Ketamine and Postoperative Depressive Symptom-PASSION

Study Overview
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Brief Summary
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Perioperative depression symptom (PDS) is one of the common mental comorbidity, and influences the clinical outcomes and prognosis. However, there is no rapid acting treatment to deal with it during the limited hospital stay. This study aims to determine whether ketamine could improve the depressive symptom of peirioperative patients. It will also examine the safety for administrating ketamine as an antidepressant intraoperatively. Meanwhile, it will show if ketamine could improve anxiety, postoperative pain or delirium. This trial also will bring great concerns on patients with perioperative mental health and explore the measures to improve their psycho-related prognosis.

Official Title
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Effect of Low-dose Ketamine on Postoperative Depressive Symptom in Patients Undergoing Intracranial Tumor Resection (PASSION)

Conditions
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Ketamine; Depressive Symptom; Neurosurgery; Perioperative Period

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Brain tumor located supratentorial area and need to receive elective craniotomy; Moderate to severe depressive symptom measured by the qualified psychiatric doctors. Ages between 18 and 65 years old. American Society of Anesthesiologists physical status I-III Exclusion Criteria: History of epilepsy; Major depression disorder patients undergoing antidepressive therapy within 2 weeks; 3 Psychiatric illness; 4 Drug abuse; 5 History of allergy to the research drug; 6 Tumor located in the Wernick area, Broca area or the frontal pole; 7 Hyperthyroidism; 8 Patients can not cooperate with investigators on psychiatric assessments; 9 Pregnant or breast-feeding woman; 10 refuse to sign inform consent.

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: ketamine group<br> | Drug: Ketamine<br>* Ketamine will be administrated intravenously at dural opening, with the total dose of 0.5 mg/kg and continual infusion for 40 minutes.<br>* Other names: Ketamine hydrochloride;|
| Placebo Comparator: normal saline group<br> | Drug: Normal saline<br>* Normal saline will be administrated intravenously at dural opening, with the total dose of 0.5 ml/kg and continual infusion for 40 minutes.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate | ≥50% reduction in MADRS scores from baseline value.The MADRS is a 10-item tool, with scores ranging from 0 to 60, and determining the severity of depression. | Postoperative 3 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The remission rate | The remission rate is defined as the absolute value of MADRS no more than 10. | Postoperative 3 days and discharge. | 
| Anxiety symptom | The anxious symptom is defined as HADS score no less than 11. | Postoperative 3 days. | 
| Postoperative delirium | Postoperative delirium will be assessed by the Confusion Assessment Method for the Intensive Care Unit Scale (CAM-ICU) at 2 hours and 1 day after surgery. | Postoperative 1 day. | 
| Severe pain | The incidence of severe pain within first postoperative three days, which is defined as mean and peak numerical rating scale (NRS) are higher than 5. | Postoperative 3 days. | 
| Postoperative 30-day quality of life reported by KPS | The quality of life will be evaluated by Karnofsky performance status (KPS) at postoperative 30 days. | Postoperative 30 days | 
| Psychiatric outcomes and complications | Postoperative complications include psychiatric symptoms evaluated by Brief Psychiatric Rating Scale (BPRS), manic symptoms assessed through the 11-item Young Mania Rating Scale (YMRS), and dissociative symptoms measured by the Clinician Administered Dissociative States Scale (CADSS). Moreover, postoperative complications also include aphasia, epilepsy, hemorrhage. | Postoperative 3 days and discharge. |