title: Association Between Antipsychotic Agents and Risk of Acute Respiratory Failure in Patients With Chronic Obstructive Pulmonary Disease.
abstract: Acute respiratory failure (ARF) is a life-threatening event that has been linked in case reports to antipsychotic use, but this association lacks population-based evidence. Particular attention should be focused on patients with chronic obstructive pulmonary disease (COPD) regarding this drug safety concern because these patients are prone to ARF and are commonly treated with antipsychotics.
  
  
  
  To determine whether the use of antipsychotics is associated with an increased risk of ARF in patients with COPD.
  
  
  
  A population-based case-crossover study analyzing the Taiwan National Health Insurance Research Database was conducted of all patients with COPD, who were newly diagnosed with ARF in hospital or emergency care settings necessitating intubation or mechanical ventilation from January 1, 2000, to December 31, 2011. Patients with prior ARF, lung cancer, and cardiogenic, traumatic, or septic ARF were excluded to analyze idiopathic ARF. The pilot study was conducted from November 1 to December 31, 2013, and full data analysis was performed from October 15, 2015, to November 8, 2016.
  
  
  
  The use of antipsychotics was self-compared during days 1 to 14 (the risk period according to previous case reports) and days 75 to 88 (control period) preceding the ARF event or index date. The antipsychotic class, route of administration, and dose were also examined.
  
  
  
  Risk of ARF.
  
  
  
  There were 5032 patients with ARF (mean [SD] age, 74.4 [9.9] years; 3533 males [70.2%]) among the 61 620 patients with COPD. Five hundred ninety patients with ARF (11.7%) filled at least 1 antipsychotic prescription during the case period compared with 443 (8.8%) during the control period, corresponding to a 1.66-fold (95% CI, 1.34-2.05; P < .001) adjusted increased risk of ARF regardless of antipsychotic class and administration route. A dose-dependent risk of ARF associated with antipsychotics was identified (test for trend, adjusted odds ratio, 1.35; 95% CI, 1.19-1.52; P < .001), which increased from a 1.52-fold risk for a low daily dose (95% CI, 1.20-1.92; P < .001) to a 3.74-fold risk for a high dose (95% CI, 1.68-8.36; P = .001). The increased risk persisted under a case-time-control analysis (adjusted odds ratio, 1.62; 95% CI, 1.16-2.27; P = .005) and nested case-control study (adjusted odds ratio, 2.16; 95% CI, 1.91-2.15; P < .001).
  
  
  
  Antipsychotic use is associated with an acute and dose-dependent increased risk of ARF in patients with COPD. Clinicians should exercise caution when prescribing antipsychotics to patients with COPD and avoid high doses if possible.
authors.affiliation: School of Pharmacy, National Defense Medical Center, Taipei, Taiwan, Republic of China.
authors.forename: Meng-Ting
authors.initials: MT
authors.lastname: Wang
authors.affiliation: Division of Pulmonary and Critical Care, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China.
authors.forename: Chen-Liang
authors.initials: CL
authors.lastname: Tsai
authors.affiliation: School of Pharmacy, National Defense Medical Center, Taipei, Taiwan, Republic of China.
authors.forename: Chen Wei
authors.initials: CW
authors.lastname: Lin
authors.affiliation: Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China.
authors.forename: Chin-Bin
authors.initials: CB
authors.lastname: Yeh
authors.affiliation: School of Pharmacy, National Defense Medical Center, Taipei, Taiwan, Republic of China.
authors.forename: Yun-Han
authors.initials: YH
authors.lastname: Wang
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Mackay Memorial Hospital, New Taipei City, Taiwan, Republic of China.
authors.forename: Hui-Lan
authors.initials: HL
authors.lastname: Lin
mesh_terms: D000368:Aged; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D016022:Case-Control Studies; D015331:Cohort Studies; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications*; D012128:Respiratory Distress Syndrome / Q000139:chemically induced*; D012306:Risk; D013624:Taiwan
chemical_list: D014150:Antipsychotic Agents