A study testing intranasal esketamine compared to midazolam for rapidly reducing symptoms of major depressive disorder in adolescents with suicidal thoughts or behavior

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What is this study about?

This study is looking at Major Depressive Disorder in teenagers who are having thoughts of suicide or suicidal behavior. Major Depressive Disorder is a condition where a person feels very sad and hopeless for long periods of time, which can affect their daily life. The study will test a medicine called esketamine, which is given as a nasal spray into the nose. Some participants will receive esketamine while others will receive either an oral placebo or an intranasal placebo. Additionally, some participants will receive midazolam, which is given by mouth as a liquid solution. All participants will also receive standard care treatment, which includes being in the hospital and taking one of several antidepressant medicines such as fluoxetine, escitalopram, or sertraline.

The purpose of this study is to see if esketamine can quickly reduce the symptoms of depression in teenagers who are having serious thoughts about suicide. The study will compare how well esketamine works compared to the other treatments when added to the standard care that these teenagers receive.

During the study, participants will be admitted to the hospital for about five days. They will receive their assigned treatment on the first day, and doctors will measure changes in their depression symptoms over the following 24 hours and beyond. Throughout the study, participants will continue to receive the standard care treatment including their prescribed antidepressant medicine and support from healthcare professionals.

1 Hospital admission and baseline assessment

On Day 1, you will be admitted to the hospital for psychiatric care due to acute suicidal thoughts or behavior.

Before receiving any study medication, your depression symptoms will be assessed using standardized rating scales. This includes the CDRS-R (Children’s Depression Rating Scale-Revised), which measures the severity of depression, and the CGI-SS-R (Clinical Global Impression-Severity of Suicidality-Revised), which assesses suicidal thoughts.

You will be asked to stay in the hospital voluntarily for a recommended period of 5 days (4 nights) starting from Day 1.

2 First dose of study medication

On Day 1, after the baseline assessment, you will receive your first dose of study medication.

You will be randomly assigned to receive either esketamine 84 mg nasal spray or a placebo. The placebo group will receive oral midazolam (a mild sedative) instead of esketamine, along with an inactive nasal spray. This is done to ensure the study is fair and unbiased.

Neither you nor the study staff will know which treatment you are receiving. This is called a double-blind study.

The nasal spray will be administered once on Day 1.

3 Standard antidepressant treatment

As part of standard care, you will begin taking one of the following antidepressant medications: fluoxetine, escitalopram, or sertraline. These belong to a class of medications called SSRIs (Selective Serotonin Reuptake Inhibitors).

You will continue taking this antidepressant throughout the double-blind treatment phase of the study.

The specific medication and dosage will be determined by the treating physician based on what is available and approved in your country.

4 Assessment 24 hours after first dose

On Day 2, which is 24 hours after receiving the first dose of study medication, your depression symptoms will be assessed again using the CDRS-R scale.

This assessment is the primary measure to determine how effective the treatment is in rapidly reducing depression symptoms.

5 Hospital stay and monitoring

You will remain in the hospital for the recommended 5-day period (4 nights) for safety monitoring and comprehensive care.

During this time, you will receive standard psychiatric care in addition to the study medication.

Your symptoms and overall condition will be monitored regularly by medical staff.

6 Continued follow-up

After the initial hospital stay, you will continue in the double-blind treatment phase.

You will continue taking the prescribed SSRI antidepressant during this phase.

Additional assessments and follow-up visits will be scheduled to monitor your progress and safety.

Who Can Join the Study?

You must be between 12 and 17 years old
You must have been diagnosed with Major Depressive Disorder, which is a condition that causes persistent feelings of sadness and loss of interest, without signs of losing touch with reality
You must have a score showing you are markedly suicidal or higher on a specific rating scale at both the first visit and before starting treatment
You must need to be admitted to a psychiatric hospital, which is a specialized hospital for mental health care, because of urgent thoughts or actions related to suicide
You must have a score of at least 58 on a depression rating scale, which indicates moderate to severe depression
You must agree to stay in the hospital voluntarily for about 5 days and 4 nights starting from the first day of treatment
You must agree to take one of the following antidepressant medications, which are medicines used to treat depression: fluoxetine, escitalopram, or sertraline, during the treatment period
You must be medically stable, meaning your overall physical health is stable enough to participate safely

Who Cannot Join the Study?

You have a diagnosis of schizophrenia, which is a mental health condition that affects how a person thinks, feels, and behaves, or schizoaffective disorder, which is a condition that includes symptoms of both schizophrenia and mood disorders, or bipolar disorder, which is a condition that causes extreme mood swings including emotional highs and lows
You have a diagnosis of borderline personality disorder, which is a mental health condition that affects how you feel about yourself and others and causes problems with managing emotions and behavior
You have a diagnosis of antisocial personality disorder, which is a mental health condition where a person shows a pattern of disregarding or violating the rights of others
You have a diagnosis of intellectual disability, which means having significant limitations in intellectual functioning and adaptive behavior
You have a diagnosis of autism spectrum disorder, which is a developmental condition that affects communication and behavior
You have active psychotic symptoms, which means experiencing things like hearing voices or seeing things that are not there, or having strong beliefs that are not based in reality
You have a known allergy or sensitivity to esketamine, ketamine, or midazolam, which are the medications being studied, or to any of their ingredients
You have a medical condition where an increase in blood pressure would present a serious risk to your health
You have brain bleeding, abnormal connections between blood vessels in the brain, a previous stroke, which occurs when blood supply to part of the brain is blocked, or a condition causing increased pressure inside the skull
You are pregnant or breastfeeding
You have used certain medications that cannot be safely combined with the study treatment within specific time periods before starting the study

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name	City	Country
Azienda Ospedaliero Universitaria Di Sassari	Sassari	Italy
Spitalul Clinic De Psihiatrie Prof.Dr.Alexandru Obregia	Bucharest	Romania
Spitalul Clinic de Psihiatrie “Dr. Gheorghe Preda” Sibiu	Sibiu	Romania
Azienda Ospedaliera Universitaria Federico II Di Napoli	Naples	Italy
Hospital Universitario De Navarra	Pamplona	Spain

Other Sites

Site Name	City	Country
IRCCS Istituto Giannina Gaslini	Genoa	Italy
Azienda Ospedaliera Universitaria Meyer IRCCS	Florence	Italy
Hospital Sant Joan De Deu Barcelona	Esplugues De Llobregat	Spain
Hospital General Universitario Gregorio Maranon	Madrid	Spain
Althaia Xarxa Assistencial Universitaria De Manresa Fundacio Privada	Manresa	Spain
Hospital Universitario Central De Asturias	Oviedo	Spain
University Of Debrecen	Debrecen	Hungary
Vadaskert Alapitvany A Gyermekek Lelki Egeszsegeert	Budapest	Hungary
Spitalul Clinic De Urgenta Pentru Copii Louis Turcanu Timisoara	Timisoara	Romania
Spitalul Clinic De Urgenta Pentru Copii Cluj-Napoca	Cluj Napoca	Romania
Hospital Clinic De Barcelona	Barcelona	Spain
Central Hospital Of Bolzano	Bolzano	Italy
ARNAS G. Brotzu	Cagliari	Italy
University Of Szeged	Szeged	Hungary
Awrrspo Sacokiefp Ptnkhfpavit Dh Cgosehh	Catania	Italy
Pkzd Twbcv Hmvbhlze Usivzfoppntj	Sabadell	Spain
Gfffeamxdetndhvpz Vilxfrmdp Poll Avbxmm Egbfvkti Omyssv Kaqpgi	Gyor	Hungary
Akpjujw Oxmvypvwmfv Ukqorijmqlskc Oprttjdj Rclhbde	Foggia	Italy
Hvlhdytj Uadjehhkqehbz Mgezhtl Dy Vbomgltjhr	Santander	Spain
Fwhgaxgsc Pqwo Ly Iljtpnekxeqhv Bdpncgcrj Dkq Htuqnpwf Usyduodzoifxf La Pzx	Madrid	Spain
Hjyrxngy Vjwv dhdevoxq	Barcelona	Spain

Trial status

Country	Status	Recruitment Start
Hungary	Recruiting	15.03.2026
Italy	Recruiting	15.03.2026
Romania	Not yet recruiting	15.03.2026
Spain	Recruiting	15.03.2026

Trial locations

Investigated drugs:

Esketamine is a nasal spray medication used to treat symptoms of major depressive disorder. In this study, it is being tested to see if it can quickly reduce depression symptoms in teenagers who are having thoughts of suicide or suicidal behavior. The medication is given in addition to standard care treatment.

Midazolam is a medication that is normally used to help people relax or feel calm. In this study, it is being given by mouth and used as a comparison treatment to help researchers understand how well esketamine works. It is called a psychoactive placebo because it has some effects that patients can feel, which helps keep the study fair.

Major Depressive Disorder – Major Depressive Disorder is a mental health condition characterized by persistent feelings of sadness, emptiness, and loss of interest in activities that were once enjoyable. People with this disorder experience changes in sleep patterns, appetite, and energy levels. They may have difficulty concentrating, making decisions, and completing daily tasks. The condition affects how a person thinks, feels, and behaves in everyday life. Symptoms must be present for at least two weeks and represent a change from previous functioning. The disorder can occur in episodes that may recur throughout a person’s life.

Trial ID:

2024-518615-19-00

Protocol code:

54135419SUI3003

Trial Phase:

Therapeutic confirmatory (Phase III)

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A study testing intranasal esketamine compared to midazolam for rapidly reducing symptoms of major depressive disorder in adolescents with suicidal thoughts or behavior

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?