Antipsychotics May Contribute to Cases of Acute Pancreatitis

While drug-associated acute pancreatitis occurs rarely, the long-term use of antipsychotics in combination with other medications may increase the risk of a patient’s experiencing the condition, according to a report appearing in the April issue of the Journal of Clinical Psychopharmacology.

Matthew Silva, Pharm.D., R.Ph., B.C.P.S., a professor of pharmacy practice at MCPHS University in Worcester, Mass., and colleagues reviewed case reports of antipsychotic pancreatitis published from 1990 to 2015 and classified these cases into groups according to the weight of published evidence for each agent and the pattern of clinical presentation of acute pancreatitis. (A system to classify drug-induced acute pancreatitis was first proposed in 2007.)

• Class I drugs are those with at least one case report and positive rechallenge (recurrent pancreatitis when the drug was reinstituted after withdrawal). Class I drugs are further divided based on whether the patient presents with any other possible cause of pancreatitis, such as alcohol, hypertriglyceridemia, gallstones, and other drugs.

• Class II drugs are those with at least four reports in the literature and consistent latency (time between drug initiation and illness).

• Class III drugs are those with at least two cases in the literature, but no consistent latency among the cases, and no rechallenge data.

• Class IV drugs are those with a weak association to pancreatitis, having demonstrated no more than a single case report in the literature and no rechallenge data.

Silva and colleagues identified 41 cases of antipsychotic medication-related acute pancreatitis, including 17 new cases since 2007. The evidence supported categorizing olanzapine and quetiapine as Class II, aripiprazole as Class III, and ziprasidone as Class IV. Risperidone, which was previously categorized as a Class IV, was moved to Class II.

“An updated classification system with new information on olanzapine, quetiapine, risperidone, and ziprasidone improves decision support when these medications are suspected during an acute presentation,” the researchers wrote. “Long-term treatment with antipsychotic medication should be readily suspected in new or repeat episodes of pancreatitis.”

The group also expressed concern that the increasing use of polypharmacy played a role in the expanded presence of antipsychotics in the classification of drugs associated with acute pancreatitis. Of the 41 cases analyzed, 53 percent of cases were associated with polypharmacy—the use of four or more medications at one time.

Matthew Silva, Pharm.D.

“Patients in this review were not otherwise unusual except for a recent history of antipsychotic polypharmacy or combinations with mood stabilizers. There were no remarkable trends in respect to patient age, sex, and metabolic features during acute pancreatitis presentations,” they wrote.

While Silva and his colleagues acknowledged the need for some patients to take antipsychotics in combination with other medications for years, they noted that providers prescribing antipsychotics should be aware of possible lifetime risk of acute or recurrent pancreatitis for their patients.

“Antipsychotic medication is an important reason for drug-associated pancreatitis especially when two or more antipsychotics are used in combination along with other medications associated with pancreatitis, as occurs in polypharmacy with uncoordinated care,” they wrote. “Acute pharmacovigilance during the first six weeks of starting antipsychotic medication or combinations [is] essential, and regular, ongoing reassessment of risks and benefits of extended antipsychotic treatment and combination therapy is necessary.”

The study authors declared no funding for this analysis of medical information. ■