Esketamine Treatment for Depressive Episodes With Suicidal Ideation in Mood Disorders

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.

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.

Eligibility Criteria:
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.