Clinical trial NCT02493868 (phase 3, status: completed)
Conditions: depressive disorder, treatment-resistant
ICD codes: F25.1, F32.89, F33.8, F33.0, F33.1, F33.9, F32.0
Drugs: esketamine, placebo, duloxetine (oral antidepressant), escitalopram (oral antidepressant), sertraline (oral antidepressant), venlafaxine extended release (xr) (oral antidepressant)
SMILES: CNC1(CCCCC1=O)C1=CC=CC=C1Cl, CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O, CNCC[C@H](OC1=CC=CC2=CC=CC=C12)C1=CC=CS1, CN(C)CCC[C@]1(OCC2=C1C=CC(=C2)C#N)C1=CC=C(F)C=C1, CN[C@H]1CC[C@@H](C2=CC(Cl)=C(Cl)C=C2)C2=CC=CC=C12, [O-][N+](=O)C1=CC2=C(NC(=O)CN=C2C2=CC=CC=C2Cl)C=C1
Eligibility criteria:

        Inclusion Criteria:

        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) 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 nonresponse (less than or equal to 25 percent [%] improvement) to greater than or
             equal to (>=1) but less than or equal to (<=) 5 oral antidepressant treatments taken
             at adequate dosage and for adequate duration, as assessed using the Massachusetts
             General Hospital (MGH-ATRQ )

          -  MGH-ATRQ and documented by medical history and pharmacy/prescription records, for the
             current episode of depression. In addition, the participant is taking different
             ongoing oral antidepressant treatment (on the MGH-ATRQ) for at least the previous 2
             weeks at or above the minimal therapeutic dose

          -  The participant's current major depressive episode, depression symptom severity (Week
             1 MADRS total score >=28 required), and treatment response to antidepressant
             treatments used in the current depressive episode (retrospectively assessed) must be
             deemed valid for participation in a clinical study based on a Site-Independent
             Qualification Assessment For Transferred-Entry Participants

          -  The participant must have completed the double-blind induction phase in ESKETINTRD3001
             or ESKETINTRD3002 and must have demonstrated response at the end of that phase (>=50%
             reduction in the MADRS total score from baseline [Day 1 pre-randomization] at the end
             of the 4-week double-blind induction phase)

        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 (ie,
             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