This multi-center, randomized, double-blind, placebo-controlled, parallel-group study will investigate the efficacy and safety of RO4995819 as adjunctive therapy in patients with major depressive disorder having inadequate response to ongoing antidepressant treatment. Patients will be randomized to receive once daily doses of 5 mg, 15 or 30 mg of RO4995819 or matching placebo. The anticipated time on study treatment is 6 weeks.

Inclusion Criteria:

• Adult patients, 18-65 years of age
• Major depression disorder without psychotic features
• Inadequate response to current, ongoing antidepressant treatment as defined by protocol
• Having at least one but no more than 2 antidepressant treatment trial failures
• Body mass index (BMI) 18.0-35.0 kg/m2 inclusive

Exclusion Criteria:

• Patient currently receives treatment with a combination of 3 or more antidepressants
• Significant ongoing use of high doses of barbiturates, benzodiazepines or other anxiolytic drugs
• Patient previously received RO4995819
• Patient participated in an investigational drug or device trial within 6 months of screening
• History of non-response to, or current use of non-pharmacological treatment including Electroconvulsive Therapy (ECT), Vagus Nerve Stimulation (VNS), or Repetitive Transcranial Magnetic Stimulation (RTMS)
• Past or present psychotic symptoms