Investigate Efficacy & Safety of RO4995819 vs. Placebo as Adjunct Tx in Patients w/Major Depressive Disorder

Inclusion Criteria: Patients are eligible for enrollment in this study if they meet all of the following criteria: 1. An outpatient w/a primary diagnosis of major depressive disorder w/out psychotic features 2. Inadequate response to current, ongoing antidepressant tx of SSRI/SNRI. 3. Having at least 1 but no more than 2 antidepressant treatment failures w/in the index depressive episode 4. Dose/duration of antidepressant treatment in index episode can be verified by documentation from one of following: 1. Med records; 2. Pharmacy records; 3. Treating and/or referring physician (indicating medication, dose, dates of treatment). 5. Documentation of clinical/treatment history must be available. 6. Index depressive episode started w/in 1 year of screening. 7. Confirmed compliance w/current SSRI/SNRI treatment based on blood screen. 8. Existing med regimens should be stable for 6 wks prior to screening 9. 18-65 y.o. at time of consent 10. BMI 18.0 to 35.0 kg/m2 inc. 11. Patients w/reproductive potential must agree to use specified contraceptive protection during tx period and for at least 90 days after last dose of study drug: * Males w/partners of childbearing potential or partners must use a barrier method of contraception or remain sexually abstinent. * Females who are not either surgically sterile (tubal ligation, removal of ovaries or uterus) or post-menopausal (no spontaneous menstrual periods for at least 1 yr confirmed by a hormone panel \[FSH and 17βestradiol\])must agree to use 2 adequate methods of contraception, including at least one method w/ failure rate of \< 1% per yr (e.g., hormonal implants, combined oral contraceptives, vasectomized partner, abstinence). 12. Able to participate and willing to give written informed consent. Exclusion Criteria: Patients are excluded from this study if the answer is 'yes' to any of the following: Current and past treatment history: 1. Currently receiving tx w/3 or more antidepressants. 2. Currently receiving tx w/prohibited meds. 3. Significant ongoing use of high doses of barbiturates, benzodiazepines or other anxiolytic drugs. 4. Previously received RO4995819. 5. Participated in investigational drug or device study w/in 6 mos of screening or in index depressive episode. 6. History of non-response to Electroconvulsive Therapy (ECT), Vagus Nerve Stimulation (VNS),or Repetitive Transcranial Magnetic Stimulation (RTMS). 7. Planning to begin/change current regimen of individual psychotherapy including cognitive behavioral therapy during the 6 week treatment period of the study and the first 2 weeks of follow-up. 8. Present DSM-IV-TR axis I diagnosis except for anxiety comorbidity 9. Past or present psychotic symptoms. 10. Mood disorder due to medical condition or substance use/abuse/dependence. 11. Established personality disorder 12. Alcohol and/or substance abuse/dependence during the last 6 months. 13. A significant risk for suicidal behavior 14. Past or present neurological disorder. 15. Present eating disorder 16. Abnormal thyroid function. 17. Active upper gastrointestinal tract disease 18. Unstable medical condition that could pose unacceptable risk to the patient in this study. 19. Positive result on hepatitis B (HBV), hepatitis C (HCV), or HIV 1 and 2. 20. Positive test for drugs of abuse. 21. Abnormality on 12-lead electrocardiogram (ECG), including a QTcF of ≥450 milliseconds. 22. Lab abnormality 23. Positive pregnancy test, breast feeding,or intention to become pregnant during the course of the trial.