Intervention: Ketamine
Trial phase: Phase 3
ATC code: N01AX03 | N01AX14 | N06AX27
SMILES: CNC1(c2ccccc2Cl)CCCCC1=O
Sex: All
Age groups: Adult
Healthy volunteers: No
Participants at risk: 114
Group description: Participants self-administered esketamine 84 milligram (mg) (1 spray containing esketamine 14 mg in each nostril at 0, 5, 10 minutes using 3 devices on single day) twice per week for 4 weeks on Days 1, 4, 8, 11, 15, 18, 22, 25 along with SOC antidepressant treatment (determined by physician based on clinical judgment and practice guidelines) on Day 1 continued for DB treatment phase. After Day 1, a single dose reduction from esketamine 84 mg to 56 mg was permitted if a participant was unable to tolerate intranasal esketamine 84 mg dose. Participants for whom dose was reduced continued to receive reduced dose for duration of DB treatment phase (Days 1 to 25).
Eligibility criteria:
Inclusion Criteria:

Participant must meet Diagnostic and Statistical Manual of Mental Disorders (5th edition) (DSM-5) diagnostic criteria for major depressive disorder (MDD), without psychotic features, based upon clinical assessment and confirmed by the Mini International Psychiatric Interview (MINI)
Participants must have current suicidal ideation with intent, confirmed by a "Yes" response to Question B3 [Think (even momentarily) about harming or of hurting or of injuring yourself: with at least some intent or awareness that you might die as a result; or think about suicide (ie, about killing yourself)?] AND Question B10 [Intend to act on thoughts of killing yourself?] obtained from the MINI
In the physician's opinion, acute psychiatric hospitalization is clinically warranted due to participant's imminent risk of suicide
Participant has a Montgomery Asberg Depression Rating Scale (MADRS) total score of greater than (>) 28 predose on Day 1
As part of standard of care treatment, participant agrees to be hospitalized voluntarily for a recommended period of 14 days after randomization (may be shorter or longer if clinically warranted in the investigator's opinion) and take prescribed non-investigational antidepressant therapy(ies) for at least the duration of the double-blind treatment phase (Day 25)

Exclusion Criteria:

Participant has a current DSM-5 diagnosis of bipolar (or related disorders), antisocial personality disorder, or obsessive compulsive disorder
Participant currently meets DSM-5 criteria for borderline personality disorder. Note: Participant not meeting full DSM-5 criteria for borderline personality disorder but exhibiting recurrent suicidal gestures, threats, or self-mutilating behaviors should also be excluded
Participant has a current clinical diagnosis of autism, dementia, or intellectual disability
Participant has a current or prior DSM-5 diagnosis of a psychotic disorder, or MDD with psychotic features
Participant meets the DSM-5 severity criteria for moderate or severe substance or alcohol use disorder, (except for nicotine or caffeine), within the 12 months before Screening. A history (lifetime) of ketamine, phencyclidine (PCP), lysergic acid diethylamide (LSD), or 3, 4-methylenedioxy-methamphetamine (MDMA) hallucinogen-related use disorder is exclusionary
Participant has a history or current signs and symptoms of liver or renal insufficiency, clinically significant cardiac (including unstable coronary artery disease and congestive heart failure, tachyarrhythmias and recent myocardial infarction) or vascular, pulmonary, gastrointestinal, endocrine (including uncontrolled hyperthyroidism), neurologic (including current or past history of seizures except uncomplicated childhood febrile seizures with no sequelae), hematologic, rheumatologic, or metabolic (including severe dehydration/ hypovolemia) disease
Participant has known allergies, hypersensitivity, intolerance or contraindications to esketamine or ketamine or its excipients