Esketamine Treatment for Depressive Episodes With Suicidal Ideation in Mood Disorders

The Efficacy and Safety of Esketamine for Rapid Treatment of Depressive Episodes With Suicidal Ideation in Mood Disorders: A Multicenter, Randomized Controlled Study

This study is a multicenter, non-inferiority, randomized, parallel-group, open-label clinical trial aimed at evaluating the effectiveness of esketamine versus modified electroconvulsive therapy (MECT) in treating suicidal ideation during depressive episodes of mood disorders. Additionally, it seeks to explore the potential mechanisms of esketamine's anti-suicidal effects.

Study Overview

• Status: Not yet recruiting
• Conditions: Mood Disorders; Suicidal Ideation; Depressive Episode
• Intervention / Treatment: Drug: Subanesthetic dose intravenous esketamine; Device: Modified electroconvulsive therapy

Detailed Description

Suicide is a significant clinical and public health issue, with about 50% of individuals who die by suicide being diagnosed with a mood disorder within the year prior to their death, and 27% of suicide deaths attributable to depression. This indicates a higher risk of suicidal ideation (SI) during depressive episodes compared to the general population, highlighting the urgent need for effective interventions to rapidly alleviate SI and reduce suicide mortality rates. Currently, the rapid intervention measures for suicidal symptoms primarily include electroconvulsive therapy (ECT)/modified electroconvulsive therapy (MECT). However, due to the complexity of the procedures and certain risks involved, some institutions cannot perform this treatment. Additionally, cognitive impairments and other adverse reactions following the treatment may lead to patient noncompliance, thus there is a clinical urgency to find a simple, effective, and safe intervention to rapidly treat SI. Esketamine has been proven in past studies to have a rapid effect in relieving SI, but there is a lack of large-scale clinical studies to clarify the efficacy of esketamine due to short clinical observation periods. Therefore, there is an urgent need to conduct large-scale, multicenter RCT studies to verify whether esketamine is as applicable as ECT/MECT for rapid improvement of suicidal ideation in individuals with depressive episodes of mood disorders. This holds significant clinical importance and will provide key evidence-based foundations for future guidelines.

This study, through a randomized controlled trial, treats patients with suicidal ideation (SI) during depressive episodes of mood disorders using esketamine or modified electroconvulsive therapy (MECT). It compares the rapid anti-suicidal effects and adverse reactions of the two treatment modalities, providing evidence-based data for the clinical application of esketamine.

• Study Type: Interventional
• Enrollment (Estimated): 340
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Gang Wang, MD; Phone Number: +86 10 58340233; Email: gangwangdoc@ccmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Outpatients or inpatients, aged 18 to 65 years (inclusive of 18 and 65), regardless of gender;
• Current episode meets the diagnostic criteria for Major Depressive Disorder or Bipolar I or II disorder depressive episodes according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5);
• Total score of ≥6 on the Scale for Suicide Ideation (SSI);
• Educational level above primary school, able to understand the content of the scales;
• The patient has signed an informed consent form.

Exclusion Criteria:

• Current or past diagnosis of neurodevelopmental disorders, neurocognitive disorders, schizophrenia spectrum and other psychotic disorders, substance-related and addictive disorders according to DSM-5 standards;
• Presents with significant psychotic symptoms (delusions, hallucinations);
• Currently has severe or unstable conditions related to the central nervous system, cardiovascular system, respiratory system, liver, kidney, endocrine system, hematological system, or other systems deemed unsuitable for participation in this study by the researchers;
• Researchers deem there to be a potential risk of substance misuse and addiction;
• Currently taking medications containing thioridazine;
• Presence of risk factors for general anesthesia;
• History of seizure episodes (childhood simple febrile seizures without residual sequelae need not be excluded);
• History of severe drug or food allergies, or known allergy to components of the study medication;
• Previous ineffectiveness of esketamine/ketamine/ECT/MECT or occurrence of severe adverse reactions;
• Participation in other clinical trials within the last 3 months;
• Female subjects who are pregnant, nursing, planning a pregnancy during the study or within 12 weeks after the last dose of the study medication, or male subjects planning to father a child;
• Subjects deemed unsuitable for participation in this study by the researchers.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Subanesthetic dose intravenous Esketamine; The dosage for intravenous infusion of esketamine is 0.2mg/kg, infused over at least 40 minutes, with treatments administered three times a week for two consecutive weeks, totaling six sessions.	Drug: Subanesthetic dose intravenous esketamine; The study, lasting 12 weeks, includes a 2-week intervention and 10-week follow-up. Esketamine (0.2mg/kg) is given intravenously three times a week for two weeks. Dosage and sessions may adjust for safety and efficacy, with study treatments limited during follow-up. Efficacy is evaluated via scales measuring suicidal ideation, depression, cognition, and social function. Adverse effects are tracked through vital signs, exams, events, and tests. Biological samples (blood, urine, feces) are collected from some participants at baseline, post-first, and sixth treatments for omics analyses. Brain imaging from some participants at baseline and post-sixth treatment aims to obtain high-resolution T1, T2 FLAIR, resting fMRI, and DTI images. Electrophysiological data, including resting state EEG signals and task paradigms, are collected from some participants at baseline, after the first, and sixth treatments.; Other Names: esketamine
Active Comparator: Modified electroconvulsive therapy; MECT will be given in a standard manner 3 times a week for 2 weeks.	Device: Modified electroconvulsive therapy; The study, lasting 12 weeks, includes a 2-week intervention and 10-week follow-up. Modified electroconvulsive therapy (MECT) is given three times a week for two weeks. Sessions may adjust for safety and efficacy, with study treatments limited during follow-up. Efficacy is evaluated via scales measuring suicidal ideation, depression, cognition, and social function. Adverse effects are tracked through vital signs, exams, events, and tests. Biological samples (blood, urine, feces) are collected from some participants at baseline, post-first, and sixth treatments for omics analyses. Brain imaging from some participants at baseline and post-sixth treatment aims to obtain high-resolution T1, T2 FLAIR, resting fMRI, and DTI images. Electrophysiological data, including resting state EEG signals and task paradigms, are collected from some participants at baseline, after the first, and sixth treatments.; Other Names: MECT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Suicide remission rate based on the Scale for Suicidal Ideation (SSI)	The Scale for Suicidal Ideation (SSI) is a psychological assessment tool that measures suicidal ideation in individuals. It consists of a series of questions that evaluate the extent and intensity of thoughts about self-harm and suicide. In many studies, an SSI score greater than or equal to 6 is typically considered to indicate significant suicide risk, while an SSI score of less than 4 is considered to indicate no clinically significant suicidal ideation.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quick Inventory of Depressive Symptoms Self Report (QIDS-SR)	Self-reported questionnaire. Scale Range: 0-27. Higher scores indicate more severe depressive symptoms.	12 weeks
Columbia Suicide Severity Rating Scale (CSSR-S)	Clinician rated scales for suicidality. The C-SSRS is a tool for assessing suicidal ideation and behavior. It includes questions that evaluate the severity of suicidal thoughts, plans, and attempts. The scale assesses ideation intensity, ideation severity, and behavior. Scoring varies based on responses, with higher scores indicating greater severity of suicidality. The total score range depends on specific responses to ideation and behavior items, aiming to identify the risk level of suicide accurately.	12 weeks
Montgomery Asberg Depression Rating Scale (MADRS)	Clinician rated scales. Scale Range: 0-60. Higher scores indicate more severe depression.	12 weeks
Clinical Global Impressions(CGI)	Clinician rated scales. Severity of Illness (CGI-S) is rated 1-7; Global Improvement (CGI-I) is also rated 1-7. For CGI-S, higher scores indicate more severe illness. For CGI-I, a score of 1 indicates "Very much improved" whereas a score of 7 indicates "Very much worse."	12 weeks
Short Form 12 Health Survey(SF-12)	Self-reported questionnaire. The Short Form 12 Health Survey (SF-12) is a condensed version of the SF-36 health survey, designed to measure health-related quality of life. It includes 12 questions covering physical and mental health domains. These questions generate two main scores: the Physical Component Summary (PCS) and the Mental Component Summary (MCS), which are standardized to a mean of 50 and a standard deviation of 10 in the general population.	12 weeks
Sheehan Disability Scale(SDS)	Self-reported questionnaire. Scale Range: 0-30. Higher scores indicate greater functional impairment.	12 weeks
Digital Span Test(DST)	Self-reported questionnaire. Scale Range: 0-22. Higher scores indicate better working memory and attention.	12 weeks
Digit Symbol Substitution Test(DSST)	Self-reported questionnaire. Scale Range: 0-90. Higher scores indicate better cognitive processing speed and attention.	12 weeks
Perceived Deficit Questionnaire for Depression 5-item(PDQ-D-5)	Self-reported questionnaire. Scale Range: 0-20. Higher scores indicate a greater perceived cognitive deficit.	12 weeks
Young Mania Rating Scale (YMRS)	Clinician rated scales. Scale Range: 0-60. Higher scores indicate more severe manic symptoms.	12 weeks
Clinician Administered Dissociative States Scale(CADSS)	Clinician rated scales. Scale Range: 0-92. Higher scores indicate more severe dissociative symptoms.	12 weeks
Adverse event	Evaluate adverse reactions	12 weeks

Collaborators and Investigators

• Sponsor: Capital Medical University
• Collaborators: The Second People's Hospital of Dali Bai Autonomous Prefecture; Wuhu Fourth People's Hospital; Inner Mongolia Autonomous Region Mental Health Center; Beijing Chaoyang District Third Hospital; Beijing Daxing District Xinkang Hospital; Capital's Funds for Health Improvement and Research
• Investigators: Principal Investigator: Gang Wang, MD, Beijing Anding Hospital, Capital Medical University

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: March 27, 2024
• First Submitted That Met QC Criteria: April 3, 2024
• First Posted (Actual): April 9, 2024

Study Record Updates

• Last Update Posted (Actual): April 9, 2024
• Last Update Submitted That Met QC Criteria: April 3, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Mood Disorders; Suicidal Ideation; Esketamine; Multicenter; Randomized Controlled Study; Depressive Episode; MECT
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Self-Injurious Behavior; Suicide; Depression; Depressive Disorder; Suicidal Ideation; Mood Disorders; Psychotropic Drugs; Antidepressive Agents; Esketamine
• Other Study ID Numbers: Shoudufazhan2024-1-2122

Plan for Individual participant data (IPD)

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

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