Subanesthetic Esketamine in Modified ECT for Severe Depression in Adolescents: Clinical and Mechanistic Study

Clinical and Mechanistic Study of Subanesthetic-dose Esketamine in Modified Electroconvulsive Therapy for Adolescents With Severe Depression

The study design was a randomized, double blind, parallel controlled trial.The goal of this clinical trial is to learn if esketamine-assisted modified electroconvulsive therapy (ESK-MECT) works to treat severe depression in adolescents. It will also learn about the safety of ESK-MECT.

The sample size was calculated based on the response rate of patients with depression undergoing electroconvulsive therapy(ECT).According to the results of the pilot study,the efficacy rate of subjects receiving adjunctive esketamine was approximately 78%,while the efficacy rate of those receiving only propofol was 63%.The expected superiority difference in remission rates between the two groups was 15%(one-sided)for the power calculation.Assuming a significance level of α=0.05 and a test power of β=0.2,with a 1:1 ratio of sample sizes between the two groups,the total sample size was calculated to be 198 using the PASS software(PASS 2023).Considering a dropout rate of 10%,a total of 220 subjects were required,with 110 subjects in each group.

1. experimental group The patients were given intravenous injection of 0.25 mg / kg esketamine, 1.5 mg / kg propofol and 1 mg / kg succinylcholine in turn. After anesthesia, the patients were given electroconvulsive therapy.
2. In the control group The patients were given normal saline consistent with esketamine injection volume, 1.5mg/kg of propofol and 1mg / kg of succinylcholine. After anesthesia, the patients were given electroconvulsive therapy.

Efficacy evaluation 1. Main efficacy indicators Response rate of depressive symptoms after MECT treatment Response is defined as two consecutive HAMD-24 scores ≤ 50% before treatment after receiving MECT treatment. The response rate is calculated as the number of patients who achieved as response divided by the total number of patients receiving MECT.In this study, the 24-item version of HAMD was utilized.

Participants will:

Be randomly assigned to the esketamine group or the control group, and receive standard MECT treatment.

Have seizure parameters, seizure duration, vital signs, and complications recorded.

Complete psychiatric scale assessments, including HAMD-24, BSS, PANSS, WMS-RC and MoCA.

Be assessed at the following time points: HAMD-24 and BSS after each treatment; PANSS after each treatment course;WMS-RC and MoCA before MECT and after one treatment course.

All subjects did not discontinue antidepressants before modified electroconvulsive therapy(MECT),and they were fasting for 8 hours and no fluids for 2 hours.Three minutes before MECT,continuous qCON monitoring(Apollo-9000A,Chongqing Xideer Medical Equipment Co.,Ltd.,China)was initiated,while monitoring blood pressure,heart rate,and peripheral capillary oxygen saturation.Preoxygenation was administered for 3 minutes.The qCON monitor uses three electrodes on the forehead to collect raw electroencephalogram(EEG)signals.The qCON monitoring includes the qCON index,qNOX index,burst suppression(BS),and signal quality index(SQI).

Study Overview

• Status: Recruiting
• Conditions: Adolescent; Depression; Esketamine; ECT
• Intervention / Treatment: Drug: Esketamine injection group (0.25 mg/kg); Other: Saline injection group (Consistent with esketamine injection volume)

• Study Type: Interventional
• Enrollment (Estimated): 220
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Xiaoge Han, Master; Phone Number: 023-89011061; Email: 3164233689@qq.com

Study Locations

• China
  • Chongqing, China
    • Recruiting
    • The First Affiliated Hospital of Chongqing Medical University
    • Contact: Su Min; Phone Number: 0086-023-89011876; Email: ms89011068@163.com
  • Chongqing, China
    • Not yet recruiting
    • The First Affiliated Hospital of Chongqing Medical University
    • Contact: Su Min, MD; Phone Number: +86-23-89011068; Email: ms89011068@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Inpatients diagnosed with Major Depressive Disorder according to the International Classification of Diseases,11th Revision(ICD-11),and scheduled for Modified Electroconvulsive Therapy(MECT);
• Aged 13 to 17 years,regardless of gender;
• Educational attainment of primary school or higher;
• Normal hearing and vision,including color perception;
• Voluntary participation in the study with signed informed consent;
• American Society of Anesthesiologists(ASA)physical status classification I-II.

Exclusion Criteria:

• Severe cardiovascular disease,significant arrhythmias,or other cardiac conditions;
• Inability to complete the assessment scales;
• History of substance abuse;
• Received electroconvulsive therapy(ECT)within 6 months prior to the study;
• Severe cerebrovascular disease,severe hypertension,intracranial hypertension,or presence of intracranial electrodes;
• Severe allergy or contraindication to propofol or succinylcholine;
• Comorbid with other psychiatric disorders.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Esketamine injection group (0.25mg/kg); The main anesthesiologist standing on the right side of the patient gave successive injections of esketamine (0.25 mg/kg), and 1 minute later, injected propofol (1.5mg/kg) for 30 s.After the loss of consciousness, all patients were administered 1 mg/kg of succinylcholine chloride and manually ventilated with a face mask until they regained full consciousness.	Drug: Esketamine injection group (0.25 mg/kg); The main anesthesiologist standing on the right side of the patient injects esketamine (0.25 mg/kg) sequentially, and then propofol (1.5 mg/kg) is injected 1 minute later for 30 s.After the loss of consciousness,all patients were administered 1 mg/kg of succinylcholine chloride and manually ventilated with a face mask until they regained full consciousness.
Sham Comparator: Saline injection group(Consistent with esketamine injection volume); The main anesthesiologist standing on the right side of the patient gave successive injections of saline (Consistent with esketamine injection volume), and 1 minute later, injected 1.5mg/kg of propofol in 30s.After the loss of consciousness,all patients were administered 1 mg/kg of succinylcholine chloride and manually ventilated with a face mask until they regained full consciousness.	Other: Saline injection group (Consistent with esketamine injection volume); The main anesthesiologist standing on the right side of the patient injects saline (Consistent with esketamine injection volume) sequentially, and then propofol (1.5 mg/kg) is injected 1 minute later, the injection time is 30s.After the loss of consciousness,all patients were administered 1 mg/kg of succinylcholine chloride and manually ventilated with a face mask until they regained full consciousness.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment response rate	Response is defined as two consecutive HAMD-24 scores ≤ 50% before treatment after receiving MECT treatment. The response rate is calculated as the number of patients who achieved as response divided by the total number of patients receiving MECT.In this study, the 24-item version of HAMD was utilized.	immediately after the end of each MECT procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Remission rate of depressive symptoms after MECT treatment	Remission is defined as a sustained HAMD scores below 10 points for two consecutive times. In this study, the 24-item version of HAMD was utilized.The remission rate is calculated as the number of patients who achieved remission divided by the total number of patients receiving MECT.	immediately after the end of each MECT procedure
Changes in cognitive function	Cognitive function changes were evaluated using the Montreal Cognitive Assessment (MoCA) scales before MECT and at the end of MECT course.	Immediately after the end of MECT course
The remission rate of suicidal ideation	Suicidal ideation were evaluated using the the Beck Scale for Suicidal Ideation.The remission rate of SI is calculated as the number of patients with SI remission after MECT divided by the total number of patients with SI.	through treatment completion, an average of 18 days
Changes in psychiatric symptoms	Changes in psychotic symptoms that accompany depression during treatment were assessed using the Positive and Negative Syndrome Scale(PANSS) after each MECT session.	Immediately after the end of MECT course
Wechsler Memory Scale-Chinese-Revision	The Wechsler Memory Scale-Chinese-Revision(WMS-RC)was used to assess patients'learning and memory functions before and at the end of Modified Electroconvulsive Therapy(MECT).	Immediately after the end of MECT course

Collaborators and Investigators

• Sponsor: Min Su
• Investigators: Principal Investigator: Su Min, First Affiliated Hospital of Chongqing Medical University

Study record dates

Study Major Dates

• Study Start (Actual): November 25, 2025
• Primary Completion (Estimated): November 20, 2026
• Study Completion (Estimated): December 20, 2026

Study Registration Dates

• First Submitted: September 24, 2025
• First Submitted That Met QC Criteria: November 21, 2025
• First Posted (Estimated): November 25, 2025

Study Record Updates

• Last Update Posted (Actual): January 7, 2026
• Last Update Submitted That Met QC Criteria: January 6, 2026
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Behavior; Depression
• Other Study ID Numbers: Esketamine2025-629-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

Individual participant data(IPD)is detailed information collected from each study participant.There are several reasons why IPD might not be shared:

• Privacy and Confidentiality Concerns
• Personal Identifiable Information:IPD contains sensitive information like medical history and genetic data.Sharing it without safeguards can violate privacy and lead to issues like discrimination.
• Regulatory Requirements:Laws like GDPR require strict handling of personal data.Sharing IPD without proper anonymization and consent can result in legal problems.
• Intellectual Property and Commercial Interests
• Research Investment:Generating IPD requires significant resources.Researchers may want to control the data to fully exploit it for further research and publications.
• Patent and Licensing Issues:Premature sharing of IPD can affect patentability and licensing agreements.
• Data Integrity and Misuse
• Quality Control:Shared IPD can be misinterpreted by others who lack context,leading

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes