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Original Research

Antipsychotic Drugs, Mood Stabilizers, and Risk of Pneumonia in Bipolar Disorder: A Nationwide Case-Control Study

Shu-Yu Yang, PhD; Ya-Tang Liao, PhD; Hsing-Cheng Liu, MD, PhD; Wei J. Chen, MD, ScD; Chiao-Chicy Chen, MD, PhD; and Chian-Jue Kuo, MD, PhD

Published: January 15, 2013

Article Abstract

Objective: Like mood stabilizers, most second-generation antipsychotics are widely used to treat patients with bipolar disorder, yet their safety is still a concern. This study explored the association between antipsychotics and mood stabilizers and the risk of pneumonia, and it provides evidence-based information for clinical practice.

Method: In a nationwide cohort of bipolar patients (ICD-9 codes 296.0 to 296.16, 296.4 to 296.81, and 296.89) derived from the National Health Insurance Research Database in Taiwan, who were admitted between July 1, 1998, and December 31, 2006 (N = 9,999), we identified 571 patients who developed pneumonia (ICD-9 codes 480 to 486 and 507) requiring hospitalization defined as cases. On the basis of risk-set sampling in a 1:4 ratio, 2,277 matched controls were selected from the same cohort. We used conditional logistic regression to assess the association between drug exposure and pneumonia and sensitivity analyses to validate the association.

Results: Current use of several antipsychotics separately, including olanzapine (adjusted risk ratio [RR] = 2.97, P < .001), clozapine (RR = 2.59, P < .01), and haloperidol (RR = 3.68, P < .001), is associated with a dose-dependent increase in the risk of pneumonia. Interestingly, lithium has a dose-dependent protective effect from pneumonia. Among certain drug combinations, olanzapine plus carbamazepine had the highest risk (RR = 11.88, P < .01), followed by clozapine plus valproic acid (RR = 4.80, P < .001).

Conclusions: Several antipsychotics, but not mood stabilizers, were associated with the risk of pneumonia, which deserves our concern regarding patient safety. Some of the combinations of therapy resulted in synergy of risk.

J Clin Psychiatry 2013;74(1):e79-e86

Submitted: June 12, 2012; accepted August 17, 2012 (doi:10.4088/JCP.12m07938).

Corresponding author: Chian-Jue Kuo, MD, PhD, Department of General Psychiatry, Taipei City Psychiatric Center, Taipei City Hospital, 309 Sung-Te Rd, Taipei, 110, Taiwan (

Volume: 74

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