Mechanisms of Treatment Change in Panic Disorder and Agoraphobia

Study Overview
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Brief Summary
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The primary goal of the present study is to identify mechanisms of therapeutic change of two theoretically contrasting therapeutic procedures: The first phase consists of comparing the outcome of the capnometry-assisted breathing therapy (BRT) with cognitive restructuring (CT). During the second phase participants of both interventions will undergo in-vivo exposure.

Detailed Description
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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. 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

Official Title
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Moderators and Mediators of Treatment Change in Panic Disorder and Agoraphobia

Conditions
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Panic Disorder With Agoraphobia

Intervention / Treatment
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* Behavioral: Cognitive Therapy
* Behavioral: Capnometry-Assisted Respiratory Training
* Behavioral: In-vivo exposure


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Cognitive Therapy<br>The training included four components: (a) educating patients about exacerbating panic symptoms through catastrophic thoughts (vicious cycle), (b) identifying negative cognitions associated with physical sensation triggers of recent panic attacks, (c) practicing replacement of maladaptive cognitions with non catastrophic explanations, and (d) instructing patients in between session exercises during Phase I. | Behavioral: Cognitive Therapy<br>* The training included four components: (a) educating patients about exacerbating panic symptoms through catastrophic thoughts (vicious cycle), (b) identifying negative cognitions associated with physical sensation triggers of recent panic attacks, (c) practicing replacement of maladaptive cognitions with non catastrophic explanations, and (d) instructing patients in between session exercises during Phase I.<br>* Other names: CT;|
| Active Comparator: Capnometry-Assisted Respiratory Training<br>The training included four components: (a) educating patients about the exacerbation of panic symptoms through hypocapnia; (b) directing patients' attention to potentially detrimental respiratory patterns; (c) teaching patients techniques to control their respiration, in particular end-tidal PCO2; and (d) instructing patients in between-session exercises. Between-session exercises using a portable capnometer were to be performed twice a day for 17 min at home or elsewhere during Phase I. | Behavioral: Capnometry-Assisted Respiratory Training<br>* The training included four components: (a) educating patients about the exacerbation of panic symptoms through hypocapnia; (b) directing patients' attention to potentially detrimental respiratory patterns; (c) teaching patients techniques to control their respiration, in particular end-tidal PCO2; and (d) instructing patients in between-session exercises. Between-session exercises using a portable capnometer were to be performed twice a day for 17 min at home or elsewhere during Phase I.<br>* Other names: CART;|
| Other: In-vivo exposure therapy<br>In this two-phase intervention, patients were randomized (within each site) to first receive five individual, weekly, 1-hr sessions of respiratory skill training (CART) or cognitive skill training (CT; Phase I, Skill Acquisition Training), followed by three weekly sessions of in-vivo exposure (Phase II, Application Training) plus a fourth session at 2-month follow-up. | Behavioral: In-vivo exposure<br>* In this two-phase intervention, patients were randomized (within each site) to first receive five individual, weekly, 1-hr sessions of respiratory skill training (CART) or cognitive skill training (CT; Phase I, Skill Acquisition Training), followed by three weekly sessions of in-vivo exposure (Phase II, Application Training) plus a fourth session at 2-month follow-up.<br>* Other names: EXP;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in panic symptom severity assessed by the Panic Disorder Severity Scale/CGI | Clinician administered; 7 items rated on 0 - 4 scale; scores over 9 suggest the need for formal diagnostic assessment | Pre (Week 0), Mid (Week 5), Post (Week 9), Follow-Up (Week 17) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cortisol assessments collecting 8 saliva samples per day | was administered to subset of patients for exposure and non exposure days | Phase II (Weeks 7 - 9) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Respiration panic, Cognitions, Panic, Treatment, Mediators, Moderators