A Case of Clozapine-Associated Pancreatitis

Acute pancreatitis is a very rare complication of clozapine treatment. We report a new case of symptomatic pancreatitis subsequent to starting of clozapine treatment. In this case, the diagnosis of pancreatitis can be considered de- finitive and the etiological link between clozapine and pancreatitis highly likely. Recovery was not complete. In a 10-year period, we treated 363 cases (196 patients) with clozapine. We diagnosed clozapine-associated pancreatitis only in this pa- tient. However, we did not check amylase and lipase plasma levels in all patients and possibly missed several cases of pancreatitis. We suggest monitoring pancreatic enzymes routinely, at least in the first months of clozapine therapy. Between 2 and 5% of cases of acute pancreatitis are drug related (1). Drugs cause pancreatitis either by a hypersensi- tivity reaction or by the generation of a toxic metabolite. The autodigestion by proteolytic enzymes activated in pancreas rather than in the intestinal lumen is the suspected patho- genic mechanism. Rechallenge tests, consistent case reports, animal experiments, data on the incidence in drug trials pro- vide evidence of a definite association with pancreatitis for didanosine, valproic acid, aminosalicylates, estrogen, cal- cium, anticholinesterases, and sodium stibogluconate. An association with pancreatitis is likely, but not definitely proven, for thiazide diuretics, pentamidine, ACE inhibitors, asparaginase, vinca alkaloids, nonsteroidal anti- inflammatory drugs, and clozapine (2). In a pharmacovigi- lance study of spontaneously reported adverse events (3), 192 patients developed pancreatitis during antipsychotic treatment. Most cases of pancreatitis occurred within 6 months after the start of antipsychotics. Of the reports of pancreatitis associated with antipsychotics, 40%, 33%, 16%, and 12% were in patients receiving clozapine, olanzapine, risperidone, and haloperidol, respectively. In 50% of the patients receiving haloperidol, an atypical antipsychotic was listed as a concomitant drug. Valproate was administered concomitantly in 23% of patients.