Antipsychotics Raise Risk of Respiratory Failure in COPD Interview with:
Meng-Ting Wang, PhD

Associate Professor
School of Pharmacy
National Defense Medical Center
Taipei, Taiwan What is the background for this study?

Response: During the past decades, there have been multiple case reports about acute respiratory distress or acute respiratory failure (ARF) from the use of antipsychotics. Nevertheless, no population-based studies have been conducted to examine this potential drug safety issue. We aimed to investigate the association between use of antipsychotics and risk of ARF in a population of chronic obstructive pulmonary disease (COPD), who is vulnerable to ARF and frequently prescribed with antipsychotics. What are the main findings?

Response: In this study, we retrospectively analyzed the healthcare claims records and medication history for antipsychotics among 5,032 patients with COPD who had developed incident and idiopathic ARF (excluding cardiogenic, traumatic, and septic causes). We adopted a case-crossover study design that compares antipsychotic use during 1-14 day before the ARF event and an earlier period among each ARF case, and observed an overall 66% increase in the risk of ARF.

Also, a dose-dependent association was found, in which the ARF risk started from 0.25 defined daily dose (DDD) and exceeded three-fold when given more than one DDD. This is the strongest evidence today to suggest an adverse respiratory effect from antipsychotics. What should readers take away from your report?

Response: These findings have important implications to the management of COPD patients.

  • First, we urge healthcare professionals to be vigilant about the development of ARF in COPD patients receiving antipsychotic treatment, especially during the initial phase of treatment.
  • Second, antipsychotic use needs to be justified given we noticed a high proportion of off-label use in our population.
  • Third, according to our dose analysis, high daily dose of antipsychotics with more than one DDD should be avoided, and the risk should not be overlooked even in patients at a dose as low as a quarter of 1 DDD.
  • Fourth, this novel finding of respiratory adverse events from antipsychotics should be considered when weighing benefits against risks of using antipsychotics in COPD patients, but patients are not suggested to discontinue antipsychotics without consulting their physicians.
  • In addition, we advise COPD patients on antipsychotics not to neglect symptoms of breathing difficulty or respiratory abnormalities and should seek medical help as soon as possible. What recommendations do you have for future research as a result of this study?

Response: Future studies are needed to extend our findings. Due to the adopted study design, we could only observe the acute effect of antipsychotics on ARF. It is not sure if the risk still exists with long-term use of antipsychotics. Also, it is not clear if the observed ARF risk from antipsychotics can be generalized to a different population. Thank you for your contribution to the community.


Wang M, Tsai C, Lin CW, Yeh C, Wang Y, Lin H. Association Between Antipsychotic Agents and Risk of Acute Respiratory Failure in Patients With Chronic Obstructive Pulmonary Disease. JAMA Psychiatry. Published online January 04, 2017. doi:10.1001/jamapsychiatry.2016.3793

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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