 This is a randomized, placebo-controlled, double-dummy, multi-center study of the safety, efficacy and tolerability of SEP-225289 in male and female subjects with MDD. Subjects meeting DSM-IV criteria for Melancholic or Atypical Features specifier are eligible for participation. The study will consist of a screening period, which may last up to 2 weeks, an eight week 56 day double-blind treatment period, a two week 14 day wash-out, and a one week 7 day follow up. Total subject participation will be approximately 91 days 13 weeks. This study was previously posted by Sepracor Inc. In October 2009, Sepracor Inc. was acquired by Dainippon Sumitomo Pharma., and in October 2010, Sepracor Incs name was changed to Sunovion Pharmaceuticals Inc. 