Pharmacological effects on 35% CO₂ panic induction: A meta-analysis

A brief inhalation of 35% CO₂ triggers subjective fear and physiological responses occurring during naturally occurring panic attacks (PAs). This CO₂ model enables to study effects of pharmacological interventions on experimental panic provocation and examine the biological mechanisms involved in PAs.

To provide a quantification of the effects of pharmacological interventions on the response to CO₂ inhalation, which was still lacking despite decades of research and numerous studies having addressed these effects.

A systematic search was performed to identify peer-reviewed papers reporting effects of pharmacological interventions to the 35% CO₂ inhalation. Multilevel meta-analyses were performed to quantify the effects of such interventions on self-reported anxiety and PA symptoms.

Thirty-six studies, containing data of 980 participants (both panic disorder patients and healthy individuals), were included. Several studies reported effects of multiple pharmacological interventions, resulting in 48 effect sizes for the meta-analysis of the effects on anxiety and 34 for the effects on PA symptoms. Significant decreases in induced anxiety (-.55 (95% confidence interval (CI): -.81 to -.29), p < 0.0001) and PA symptoms (-0.31 (95%CI: -.51 to -.11), p = 0.0026) were seen after pharmacological interventions aimed at symptom reduction. Induced anxiety was significantly decreased (-.81 (95%CI: -1.13 to -.48), p < 0.0001) after pharmacological interventions that enhanced the serotonergic system.

This meta-analysis supports the notion that specific drugs can reduce the sensitivity to 35% CO₂ challenge, supporting a role for this procedure as experimental model to investigate panic pharmacology.