Benzodiazepines and risk of pneumonia in schizophrenia: a nationwide case-control study

Abstract

Objectives: To investigate the relationship between benzodiazepine and risk of developing pneumonia in patients with schizophrenia, whose benzodiazepine dosage and usage frequency was higher than that of the general population.

Methods: We conducted a nested case-control study to assess the association between benzodiazepine use and pneumonia among patients with schizophrenia. By using the Taiwan National Health Insurance Research Database, we identified a schizophrenia cohort comprising 34,929 patients during 2000-2010. Within the schizophrenia cohort, 2501 cases of pneumonia and 9961 matched control patients (1:4 ratio) were identified. Benzodiazepine exposure was categorized by drug, treatment duration, and daily dose. Conditional logistic regression models were used to examine the association between benzodiazepine exposure and the risk of pneumonia.

Results: The current use (within 30 days) of midazolam led to the highest pneumonia risk (adjusted risk ratio = 6.56, P < 0.001), followed by diazepam (3.43, P < 0.001), lorazepam (2.16, P < 0.001), and triazolam (1.80, P = 0.019). Furthermore, nearly all the benzodiazepines under current use had a dose-dependent effect on pneumonia risk. The risk of pneumonia was correlated with the affinities of γ-aminobutyric acid A α1, α2, and α3 receptors.

Conclusions: Benzodiazepines had a dose-dependent relationship with pneumonia in patients with schizophrenia. The differences in risk and mechanism of action of the individual drugs require further investigation. Clinicians should be aware of the early signs of pneumonia in patients with schizophrenia receiving benzodiazepines.

Keywords: Benzodiazepine; Dose dependency; Gamma aminobutyric acid a; Pneumonia; Schizophrenia.