Esketamine Treatment for Depressive Episodes With Suicidal Ideation in Mood Disorders

Phase 4

Not yet recruiting

• Conditions: Mood Disorders; Suicidal Ideation; Depressive Episode
• Interventions: Drug: Subanesthetic dose intravenous esketamine; Device: Modified electroconvulsive therapy

• Registration Number: NCT06355180
• Lead Sponsor: Capital Medical University

Brief Summary

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.

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 Timeline

• Study First Submitted: 2024-03-27
• Status Verified: 2024-04
• Study Start: 2024-04
• Study First Submitted QC: 2024-04-03
• Last Update Submitted: 2024-04-03
• Study First Posted: 2024-04-09
• Last Update Posted: 2024-04-09
• Primary Completion: 2026-12
• Study Completion: 2026-12

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 340

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Subanesthetic dose intravenous Esketamine	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.
Modified electroconvulsive therapy	Modified electroconvulsive therapy	MECT will be given in a standard manner 3 times a week for 2 weeks.

Primary Outcome Measures

Name	Time	Method
Suicide remission rate based on the Scale for Suicidal Ideation (SSI)	12 weeks	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.

Secondary Outcome Measures

Name	Time	Method
Columbia Suicide Severity Rating Scale (CSSR-S)	12 weeks	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.
Sheehan Disability Scale(SDS)	12 weeks	Self-reported questionnaire. Scale Range: 0-30. Higher scores indicate greater functional impairment.
Digital Span Test(DST)	12 weeks	Self-reported questionnaire. Scale Range: 0-22. Higher scores indicate better working memory and attention.
Perceived Deficit Questionnaire for Depression 5-item(PDQ-D-5)	12 weeks	Self-reported questionnaire. Scale Range: 0-20. Higher scores indicate a greater perceived cognitive deficit.
Quick Inventory of Depressive Symptoms Self Report (QIDS-SR)	12 weeks	Self-reported questionnaire. Scale Range: 0-27. Higher scores indicate more severe depressive symptoms.
Montgomery Asberg Depression Rating Scale (MADRS)	12 weeks	Clinician rated scales. Scale Range: 0-60. Higher scores indicate more severe depression.
Digit Symbol Substitution Test(DSST)	12 weeks	Self-reported questionnaire. Scale Range: 0-90. Higher scores indicate better cognitive processing speed and attention.
Clinical Global Impressions(CGI)	12 weeks	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."
Adverse event	12 weeks	Evaluate adverse reactions
Short Form 12 Health Survey(SF-12)	12 weeks	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.
Young Mania Rating Scale (YMRS)	12 weeks	Clinician rated scales. Scale Range: 0-60. Higher scores indicate more severe manic symptoms.
Clinician Administered Dissociative States Scale(CADSS)	12 weeks	Clinician rated scales. Scale Range: 0-92. Higher scores indicate more severe dissociative symptoms.