 In this study we propose to compare the ampakine receptor potentiator Org 24448 to placebo for the treatment of Major Depression. Inpatients and outpatients primarily outpatients, ages 21 to 70, with a diagnosis of Major Depression without psychotic features, will be randomized to double-blind treatment to either Org 24448 or placebo for a period of 8 weeks. Acute efficacy will be determined by demonstrating a greater response rate using specified criteria. Approximately 90 patients with acute major depression will be enrolled in the study in order to reach the goal of randomizing 70 patients in the controlled trial. 