Clinical Research Directory

Inclusion Criteria: * Must have a confirmed diagnosis of major depressive disorder (MDD) according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition at the time of enrollment, without psychotic features, based on clinical assessment, and confirmed by mini international neuropsychiatric interview (MINI) * Must have a Hamilton depression rating scale (HAM-D; 17-item) total score greater than or equal to (\>=) 22 at screening and Day 1 * Participants must have had non-response (less than or equal to \[\<=\] 25 percent \[%\] improvement of symptoms) to \>= 2 oral antidepressant treatments in the current moderate to severe episode of depression after having been given at an adequate dosage for an adequate duration of at least 6 weeks * At baseline (Day 1), the investigator will evaluate any changes in the participant's signs/symptoms of depression since the screening assessment and confirm that the inclusion criteria for the current antidepressant (AD) treatment are still met (that is, nonresponse and minimal clinical improvement) * A female participant of childbearing potential must have a negative serum pregnancy test at screening and urine prior to the first dose of study intervention on Day 1 Exclusion Criteria: * Participants with hyperthyroidism that has not been sufficiently treated * History of malignancy within 5 years of enrollment before screening * Known allergies, hypersensitivity, or intolerance to esketamine/ketamine or its excipients * Received an investigational intervention or used an invasive investigational medical device within 60 days before the planned first dose of study intervention or first data collection time point * Currently enrolled in an investigational study that involves treatments for MDD or may otherwise be expected to impact mood