The carbon dioxide challenge test in panic disorder: a systematic review of preclinical and clinical research

Braz J Psychiatry. Jul-Sep 2013;35(3):318-31. doi: 10.1590/1516-4446-2012-1045.


This systematic review assesses the current state of clinical and preclinical research on panic disorder (PD) in which the carbon dioxide (CO2) challenge was used as a trigger for panic attacks (PAs). A total of 95 articles published from 1984 to 2012 were selected for inclusion. Some hypotheses for PD evolved greatly due to the reproducibility of PAs in a controlled environment using the safe and noninvasive CO2 test. The 35% CO2 protocol was the method chosen by the majority of studies. Results of the test report specific sensitivity to hypercapnia in PD patients of the respiratory PD subtype. The CO2 challenge helped assess the antipanic effects of medication and non-pharmaceutical approaches such as physical exercise and cognitive behavioral therapy. The test was also used in studies about the genetic component of PD, in which twins and relatives of PD patients were analyzed.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Carbon Dioxide*
  • Humans
  • Panic Disorder / chemically induced*
  • Panic Disorder / psychology
  • Respiration Disorders / chemically induced*
  • Respiration Disorders / psychology
  • Respiratory Function Tests
  • Sensitivity and Specificity


  • Carbon Dioxide