Esketamine plus standard care for adolescents with major depressive disorder and acute suicidal thoughts or behavior

A Double-blind, Randomized, Psychoactive Placebo-controlled Study to Evaluate the Efficacy and Safety of Intranasal Esketamine 84 mg in Addition to Comprehensive Standard of Care for the Rapid Reduction of the Symptoms of Major Depressive Disorder in Adolescent Participants With Acute Suicidal Ideation or Behavior

Phase 3 Interventional Janssen Research & Development, LLC · NCT07227454

This will test whether adding intranasal esketamine to usual care helps hospitalized adolescents with major depressive disorder and acute suicidal thoughts or behavior feel better faster than a psychoactive placebo plus usual care.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment258 (estimated)
Ages12 Years to 17 Years
SexAll
SponsorJanssen Research & Development, LLC Industry-sponsored
Locations9 sites (Birmingham, Alabama and 8 other locations)
Trial IDNCT07227454 on ClinicalTrials.gov

What this trial studies

This Phase 3, randomized, double-blind trial compares intranasal esketamine plus comprehensive standard of care (SoC) versus a psychoactive placebo plus SoC in adolescent participants hospitalized for acute suicidal ideation or behavior. Eligible participants must meet DSM-5 criteria for major depressive disorder and high severity thresholds (CDRS-R ≥58 and CGI-SS-R ≥4) and be medically stable for participation. The psychoactive placebo arm includes an active agent to preserve blinding, and outcomes focus on rapid reduction of depressive symptoms and suicidality after dosing in the inpatient setting. The trial is conducted at multiple U.S. centers and uses standardized rating scales and clinician assessments to measure safety and efficacy.

Who should consider this trial

Good fit: Adolescents with DSM-5 major depressive disorder who are hospitalized for acute suicidal ideation or behavior and meet high severity scores (CDRS-R ≥58 and CGI-SS-R ≥4) are the intended participants.

Not a fit: Patients with diagnoses excluded by the protocol such as bipolar or certain psychotic disorders, or those who are not medically stable or do not require hospitalization, are unlikely to be eligible or to benefit from this study.

Why it matters

Potential benefit: If successful, this approach could produce faster reductions in depressive symptoms and suicidal ideation for hospitalized adolescents than standard care alone.

How similar studies have performed: Esketamine has demonstrated rapid antidepressant effects in adults, but controlled Phase 3 evidence specifically in adolescents with acute suicidality is limited.

Eligibility criteria

Show full inclusion / exclusion criteria
Inclusion Criteria:

* Must meet diagnostic and statistical manual of mental disorders (5th edition) (DSM-5) diagnostic criteria for major depressive disorder (MDD) based upon clinical assessment and confirmed by the mini-international neuropsychiatric interview for children and adolescents (MINI-KID)
* Must have a clinical global impression - severity of suicidality - revised (CGI-SS-R) score of "Markedly" or greater (that is, greater than or equal to \[\>=\] 4) at both screening and baseline (predose) visits
* Must have a children's depression rating scale - revised (CDRS-R) total score \>= 58 at baseline (predose)
* In the physician's opinion, acute psychiatric hospitalization is clinically warranted due to subject's acute suicidality
* Must be medically stable based on physical examination, medical history, vital signs, and 12-lead electrocardiogram (ECG) performed at screening

Exclusion Criteria:

* Participant has a current DSM-5 diagnosis of bipolar (or related disorders), intellectual disability, autism spectrum disorder, conduct disorder, oppositional defiant disorder
* Participant currently meets DSM-5 criteria for borderline personality disorder
* Participant has a current or prior DSM-5 diagnosis of a psychotic disorder, or MDD with psychosis
* Participant has a history of seizure disorder
* Participant has known allergies, hypersensitivity, intolerance or contraindications to midazolam, esketamine or ketamine, or their excipients

Where this trial is running

Birmingham, Alabama and 8 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions Depressive Disorder, Major
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.