 The proposed study involves three phases. The first phase is an 8-week, open-label trial of an SSRI for MDD. Patients who do not experience sufficient symptom improvement following this open-label trial will be enrolled in a 6-week, double-blind, placebo controlled trial of ziprasidone augmentation second phase. Ziprasidone and placebo-remitters will then enter a 12-month, double-blind extension phase third phase. We estimate that approximately 400 patients will enter phase 1 of the study so that a minimum of 180 subjects will enter double-blind treatment phase 2 over 5 years. Each treatment arm during phase 2 will have 90 subjects. 