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Published Online:https://doi.org/10.1176/ajp.156.7.1007

OBJECTIVE: The purpose of this study was to compare the acute outcomes of antidepressant medication and cognitive behavior therapy in the severely depressed outpatient subgroups of four major randomized trials. A secondary objective was to compare the results obtained in the National Institute of Mental Health Treatment of Depression Collaborative Research Program, upon which treatment guidelines have been based, with those obtained in the other three studies. METHOD: Outcomes of antidepressant medication and cognitive behavior therapy were compared within each of the four studies separately and for patients aggregated across the four studies. In addition, the outcomes in the antidepressant medication and cognitive behavior therapy conditions of the Treatment of Depression Collaborative Research Program were compared with those obtained in the other three studies. RESULTS: The overall effect sizes comparing antidepressant medication to cognitive behavior therapy favored cognitive behavior therapy, but tests comparing the two modalities did not reveal a significant advantage for either modality overall. CONCLUSIONS: Cognitive behavior therapy has fared as well as antidepressant medication with severely depressed outpatients in four major comparisons. Until findings emerge from current or future comparative trials, antidepressant medication should not be considered, on the basis of empirical evidence, to be superior to cognitive behavior therapy for the acute treatment of severely depressed outpatients.