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Acute pancreatitis is an inflammatory condition of the pancreas with variable involvement ofextrapancreatic organs. Gallstones, alcohol and hypertriglyceridemia are the most commonly recognized etiologies of acute pancreatitis. Medications, autoimmune pancreatitis and ERCP (Endoscopic Retrograde Cholangiopancreatography) pancreatitis, apart from other rare causes, have also been implicated in the causation of the disease. Second-generation antipsychotics (SGAs) such as Quetiapine, olanzapine and risperidone, have well known metabolic side effects such as hyperlipidemia and hyperglycemia.1 Quetiapine is a widely used antipsychotic in the treatment of delirium. Although second-generation antipsychotics are associated with pancreatitis, Quetiapine-associated pancreatitis is extremely rare.2

We present what we believe to be the first report of Quetiapine induced acute pancreatitis seen at our tertiary care hospital in Eastern Nepal.

A 32 year old male presented to the emergency room with progressive, moderate to severe epigastric pain for 3 days associated with nausea and post prandial bloating. The pain radiated to the back and right shoulder. He reported no history of fever, jaundice, vomiting of blood or dark stool. The patient reported no history of smoking or alcohol use and he consumed a vegan diet. He recently survived a major road traffic accident one and a half months ago, where he sustained a head concussion for which he was hospitalized and kept in the ICU for observation. During the hospital stay the patient developed delirium and was diagnosed to have depression on detailed psychiatric assessment. He was put on Quetiapine 25 mg twice daily along with midazolam 5mg at bed time. He was on the atypical antipsychotic for one and half months before presenting with this episode of abdominal pain.

On examination he was in distress with abdominal pain. He had generalized tenderness, guarding and rigidity of the abdomen. He had not passed flatus for 3 days and his bowel sounds was sluggish. He was kept NPO (Nil per Oral),with a nasogastric tube, started on intravenous opioids and was given judicious hydration while closely monitoring his urine output. His investigations revealed high amylase 920 IU/ml, lipase 1010 U/l, hematocrit 42.5%, total leukocyte count 17000 cells/mm3 and hsCRP (high sensitivity C-reactiveprotein) 198.4 mg/l. There was no evidence of hypertriglyceridemia, diabetic ketoacidosis or other metabolic abnormalities. His abdominal CT revealed moderate severity of the disease (Modified CTSI score- 4) with minimal left sided pleural effusion. 

With the temporal relationship of use of Quetiapine for 6 weeks and the absence of typical etiological factors (eg. Alcohol, gallstones, hypertriglyceridemia) Quetiapine was implicated for the patient’s acute pancreatitis. Psychiatric consultation was done and Quetiapine was stopped and replaced with escitalopram. The patient became medically stable after 3 days of hospitalisation. His amylase and lipase dropped down to 560 IU/l and 600 U/l respectively. His leukocytecount normalized and hematocrit came down to 30%. He was discharged and asked to follow up after 2 weeks in the Gastroenterology Out Patient Department. On follow up he continued to improve with good medication compliance and remained symptom free.

Acute pancreatitis has varied etiologies, though the commonly implicated ones are alcohol, gallstones and hypertriglyceridemia. Quetiapine, an atypical antipsychotic which our patient was using is prescribed along with haloperidol in the ICU for delirium. Though SGAs (Second generation antipsychotics) are known to cause metabolic disturbances like hyperglycemia and hypertriglyceridemia, complications from these metabolic side-effects, such as acute pancreatitis and diabetic ketoacidosis, are exceedingly rare.3 Quetiapine induced hypertriglyceridemia causing acute pancreatitis has been reported in only five published case reports.4

In this case, the use of quetiapine could not be linked to serious metabolic side effects. In the absence of other potential risk factors, we presumed that the development of pancreatitis could be attributed to Quetiapine. Hypertriglyceridaemiainduced acute pancreatitis from Quetiapine use does not appear to be dose dependant, but appears instead to be related to the duration of intake of the drug. All cases have been reported within the first 8 months of an established dose, most frequently at 3 months of treatment, with one report of occurrence within 72 h.1,4 The mechanism by which quetiapine causes hyperlipidemic disturbances is not entirely understood though some hypothesise altered triglyceride metabolism leading to oxidative stress ultimately causing acute pancreatitis.

SGAs also possess a well-documented side effect of blood dyscrasias, such as agranulocytosis. Leukopenia associated with quetiapine is most predominantly pronounced by selective absolute neutrophil depression, though the exact incidence is not known.5 Although our patient did not have any hematological adverse effect to the drug, presence of pancytopenia, specially neutropenia, could assist in the diagnosis of quetiapine induced pancreatitis. 

Clinicians must be careful not to blame a drug when a patient with acute pancreatitis does not have an obvious underlying cause. Many of the published case reports suffer from a combination of inadequate criteria for the diagnosis of acute pancreatitis, failure to rule out more common causes, or a lack of a re-challenge with the medication. We excluded the classic causes of pancreatitis such as alcohol, gallstones, hyperglyceridemia and hypercalcemia in our patient. However we did not re-challenge the patient with the same drug to confirm the cause and effectdue to possible ethical issues attached to such an approach. Although a positive re-challenge with a drug is the best evidence available for cause and effect, it is not proof.

We conclude from our observations that while second-generation antipsychotics (SGAs) are generally safe, they can occasionally cause serious metabolic and haematologicalcomplications. Acute pancreatitis is rarely caused by medications and Quetiapine has been implicated in only a few published case reports. To our knowledge this is the first case report of Quetiapine induced pancreatitis noted here in a tertiary care hospital in eastern Nepal.