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

NCT06957704 | Not Yet Recruiting Phase 3 FDA Drug

• 1 other identifier: 82712924300005505
• Study Type: interventional
• Target: 60
• Locations: 0 countries
• Sites: N/A

Brief Summary

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).

Conditions

Depressive Disorder; Suicidal Ideas

Keywords

Adolescent; Ketamine; Major Depressive Disorder; Midazolam

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Montgomery-Asberg Rating Scale (MADRS) Total Score at 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 Outcomes (1)

• Remission and Response of Suicidal Ideation and Behavior Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS)

  Baseline (predose) and 24 hours post first dose

Study Arms (2)

Ketamine

EXPERIMENTAL

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

Midazolam

PLACEBO COMPARATOR

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

Interventions

ketamine DRUG

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.

Ketamine

Midazolam DRUG

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.

Midazolam

Eligibility Criteria

• Age: 12 Years - 19 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Federal University of São Paulo: lead

Related Publications (56)

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MeSH Terms

Conditions

Depressive Disorder; Depressive Disorder, Major

Interventions

Ketamine; Midazolam

Condition Hierarchy (Ancestors)

Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Central Study Contacts

Sheila C Caetano, Phd

CONTACT

551197824398; sheila.caetano@unifesp.br

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor; Post doctor

Study Record Dates

• First Submitted: March 29, 2025
• First Posted: May 4, 2025
• Study Start: May 1, 2025
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): April 1, 2028
• Last Updated: May 4, 2025

Record last verified: 2025-03