Mechanisms of Treatment Change in Panic Disorder and Agoraphobia

The primary goal of the present study is to identify mechanisms of therapeutic change of two
theoretically contrasting therapeutic procedures: While the rationale of breathing training
is based on the assumption that hypocapnea (lower than normal levels of pCO2) is responsible
for the development and maintenance of panic disorder, the rationale of cognitive
interventions is that the primary mechanism in PD is the cognitive misinterpretation of
benign bodily sensations (Clark, 1986). Further, while breathing training should induce a
low-anxiety state (through parasympathetic activation) and, therefore, facilitate habituation
to fearful situations, voluntary increases in arousal through hyperventilation (sympathetic
activation) has been suggested to facilitate cognitive restructuring during exposure.

In order to study mechanisms that potentially produce clinical improvement, the investigators
propose a 2-phase therapeutic intervention: The first phase consists of comparing the outcome
of the capnometry-assisted respiratory training (CART) with cognitive restructuring (CT).
During the second phase participants of both interventions will undergo in-vivo exposure
therapy.

With the data collected from the study, the investigators will test the following hypotheses:
(a) CART will produce more reduction in psycho-physiologically relevant measures of panic
symptoms compared to CT, while cognitive restructuring will produce more reduction in
cognitive parameters of panic symptoms; (b) CART will influence the response to voluntary
hyperventilation tests by leading to faster recovery compared to CT. Improvement in
respiratory psychophysiology will be correlated with improvement in panic symptom severity;
(c) Breathing techniques during exposure will lead to a lower-anxiety state, facilitating but
not inhibiting fear extinction as suggested by the safety aid theory

Inclusion Criteria:

- A current DSM-IV diagnosis of panic disorder with agoraphobia that is designated by
the patient as the most important source of current distress

- Patients must be willing to engage in exposure to fearful situations and sensations

Exclusion Criteria:

- A history of bipolar disorder, psychosis or delusional disorders, current substance
abuse or dependence

Medical Exclusion Factors:

- Patients with severe unstable medical illness, or serious medical illness for which
hospitalization may be likely within the next three months

- Patients with a history of seizures, angina, myocardial infarction, congestive heart
failure, clinically significant arrhythmias, transient ischemic attacks,
cerebrovascular accidents, diabetes mellitus, significant asthma, emphysema, or
chronic obstructive pulmonary disease