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

        Inclusion Criteria:

          -  At the time of signing the informed consent form (ICF), participant must be a man or
             woman 65 years of age or older

          -  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 (>=) 31

          -  At the start of the Screening/Prospective observational Phase, participants must have
             had nonresponse (less than or equal to 25% improvement) to >=1 but less than or equal
             to (<=) 8 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 records by medical and
             pharmacy/prescription records, or a letter from the treating physician, for the
             current episode of depression

          -  Participant must be taking one of the oral antidepressant treatment with nonresponse
             that is documented on the MGH-ATRQ at the start of the screening/prospective
             observational phase

          -  The participant's current major depressive episode, depression symptom severity (Week
             1 MADRS total score greater than or equal to 24 required) and treatment response to
             antidepressant treatments used in the current depressive episode (retrospectively
             assessed) must be confirmed for participation in a clinical study based on a
             Site-Independent Qualification Assessment

          -  Participant must be medically stable on the basis of clinical laboratory tests
             performed in the screening/prospective observational phase

        Exclusion Criteria:

          -  The participant's depressive symptoms have previously demonstrated nonresponse to:
             Esketamine or ketamine in the current major depressive episode per clinical judgment,
             or all of the 4 oral antidepressant treatment options available for the double-blind
             induction Phase (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 ECT

          -  Participants who has received vagal nerve stimulation (VNS) or who 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
             psychosis, bipolar or related disorders (confirmed by the MINI), obsessive compulsive
             disorder (current episode only), intellectual disability ( intellectual disability
             [DSM-5 diagnostic codes 317, 318.0, 318.1, 318.2, 315.8, and 319]), 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) and also
             includes history of suicidal behavior within the past year prior to start of the
             screening/prospective observational phase

          -  Participant has a history (lifetime) of ketamine, phencyclidine (PCP), lysergic acid
             diethylamide (LSD), or 3, 4-methylenedioxy-methamphetamine (MDMA) hallucinogen-related
             use disorder\

          -  Participant has a Mini Mental State Examination (MMSE) < 25 or <22 for those
             participants with less than an equivalent of high school education

          -  Participant has neurodegenerative disorder (eg, Alzheimer's Disease, Vascular
             dementia, Parkinson's disease with clinical evidence of cognitive impairment) or
             evidence of mild cognitive impairment (MCI)

          -  Participant has a history of uncontrolled hypertension; current or past history of
             significant pulmonary insufficiency/condition;clinically significant ECG
             abnormalities; current or past history of seizures; clinically significant
             cardiovascular disorders including cerebral and cardiac vascular disease
      