种抗抑郁药(ADs)和抗精神病药(APs)的肝毒性受到了广泛关注。本研究对这一问题的累积文献数据进行了全面回顾和讨论,对最常开处方的 ADs 和 APs 的肝毒性进行了分类、描述和讨论。该综述侧重于具有引起肝损伤风险的 ADs 和 APs,并强调了那些已被发现可引起危及生命或严重 DILI 病例的药物。同时,提供了 DILI 潜在的肝氧化应激、炎症和脂肪变性概述,随后对 AD 和 AP 引起的 DILI 的病例报告、动物和体外研究中揭示的病理生理学进行了广泛的回顾和讨论。一些 ADs 和 APs 影响药物代谢酶从而引发药物相互作用的能力所带来的后果也得到了处理。持续收集关于 DILI 的药物、机制和风险因素的数据,并对数据进行严格审查,对于更轻松地诊断 DILI 以及更有效地评估 AD 和 AP 引起的 DILI 的风险至关重要。提高对 ADs 和 APs 肝毒性的认识是安全使用和优化剂量的前提。