The main purpose of this investigation is to evaluate the clinical effectiveness of imipramine hydrochloride in the treatment of school phobic children and adolescents. Specifically, the study will determine whether imipramine enhances/facilitates the effects of behavioral exposure treatment in eliminating anxiety-based school refusal. One hundred non-depressed children and adolescents with anxiety-based school refusal will participate in a 12-week double-blind placebo controlled treatment trial. Youngsters will be assigned to one of two treatment conditions: 1) Imipramine + Behavior Therapy (n=50), or 2) Placebo + Behavior Therapy (n=50), in which they will receive weekly medication and behavioral treatment. Clinical response will be evaluated throughout the 12 weeks of the study through multi-method, multiple-informant (parent, child, therapist, teacher) assessments. Plasma level assays will be conducted for subjects in the Imipramine + Behavior Therapy treatment condition at 4, 8, and 12 weeks, in order to examine whether there is a relationship between plasma imipramine and desipramine concentration and clinical response. Comparison of findings for the two treatment conditions on clinical outcome measures will allow determination of whether imipramine enhances/facilitates clinical response in this population. Moreover, analysis of the effects of demographic and diagnostic covariates-pubertal status, sex, diagnostic status, severity of school refusal - on treatment outcome, will permit determination of whether particular subgroups of school refusers respond differentially to imipramine. Finally, analysis of the relationship between plasma imipramine/desipramine levels and clinical outcome will enable determination of whether there is a specific plasma level range or threshold associated with imipramine response.
