The general aim of the proposed research is to investigate the use of the antidepressant drug imipramine in the treatment of agoraphobia. More specifically we propose to separate the effects of imipramine from those of exposure to the phobic situation, a major confound affecting the interpretation of the results of previous studies. In addition, we propose to test several specific hypotheses concerning the mechanism of action of imipramine, including the questions whether such action is via panic suppression, an antidepressant effect, or the facilitation of self-exposure. To achieve these aims, 160 patients with agoraphobia, stratified as to initial levels of panic and depression, will be randomly allocated to either imipramine or placebo with or without exposure therapy, sequentially studying the panic suppression hypothesis, the interaction between imipramine and exposure, and the enduring effects of these treatments separately or in combination, by following patients over a two year period. A multidimensional assessment package will include self-report, behavioral assessment, ambulatory measurement of panic, and physiological recordings. The large sample size will allow us to examine the effects of various baseline measures upon outcome and the maintenance of treatment effects, including physiological parameters such as cardiovascular activation, and the response of such activation to treatment. This will begin to approach the issue of the right treatment (or combination of treatments) for specific subgoups of patients, an important consideration in the treatment of this common and often disabling disorder.
