Olanzapine-induced acute necrotising pancreatitis leading to recurrent multiple organ dysfunction syndrome

Abstract

A married mother in her 50s acutely developed vomiting, diarrhoea and severe epigastric pain 2 weeks following discharge from an acute psychiatric inpatient unit. She presented to the emergency department complaining of a 2-day history of the above symptoms. Blood tests revealed neutrophilia, grossly raised inflammatory markers and amylase levels triple the normal range. Based on radiological investigations, she was treated for necrotising pancreatitis that quickly escalated to multi-system organ failure and a lengthy intensive care unit admission. Common causes of pancreatitis, including cholelithiasis, alcohol and other drugs, were ruled out. Despite this, she suffered recurrent episodes of pancreatitis with significant morbidity. Olanzapine, started during her psychiatric admission, was determined to be the offending agent. Two years following the discontinuation of olanzapine, the patient has had no further episodes of acute pancreatitis.

Antipsychotic drugs and risk of acute pancreatitis: A nationwide case–control study

“…In theory, if a physician is aware of the case reports on antipsychotic drugs and acute pancreatitis, such outcome misclassification could be differential with respect to exposure status. However, since the bulk of the case reports has detailed second‐generation agents, for which we observed a null association (except for past use of the highly publicized agents Clozapine and Olanzapine 5–9 ), the practical implications were most likely negligible. Second, we could not control whether the study subjects had taken their dispensed prescriptions (reducing the specificity of the exposure) and had no access to in‐hospital use of antipsychotic drugs (reducing the sensitivity of the exposure).…”

“…The notion of second‐generation antipsychotic drugs as causes of acute pancreatitis, originating from multiple case reports on the subject, 5–9 has received little support from well‐controlled pharmacoepidemiological studies. Gasse et al, who analyzed data from 3083 Danish patients with acute pancreatitis (of whom 20 were exposed to second‐generation agents), observed no association between second‐generation agents and risk of acute pancreatitis 12 .…”

“…(Nota bene: No case or control subject had a prescription of Levosulpiride [N05AL07].) Separate categorization of Clozapine and Olanzapine, that is the antipsychotic agents most commonly linked to acute pancreatitis in case report data, [5][6][7][8][9] was also performed.…”

“…More than 40 case reports have been published on the association between antipsychotic drugs and risk of acute pancreatitis, with the bulk of them detailing the second‐generation (atypical) agents Clozapine and Olanzapine 5–9 . However, data from well‐controlled pharmacoepidemiological studies are sparse and somewhat inconsistent with case report data.…”

“…[2][3][4] More than 40 case reports have been published on the association between antipsychotic drugs and risk of acute pancreatitis, with the bulk of them detailing the second-generation (atypical) agents Clozapine and Olanzapine. [5][6][7][8][9] However, data from well-controlled pharmacoepidemiological studies are sparse and somewhat inconsistent with case report data. While a multinational European case-control study (724 cases) observed an increased risk of acute pancreatitis with use of antipsychotic drugs (the included agents were, however, not specified), 10 a Swedish case-control study (462 cases) found no such association with use of first-generation (conventional) phenothiazines after adjustment for potential confounders.…”