Recurring episodes of acute pancreatitis following Clozapine, Olanzapine, and Quetiapine in a bipolar patient

Abstract

Clozapine, Olanzapine, and Quetiapine are three commonly prescribed atypical antipsychotics that fall into the category of “-pines” due to pharmacological affinities. Clozapine,the prototype of this class, is burdened by the risk of severe hematological side effects, namely agranulocytosis and neutropenia. Olanzapine and Quetiapine are not associated with similar hematological risk, despite being effective atypical antipsychotics. Nonetheless, some evidence suggests that all three antipsychotics are associated with the risk of acute pancreatitis, a rare but potentially fatal side effect. In this report, we describe the first case of a patient with bipolar disorder (BD) who presented multiple episodes of acute pancreatitis, under Clozapine treatment, and while on Olanzapine and Quetiapine. He presented a first episode of pancreatitis after three months since the introduction of Clozapine in combination with Valproate. After several months of discontinuation, a positive rechallenge for Clozapine was performed. One year later, the patient presented another episode of acute pancreatitis while on Olanzapine therapy, following the introduction of Quetiapine as a combination strategy. The two drugs were stopped and the clinical picture was restored.Acute pancreatitis associated with each atypical antipsychotic alone is a rare occurrence, yet is more likely to occur in polytherapy. In our description, we hypothesize that pancreatitis occurred as a combined result of metabolic risk factors and accumulation of cytotoxic metabolites. We speculate that the first episode of pancreatitis was Clozapine-induced, while Olanzapine may have been a risk factor facilitating the third Quetiapine-induced pancreatitis.This unique pattern of side effects provides novel information on potential risk factors for acute pancreatitis associated with atypical antipsychotics and caveats for future clinical and research practice.