Esketamine Treatment for Depressive Episodes With Suicidal Ideation in Mood Disorders

Suicidal Ideation Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06355180
• Other study ID #: Shoudufazhan2024-1-2122
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: April 2024
• Est. completion date: December 2026

Study information

• Verified date: April 2024
• Source: Capital Medical University
• Contact: Gang Wang, MD
• Phone: +86 10 58340233
• Email: gangwangdoc[@]ccmu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 340
• Est. completion date: December 2026
• Est. primary completion date: December 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Episode
• Mood Disorders
• Suicidal Ideation

Intervention

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.

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.

Locations

Country	Name	City	State
n/a

Sponsors (7)

Lead Sponsor	Collaborator
Capital Medical University	Beijing Chaoyang District Third Hospital, Beijing Daxing District Xinkang Hospital, Capital's Funds for Health Improvement and Research, Inner Mongolia Autonomous Region Mental Health Center, The Second People's Hospital of Dali Bai Autonomous Prefecture, Wuhu Fourth People's Hospital

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	Montgomery Asberg Depression Rating Scale (MADRS)	Clinician rated scales. Scale Range: 0-60. Higher scores indicate more severe depression.	12 weeks
Secondary	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
Secondary	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
Secondary	Sheehan Disability Scale(SDS)	Self-reported questionnaire. Scale Range: 0-30. Higher scores indicate greater functional impairment.	12 weeks
Secondary	Digital Span Test(DST)	Self-reported questionnaire. Scale Range: 0-22. Higher scores indicate better working memory and attention.	12 weeks
Secondary	Digit Symbol Substitution Test(DSST)	Self-reported questionnaire. Scale Range: 0-90. Higher scores indicate better cognitive processing speed and attention.	12 weeks
Secondary	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
Secondary	Young Mania Rating Scale (YMRS)	Clinician rated scales. Scale Range: 0-60. Higher scores indicate more severe manic symptoms.	12 weeks
Secondary	Clinician Administered Dissociative States Scale(CADSS)	Clinician rated scales. Scale Range: 0-92. Higher scores indicate more severe dissociative symptoms.	12 weeks
Secondary	Adverse event	Evaluate adverse reactions	12 weeks