Quetiapine-induced hypertriglyceridemia causing acute pancreatitis

LEARNING OBJECTIVE #1: Recognize rare triggers of acute pancreatitis such as hypertriglyceridemia caused by a rare complication of antipsychotic medications LEARNING OBJECTIVE #2: Highlight the frequently ignored metabolic complications of quetiapine use for the education of the general internist

CASE:

A 50 year-old Caucasian veteran presented with progressive 10/10 epigastric pain radiating to the back, associated with nausea since six days. Additionally, he endorsed fatigue, polyuria, and polydipsia for the past one month. He had a history of bipolar disorder, hyperlipidemia, type-2 diabetes mellitus, morbid obesity, irritable bowel syndrome, generalized anxiety disorder and a history of alcohol abuse. The previous day his primary physician, for these complaints, saw him where routine laboratory parameters revealed triglycerides 3590 mg/dL, lipase 2079 IU/L and elevated blood glucose of 533 mg/dL with a hemoglobin A1C of 10.4 gm%. Admission laboratory parameters revealed pancytopenia with 3.9 leucocytes/mm3, hemoglobin of 12.4 gm/dL and platelets of 129/mm3. Differential leukocyte count revealed 40.8 % neutrophils and 44 % lymphocytes. Metabolic panel demonstrated normal electrolytes, hepatic and renal function. Abdominal ultrasound was unrevealing for gall bladder or bile duct pathology. He was managed conservatively for acute pancreatitis with bowel rest, intravenous hydration and adequate pain controlled. He was started on intravenous insulin for suspected hyperglycemic hyperosmolar syndrome and triglyceridemia. Additionally, he was started on oral gemfibrozil and within 24 h of initiating treatment, the patient's triglycerides decreased to 1334 mg/dL and blood glucose blood glucose levels were better controlled. The triglyceride levels continued to improve to 684 mg/dL at 72 h. He started to tolerate an oral diet and was transitioned to his home medications of atorvastatin with the addition of fenofibrate. The combination of hypertriglyceridemia, hyperglycemia, and pancytopenia with predominant neutrophil depression made us suspect quetiapine as the cause for these abnormalities. The patient was tapered off of quetiapine over the subsequent two days and ziprasidone was initiated. He was subsequently discharged on hospital day seven with triglyceride levels of 628 mg/dL and serum glucose<200 mg/dL for over 24 h. His leukocyte count was 6.0/mm3 with additional normalization of other cell lines. At 2- month post-hospitalization follow-up, the patient continued to improve with good medication compliance and remained symptom-free.

DISCUSSION:

Quetiapine is a second-generation antipsychotic (SGAs) that is frequently-prescribed for patients with major depressive and bipolar-type disorders, shown to significantly reduce the number of psychiatric admissions (P<0.001) and episodes of emergent suicidality compared to placebo (0.3 and 0.5 %, respectively). Metabolic disturbances including hyperglycemia, hypertriglyceridemia are welldocumented side effects of SGAs, seen in up to 10 % of patients treated with olanzapine or quetiapine. The mechanism by which quetiapine causes hyperlipidemic disturbances is not entirely understood. Some hypothesize that the medication stimulates hepatic triglyceride production and secretion or alters lipase-mediated triglyceride hydrolysis. Medications are attributed as the cause for only 0.1-7 % of acute pancreatitis cases. Acute pancreatitis caused by hypertriglyceridemia side effects of quetiapine use has only been reported in as few as five published case reports. Hypertriglyceridemia (>600 mg/dL) is frequently reported with quetiapine use in asymptomatic patients, but severe hypertriglyceridemia (>1000 mg/dL) has been reported in fewer than 10 patients treated with quetiapine. SGAs also possess a well-documented side effect of blood dyscrasias, such as agranulocytosis. While this side effect is documented most frequently with clozapine use, seen in up to 3% of patients taking this medication, quetiapine has also been shown to depress leukocyte cell lines with unknown incidence. Leukopenia associated with quetiapine is most predominantly pronounced by selective absolute neutrophil depression. We reported a case of hypertrigliceridemic pancreatitis likely as a result of caused by quetiapine use. This case also emphasizes the importance of routine laboratory follow-up when initiating therapy with SGAs. We believe that this case study will aid clinicians identify, with confidence, a rarely published serious side effect of a common antipsychotic medication.