Evaluation of the Efficacy and Safety of Subcutaneous Ketamine in the Treatment of Depressive Episode With Suicidal Ideation and/or Behavior in Adolescents

May 2, 2025 updated by: Sheila Cavalcante Caetano, Federal University of São Paulo
Evaluate the efficacy and safety of subcutaneous ketamine added to usual treatment in the management of depressive episodes with suicidal ideation or behavior in adolescent patients, compared to usual treatment added to placebo (midazolam).

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Depression affects approximately 8% of adolescents, with an estimated 60% showing inadequate response to current standard treatments. Ketamine, a glutamatergic modulator, has demonstrated efficacy in adults with treatment-resistant depression and has shown promising preliminary results in adolescent populations. This Phase III, randomized, double-blind, placebo-controlled clinical trial aims to evaluate the efficacy and safety of subcutaneous ketamine as an adjunctive treatment for adolescents experiencing a major depressive episode with active suicidal ideation and/or behavior.

Participants will be randomized into two parallel groups to receive either subcutaneous ketamine (0.5 to 1 mg/kg) or an active placebo (1 mg midazolam diluted in 5 ml of 0.9% saline), administered twice weekly for four weeks. All participants will continue their usual treatment regimens. A two-week post-treatment follow-up period will be conducted to assess the persistence of effects and monitor safety outcomes.

Clinical assessments include diagnostic and symptom severity scales validated for pediatric populations. The efficacy will be primarily measured by depression remission and response, while safety will be assessed via adverse event monitoring and clinical examination. The trial will include 30 participants per group, providing 80% power to detect a clinically significant difference of 8.7 points on the Montgomery-Åsberg Depression Rating Scale (MADRS) between groups.

Study Type

Interventional

Enrollment (Estimated)

60

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age between 12 and 19 years.
  • Diagnosis of Major Depressive Episode, unipolar, made through the Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS-PL) administered by experienced evaluators, using DSM-5 criteria.
  • Under usual treatment for Major Depressive Episode, including clinically indicated psychopharmacological treatment and/or psychosocial treatment at one of the two collaborating clinics (DICA and Conversas de Vida / Unifesp).
  • Score ≥ 25 on the MADRS (Montgomery-Åsberg Depression Rating Scale).
  • Score ≥ 28 on the CDRS (Children Depression Rating Scale).
  • Score ≥ 2 on the Columbia Suicide Severity Rating Scale (C-SSRS).
  • History of suicide attempt or significant suicidal ideation or planning with a plan or intention requiring emergency evaluation in the last 30 days.

Exclusion Criteria:

  • Presence of the following psychiatric comorbidities: Autism Spectrum Disorder, Bipolar Disorder, Schizophrenia, Schizoaffective Disorder, or psychiatric disorder secondary to physical illness, and history of ketamine or other substance abuse or dependence in the last 6 months.
  • Presence of Intellectual Disability (assessed by IQ testing).
  • Presence of the following clinical comorbidities: history of myocardial infarction, congenital heart disease, decompensated cardiac arrhythmia, decompensated hypertension, porphyria, stroke, brain trauma with loss of consciousness, intracranial hypertension, hydrocephalus, central nervous system tumors, or central nervous system abnormalities.
  • Previous treatment for depression with esketamine.
  • Allergy to esketamine.
  • If female: pregnancy or breastfeeding.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Ketamine
Participants were randomly by assigned. ketamine will be used as an adjunctive treatment at an initial dose of 0.5 mg/kg, administered subcutaneously twice weekly for four weeks under double-blind conditions. Dose adjustments between 0.5 to 1.0 mg/kg may occur based on patient response and tolerability.
Drug: ketamine
Ketamine will be administered as adjunctive therapy at an initial dose of 0.5 mg/kg via subcutaneous injection, twice weekly for four weeks, under double-blind conditions. Dose adjustments between 0.5 and 1.0 mg/kg will be based on depressive symptoms, efficacy, and tolerability. All procedures will occur at the Ketamine Clinic of Federal University of São Paulo.
Placebo Comparator: Midazolam
For the placebo group, midazolam will be administered subcutaneously at a dose of 1 mg diluted in 5 ml of 0.9% saline, twice weekly for four consecutive weeks, also under double-blind conditions.
Drug: Midazolam
Midazolam will be administered subcutaneously twice weekly for four consecutive weeks, also under double-blind conditions. The subject will be monitored continuously during the procedure, and every hour for three hours after the infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in Montgomery-Asberg Rating Scale (MADRS) Total Score at 24 Hours Post First Dose
Time Frame: Baseline (predose) and 24 hours post first dose

The Montgomery-Åsberg Depression Rating Scale (MADRS) has a minimum score of 0 and a maximum score of 60; higher scores indicate worse depression. The primary efficacy endpoint of ketamine will be evaluated as follows:

  • Remission: Total score on the MADRS ≤ 12
  • Response: A reduction of more than 50% in the total MADRS score.
  • Lack of response: A reduction of less than 50% in the baseline MADRS scores.
Baseline (predose) and 24 hours post first dose

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Remission and Response of Suicidal Ideation and Behavior Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS)
Time Frame: Baseline (predose) and 24 hours post first dose

The Columbia-Suicide Severity Rating Scale (C-SSRS) has a range from 0 to 5, where higher scores indicate greater severity of suicidal ideation or behavior.

Secondary Efficacy Endpoint:

  • Remission of Suicide Risk: C-SSRS score = 0
  • Response: A 50% or greater improvement in the C-SSRS score.
Baseline (predose) and 24 hours post first dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Federal University of São Paulo

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

May 1, 2025

Primary Completion (Estimated)

April 1, 2028

Study Completion (Estimated)

April 1, 2028

Study Registration Dates

First Submitted

March 29, 2025

First Submitted That Met QC Criteria

May 2, 2025

First Posted (Actual)

May 4, 2025

Study Record Updates

Last Update Posted (Actual)

May 4, 2025

Last Update Submitted That Met QC Criteria

May 2, 2025

Last Verified

March 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 82712924300005505

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Depressive Disorder

Clinical Trials on ketamine

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Bulgaria

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe