Clinical trial NCT00000368: Treatment of Panic Disorder: Long Term Strategies
Official title: Treatment of Panic Disorder: Long Term Strategies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Panic Disorder
Agoraphobia
Keywords: 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
Lead sponsor: New York State Psychiatric Institute
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 1999-11-03
Enrollment: 379
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Panic Disorder Severity Scale
timeFrame: At baseline and major assessment points plus monthly.
measure: Clinical Global Impressions
timeFrame: Monthly, including all nonpretreatment major assessments.
Secondary outcomes:
measure: Albany Panic and Phobia Questionnaire
timeFrame: All major assessment points.
measure: Anxiety Sensitivity Index
timeFrame: All major assessments and treatment visits.
measure: Subjective Symptoms Scale
timeFrame: All major assessment points
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale University, Department of Psychiatry, Anxiety Disorders Research Clinic
state: Connecticut
city: Boston
country: United States
facility: Boston University, Department of Psychology, Center for Anxiety and Related Disorders
state: Massachusetts
city: New York
country: United States
facility: Hillside Hospital Phobia Clinic
state: New York
city: Pittsburgh
country: United States
facility: University of Pittsburgh, Department of Psychiatry, Panic, Anxiety and Traumatic Grief Program
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Katherine H. Shear, MD
role: STUDY_CHAIR
affiliation: Boston University Department of Psychology
name: David H Barlow, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Columbia University School of Medicine
name: Jack Gorman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Yale University
name: Scott Woods, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Barlow DH, Gorman JM, Shear MK, Woods SW. Cognitive-behavioral therapy, imipramine, or their combination for panic disorder: A randomized controlled trial. JAMA. 2000 May 17;283(19):2529-36. doi: 10.1001/jama.283.19.2529.
citation: Shear MK, Brown TA, Barlow DH, Money R, Sholomskas DE, Woods SW, Gorman JM, Papp LA. Multicenter collaborative panic disorder severity scale. Am J Psychiatry. 1997 Nov;154(11):1571-5. doi: 10.1176/ajp.154.11.1571.
citation: Gorman JM. A 28-year-old woman with panic disorder. JAMA. 2001 Jul 25;286(4):450-7. doi: 10.1001/jama.286.4.450. No abstract available.
citation: Grilo CM, Money R, Barlow DH, Goddard AW, Gorman JM, Hofmann SG, Papp LA, Shear MK, Woods SW. Pretreatment patient factors predicting attrition from a multicenter randomized controlled treatment study for panic disorder. Compr Psychiatry. 1998 Nov-Dec;39(6):323-32. doi: 10.1016/s0010-440x(98)90043-8.
citation: Huppert JD, Bufka LF, Barlow DH, Gorman JM, Shear MK, Woods SW. Therapists, therapist variables, and cognitive-behavioral therapy outcome in a multicenter trial for panic disorder. J Consult Clin Psychol. 2001 Oct;69(5):747-55. doi: 10.1037//0022-006x.69.5.747.
citation: Hofmann SG, Barlow DH, Papp LA, Detweiler MF, Ray SE, Shear MK, Woods SW, Gorman JM. Pretreatment attrition in a comparative treatment outcome study on panic disorder. Am J Psychiatry. 1998 Jan;155(1):43-7. doi: 10.1176/ajp.155.1.43.
citation: Payne LA, White KS, Gallagher MW, Woods SW, Shear MK, Gorman JM, Farchione TJ, Barlow DH. SECOND-STAGE TREATMENTS FOR RELATIVE NONRESPONDERS TO COGNITIVE BEHAVIORAL THERAPY (CBT) FOR PANIC DISORDER WITH OR WITHOUT AGORAPHOBIA-CONTINUED CBT VERSUS SSRI: A RANDOMIZED CONTROLLED TRIAL. Depress Anxiety. 2016 May;33(5):392-9. doi: 10.1002/da.22457. Epub 2015 Dec 10.