The purpose of this research study is to determine the effectiveness of 2 target doses of R228060 in comparison with placebo during 6 weeks of treatment in moderately to severely depressed adult subjects with major depressive disorder.

Approximately 488 subjects will be involved in the study.

• Generally healthy adults on the basis of a physical examination, medical history, ECG and laboratory work-up.
• Subject needs to meet criteria for diagnosis of moderate or severe major depression as defined by the protocol.
• The subject also needs to be an outpatient to participate in this study.