Association Between Antipsychotic Agents and Risk of Acute Respiratory Failure in Patients with Chronic Obstructive Pulmonary Disease

Association Between Antipsychotic Agents and Risk of Acute Respiratory Failure in Patients with Chronic Obstructive Pulmonary Disease
Anjoli Punjabi, Pharm.D., MPH, Broadway Family Medicine

Background: Chronic obstructive pulmonary disease (COPD) affects 210 million people and is the leading cause of mortality globally. COPD patients are particularly prone to acute respiratory failure (ARF) after COPD exacerbation. After an episode of ARF, as many as 80% of COPD patients are rehospitalized requiring mechanical ventilation. There have been multiple case studies of ARF occurring in COPD patients within 10 days of initiating a typical or atypical antipsychotic. However, population-based evidence for the association between antipsychotic use and ARF in COPD patients is lacking. 

Objective: To determine if antipsychotic use is associated with an increased risk of ARF in those patients with COPD. 

Study Design: The Taiwan National Health Insurance Research Database was utilized to conduct a population-based case-crossover study analyzing all patients with COPD (n=61620), who were newly diagnosed with ARF in hospital or emergency care settings, requiring intubation or mechanical ventilation over a 10-year period. Patients with prior ARF, lung cancer, and cardiogenic, traumatic, or septic ARF were excluded.

The use of antipsychotics during days 1 to 14 (case period) and days 75 to 88 (control period) preceding the ARF event were compared. This within-self comparison design was utilized to minimize interpersonal variation and control time invariant covariates. The 14-day period and 60-day buffer period were selected based on the short timeframe for ARF events following antipsychotic use in the case reports and the and half-lives of depot antipsychotics, respectively. The antipsychotic class, route of administration, and dose were also considered. 

Results: It was found that there was a 1.66-fold (95% CI, 1.34-2.05; p<0.001] increased risk of ARF in COPD patients taking antipsychotic medications regardless of antipsychotic class and administration route. Additionally, a dose-dependent risk of ARF associated with antipsychotics was identified, adjusted odds ratio of 1.35 [95% CI 1.19-1.52; p<0.001], which increased from a 1.52-fold risk for a low daily dose [95% CI 1.20-1.92; p<0.001) to a 3.74-fold risk for a high dose [95% CI, 1.68-8.36; P=0.001]. 

Conclusions: Antipsychotic medication use is associated with an acute and dose-dependent increased risk of ARF in patients with COPD. Future studies are required to confirm these observed associations. 

Key Point: Clinicians should be cautious when prescribing antipsychotics to patients with COPD and avoid high doses if possible. 


Wang MT, Tsai CL, Lin CW, Yeh CB, Wang YH, Lin HL. Association between antipsychotic agents and risk of acute respiratory failure in patients with chronic obstructive pulmonary disease. JAMA Psychiatry. 2017; 74(3):252-260. doi: 10.1001/jamapsychiatry.2016.3793.