Pancreatitis associated with atypical antipsychotics: from the Food and Drug Administration's MedWatch surveillance system and published reports.
OBJECTIVE
To investigate the relative numbers and clinical characteristics of pancreatitis in patients treated with the atypical antipsychotic agents, clozapine, olanzapine, and risperidone, versus the conventional neuroleptic, haloperidol.


METHODS
Pharmacovigilance study of pooled, spontaneously reported adverse events.


METHODS
Government-affiliated drug evaluation center.


METHODS
One hundred ninety-two patients who developed pancreatitis during treatment with one or more antipsychotic agents.


METHODS
Patients were identified with the Food and Drug Administration's MedWatch surveillance program and a MEDLINE search.


RESULTS
Most cases of pancreatitis occurred within 6 months after the start of therapy with one or more antipsychotic agents. Of the reports of pancreatitis occurring in conjunction with these drugs, 40%, 33%, 16%, and 12% were in patients receiving treatment with 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. Hyperglycemia and acidosis, although uncommon, developed with all the drugs except haloperidol. Twenty-two patients died. In contrast to patients who developed pancreatitis while receiving an atypical antipsychotic, those who developed the disease while receiving haloperidol were women and tended to be older.


CONCLUSIONS
The number of reports involving the three atypical antipsychotic agents and the relative paucity of reports involving haloperidol, despite its more extensive patient exposure, suggest that atypical antipsychotics may precipitate pancreatitis. However, the risk may not be the same with all agents; pancreatitis was reported most frequently with clozapine, followed by olanzapine, and then risperidone. The temporal relationship of the onset of pancreatitis with the start of drug therapy further supports a cause-and-effect relationship.
Koller
Elizabeth A
EA
Division of Metabolic and Endocrine Drug Products, Center for Drug Evaluation and Review, Food and Drug Administration, Rockville, Maryland, USA.
Cross
James T
JT
Doraiswamy
P Murali
PM
Malozowski
Saul N
SN
D016907:Adverse Drug Reaction Reporting Systems; D000368:Aged; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000145:classification; D006801:Humans; D010195:Pancreatitis / Q000139:chemically induced* / Q000453:epidemiology*; D014481:United States; D014486:United States Food and Drug Administration
D014150:Antipsychotic Agents