ANTIDEPRESSANTS IN THE TREATMENT OF ANXIETY DISORDERS

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The study consists of a double-blind, randomized, placebo- controlled prospective one year maintenance study of imipramine in panic disorder with agoraphobia patients who have shown good and stable response to open treatment with imipramine at the fixed weight adjusted dosage of 2.25 mg/kg/day and exposure instruction, in the preceding six months of active treatment. The first 90 patients to show marked response at both the four months and six months assessments of active treatment will be randomly assigned to one year maintenance, either on the full dose (2.25 mg/kg/day), half that dose (1.125 mg/kg/day) or placebo with planned assessments every two months. Assessments will include demographic and clinical information and a comprehensive battery of clinician and patient ratings of the three most salient major symptom domains of the disorder: panic, phobia and dysphoria/depression, as well as operationalized and clinically relevant definitions of dose response and relapse. The specific aim of the study is to determine the extent to which long-term improvement and response in panic disorder agoraphobia depend on the continued administration of imipramine, the maintenance dose and its bioavailability. In view of the chronic and fluctuating course of this disorder and the increasing numbers of patients who are effectively treated with imipramine or similar drugs, the results of the study should have important practical/clinical implications for the long-term management of panic disorder/agoraphobic patients with pharmacological agents i.e., relapse and duration to relapse upon discontinuation of imipramine, risk-benefit ratio of maintenance treatment and compliance. In addition, the study extends our programmatic research in the characterization of imipramine's short-term effects in panic disorder and agoraphobia. Thus, the delineation of different dose/plasm concentration response patterns during the active and long-term maintenance treatment phases would suggest that mechanisms which mediate improvement in this disorder may be different from those which maintain improvement.