Antidepressants- and antipsychotics-induced hepatotoxicity

• Published in: Archives of toxicology Vol. 95; no. 3; pp. 767 - 789
• Main Authors: Todorović Vukotić, Nevena, Đorđević, Jelena, Pejić, Snežana, Đorđević, Neda, Pajović, Snežana B.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-03-2021; Springer Nature B.V
• Subjects: Animals; Antidepressants; Antidepressive Agents - administration & dosage; Antidepressive Agents - adverse effects; Antipsychotic Agents - administration & dosage; Antipsychotic Agents - adverse effects; Antipsychotics; Biomedical and Life Sciences; Biomedicine; Case reports; Chemical and Drug Induced Liver Injury - diagnosis; Chemical and Drug Induced Liver Injury - etiology; Chemical and Drug Induced Liver Injury - physiopathology; Drug Interactions; Environmental Health; Hepatotoxicity; Humans; Liver; Liver diseases; Metabolic disorders; Occupational Medicine/Industrial Medicine; Oxidative stress; Oxidative Stress - drug effects; Pharmacology/Toxicology; Psychotropic drugs; Review; Review Article; Risk analysis; Risk Assessment; Risk Factors; Severity of Illness Index; Steatosis; Antipsychotics; Oxidative stress; Inflammation; Antidepressants; Hepatotoxicity; Steatosis
• ISSN: 0340-5761; 1432-0738
• DOI: 10.1007/s00204-020-02963-4

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.