Amid the controversy surrounding warnings of increased risk of patients developing diabetes while taking atypical antipsychotic medications (see article on
page 1), a report focusing on a potential rare risk of pancreatitis associated with the same medications garnered little attention.
The report by former Food and Drug Administration (FDA) staff member Elizabeth Koller, M.D., now an assistant professor of internal medicine at the University of Nebraska Health Sciences Center, and her colleagues was published in the September Pharmacotherapy. The study was completed with no outside sources of funding.
Koller and her associates conducted a systematic review of the FDA’s MedWatch database of adverse-event reports for cases of pancreatitis in patients taking clozapine (Clozaril and generics), olanzapine (Zyprexa), or risperidone (Risperdal). They used haloperidol (Haldol and generics) as a “control” representing an older typical neuroleptic. The MedWatch data spanned the period from January 1981 through February 2002. In addition, a MEDLINE search was conducted for any published reports of antipsychotic-associated pancreatitis during the same period.
The researchers found 177 reports of pancreatitis associated with the four antipsychotic medications. In addition, they noted 31 cases where patients were taking more than one of the medications, most often a combination of one atypical plus haloperidol.
Of the cases occurring in patients on monotherapy, 72 cases (40.7 percent) were associated with clozapine, 62 cases (35 percent) with olanzapine, 31 cases (17.5 percent) with risperidone, and 12 cases (6.8 percent) with haloperidol.
Most cases occurred within the first six months of therapy; however, there was no association between daily dose of any of the four medications and the time to diagnosis of pancreatitis. Of the patients who developed pancreatitis, 22 died. Deaths did not differ significantly between the four medications.
The investigators stressed that the presentation of pancreatitis in patients taking an atypical antipsychotic is very rare and that causality cannot be proven by methods such as theirs. Sedentary lifestyle, obesity, weight gain, diabetes, alcoholism, hyperlipidemia, and gall stones are all risk factors for pancreatitis, they noted, and all are common in patients with schizophrenia.
Koller’s team concluded that it is reasonable to entertain a diagnosis of pancreatitis as a differential for any schizophrenia patient with unexplained abdominal pain. While clinicians should be aware of adverse-event reports, the researchers called for more definitive prospective studies to determine whether a clear causal link exists.
An abstract of “Pancreatitis Associated With Atypical Antipsychotics: From the Food and Drug Administration’s MedWatch Surveillance System and Published Reports” is posted on the Web at www.accp.com/pharmacotherapy/pharm2309.php#5. ▪
