Aripiprazole Causes Cholelithiasis and Hepatitis

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Introduction: Aripiprazole is an effective antipsychotic with a favorable side effect profile. The purpose of this case report is to indicate that rare and potentially fatal side effects can occur on aripiprazole therapy. Case: A 54 year old male with a history of schizophrenia, cholecystectomy, on warfarin, presents with 8-day history of vomiting, diarrhea and light colored stools. He has no history of hepatitis B and C; recent travel, alcohol or acetaminophen use. Patient was started on aripiprazole for schizophrenia, two weeks prior to admission. At admission the patient was icteric with mild hepatomegaly. Aripiprazole was discontinued and coumadin held. Normal labs included ferritin, anti-smooth muscle antibody, ANA, anti-LKM1, CA 19–9 and viral hepatitis panel. In hospital after a dose of vitamin K the INR reversed to 1.7. Endoscopic ultrasound showed moderate pancreatitis without ductal dilatation or stone. CT scan showed minimal hepatomegaly with normal tissue density. The patient improved significantly after discontinuing aripiprazole and was subsequently discharged. On outpatient visit, 18 days later, the labs were: albumin 3.5 g/dl, alkaline phosphatase 95 IU/L, ALT 80 IU/L, AST 68 IU/L and INR 1.1. The patient had fully recovered. Discussion: Aripiprazole is a novel atypical antipsychotic with a favorable side effect profile. The incidence of cholelithiasis and hepatitis is less than 1%. In the absence of a biopsy, the hepatic injury could be due to an ischemic event or aripiprazole. However, the obstructive pattern of injury does not favor ischemic hepatitis. Instead the 2-week delay of adverse hepatobiliary effects is consistent with the pharmacokinetics of aripiprazole which achieves a steady state at 2 weeks. This cumulative phase is associated with a 4-fold increase in mean peak plasma concentration; which is possibly hepatotoxic, given that the metabolism of aripiprazole is hepatic. Considering the above temporal profile and pattern of hepatic injury, the likely culprit appears to be aripiprazole and not an ischemic event. Conclusion: This case report demonstrates that rare and potentially fatal side effects can occur on aripiprazole therapy, requiring close monitoring when initiating therapy.Table: Labs in Hospital