Treatment of atypical depression with cognitive therapy or phenelzine: A double-blind, placebo-controlled trial

Background: Patients with atypical depression are more likely to respond to monoamine oxidase inhibitors than to tricyclic antidepressants. They are frequently offered psychotherapy in the absence of controlled tests. There are no prospective, randomized, controlled trials, to our knowledge, of psychotherapy for atypical depression or of cognitive therapy compared with a monoamine oxidase inhibitor. Since there is only 1 placebo-controlled trial of cognitive therapy, this trial fills a gap in the literature on psychotherapy for depression. Methods: Outpatients with DSM-III-R major depressive disorder and atypical features (N = 108) were treated in a 10- week, double-blind, randomized, controlled trial comparing acute-phase cognitive therapy or clinical management plus either phenelzine sulfate or placebo. Atypical features were defined as reactive mood plus at least 2 additional symptoms: hypersomnia, hyperphagia, leaden paralysis, or lifetime sensitivity to rejection. Results: With the use of an intention-to-treat strategy, the response rates (21-item Hamilton Rating Scale for Depression score, ≤9) were significantly greater after cognitive therapy (58%) and phenelzine (58%) than after pill placebo (28%). Phenelzine and cognitive therapy also reduced symptoms significantly more than placebo according to contrasts after a repeated-measures analysis of covariance and random regression with the use of the blind evaluator's final Hamilton Rating Scale for Depression score. The scores between cognitive therapy and phenelzine did not differ significantly. Supplemental analyses of other symptom severity measures confirm the finding. Conclusions: Cognitive therapy may offer an effective alternative to standard acute-phase treatment with a monoamine oxidase inhibitor for outpatients with major depressive disorder and atypical features.