Key Inclusion Criteria:  Subjects must meet all of the following key inclusion criteria:  Completed written informed consent. Aged 18 to 65 years, inclusive, at the time of informed consent. Diagnosis of MDD meeting the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) and International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10). Subject is currently on stable pharmacological treatment for depression, defined as ≤50% change in dose during the 6 weeks prior to randomization to ≥1 of the oral antidepressant medications listed in the MGH ATRQ. Snaith Hamilton Pleasure Scale (SHAPS) score is ≥30 at screening and Day 1.  Key Exclusion Criteria:  Subjects will be excluded from the study if they meet any of the following key criteria:  Any psychiatric disorder disallowed per protocol and electroconvulsive therapy (ECT) within 6 months prior to screening. Comorbid anxiety disorders are not exclusionary. Have a significant risk of suicidal or violent behavior. Subjects with any suicidal ideation of type 4 (active suicidal ideation with some intent to act, without specific plan) or type 5 (active suicidal ideation with specific plan and intent) in the past 12 months before screening based on the C-SSRS or according to the investigator's clinical judgment should be excluded. A history of seizure disorder, stroke, Alzheimer disease, Parkinson disease, multiple sclerosis, head injury associated with loss of consciousness for more than 15 minutes, or other neurodegenerative disorder.