Aripiprazole is a new atypical antipsychotic agent that is increasingly prescribed due to a lower incidence of metabolic side effects compared with other agents in this class. Case reports have suggested an association between aripiprazole and drug-induced diabetic ketoacidosis (DKA) (1,,–4). We report the case of a 29-year-old obese man managed with aripiprazole for schizophrenia who presented unwell with DKA and a markedly elevated serum lipase.
A 29-year-old male Filipino immigrant with schizophrenia presented to a hospital emergency department with a 3-day history of lethargy and a nonproductive cough. He described polyuria, polydipsia, and subjective weight loss over the preceding 4 weeks. He denied abdominal pain or vomiting.
His schizophrenia had been effectively controlled with aripiprazole 20 mg twice daily for 12 months. Weight gain over this period was ∼20 kg. There were no other medications. The patient had no family history of diabetes or autoimmune disorders. He did not drink alcohol to excess and had no other risk factors for pancreatitis.
Clinical examination revealed an obese man (BMI 40 kg/m2) who was disorientated to time and place. He was tachypneic and volume-depleted but afebrile and had no obvious focus of infection. Abdominal examination was unremarkable. Arterial blood gases showed a metabolic acidosis pH 7.01 (7.38–7.44), bicarbonate 7 mmol/l (23–29 mmol/l), and base excess −22 (−3.0 to +3.0). Blood glucose was 43.4 mmol/l, and ketones were >160 mg/dl. The patient received fluid resuscitation and an intravenous insulin infusion with resolution of the hyperglycemia, acidosis, and ketosis.
He was subsequently found to have an A1C of 15.9% and was insulinopenic with a fasting C-peptide of 0.29 nmol/l (0.33–2.50 nmol/l) in the context of a fasting glucose of 8.1 mmol/l. GAD and IA2 autoantibodies were not elevated.
Lipase was markedly elevated to 4,354 units/l (23–300 units/l), and amylase was only mildly elevated. Triglycerides were elevated to 5.9 mmol/l (<1.7 mmol/l). Ultrasonography and computerized tomography imaging showed changes consistent with fatty liver disease and no evidence of pancreatitis. The chest radiograph showed collapse at the left heart border.
The aripiprazole dose was halved from admission on the advice of the psychiatry team. The pancreatic enzymes and β-cell function improved over 7 days. He was discharged home on a basal bolus insulin regimen requiring a total of 330 units/day.
This case suggests that aripiprazole can cause relative insulin deficiency and weight-associated insulin resistance, precipitating DKA. Serum lipase can be elevated in conditions that do not involve pancreatic inflammation, with the incidence of nonspecific lipase elevation in DKA ranging from 16–25% (5). The etiology of this elevation remains unclear, although it is likely to be related to the degree of oxidative stress. There was no evidence of acute pancreatitis in our patient, suggesting that the elevation in serum lipase was due to DKA.
This case illustrates the need for vigilance in monitoring patients treated with aripiprazole for the presence of potentially life-threatening insulin deficiency in addition to insulin resistance. Although the psychiatric benefits of atypical antipsychotic agents are established, all prescribers should consider the potential for serious metabolic adverse effects.
Acknowledgments
The authors report no potential conflicts of interest relevant to this article.
K.J.K. and A.M.R. wrote the manuscript. G.C.N. reviewed and edited the manuscript.
