Drug-induced liver injury is one of the leading causes for acute liver failure and drug withdrawal after marketing approval. One important risk factor is the extent of exposure of the hepatocytes to a substance, either by high doses or by long-term medication. In many psychiatric diseases, like schizophrenia long-term use of drugs is common. However, systematic data on the hepatotoxic potential of antipsychotics is scarce.

To perform an explorative analysis of pharmacovigilance data on the risk of hepatotoxicity related to the use of antipsychotics.

We conducted an explorative case/non-case study based on data from VigiBase for 30 antipsychotics marketed in the European Union. Reporting odds ratios were calculated for antipsychotics associated with the SMQ “Drug related hepatic disorders - comprehensive search” and the SMQ “Drug related hepatic disorders - severe events only”.

We found several associations of antipsychotics with drug-induced liver injury including associations with severe events. 17/30 antipsychotics were associated with “Drug related hepatic disorders - comprehensive search”, and for 10/30 substances were associated with severe hepatic events.

Several antipsychotics are associated with the risk for hepatotoxic side effects, even severe ones. Further research is warranted on patient and substance-dependent risk factors.

No significant relationships.

Neuropsychiatric drugs account for 16% of drugs that can lead to hepatotoxicity and psychiatric patients can have multiple comorbidities that can increase the incidence of liver disorders such as alcoholism, drug abuse and polymedication. The continuous use of atypical antipsychotic drugs (AAD) has raised questions over their tolerability over endocrine, metabolic and cardiovascular systems. They are also associated with mild elevation of aminotransferases and occasionally cause idiosyncratic liver injury with varying phenotypes. Hepatotoxicity is defined based on biological parameters such as elevation of alkaline phosphatase enzyme, SGPT, SGOT and GGT or clinical abnormalities (jaundice and hepatitis).

This work reviewed the current available evidence on the hepatic damage produced by AAD.

Non-systematic review of the literature with selection of scientific articles published in the past 10 years; by searching Pubmed and Medscape databases using the combination of MeSH descriptors. The following MeSH terms were used: atypical antipsychotic drugs; hepatotoxicity; hepatic; Olanzapine; Clozapine; Risperidone; Aripiprazol; Paliperidone.

Atypical Antipsychotic Drugs are generally well tolerated and hepatic alterations are in general very low or rare. The cases published were observed with Clozapine, Olanzapine and Risperidone. Atypical Antipsychotic drugs have a better profile than Chlorpromazine.

In conclusion, the hepatic injury generally occurs within the first weeks of treatment and is usually reversible with drug withdrawal. Hepatic check-ups may be relevant, especially in the beginning of treatment.

No significant relationships.

To examine the adverse effects of benzene exposure in adults from a prolonged flaring disaster at the BP refinery in Texas City, Texas.

Adults aged 18 years and older who had been exposed and unexposed to benzene were included. We reviewed medical charts and compared measures of white blood cells (WBCs), platelets, hemoglobin, hematocrit, blood urea nitrogen (BUN), creatinine, alkaline phosphatase (ALP), aspartate amino transferase (AST), and alanine amino transferase (ALT) in exposed and unexposed adults.

Records from 2213 adults (benzene exposed, n=1826; unexposed, n=387) were reviewed. Benzene-exposed subjects had significantly higher WBC counts (7.9±2.3 vs 6.8±1.6×103 per µL, P=0.0000) and platelet counts (270.8±60.9 vs 242.5±53.7×103 per µL, P=0.0000) than did the unexposed subjects. Serum creatinine levels were also significantly higher in the exposed group than in the unexposed group (1.0±0.2 vs 0.8±0.2 mg/dL, P=0.000). Serum levels of ALP were significantly higher in the exposed subjects than in the unexposed subjects (82.1±15.6 vs 71.8±8.2 IU/L, P=0.000). Similarly, benzene-exposed subjects had significantly higher levels of AST (26.2±6.4 vs 19.7±5.3 IU/L, P=0.000) and ALT (30.6±10.8 vs 20.9±9.6 IU/L, P=0.000) than in those unexposed to benzene.

Benzene exposure resulted in significant alterations in hematologic and liver profiles in adults. (Disaster Med Public Health Preparedness. 2016;10:233–239)

A case of agomelatine-induced hepatotoxicity is described in a 47-year female patient who has received the drug, 25 mg/day, for 4 months, for the treatment of depression.

The patient was admitted to the Department of Gastroenterology because of fatigue and nausea, with concomitant elevation of alanine aminotransferase (ALT), 550 U/L, and asparagine aminotransferase (AST), 300 U/L.

Liver biopsy showed diffuse lymphocyte infiltration in the dilated portal spaces without lesion of hepatic lobules. Several weeks after stopping agomelatine, the liver enzymes returned to normal. Subsequently, small gallstones in common bile duct were detected and removed by the endoscopic sphincterotomy.

It is hypothesized that choledocholithiasis could theoretically increase a risk of developing agomelatine-induced hepatotoxicity in this patient. Any pre-existing liver disease should be a contraindication for treatment with agomelatine.