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J Affect Disord. 1999 Aug;54(3):237-47.

Pharmacotherapy response and diagnostic validity in atypical depression.

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The George Washington University Medical Center, Department of Psychiatry and Behavioral Sciences, Washington, DC 20037, USA.



The validity of diagnostic criteria and the efficacy of tricyclic antidepressant pharmacotherapy for atypical depression were studied in the NIMH Treatment of Depression Collaborative Research Program.


Outpatients 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. Features of atypical depression were rated on the SADS and ISI and clinical outcome was measured on the HRSD and GAS.


Atypical features of mood reactivity and at least one reversed vegetative symptom of hypersomnia, hyperphagia or weight gain (25.2% patients) were predictive of pharmacotherapy non-responsiveness with imipramine compared to placebo. The additional features of diurnal mood variation, 'leaden paralysis', and 'rejection sensitivity' did not further distinguish animipramine non-responsive subgroup. Imipramine did show significant effectiveness compared to placebo among non-atypical patients on measures of depressive symptom change.


The predictive influence of atypical features was not accounted for on the basis of depression severity.


This study provides evidence for the predictive validity of atypical features of major depressive disorder, including mood reactivity and at least one reversed vegetative symptom of either hypersomnia, hyperphagia, or weight gain, supporting the inclusion of atypical depressive features, with these criteria, in the DSM-IV.

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