Add-On Study of MSI-195 (S-Adenosyl-L-Methionine, SAMe) for Patients With Major Depressive Disorder (MDD)

Inclusion Criteria: * Meets the Diagnostic and Statistical Manual of Mental Disorder, 4th Edition, Text Revision (DSM-IV-TR) criteria for Major Depressive Disorder (MDD) * A total score of 16 or higher on the Hamilton Rating Scale for Depression- 17 item version (HAM-D17) at the Screening and Baseline Visits, with a score of ≥2 on mood item 1. * Have experienced 1-4 prior Major Depressive Episodes. Patients with more than 5 lifetime episodes (including current episode) will require discussion with the medical monitor prior to inclusion. * Failed 1-3 treatment regimens in the current depressive episode * Received an adequate dose and duration of Antidepressant Therapy (ADT) (on ADT for at least 6 weeks with a stable dose for at least 3 weeks) Exclusion Criteria: * Failed 4 or more adequate treatment regimens in current episode of depression * patient may have a significant risk for suicidal behavior during the course of their participation in the study * Intolerance to SAMe; Prior use of MSI-195 * History of any of the following psychiatric disorders: eating disorder within 6 months; obsessive compulsive disorder, psychotic disorder, bipolar disorder, mental retardation, dementia or other forms of cognitive impairment at any time or alcohol or substance abuse * \>3X upper limit of normal (ULN) Alkaline Phosphatase, aspartate aminotransferase (AST), alanine aminotransferase (ALT); \>1.5X ULN total bilirubin * Pregnant or lactating women * Any history of seizures, excluding febrile seizures * Known positivity for human immunodeficiency virus