Journal
ARCHIVES OF TOXICOLOGY
Volume 95, Issue 3, Pages 767-789Publisher
SPRINGER HEIDELBERG
DOI: 10.1007/s00204-020-02963-4
Keywords
Hepatotoxicity; Antidepressants; Antipsychotics; Oxidative stress; Inflammation; Steatosis
Categories
Funding
- Ministry of Education, Science, and Technological Development of the Republic of Serbia [451-03-68/2020-14/200017, 451-03-68/2020-14/200178]
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Drug-induced liver injury (DILI) is a significant health burden with increasing incidence due to the rise in psychotropic drug use. This study comprehensively reviews and discusses the hepatotoxic effects of commonly prescribed antidepressants (ADs) and antipsychotics (APs), highlighting those that can cause severe DILI cases. By exploring the pathophysiology of DILI and the effects of ADs and APs on drug metabolism enzymes, the study emphasizes the importance of continuous data collection for easier diagnosis and risk assessment of DILI. Increased awareness of the hepatotoxicity of ADs and APs is crucial for their safe and optimal use.
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.
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