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

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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.

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Acknowledgments

The authors thank Yi-Chang Chou, MS, at the Department of Education and Research, Taipei City Hospital, and Yen-Chung Chen, MS, at the Department of General Psychiatry, Taipei City Psychiatric Center, Taipei City Hospital, for the data management and help with the statistical analyses. This manuscript was edited by Wallace Academic Editing, Taipei, Taiwan.

Funding

This research was supported by grants from the Ministry of Science and Technology, Taiwan (NSC 102-2628-B-532-001-MY3; MOST 105-2314-B-532-006-MY3), and Taipei City Hospital (10301-62-041; 10401-62-013; 10501-62-105). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Author information

Authors and Affiliations

  1. Taipei City Psychiatric Center, Taipei City Hospital, Taipei, Taiwan

    Sheng-Yun Cheng, Wen-Yin Chen, Hsing-Cheng Liu, Tien-Wei Yang, Chun-Hung Pan, Shu-Yu Yang & Chian-Jue Kuo

  2. Graduate Institute of Epidemiology and Preventive Medicine, National Taiwan University College of Public Health, Taipei, Taiwan

    Wen-Yin Chen

  3. Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

    Hsing-Cheng Liu, Tien-Wei Yang & Chian-Jue Kuo

  4. Psychiatric Research Center, Taipei Medical University Hospital, Taipei, Taiwan

    Hsing-Cheng Liu, Tien-Wei Yang & Chian-Jue Kuo

  5. Department of Psychology, National Chengchi University, Taipei, Taiwan

    Chun-Hung Pan

  6. Graduate Institute of Clinical Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan

    Shu-Yu Yang

  7. Department of General Psychiatry, Taipei City Psychiatric Center, 309 Sung-Te Road, Taipei, 110, Taiwan

    Chian-Jue Kuo

Authors
  1. Sheng-Yun Cheng
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  2. Wen-Yin Chen
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  3. Hsing-Cheng Liu
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  5. Chun-Hung Pan
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  7. Chian-Jue Kuo
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Contributions

Drs. Cheng and Kuo conceived and designed the study. Dr. Shu-Yu Yang acquired the data and performed the statistical analysis. Drs. Liu and Tien-Wei Yang provided administrative and material support. Drs. Cheng and Kuo drafted the manuscript. Drs. Chen and Kuo made critical revisions to the manuscript for important intellectual content. Dr. Kuo supervised the study.

Corresponding author

Correspondence to Chian-Jue Kuo.

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Cheng, SY., Chen, WY., Liu, HC. et al. Benzodiazepines and risk of pneumonia in schizophrenia: a nationwide case–control study. Psychopharmacology 235, 3329–3338 (2018). https://doi.org/10.1007/s00213-018-5039-9

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  • DOI: https://doi.org/10.1007/s00213-018-5039-9

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