Anxiogenic effects of CO₂ and hyperventilation in patients with panic disorder

Objective: Previous studies have indicated that patients with panic disorder are more likely than normal subjects to have acute panic attacks during inhalation of CO₂, but methodological objections have been raised. In this study the authors attempted to address three of these methodological problems by ensuring that raters who assessed whether panic attacks occurred were blind to subjects' diagnoses, by randomizing the order of administration of 5% CO₂ and hyperventilation, and by challenging a greater number of subjects with 7% CO₂. Method: Patients with panic disorder and normal subjects underwent 20-minute inhalations of 5% CO₂ and 7% CO₂ and 15 minutes of room-air hyperventilation. Ratings of panic/no panic during each condition were made separately by an assessor blind to diagnosis and by the subject. Scores on four panic rating scales were also recorded before and after each intervention. Results: Room-air hyperventilation caused panic attacks in a small number of patients; the difference in panic rate between patients and comparison subjects was statistically significant by the subjects' but not by the raters' assessment. Panic rates during 5% CO₂ and 7% CO₂ were significantly greater among the patients by both assessments; the panic rate was greatest during 7% CO₂. Order of administration did not significantly affect panic rates for hyperventilation and 5% CO₂. Conclusions: Panic patients were clearly more sensitive to the anxiogenic effects of CO₂ than comparison subjects, and CO₂ was a more potent anxiogenic stimulus than room-air hyperventilation. Seven percent CO₂ discriminated best between patients and comparison subjects and should be the focus of further research.