Effect of Subanesthetic Dose of Ketamine Combined With Propofol on Cognitive Function in Depressive Patients Undergoing Electroconvulsive Therapy

Study Overview
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Brief Summary
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Electroconvulsive therapy (ECT) is an effective treatment for depression compared with the current antidepressant agents，but the most important side effect is cognitive dysfunction. The purpose of this study is to determine whether subanesthetic dose of ketamine combined with propofol is superior to propofol anesthesia alone in improving cognitive function in depressive patients undergoing ECT.

Detailed Description
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Depression is one of the most debilitating and widespread illnesses affecting up to 20% of individuals in their lifetime. However, the current antidepressant agents take weeks to work, and fail to help at least 40% of depressed patients. Electroconvulsive therapy (ECT) is a remarkably effective treatment for depression, but its use is limited by cognitive dysfunction. As a result, it is becoming a clinical problem which need to be settled urgently. Previous clinical study showed that subanesthetic dose of ketamine could play a role in antidepressant effects with safety and minimal positive psychotic symptoms.The investigators also found that subanesthetic dose of ketamine combined with other anesthetics could improve cognitive function in depressive rats receiving electroconvulsive shock (a model for analogy with ECT). Few clinical researches concerned the effects of subanesthetic dose of ketamine combined with propofol anesthesia on cognitive function in patients after ECT, therefore the investigators conduct this randomized controlled double-blind trial. In this study, cognitive function will be rated by Mini-Mental State examination score.

Official Title
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Effect of Subanesthetic Dose of Ketamine Combined With Propofol on Cognitive Function in Depressive Patients Undergoing Electroconvulsive Therapy ---a Randomized Control Double-Blind Clinical Trial

Conditions
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Depressive Symptoms, Impaired Cognition, Electroconvulsive Therapy

Intervention / Treatment
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* Drug: ketamine and propofol
* Drug: propofol and normal saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: diagnosed with moderate or severe depression according to Diagnostic and Statistical Manual of Mental Disorders aged from 18 to 65 years old Exclusion Criteria: cerebrovascular malformation, arterial aneurysm, hypertension, or glaucoma; classification of American Society of Anesthesiologists physical status score IV or V; complications such as respiratory disease, cardiovascular disease, intracranial hypertension, cerebral vascular disorder; presence of a foreign body such as pacemaker, intracranial electrode, and clips; history of seizures; history of drug abuse; concomitant presence of a mental disorder; pregnancy; history of serious adverse effects related to anesthetics; refusal to consent for the study, or refusal to undergo one single ECT during the first week of therapy. hyperthyreosis

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PK group (ketamine and propofol)<br>propofol 1.5 mg/kg and ketamine 0.3 mg/kg will be administered to participants separately by intravenous infusion.When patients become unconscious, succinylcholine 1 mg/kg (a muscle relaxant) will be administered intravenously. After 1 minute of succinylcholine infused, ECT will be performed with bitemporal electrode placement using a stimulus dose of 1.0-millisecond pulse width, 60-Hz frequency, 6.0-second stimulus duration, and 0.8-A maximal stimulus intensity. | Drug: ketamine and propofol<br>* propofol 1.5 mg/kg and ketamine 0.3 mg/kg will be administered to participants separately by intravenous infusion.<br>|
| Active Comparator: P group (propofol group)<br>propofol 1.5 mg/kg and normal saline [weight(kg)×0.3÷10]ml will be administered to participants separately by intravenous infusion.When patients become unconscious, succinylcholine 1 mg/kg (a muscle relaxant) will be administered intravenously. After 1 minute of succinylcholine infused, ECT will be performed with bitemporal electrode placement using a stimulus dose of 1.0-millisecond pulse width, 60-Hz frequency, 6.0-second stimulus duration, and 0.8-A maximal stimulus intensity. | Drug: propofol and normal saline<br>* propofol 1.5 mg/kg and normal saline [weight(kg)×0.3÷10]ml will be administered to participants separately by intravenous infusion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mini-Mental State examination score | Mini-Mental State examination score will be measured at 24 hours after the sixth ECT. | at 24 hours after the sixth ECT | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mini-Mental State examination score | Mini-Mental State examination score will be measured at 24 hours before the first ECT and 24 hours after each ECT, except the sixth ECT. | at 24 hours before the first ECT and 24 hours after each ECT, except the sixth ECT. | 
| Effects on Antidepression (Hamilton Depression Rating Scale(HDRS) | Effect on antidepression will be measured by 24-item Hamilton Depression Rating Scale(HDRS) | at 24 hours before the first ECT and 24 hours after each ECT | 
| Seizure Duration and Seizure Energy Index | Seizure duration and Seizure energy index will be recorded by the ECT apparatus. | at 30 seconds after each ECT | 
| Brief Psychiatric Rating Scale（BPRS） | Brief Psychiatric Rating Scale is related to psychotomimetic side-effect. | 60 minutes prior to the first ECT and at 40, 80, 110, and 230 minutes after each ECT | 
| Adverse Effects include nausea, vomit, headache, tachycardia and increased blood pressure. | Adverse effects include nausea, vomit, headache, tachycardia and increased blood pressure. | at 40 minutes after each ECT | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ketamine, Electroconvulsive Therapy, Cognitive Function