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