Treatment of Panic Disorder: Long Term Strategies

Study Overview
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Brief Summary
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Cognitive behavior therapy (CBT) with or without medication has been used in the treatment of panic disorder (PD). The purpose of this study is 1) to determine whether nine months of maintenance cognitive-behavior therapy (CBT) significantly improves the likelihood of sustained improvement; and 2) to determine the acute acceptability and efficacy of medication therapy or continued CBT alone among patients who fail to respond sufficiently to an initial course of CBT alone. It has been found that patients with PD respond as well to CBT or medication alone as they do to a combination of the two. Since the combined treatments are expensive and CBT is associated with less risk of medical toxicity compared to medications, CBT alone will be used first. All patients will first receive CBT alone. If the patient responds to this therapy, the patient will be assigned randomly (like tossing a coin) to 1 of 2 groups. One group will continue to receive CBT (maintenance therapy) for 9 months. The other group of responders will not receive any further therapy. If a patient does not respond to CBT alone, he/she will be assigned randomly to 1 of 2 different groups. One group will receive paroxetine; the other will continue to receive CBT for a longer period. The response to treatment will be evaluated to see which regimen works best to treat PD. The study will last approximately 3 years. An individual may be eligible for this study if he/she has panic disorder with no more than mild agoraphobia (fear of being in public places) and is at least 18 years old.

Detailed Description
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To determine if maintenance CBT produces a more sustained improvement among patients with panic disorder (PD) who respond to an initial course of cognitive behavior therapy (CBT) alone. For those who do not respond sufficiently to CBT alone, to determine if the addition of pharmacotherapy is acceptable and if this improves response among those inadequate responders to CBT alone. This multicenter study builds upon the findings of a prior study comparing imipramine, placebo, CBT, and their combination in the treatment of PD patients with no more than mild agoraphobia. That study found response rates were as high with CBT or imipramine alone as with their combination. Given the added cost of combined treatments, it therefore seems reasonable to begin with monotherapy. Further, following general principles of medical practice, it would be reasonable to initiate treatment with the less invasive cognitive behavioral intervention. It is then important to learn what should be done following initial treatment. All patients initially receive CBT alone. Patients are then randomized into 1 of 2 post-acute studies, depending on response status. Responders are randomized to a maintenance study comparing no maintenance with 9 months of continued CBT. Nonresponders are randomized to a study comparing paroxetine with continued CBT. The following outcomes will be examined: the necessity of maintenance therapy in maintaining response; the ability of adjunct pharmacotherapy to improve the response of patients who did not respond to CBT alone; possible predictors of response and relapse; and possible mediators of response.

Official Title
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Treatment of Panic Disorder: Long Term Strategies

Conditions
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Panic Disorder, Agoraphobia

Intervention / Treatment
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* Behavioral: Cognitive behavior therapy
* Drug: Paroxetine or other medication - algorithm used


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - primary diagnosis of Panic disorder with or without Agoraphobia (all levels of agoraphobia are included). Exclusion Criteria: current substance abuse or dependence, current active suicidal potential; any history of psychosis, bipolar disorder (I or II) or cyclothymia; pending application or existing medical disability claim; significant cognitive impairment, current uncontrolled general medical illness requiring intervention, psychotherapy directed at anxiety or panic which will not be discontinued by the first treatment visit, and daily use of 2mg of Xanax or equivalent. Exclusion criteria for paroxetine study: hypersensitivity to Selective Serotonin Reuptake Inhibitors (SSRI), pregnancy, lactation, or planned pregnancy during the course of the study, contemporaneous medication that may interfere or interact with paroxetine, prior treatment with therapeutic doses of paroxetine (40mg/d for 1 mo), concurrent treatment with antidepressants.

Ages Eligible for Study
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Minimum Age: 18 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: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Behavioral: Cognitive behavior therapy|nan|
|Drug: Paroxetine or other medication - algorithm used|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Panic Disorder Severity Scale | This is a 7-item scale providing ratings of core features of panic disorder and the degree of work and social impairment/interference due to the disorder. | At baseline and major assessment points plus monthly. | 
| Clinical Global Impressions | Commonly used global rating of improvement. | Monthly, including all nonpretreatment major assessments. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Albany Panic and Phobia Questionnaire | This is a 27-item scale consisting of three subscales that assess fear of agoraphobic situations, social situations, and situations and activities that produce bodily sensations commonly feared by individuals with panic disorder. | All major assessment points. | 
| Anxiety Sensitivity Index | This is a 16-item scale that assesses person's tendency to regard physiologic arousal as harmful. | All major assessments and treatment visits. | 
| Subjective Symptoms Scale | This is an individual's rating of the extent to which anxiety symptoms interfere with five areas of daily functioning: work, home management, private leisure, social leisure, and family relationships. | All major assessment points | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Adult, Cognitive Behavioral Therapy, Pharmacotherapy, Long term treatment, Remission and relapse, Male, Panic Disorder, Paroxetine, Serotonin Uptake Inhibitors, Panic Disorder -- *therapy, Panic Disorder -- drug therapy, Paroxetine -- *therapeutic use, Serotonin Uptake Inhibitors -- *therapeutic use