Persistent respiratory irregularity in patients with panic disorder

The respiratory stimulant doxapram is a potent and specific panicogenic agent which produces excessive ventilatory responses in panic patients. We have shown that a brief cognitive intervention substantially modified patientsʹ ventilatory abnormalities in this model, suggesting that an hypothesized abnormality in brainstem respiratory control centers in panic patients could be partly due to cognitive/psychological factors. However, some respiratory disturbance persisted and could reflect primary respiratory dyscontrol. Increased irregularity of tidal volume (Vt) during sleep has been reported in panic by others and supports the hypothesis of primary respiratory dyscontrol. To further explore respiratory dysregulation in our doxapram model, we obtained breath-by-breath records of Vt on our previously studied subjects and used von Neumannʹs statistic (sum of squared differences between successive points) to quantify Vt irregularity. Sixteen patients and 16 matched controls were studied. Half of each group received a standard orientation to the experiment and half received a cognitive intervention designed to reduce catastrophic misinterpretation of symptoms and to increase perceived controllability. Vt irregularity was calculated over 5 min blocks during a 5 min accommodation phase, a 15 min placebo injection phase, and a 30 min doxapram injection phase. Patients had robust elevations (p < .003) in Vt irregularity, compared to controls, in all 3 phases. Neither the cognitive intervention nor doxapram-induced hyperventilation produced significant changes in Vt irregularity. Thus, despite fluctuations in other respiratory measures, Vt irregularity remained relatively stable; and panic patients demonstrated a consistent and robust abnormality on this measure. This may reflect increased frequency of sighing. Panic patients may have intrinsically irregular breathing patterns, perhaps due to a basic brainstem/autonomic nervous system hyperactivity and instability.