Antipsychotic Reexposure and Recurrent Pneumonia in Schizophrenia: A Nested Case-Control Study

Objective: Few studies have used systematic datasets to assess the safety of antipsychotic rechallenge after an adverse event. This nested case-control study estimated the risk for recurrent pneumonia after reexposure to antipsychotic treatment.

Method: In a nationwide schizophrenia (ICD-9-CM code 295) cohort (derived from the National Health Insurance Research Database in Taiwan) who were hospitalized for pneumonia (ICD-9-CM codes 480-486, 507) between 2000 and 2008 (N = 2,201), we identified 494 subjects that developed recurrent pneumonia after a baseline pneumonia episode. Based on risk-set sampling in a 1:3 ratio, 1,438 matched controls were selected from the cohort. Exposures to antipsychotics were categorized by type, duration, and defined daily dose. Using propensity score-adjusted analysis, we assessed individual antipsychotics for the risk of recurrent pneumonia; we furthermore assessed the effect of reexposure to these antipsychotics on the risk of recurrent pneumonia.

Results: Of the antipsychotics studied, current use of clozapine was the only one associated with a clear dose-dependent increase in the risk for recurrent pneumonia (adjusted risk ratio = 1.40, P = .024). Intriguingly, patients reexposed to clozapine had a higher risk for recurrent pneumonia (adjusted risk ratio = 1.99, P = .023) than those receiving clozapine only prior to the baseline pneumonia, and this risk was associated with gender. Women reexposed to clozapine were more susceptible to recurrent pneumonia (adjusted risk ratio = 4.93, P = .050).

Conclusions: In patients experiencing pneumonia while undergoing clozapine treatment, physicians should carefully consider the increased risk of pneumonia recurrence when clozapine is reintroduced. Future studies should try to quantify the risk of other medical conditions associated with clozapine reexposure.