The study will involve 100 patients with panic disorders with agoraphobia who have shown good and stable response to uniform treatment with imipramine 2.25 mg/kg/day. The first 100 patients to show marked response at both the 16 and 24 week assessments of active treatment will be randomly assigned to double blind maintenance on the same dose of imipramine or placebo substitution with planned assessments every two months for a duration of 1 year (months 0-12). This will be followed by a one year double blind extension phase (months 12-24) during which placebo patients will continue in the same condition while imipramine patients will imdergo a second randomization to continued imipramine maintenance or to placebo substition. Finally, all subjects, completers/relapsers as well as dropouts from the different stages of double blind treatment will be followed in an open discontinuation/no pill paradigm for up to four years post randomization. Repeated assessments will include clinician and patient rating of panic, phobia, anxiety and dysphoria/depression, operationalized criteria of response and relapse, plasma concentration of imipramine and metabolites and the assessment of life events, personality and health status/well being. The primary aim of the study is to assess the extent of reversals/relapse due specifically to withdrawal of imipramine over a 2 year period and to characterize imipramine's long term effects as well as the net beneficial effects of imipramine maintenance in this disorder. In addition, the project will provide systematic data on the comparative rate of relapse after acute and maintenance treatments and rigorous longitudinal data of open discontinuation/relapse after varying lengths of imipramine maintenance. The results should have significance for the long term management of panic disorder patients i.e., the extent to which maintenance pharmacotherapy is necessary and for how long, the risk benefit ration of long term treatment and compliance, and the quality of life and cost effectiveness implications of maintenance/discontinuation in this disorder.
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