The pathogenesis depends on the particular etiology. Pathogenesis of drug-induced pancreatitis is not well understood.

In the United States, gall stones and alcohol use account for the majority of cases of acute pancreatitis. Other less common causes are hypertriglyceridemia, pancreatic duct obstruction, iatrogenic (after cholangiopancreatography), systemic infections, ischemia, and blunt trauma. Medications are a rare cause of pancreatitis; however, many medications, including several psychotropics, are reported to be associated with pancreatitis. Most patients who develop pancreatitis carry multiple risk factors .

It is a rare (<1%) and idiosyncratic phenomenon and is based mostly on case reports. It is reported with valproate , which carries a black box warning regarding its association with pancreatitis. It is less commonly reported with carbamazepine . It is also associated with some antipsychotic medications. Antidepressants do not carry an increased risk for pancreatitis [1].

The exact mechanism of pancreatitis is unknown but two hypotheses are cell damage from toxic free radicals and immunologic reactions.

The pancreatic damage can occur at any time in treatment, though the majority of cases are within 12 months for valproate [2] and within 6 months for antipsychotics [3]. Among antipsychotics, case reports are most frequent with clozapine and olanzapine . In one review of FDA surveillance data and case reports, atypical antipsychotics were more likely to be associated with pancreatitis than haloperidol, which was used as the comparator drug [3]. Among the three atypical antipsychotics reviewed, frequency of association was clozapine > olanzapine > risperidone.