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

        Inclusion Criteria:

        A). For Direct-Entry Participants

          -  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)

          -  At the start of the screening 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 screening, participant must have a MADRS total score of >=22

          -  At the start of the screening phase, participants must have had nonresponse to >=2
             oral antidepressant treatments in the current episode of depression, as assessed using
             the the MGHATRQ and confirmed by documented records (example
             medical/pharmacy/prescription records or a letter from treating a physician, etc,) B).
             For Transferred-entry Participants

          -  All participants who completed the double-blind induction phase of ESKETINTRD3005
             study, regardless of their response status, will be eligible to participate in this
             study, if they meet the study specific eligibility criteria

        Exclusion Criteria:

        A). For Direct-Entry Participants

          -  Participant's depressive symptoms have previously not responded to: Esketamine or
             ketamine in the current major depressive episode per clinical judgment or All of the 4
             oral antidepressant treatment options available in the respective country for the
             open-label induction phase (that is, duloxetine, escitalopram, sertraline, and
             venlafaxine XR) in the current major depressive episode (based on Massachusetts
             General Hospital - Antidepressant Treatment Response Questionnaire [ MGH-ATRQ])

          -  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 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

          -  Participants who has a Mini Mental State Examination (MMSE) <25; Has neurodegenerative
             disorder (example, Alzheimer's disease, vascular dementia, Parkinson's disease), or
             evidence of mild cognitive impairment (MCI) B). Transferred-Entry Participants

          -  Participant has taken any prohibited therapies that would not permit dosing on Day 1
      