Clozapine, an atypical antipsychotic drug, has some well-known adverse reactions [1]. The most important is agranulocytosis, which necessitates regular monitoring of leukocyte counts. This agent has also been associated with gastrointestinal complications, but, to our knowledge, only two cases of pancreatitis have been reported [2, 3]. We report a new case of pancreatitis related to an acute overdosage of clozapine.

A 63-year-old woman with a history of dysthymic disorder and a personality disorder with histrionic traits attempted suicide by ingesting more than 1000 mg of clozapine—a drug that had been used to treat chronic schizophrenia in her son. She had no history of alcohol or drug intake.

She arrived at the hospital in a coma (Glasgow coma score of 7) and was intubated for mechanical ventilation. Results of blood screening for common toxic drugs (benzodiazepines, cocaine, opiates, cyclic antidepressants) were negative. Abnormal laboratory determinations included a leukocyte count of 2000 cells/mm³, a serum amylase level of 7000 UI/L (normal, <200 UI/L), a lipase level of 459 UI/L (normal, <190 UI/L), a total bilirubin level of 1.5 mg/dL (normal, <1.1 mg/dL), and a direct bilirubin level of 1.1 mg/dL. No electrocardiographic changes were detected.

On the second day, her neurologic status improved to a Glasgow coma score of 11, but she developed delirium (probably caused by the anticholinergic effect of clozapine). On the fourth day, she was conscious and well oriented and was extubated. Her leukocyte count recovered in 5 days to 5200 cells/mm³. Her amylase level progressively decreased to normal within a week. The patient did not report abdominal pain.

An echographic study done on the third day showed a decrease in echogenicity through the pancreatic parenchyma, which is consistent with an inflammatory process Figure 1, and showed no evidence of gallstones. A new study repeated before the patient was discharged showed a normal echogenicity of the pancreatic parenchyma (Figure 1).

View larger version (79K): [in this window] [in a new window]   Figure 1. Ultrasonographic transverse scan at the epigastric level. Top. Low echogenicity of the pancreatic parenchyma (arrows). Bottom. Normal echogenicity of the pancreatic parenchyma (arrows).

The diagnosis of pancreatitis in our patient is supported by the hyperamylasemia and hyperamylasuria, elevated serum lipase level (specificity approaching 90%), and ultrasonographic images. Hypersalivation is a common and unexplained effect of clozapine [1, 4]. This hypersalivation can produce mild hyperamylase levels, but the range of amylase levels and the associated increase in lipase levels in this case favor a diagnosis of acute pancreatitis.

The temporal association of clozapine intake and the diagnosis of pancreatitis, excluding other causes of pancreatitis, allows us to suggest a drug-related event.

The two patients previously described had clinical, overt pancreatitis diagnosed from abdominal pain and abnormal laboratory and echographic findings. In our patient, routine amylase monitoring detected a subclinical asymptomatic pancreatitis. Routine amylase level monitoring in patients treated with high doses of clozapine is advisable and will probably show a more frequent pancreatic involvement than is currently reported.