Esketamine vs ECT for Acute Suicidality

Not Applicable

Completed

• Conditions: Mood Disorders; Suicidal Ideation; Depressive Episode
• Interventions: Drug: Esketamine; Device: Electroconvulsive therapy

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

Brief Summary

This study is a multicenter, randomized, non-inferiority, parallel-group clinical trial designed to evaluate the efficacy and safety of esketamine compared with electroconvulsive therapy (ECT) in the treatment of suicidal ideation during depressive episodes in patients with mood disorders. Furthermore, it aims to investigate the potential mechanisms underlying the anti-suicidal effects of esketamine.

Detailed Description

Suicide is a major global public health concern, yet current treatments for suicidal ideation (SI) remain limited in efficacy. This study evaluates whether a two-week course of six administrations of adjunctive intravenous esketamine is non-inferior to electroconvulsive therapy (ECT) in reducing SI among adults experiencing depressive episodes of mood disorders. This multicenter, randomized, non-inferiority, parallel-group trial will enroll 340 adults diagnosed with mood disorders with clinically significant SI during a depressive episode. Participants will be randomized in a 1:1 ratio to receive either six administrations of adjunctive intravenous esketamine or ECT over a two-week intervention period, followed by a 10-week observational follow-up phase (the total study duration will be 12 weeks). The primary outcome is the rate of remission of SI, defined as a Scale for Suicidal Ideation (SSI) score of less than 4, at the end of the two-week intervention. Secondary outcomes include comparative evaluations of treatment efficacy on depressive symptoms, cognitive function, quality of life, and social functioning, as well as safety. Exploratory outcomes include the identification of biomarker and neurobiological mechanisms of treatment response through analyses of biological specimens (blood, urine, and feces), multimodal magnetic resonance imaging (MRI), and electroencephalographic (EEG) measures.

Study Timeline

• Study First Submitted: 2024-03-27
• Study First Submitted QC: 2024-04-03
• Study First Posted: 2024-04-09
• Study Start: 2024-04-16
• Primary Completion: 2025-06-13
• Status Verified: 2025-08
• Study Completion: 2025-08-28
• Last Update Submitted: 2025-08-28
• Last Update Posted: 2025-09-05

Recruitment & Eligibility

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

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intravenous esketamine	Esketamine	The experimental group will receive six administrations of adjunctive intravenous esketamine over a two-week intervention period, followed by a 10-week observational follow-up phase.
Electroconvulsive therapy	Electroconvulsive therapy	The control group will receive six administrations of adjunctive ECT over a two-week intervention period, followed by a 10-week observational follow-up phase.

Primary Outcome Measures

Name	Time	Method
Remission rate of suicidal ideation	Baseline, after the sixth treatments (week 2)	The Scale for Suicide Ideation (SSI) is a 19-item clinician-administered scale assessing the severity of suicidal ideation. Each item is scored from 0 to 2, yielding a total score ranging from 0 to 38, with higher scores indicating greater suicidal intent.; The primary outcome is the rate of remission of suicidal ideation following the 2-week intervention (after 6 treatments), with the remission of suicidal ideation defined as having an SSI score of less than 4 (which indicates the absence of clinically significant suicidal ideation).

Secondary Outcome Measures

Name	Time	Method
Rates of sustained remission and recurrence of suicide ideation	Baseline, after the first treatment, after the third treatment, after the sixth treatment (week 2), at week 4, week 8, and week 12	Sustained remission: Defined as having SSI scores of less than 4 in two consecutive assessments.; Recurrence: Defined as the emergence of suicidal behavior, an SSI score of 6 or more, or other composite indicators, following two consecutive assessments with SSI scores of less than 4.; Compare the sustained remission rates and recurrence rates of suicidal ideation between the two groups after the first treatment, after the third treatment, after the sixth treatment (week 2), at week 4, week 8, and week 12.
Changes in SSI Scores	Baseline, after the first treatment, after the third treatment, after the sixth treatment (week 2), at week 4, week 8, and week 12	Compare the changes in SSI scores at each visit compared to baseline.
Changes in Columbia-Suicide Severity Rating Scale (C-SSRS) Scores	Baseline, after the third treatment, after the sixth treatment (week 2), at week 4, week 8, and week 12	Compare the changes in C-SSRS scores at each visit compared to baseline.
Response rate of depressive symptoms	Baseline, after the third treatment, after the sixth treatment (week 2), at week 4, week 8, and week 12	Response of depressive symptoms is defined as a 50% or more reduction from baseline in the Montgomery-Åsberg Depression Rating Scale(MADRS) score. Compare the response rates of depressive symptoms between the two groups at each visit.
Remission rate of depressive symptoms	Baseline, after the third treatment, after the sixth treatment (week 2), at week 4, week 8, and week 12	Remission of depressive symptoms is defined as a MADRS score of less than 12. Compare the remission rates of depressive symptoms between the two groups at each visit.
Changes in Montgomery Asberg Depression Rating Scale (MADRS) Scores	Baseline, after the first treatment, after the third treatment, after the sixth treatment (week 2), at week 4, week 8, and week 12	Compare the changes in MADRS scores at each visit compared to baseline.
Changes in Quick Inventory of Depressive Symptoms Self Report (QIDS-SR-16) Scores	Baseline, after the first treatment, after the third treatment, after the sixth treatment (week 2), at week 4, week 8, and week 12	Compare the changes in QIDS-SR-16 scores at each visit compared to baseline.
Changes in Clinical Global Impressions (CGI) Scores	Baseline, after the first treatment, after the third treatment, after the sixth treatment (week 2), at week 4, week 8, and week 12	Compare the changes in CGI scores at each visit compared to baseline.
Changes in Short Form 12 Health Survey (SF-12) Scores	Baseline, after the sixth treatment (week 2), at week 4, week 8, and week 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.; Compare the changes in SF-12 scores at each visit compared to baseline.
Changes in Sheehan Disability Scale (SDS) Scores	Baseline, after the sixth treatment (week 2), at week 4, week 8, and week 12	Self-reported questionnaire. Scale Range: 0-30. Higher scores indicate greater functional impairment.; Compare the changes in SDS scores at each visit compared to baseline.
Changes in Digital Span Test (DST) Scores	Baseline, after the third treatment, after the sixth treatment (week 2), at week 4, week 8, and week 12	Self-reported questionnaire. Scale Range: 0-22. Higher scores indicate better working memory and attention.; Compare the changes in DST scores at each visit compared to baseline.
Changes in Digit Symbol Substitution Test (DSST) Scores	Baseline, after the third treatment, after the sixth treatment (week 2), at week 4, week 8, and week 12	Self-reported questionnaire. Scale Range: 0-90. Higher scores indicate better cognitive processing speed and attention.; Compare the changes in DSST scores at each visit compared to baseline.
Changes in Perceived Deficit Questionnaire for Depression 5-item (PDQ-D-5) Scores	Baseline, after the third treatment, after the sixth treatment (week 2), at week 4, week 8, and week 12	Self-reported questionnaire. Scale Range: 0-20. Higher scores indicate a greater perceived cognitive deficit.; Compare the changes in PDQ-D-5 scores at each visit compared to baseline.
Changes in Young Mania Rating Scale (YMRS) Scores	Baseline, after the third treatment, after the sixth treatment (week 2), at week 4, week 8, and week 12	Clinician rated scales. Scale Range: 0-60. Higher scores indicate more severe manic symptoms.; Compare the changes in YMRS scores at each visit compared to baseline.
Changes in Clinician Administered Dissociative States Scale (CADSS) Scores	Baseline, after the 1st, 2nd, 3rd, 4th, 5th, and 6th esketamine treatments	Clinician rated scales. Scale Range: 0-92. Higher scores indicate more severe dissociative symptoms.; Compare the changes in CADSS scores at each esketamine treatment compared to baseline.
Adverse event	Baseline, after the first treatment, after the third treatment, after the sixth treatment (week 2), at week 4, week 8, and week 12	Compare the incidence of adverse events and serious adverse events between the two groups.
Changes in neuroimaging metrics	Baseline, after the sixth treatments (week 2)	Explore changes in neuroimaging metrics after the sixth treatment compared to baseline.
Changes in Electroencephalogram (EEG) metrics	Baseline, after the first treatment, after the sixth treatments (week 2)	Explore changes in EEG metrics after the first and sixth treatment compared to baseline.
Changes in biological indicators	Baseline, after the first treatment, after the sixth treatments (week 2)	Biological samples (blood, urine, and feces) will be collected from a subset of participants at baseline, after the first treatment, and after the sixth treatment for multi-omics profiling, including genomic, transcriptomic, epigenomic, metabolomic, microbiome, immunological, proteomic, and pharmacogenomic analyses.
Remission rate of suicidal ideation	Baseline, after the first treatment, after the third treatment, at week 4, week 8, and week 12	Compare the suicide ideation remission rates between the two groups after the first treatment, after the third treatment, at week 4, week 8, and week 12. Suicide remission rate is defined as an SSI score of less than 4.

Trial Locations

Locations (6)

Wuhu Fourth People's Hospital; 🇨🇳 Wuhu, Anhui, China

Beijing Anding Hospital; 🇨🇳 Beijing, Beijing Municipality, China

Beijing Chaoyang District Third Hospital; 🇨🇳 Beijing, China

Beijing Daxing District Xinkang Hospital; 🇨🇳 Beijing, China

The Second People's Hospital of Dali Bai Autonomous Prefecture; 🇨🇳 Dali, China

Inner Mongolia Autonomous Region Mental Health Center; 🇨🇳 Hohhot, China