Use of Antipsychotics and the Risk of Acute Respiratory Failure

Background: In addition to the known adverse effects of antipsychotics, findings from case reports and two population-based Taiwan studies, conducted by the same investigators, have indicated a potential new safety signal of severe adverse respiratory distress and failure associated with antipsychotic medications. Further population-based research is warranted to evaluate the association between antipsychotics and acute respiratory failure, and to provide evidence that is generalizable to the United States.

Objectives: To evaluate the association between the use of antipsychotics and risk of respiratory depression among commercially insured adults in the United states.

Methods: We performed a retrospective new-user cohort study of adults ≥18 years prescribed an antipsychotic or an active comparator, anticonvulsant medication, during an eight-year period spanning 2007 to 2015, using a 1% random sample of enrollees within the IQVIA PharMetrics® Plus for Academics Database. Propensity score-adjusted Cox models were used to estimate hazard ratio (HR) and 95% confidence interval (CI) for the outcome of acute respiratory failure comparing antipsychotics users to anticonvulsants users. Bias analysis was conducted to assess the sensitivity of the observed relationship between antipsychotics and respiratory depression to an unmeasured confounder.

Results: A total of 8,232 antipsychotic initiators and 4,400 anticonvulsant initiators contributed 113,722 person-years of follow-up (median duration 923 days/person). During follow-up, there were 1,041 respiratory depression events. In the unadjusted analysis, antipsychotic exposure was associated with increased hazard of respiratory depression compared with anticonvulsant exposure (HR: 1.18; 95% CI: 1.03, 1.34). After inverse probability of treatment weighting adjustment, the hazard increased (HR: 1.21, 95% CI: 1.07, 1.36). Propensity score matching and stratification resulted in similar accentuation of the HR estimates, 1.27 (95% CI: 1.09, 1.47) and 1.21 (1.14, 1.65), respectively. These findings were robust to bias analysis as the results did not suggest an unmeasured confounder would explain away the observed association.

Conclusions: In commercially insured adult patients, antipsychotics were associated with an increased hazard of acute respiratory failure. This finding warrants enhanced clinical guidelines to ensure patient safety.