Esketamine and Perioperative Depressive Symptoms

Study Overview
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Brief Summary
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Perioperative depressive symptoms (PDS) are common in population undergoing surgery, and this would be sharpened especially for complicated, high-risk major surgery. However, None of treatments could resolve this clinical problem during limited perioperative period. The remarkable effects of ketamine on treatment resistant depression have been verified by several clinical trials and the enantiomer S-ketamine (esketamine) showed similar antidepressant efficacy with better safety in recent studies. The efficacy and safety of esketamine administrated intra-operatively for PDS will be verified in this study. Other secondary outcomes such as anxiety, postoperative pain and psychiatric symptoms will also be investigated.

Official Title
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Effect of Esketamine on Perioperative Depressive Symptoms in Patients Undergoing Major Surgery

Conditions
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Depressive Symptoms, Esketamine, Perioperative Complication, Major Surgery

Intervention / Treatment
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* Drug: Esketamine
* Drug: Normal saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient undergoing elective major surgery Ages between 18 and 65 years old Moderate to severe depressive symptoms ( the Patient Health Questionnaire-9 scores equal to or more than 10 and Montgomery-Åsberg Depression Rating Scale scores equal to or more than 22 ) Signed informed consent Exclusion Criteria: Patients combined with aphasia or other conditions leads that patients inability to cooperate with the metal assessments; Tumor related injury of the 9th, 10th, 11th, 12th cranial nerve or patients need keeping intubation after surgery; Medical history of psychotic or bipolar disorder; Laboratory evidence of hormone levels disorder due to primary diseases; Body Mass Index more than 30 kg/㎡; Child-Pugh grade B or C; Major depressive disorder with antidepressant therapy in the past 2 weeks before screening; History of adverse events to ketamine or esketamine; Patients with repeated suicide attempts (QIDS-SR 12-item more than or equal to 3); History of drug abused; Pregnant or breastfeeding woman.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Esketamine<br> | Drug: Esketamine<br>* Esketamine will be administrated intravenously when suturing incision, with total dose of 0.2mg/kg and continuous infusion for 40 minutes.<br>|
| Placebo Comparator: Placebo<br> | Drug: Normal saline<br>* Equivalent amount of normal saline will be administrated intravenously suturing incision.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Depressive symptoms remission | Remission is defined as MADRS total score no more than 10 | Postoperative 3-day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MADRS scores | The differences in MADRS scores | Postoperative 3-day | 
| Depressive symptoms response | The rates of patients achieving a response | Postoperative 3-day | 
| Severe pain | The rate of severe pain after surgery | postoperative 3-day | 
| Side-effects and Adverse events | All drug-related adverse events during surgery or before discharge | During surgery or up to 7 days after surgery |