MON-675 Ziprasidone Induced Diabetic Ketoacidosis

Introduction: Atypical antipsychotics are known to cause increased risk of type 2 Diabetes Mellitus (DM2), dyslipidemia, and weight gain (metabolic syndrome). Clozapine, a commonly used anti-psychotic, is known to cause Diabetic Ketoacidosis (DKA), but literature has rarely shown an association of DKA with Ziprasidone. Case: A 42-year-old African American female presented with two weeks of polyuria, polydipsia, 23-pound weight loss, blurriness of vision, and dry mouth. Before the presentation, she had been drinking several drinks with high sugar content. Her medications included Ziprasidone (Geodon), Trileptal, and Cogentin for her bipolar disorder. She was started on Ziprasidone in 2007, changed to Brand name Geodon in 2014. Except for dry mouth, her exam was unremarkable. Labs were significant for blood glucose of 1114 mg/dL, bicarbonate of 18mmol/L, beta-hydroxybutyrate of 3.33 mmol/L, serum osmolality of 334 mOsm/kg. She was diagnosed with new-onset diabetes mellitus presenting as diabetic ketoacidosis. Her mother was diagnosed with DM2 in her 40s. She ha difficult to control blood sugars despite aggressive hydration and required regular insulin drip for 3 days for her anion gap to close. Managing her BGs was challenging. Discussion: Clozapine and olanzapine are the common atypical antipsychotics that can cause DKA(1, 2). To our knowledge, Ziprasidone is associated with hyperglycemia within days of starting the drug and HHS but not with DKA. For atypical antipsychotic associated DKA, risk factors include the duration of antipsychotic therapy, polypharmacy with multiple antipsychotic agents, non-Caucasians, obesity and pre-diabetes(2, 3). Proposed mechanisms include peripheral insulin resistance, alteration of pancreatic beta-cell function by inhibiting 5-HT1A/2A/2C and alpha 2 adrenergic receptors(1-3). However, there is no explanation of why few people develop complications while others do not. There is hypothesis regarding leptin gene polymorphisms of receptors that may play a role(4). While starting patients on Ziprasidone, close monitoring of blood glucose is necessary before initiation and regular follow up thereafter(3). 1. Henderson DC. Atypical antipsychotic-induced diabetes mellitus: How strong is the evidence? CNS Drugs. 2002. 2. Vuk A. Diabetic ketoacidosis associated with antipsychotic drugs: Case reports and a review of literature. Psychiatr Danub. 2017. 3. Schwenkreis P. Atypical antipsychotics and diabetes mellitus. World J Biol Psychiatry. 2004. 4. 1. Reynolds GP. Metabolic side effects of antipsychotic drug treatment - pharmacological mechanisms. Pharmacol Ther. 2010.