Acute Necrotizing Pancreatitis following Long-Term Antipsychotic Use

Abstract

Introduction. Psychiatrists commonly use antipsychotic medications in the treatment of psychotic and mood disorders. A rare but known side effect of atypical antipsychotics is acute pancreatitis. Most cases of antipsychotic-induced pancreatitis occur within six months of initiation. The mechanism believed to cause this reaction is hypertriglyceridemia. Here, we present a unique case of antipsychotic-induced pancreatitis that deviates from previous cases in the time to onset of the pancreatitis and the mechanism of presentation. Case Presentation. We present a case of a patient with treatment-resistant schizophrenia managed for over a decade on olanzapine and haloperidol. Twelve years after stabilization on this medication regimen, the patient developed acute pancreatitis, which after extensive medical workup was attributed to his psychotropic medications. We review his medical and psychiatric history, his medical course and workup during the episode of pancreatitis, and review recommendations for patients at risk for antipsychotic-induced pancreatitis based on this case and the current literature. Discussion. This case illustrates that acute pancreatitis can occur long after the initiation of antipsychotic medications and may be mediated by mechanisms other than hypertriglyceridemia. While there are reports of antipsychotic-induced psychosis occurring within months, and in a limited set of cases, years, after medication initiation, the twelve-year time interval in the present case is by far the longest duration of an antipsychotic precipitating this adverse event recorded in the literature. This case highlights that although exceedingly rare, prescribers should be aware of the risk for drug-induced pancreatitis in patients stable on antipsychotic medications.

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.…”