title: Antipsychotic drugs, mood stabilizers, and risk of pneumonia in bipolar disorder: a nationwide case-control study.
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.
  
  
  METHODS
  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.
authors: Taipei City Psychiatric Center, Taipei City Hospital, Taiwan.
authors: Shu-Yu
authors: SY
authors: Yang
authors: Ya-Tang
authors: YT
authors: Liao
authors: Hsing-Cheng
authors: HC
authors: Liu
authors: Wei J
authors: WJ
authors: Chen
authors: Chiao-Chicy
authors: CC
authors: Chen
authors: Chian-Jue
authors: CJ
authors: Kuo
mesh_terms: D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects* / Q000627:therapeutic use*; D018692:Antimanic Agents / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000009:adverse effects / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D002220:Carbamazepine / Q000009:adverse effects / Q000627:therapeutic use; D016022:Case-Control Studies; D003024:Clozapine / Q000009:adverse effects / Q000627:therapeutic use; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D019317:Evidence-Based Medicine; D005260:Female; D006760:Hospitalization; D006801:Humans; D016651:Lithium Carbonate / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D000077152:Olanzapine; D011014:Pneumonia / Q000139:chemically induced* / Q000453:epidemiology; D057216:Propensity Score; D012307:Risk Factors; D013624:Taiwan; D014635:Valproic Acid / Q000009:adverse effects / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D018692:Antimanic Agents; D014150:Antipsychotic Agents; D001569:Benzodiazepines; D016651:Lithium Carbonate; D002220:Carbamazepine; D014635:Valproic Acid; D003024:Clozapine; D000077152:Olanzapine