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Clozapine use tied to URI progression to pneumonia in patients with schizophrenia

Key clinical point: Clozapine is the only antipsychotic drug associated with an increased risk of upper respiratory infection (URI) progression to pneumonia both before and after URI in patients with schizophrenia.

Major finding: Among first- and second-generation antipsychotics, clozapine was the only medication associated with an elevated risk of developing pneumonia before (adjusted hazard ratio [aHR], 2.05; P = .024) and after (aHR, 1.92; P = .027) URI. A clear dose-dependent relationship was also seen between clozapine use after URI and an increased risk of developing pneumonia (aHR, 1.95; P = .003).

Study details: This study included 22,771 patients (age range, 15-65 years) who had a first URI episode and a consistent diagnosis of schizophrenia using data from Taiwan's psychiatric inpatient claims database.

Disclosures: This study was supported by grants from the Ministry of Science and Technology, Taiwan and Taipei City Hospital. The authors declared no conflicts of interest.


“Clozapine is unique among antipsychotic drugs in that it has demonstrated efficacy in treatment-refractory schizophrenia. In spite of this advantage, clozapine remains relatively under-used when one considers the fact that many individuals with apparently drug-resistant symptoms never receive a trial of clozapine. This national case registry study from Taiwan highlights the link between clozapine therapy, upper respiratory infection and pneumonia. Findings suggest that clinicians need to be attentive to the emergence of new infections, as they balance risk vs. burden of clozapine therapy among individuals with schizophrenia. Safe and appropriate use of clozapine therapy is likely best accomplished in a setting of enhanced prescribed education and support as well as a care setting that allows for close monitoring and follow-up should new side effects occur.”

Martha Sajatovic, MD

Professor of Psychiatry and of Neurology

Willard Brown Chair in Neurological Outcomes Research

Director, Neurological and Behavioral Outcomes Center, University Hospitals Cleveland Medical Center

Case Western Reserve University School of Medicine


Chang CK et al. Schizophr Res. 2020 Jun 2. doi: 10.1016/j.schres.2020.05.013.