A Meta-Analysis of Efficacy of Carbon Dioxide Inhalation as a Challenge Test in Panic Disorder

Abstract

The objective of this study is to perform a systematic review and meta-analysis on whether patients with panic disorder (PD) and their healthy first-degree relatives have an increased sensitivity to carbon dioxide inhalation test compared to healthy controls (HC) or patients with psychiatric disorders other than panic disorder. The databases of PubMed, EMBASE and PsycNET were searched using Boolean operators "panic AND carbon dioxide" and "panic AND CO2". Selected research articles were classified according to the carbon dioxide concentrations used in testing and the clinical characteristics of the samples. The assumption of heterogeneity across the studies was assessed by chi square based Q and I2 statistics. Publication biases were explored by Begg-Mazumdar's and Egger's tests in addition to funnel graphics. Odds ratios representing effect size of the carbon dioxide inhalation procedure were calculated according to fixed effect and random effect models after obtaining percent weight effects of each study. Meta-Analysis was conducted on 33 research studies that include 2114 participants totally. Participants with PD experienced significantly more frequent panic attacks (PA) compared to HC following in both 5% (OR=14.713, 95% CI 7.532 - 28.739) and 35% carbon dioxide inhalation (OR=11.507, 95% CI 7.775 - 17.031). HC who have a first-degree relative with PD experienced PA approximately 3 times more than HC who have not a first-degree relative with PD (OR=2.658, 95% CI 1.678 - 4.212) following carbon dioxide inhalation test. Participants with PD experienced significantly more frequent PA than the patients with other psychiatric disorders following the carbon dioxide inhalation test (OR = 3.524, 95% CI 1.945 - 6.384). There is an increased sensitivity of carbon dioxide inhalation in patients with PD and their healthy first-degree relatives. The role and possible mechanisms of carbon dioxide in etiology and physiopathology of PD should be studied extensively.