Clozapine Rechallenge With Recurrent Pancreatitis

Clozapine is the gold standard for treatment-resistant schizophrenia. Clozapine is thought to trigger an inflammatory response mediated through proinflammatory cytokines interleukins 1–6 and tumor necrosis factor α, often leading to fever and elevated C-reactive protein (CRP). This effect is most pronounced in the first month after clozapine initiation.

This clozapine-induced inflammatory response is potentially related to benign hyperthermia, myocarditis, and agranulocytosis. Clozapine is also strongly associated with the risk of pneumonia, which is more severe during titration with accompanying high mortality.2 The mechanism of clozapine increasing the risk of pneumonia is likely multifactorial, related to a combination of reducing the defensive mechanisms against infection and aspiration.3 Eight clozapine-induced pancreatitis cases are documented, with only 2 reported cases of successful clozapine rechallenge.4–6 We present a unique case of concurrent pneumonia and pancreatitis following clozapine initiation and recurrence of pancreatitis upon rechallenge.