Fluphenazine-Induced Severe Hypertriglyceridemia

Introduction: Antipsychotics are known to result in lipid dysregulation, possibly through their effects on weight, appetite and increased glucose intolerance. These effects are seen in varying degrees with both typical and atypical antipsychotics. This results in a cohort of patients with drug-induced hyperlipidemia, who benefit from lipid-lowering therapy. We describe an extreme scenario where the use of fluphenazine resulted in very severe hypertriglyceridemia, in addition to new onset diabetes requiring inpatient management. Case: A 42-year-old man with schizophrenia and a history of mild hypertriglyceridemia presented to the emergency department with one month of polyuria and polydipsia, and a home glucose measurement of >500 mg/dL. Six months earlier, he had been started on fluphenazine for schizophrenia. Laboratory testing at that time showed Hemoglobin A1c of 6.0% and a mild elevation in triglycerides to 188 mg/dL. He endorsed a family history of hypertriglyceridemia and type two diabetes. On physical exam, he appeared healthy with no abnormal focal findings. Labs revealed Hemoglobin A1c of 14% and a triglyceride level of 15,213 mg/dL. His blood samples became rapidly lipemic within a few minutes of the blood draw, corrupting the majority of the lab values. He was admitted to the ICU for continuous IV insulin, which improved his severe hypertriglyceridemia over the course of one week. Fluphenazine was switched to ziprasidone for schizophrenia. Pancreatic autoimmune workup was negative. Once the patient’s triglyceride level was <1000 mg/dL, insulin drip was discontinued and gemfibrozil was started. His triglyceride level at discharge was 449 mg/dL, and decreased to within the normal range over the course of a few months at outpatient follow up. Discussion: The highest on the differential for this case is fluphenazine-associated worsening of pre-existing hypertriglyceridemia in a patient with risk factors for metabolic syndrome. Antipsychotics can result in new-onset or worsening of metabolic syndrome. These patients can usually be managed in the outpatient setting with lipid-lowering therapies and glycemic control. This case represents a rare scenario of a dramatic hypertryglyceridemia and worsening of diabetes secondary to the use of the typical antipsychotic fluphenazine.