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

Abstract

This systematic review assesses the current state of clinical and preclinical research on panic disorder (PD) in which the carbon dioxide (CO 2 ) 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 CO 2 test. The 35% CO 2 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 CO 2 challenge helped assess the antipanic effects of medication and nonpharmaceutical 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.

Clinical experimental stress studies: methods and assessment

“…In comparison to psychological stress-based protocols, scientists have also employed physiological stressors such as CO 2 and environmental stimulus-based stressor such as noise stress. The CO 2 challenge test produces panic attacks and short-lived paroxysms of fear accompanied by physical symptoms in most persons with panic disorder, and hence, it is widely used as an investigative tool in the pathogenicity of anxiety disorders, particularly panic disorder (Freire et al, 2008;Amaral et al, 2013). The employment of noise as a stressor may be important as it is a common stressor in day-to-day life and hence is ethologically relevant stimuli.…”

“…-CO 2 reliably stimulates the key brain center involved in the human stress response and activates psychological, SAM, and HPA axis, and therefore, it is considered as four-dimensional stressor. Fyer et al, 1987;Wetherell et al, 2006;Amaral et al, 2013 5. MMST -There is induction of a high degree of stress, even in the absence of social evaluative threat, by combining different stressors, including cognitive, emotional, acoustic, and motivational stressors.…”

“…The study concluded that the 35% CO 2 challenge is a safe and simple method to provoke panic attacks and a potential laboratory model for the study of panic disorder (Fyer et al, 1987). The CO 2 challenge has been regarded as a safe, noninvasive, time-efficient, and reproducible method to provoke different forms of stress and anxiety, including panic attacks in panic disorder patients (Amaral et al, 2013). CO 2 has minimal taste or odor, and the established test approach involving inhalation of 35% carbon dioxide enriched air is safe and produces transient symptoms of breathlessness, dizziness, minor anxiety, and general autonomic arousal in most participants, without any longterm alterations.…”

Sleep Apnea and Risk of Panic Disorder

“…[27][28][29][30] Lastly, hypercapnia may play a role based on the evidence that panic attack can be provoked by inhalation of carbon dioxide. 31 The strengths of our study are its nationwide, population-based study design and that all respiratory and psychiatric practices were covered in the database, which allowed us to trace all cases of newly diagnosed sleep apnea and panic disorder. Additionally, the large sample size in our study offered substantial statistical power for detecting real, even subtle, differences between the 2 cohorts.…”

Anxiety and Anxiety Disorders

“…In the respiratory subtype, there is often increased sensitivity to carbon dioxide (Amaral et al, 2013 ;Freire et al, 2010 ). There is also signifi cant comorbidity between panic disorder and chronic obstructive pulmonary disease, irritable bowel syndrome, and migraine headache.…”