Specificity of Panic Response to CO₂ Inhalation in Panic Disorder: A Comparison With Major Depression and Premenstrual Dysphoric Disorder

OBJECTIVE: The behavioral response to CO₂ inhalation has been used to differentiate panic disorder patients from normal subjects and other clinical populations. This study extended examination of the diagnostic specificity of CO₂-induced anxiety by testing panic disorder patients and clinical populations with reported low and high sensitivity to CO₂ inhalation (patients with major depression and patients with premenstrual dysphoric disorder, respectively). METHOD: The behavioral responses to inhalation of 5% and 7% CO₂, administered by means of a respiratory canopy, were studied in 50 patients with panic disorder, 21 with major depression, and 10 with premenstrual dysphoric disorder and in 34 normal comparison subjects. Occurrence of panic attacks was judged with DSM-IV criteria by a blind rater. Subjects were rated on three behavioral scales at baseline and after each CO₂ inhalation. RESULTS: Panic disorder patients had a higher rate of CO₂-induced panic attacks than depressed patients and normal subjects, whose panic rates were not distinguishable. The panic rate for patients with premenstrual dysphoric disorder was similar to that for panic disorder patients and higher than that for normal subjects. Subjects with CO₂-induced panic attacks had similarly high ratings on the behavioral scales, regardless of diagnosis, including the small number of panicking normal subjects. Seven percent CO₂ was a more robust panicogen than 5%, and response to 7% CO₂ better distinguished panic disorder patients from normal subjects than response to 5% CO₂. CONCLUSIONS: Patients with panic disorder and patients with premenstrual dysphoric disorder are highly susceptible to CO₂-induced panic attacks, and depressed patients appear to be insensitive to CO₂ inhalation. The symptoms of CO₂-induced panic attacks have a similar intensity regardless of the subject’s diagnosis.