The relationship of plasma imipramine and N-desmethylimipramine to response in panic disorder.

This report is a descriptive summary of the relationship between response and plasma tricyclic concentrations found in our previously reported dose-ranging study of imipramine (IMI) in panic disorder (Mavissakalian & Perel 1995). In addition, we explore the relative strength with which plasma levels of the parent compound (IMI) and N-desmethylimipramine predict the probability of response in the total plasma range for which there was continued improving response. The results, which indicated that IMI was the better predictor, are briefly discussed from a neurobiochemical perspective. Specifically, it is suggested that imipramine's effects are mediated predominantly through its serotonergic action and that the increased noradrenergicity of the drug with increasing total plasma concentrations reduces its potency, in particular its antiphobic effects, in panic disorder with agoraphobia.