Atypical features and treatment response in the National Institute of Mental Health Treatment of Depression Collaborative Research Program.

Because depression with atypical features is poorly responsive to imipramine, treatment trials including a tricyclic antidepressant arm should assess depressive subtype. Sotsky and Simmens had previously reanalyzed data from the National Institute of Mental Health Treatment of Depression Collaborative Research Program (TDCRP) providing independent confirmation that imipramine is ineffective for patients with atypical features. The TDCRP was a 16-week study in which 239 outpatients with major depression were randomly assigned to cognitive behavior therapy (CBT), interpersonal psychotherapy (IPT), imipraminecase management (IMI-CM), or pill placebo-case management (Pbo-CM). We used Sotsky and Simmens' algorithm to investigate the effect of diagnostic subtype on all four treatments. Hierarchical multiple regression analyses demonstrated IMI-CM benefit relative to Pbo-CM in patients without but not in those with atypical features. These analyses did not demonstrate differential psychotherapy efficacy between depressive subtypes. In conclusion, subsequent analyses of the TDCRP study demonstrated the need to identify the subgroup of depressed patients who have atypical features. Failure to identify this subtype underestimates imipramine's benefit in the appropriately treated subgroup. Comparisons of other treatments with imipramine may be misleading if they do not account for diagnostic subtype.