Abstract
Effects of aripiprazole on dopamine regulation are being tested as a treatment for patients with a dual diagnosis of schizophrenia and addictions, often cocaine dependence. Aripiprazole has one of the fewest side-effects among the second-generation antipsychotics. Nevertheless, severe aripiprazole hepatotoxicity was reported in persons with a history of cocaine and alcohol abuse. Here we report that therapeutically relevant aripiprazole concentrations, equal to laboratory alert levels in patients' serum, reduce the rate of hepatocytes' division. This could be an underlying mechanism of severe liver injury development in the patients with a history of alcohol and cocaine abuse, the two hepatotoxic agents that require increased ability of liver self-regeneration. Monitoring liver functions is, therefore, important in the cases when aripiprazole is co-prescribed or used with drugs with potential hepatotoxic effects.
Highlights
Aripiprazole (ARI) has fewer reported metabolic side-effects compared to some other frequently used second-generation antipsychotics
Primary hepatocytes survive in cell cultures for only about a week and there is a transition from the G0 into the G1 phase induced at isolation, they do not divide in cell culture [28, 31, 32]
Because of reports that human hepatocyte carcinoma, HepG2 cells, were not sensitive enough to detect hepatotoxic effects of drugs in preclinical studies [24], we used rat hepatoma cells Fao, which divide in cell cultures and are suitable for metabolic studies [33,34,35], and confirmed the crucial results on immortalized mouse hepatocytes [26, 27]
Summary
Aripiprazole (ARI) has fewer reported metabolic side-effects compared to some other frequently used second-generation antipsychotics. A severe aripiprazole-caused liver injury occurred in a 28-year female patient, only 21 days after she started taking 10 mg ARI and three times 2.5 mg lorazepam per day for 12 days. The ARI dose was after that increased to 20 mg per day up to the onset of the liver adverse effects [5]. The patient had previously no known medical conditions, even no psychiatric disease, as she was only first diagnosed 21 days before the DILI development. She reported inhaling cocaine once per month
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