['treatment-resistant depression']
['esketamine', 'placebo', 'duloxetine (oral antidepressant)', 'escitalopram (oral antidepressant)', 'sertraline (oral antidepressant)', 'venlafaxine extended release (xr) (oral antidepressant)']

        Inclusion Criteria:

          -  At the time of signing the informed consent form (ICF), participant must be a man or
             woman 18 (or older if the minimum legal age of consent in the country in which the
             study is taking place is greater than [>]18) to 64 years of age, inclusive

          -  At the start of the screening/prospective observational phase, participant must meet
             the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) diagnostic criteria
             for single-episode major depressive disorder (MDD) (if single-episode MDD, the
             duration must be greater than or equal to [>=] 2 years) or recurrent MDD, without
             psychotic features, based upon clinical assessment and confirmed by the
             Mini-International Neuropsychiatric Interview (MINI)

          -  At the start of the screening/prospective observational phase, participant must have
             an Inventory of Depressive Symptomatology-Clinician rated ( IDS-C30) total score of
             greater than or equal to (>=) 34

          -  At the start of the screening/prospective observational phase, participants must have
             had non-response (less than or equal to [<=25] percent [%] improvement) to >=1 but
             less than or equal to (<=) 5 (if current episode is >2 years, upper limit is
             applicable to only the last 2 years) oral antidepressant treatments taken at adequate
             dosage and for adequate duration, as assessed using the Massachusetts General Hospital
             - Antidepressant Treatment Response Questionnaire (MGH-ATRQ) and documented by medical
             history and pharmacy/prescription records, for the current episode of depression.

        Participant is taking a different oral antidepressant treatment on the MGH-ATRQ for at
        least the previous 2 weeks at or above the minimum therapeutic dose

        - The participant's current major depressive episode, depression symptom severity (Week 1
        MADRS total score >=28 required), and antidepressant treatment response in the current
        depressive episode, must be confirmed using a Site Independent Qualification Assessment

        Exclusion Criteria:

          -  Participants who have previously demonstrated nonresponse of depressive symptoms to
             esketamine or ketamine in the current major depressive episode, to all 4 of the oral
             antidepressant treatment options available for the double-blind induction phase (i.e,
             duloxetine, escitalopram, sertraline, and venlafaxine extended release [XR]) in the
             current major depressive episode (based on MGH-ATRQ), or an adequate course of
             treatment with electroconvulsive therapy (ECT) in the current major depressive
             episode, defined as at least 7 treatments with unilateral/bilateral ECT

          -  Participant has received vagal nerve stimulation (VNS) or has received deep brain
             stimulation (DBS) in the current episode of depression

          -  Participant has a current or prior DSM-5 diagnosis of a psychotic disorder or MDD with
             psychotic features bipolar or related disorders (confirmed by the MINI), obsessive
             compulsive disorder (current only), intellectual disability (DSM-5 diagnostic codes
             317, 318.0, 318.1, 318.2, 315.8, and 319), autism spectrum disorder, borderline
             personality disorder, antisocial personality disorder, histrionic personality
             disorder, or narcissistic personality disorder

          -  Participant has homicidal ideation/intent, per the investigator's clinical judgment,
             or has suicidal ideation with some intent to act within 6 months prior to the start of
             the screening/prospective observational phase, per the investigator's clinical
             judgment or based on the Columbia Suicide Severity Rating Scale (C-SSRS)

          -  Participants with history of moderate or severe substance or alcohol use disorder
             according to DSM-5 criteria
      