Associação entre uso de clozapina e alterações hepáticas em portadores de esquizofrenia

• Autor(a) principal: Dias, Cíntia Lopes [UNIFESP]
• Data de Publicação: 2023
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Repositório Institucional da UNIFESP
• Texto Completo: https://hdl.handle.net/11600/70943
• topic: Antipsicóticos; Hepatotoxicidade; Lesão hepática induzida por drogas; Lesão hepática; Hepatite; Clozapina

Objective: To conduct a narrative review of the literature on the physiopathological mechanisms of liver injury induced by antipsychotic drugs, as well as the protocols and methods for detection and management of treatment. Methods: A search was performed on the PUBMED database using the terms "antipsychotics" and "hepatotoxicity," "hepatic injury," "drug-induced liver injury," or "hepatitis." Additionally, two cases were reported that presented symptoms and laboratory alterations indicative of liver injury upon the introduction of Clozapine. Results: Antipsychotic drugs mainly cause liver injury through an idiosyncratic pathway. The three patterns involved in the etiology of this phenomenon are cholestatic, often associated with phenothiazines; hepatocellular, in which the accumulation of drug metabolites in hepatocytes causes mitochondrial damage and imbalance in cellular repair pathways through increased oxidative stress by the endoplasmic reticulum, leading to damage and cell death by necrosis and autophagy; and steatosis pattern, where the accumulation of fat leads to hepatocyte death over the long term. Liver disease caused by antipsychotics is more common with Clozapine, even though it is a rare event (0.001%). It is important to differentiate transient and asymptomatic increases in liver function tests, which occur more frequently (60% of cases with Clozapine use) and do not imply damage or the need to discontinue the drug as they resolve within the first three months of use, from antipsychotic-induced liver disease, which would indicate drug withdrawal and clinical care. Antipsychotic- induced liver disease should be suspected when there is an increase in alanine aminotransferase above five times the upper limit, an increase in alkaline phosphatase above two times the upper limit, or an increase in alanine aminotransferase three times above the upper limit in association with an increase in bilirubin two times above the upper limit. In addition, if there is an increase in aminotransferases above three times the upper limit associated with any signs of hepatitis such as fever, eosinophilia, rash, or jaundice. Although the Food and Drug Administration provides various specific criteria for withdrawing any drug that induces liver disease, in general, for antipsychotics, it is recommended to discontinue the drug in the presence of an increase in alanine aminotransferase above three times the upper limit, alkaline phosphatase two times above the upper limit, or any alteration in liver function tests associated with clinical signs or symptoms. Conclusion: Since antipsychotic drugs are often necessary for the treatment of various psychiatric disorders, with Clozapine being the best available treatment for some cases, it is essential to define a more accurate protocol for monitoring liver function tests to screen for medication- induced liver disease without causing unnecessary discontinuations. There is no consensus in the literature on when to request these tests, but it is suggested that, in the presence of the above-mentioned changes, medication should be discontinued immediately, and the individual should be referred for appropriate clinical support.