A Study of Rapastinel as Adjunctive Therapy in Major Depressive Disorder (RAP-MD-03)

* Meet Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for MDD * Current major depressive episode of at least 8 weeks and not exceeding 18 months in duration at Visit 1 * Have no more than partial response (\< 50% improvement) to ongoing treatment with a protocol-allowed antidepressant * If female of childbearing potential, have a negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test.

* DSM-5-based diagnosis of any disorder other than MDD that was the primary focus of treatment within 6 months before Visit 1 * Lifetime history of meeting DSM-5 criteria for: 1. Schizophrenia spectrum or other psychotic disorder 2. Bipolar or related disorder 3. Major neurocognitive disorder 4. Neurodevelopmental disorder of greater than mild severity or of a severity that impacts the participant's ability to consent, follow study directions, or otherwise safely participate in the study 5. Dissociative disorder 6. Posttraumatic stress disorder 7. MDD with psychotic features * Significant suicide risk, as judged by the Investigator.