Pharmacotherapy response and diagnostic validity in atypical depression

Background: The validity of diagnostic criteria and the efficacy of tricycl ic antidepressant pharmacotherapy for atypical depression were studied in t he NIMH Treatment of Depression Collaborative Research Program. Methods: Ou tpatients with major depressive disorder (N=239) entered a 16-week clinical trial and were randomly assigned to interpersonal psychotherapy, cognitive behavior therapy, and imipramine or placebo with clinical management. Feat ures of atypical depression were rated on the SADS and ISI and clinical out come was measured on the HRSD and GAS. Results: Atypical features of mood r eactivity and at least one reversed vegetative symptom of hypersomnia, hype rphagia or weight gain (25.2% patients) were predictive of pharmacotherapy non-responsiveness with imipramine compared to placebo. The additional feat ures of diurnal mood variation, 'leaden paralysis', and 'rejection sensitiv ity' did not further distinguish an imipramine non-responsive subgroup. Imi pramine did show significant effectiveness compared to placebo among non-at ypical patients on measures of depressive symptom change. Limitations: The predictive influence of atypical features was not accounted for on the basi s of depression severity. Conclusions: This study provides evidence for the predictive validity of atypical features of major depressive disorder, inc luding mood reactivity and at least one reversed vegetative symptom of eith er hypersomnia, hyperphagia, or weight gain, supporting the inclusion of at ypical depressive features, with these criteria, in the DSR I-IV. (C) 1999 Elsevier Science B.V. All rights reserved.