Three broad goals underlie this continuation application for a multicenter collaborative study of the treatment of panic disorder: l) completion of the originally proposed acute treatment study, comparing cognitive behavioral panic control treatment (PCT), imipramine or placebo administered double blind (MED) and their combination (COM), 2) comparison of treatment durability over 6 or 24 month maintenance with further no treatment follow-up, and 3) cross-over treatment of MED and PCT nonresponders to the opposite treatment. It is clearly important to complete enrollment of the remaining 37% of 480 patients needed to answer key questions related to the relative efficacy of PCT, MED and COB Study enrollment began somewhat later than we predicted because of rigorous attention to state-of-the-art assessment and treatment quality control procedures. Due to these efforts, not only are the procedures we developed working well, but they have been used already by other investigators in the field and have influenced recent consensus on assessment of panic disorder. We also devoted great care to training and certifying therapists and to developing extensive quality assurance procedures, essential to a cross site study. With efficacy of short term treatment for panic disorder well established, there is growing recognition of the need to address durability of treatment, especially medication. Naturalistic follow-up of patients who participated in efficacy trials documented continued intermittent symptoms and ongoing functional impairment even with continued naturalistic treatment, and a high rate of relapse following medication discontinuation. However, naturalistic studies can confound the issues of treatment maintenance and treatment discontinuation. There are few prospective studies of long term outcome using quality controlled maintenance treatment, prospective discontinuation and rigorous blinded assessment procedures. In addition, there is a need to examine whether nonresponders to one treatment modality will respond to the other. Our original study will provide definitive information for clinicians regarding the best choices for acute treatment of panic disorder. We now recognize that the cohort of subjects we have assembled also provide a unique opportunity to conduct a large scale study of treatment durability during different lengths of maintenance treatment as well as after discontinuation. This large cohort of patients also allows for a systematic study of effectiveness of cross-over treatment for nonresponders.
