Comparison of Ketamine Combine Propofol vs Propofol Anesthesia in Schizophrenia Electroconvulsive Therapy

• ClinicalTrials.gov Identifier: NCT03829124
• Recruitment Status: Unknown
• First Posted: February 4, 2019
• Last Update Posted: May 29, 2019
• Sponsor: Chang Gung Memorial Hospital
• Information provided by (Responsible Party): Chang Gung Memorial Hospital

Study Description

Brief Summary:

Electroconvulsive therapy (ECT) serves as an effective adjuvant modality for major depressive disorder, schizophrenia, or bipolar affective disorder refractory to or contraindicated to psychopharmacological treatment. Anesthetics have been introduced into ECT sessions to alleviate ECT-inducing discomfort sensation, tachycardia, arrhythmia, hypertension, and anxiety.

Propofol is able to rapidly cross the blood-brain barrier (BBB), which leads to rapid onset of sedation and hypnosis. Meanwhile, propofol has hemodynamic depressant effect and attenuates hypertensive surge during ECT. Characteristics mentioned above make propofol one of widely used anesthetics for anesthetized ECT. However, propofol is also well known for anticonvulsant property. Thus, dosage of electrical stimulus may be increased to achieve ideal seizure quality in this setting, which also leads to higher risk of subsequent cognitive impairment or other complications.

Ketamine has also been widely used in the induction of anesthesia for the treatment of major depressive disease in recent years. It has been found to increase the permeability and therapeutic effect of antidepressants. Compared to traditional Barbiturate drugs or propofol, do not increase the threshold of electricity required by electroporation, which can reduce the time required for symptom relief of those drugs, It is a viable alternative induction drug.

There have been confirmed that ketamine combine propofol can be used for electroconvulsive treatment in patients with major depression and bipolar disorder, and even better Electroconvulsive quality can be obtained. Reduce the number of Electroconvulsive treatments and reduce the duration of treatment. However, the current literature has not yet verified the clinical benefit of ketamine combine propofol as an anesthetic induction drug in patients with schizophrenia who are receiving electroconvulsive therapy, and it is worthy of further study.

In the investigator's clinical practice, the purpose of this experiment is to explore: compared with propofol base anesthesia alone, and the combine use of ketamine and propofol may reduce the threshold of seizure, improve the quality of Electroconvulsive therapy and shorten the course of treatment. The combine use and titrate the drugs helps to reduce the side effects of both ketamine and propofol (such as cardiovascular side effects and positive symptoms) , achieve better Electroconvulsive therapy and effects.

Condition or disease	Intervention/treatment	Phase
Schizophrenia	Drug: Propofol; Drug: Ketamine	Phase 4

Detailed Description:

Electroconvulsive therapy (ECT) serves as an effective adjuvant or alternative modality for major depressive disorder, schizophrenia, or bipolar affective disorder refractory to or contraindicated to psychopharmacological treatment. Anesthetics have been introduced into ECT sessions to alleviate ECT-inducing discomfort sensation, tachycardia, arrhythmia, hypertension, and anxiety.

Propofol is highly lipid soluble and able to rapidly cross the blood-brain barrier (BBB), which leads to rapid onset of sedation and hypnosis. Meanwhile, propofol has hemodynamic depressant effect and attenuates hypertensive surge during ECT. Characteristics mentioned above make propofol one of widely used anesthetics for anesthetized ECT. However, propofol is also well known for anticonvulsant property, which may inevitably interfere with seizure propagation by electroconvulsive stimulus and diminish consequent efficacy. Thus, dosage of electrical stimulus may be increased to achieve ideal seizure quality in this setting, which also leads to higher risk of subsequent cognitive impairment or other complications.

Ketamine has also been widely used in the induction of anesthesia for the treatment of major depressive disease in recent years. It has been found to increase the permeability and therapeutic effect of antidepressants. Compared to traditional Barbiturate drugs or propofol, do not increase the threshold of electricity required by electroporation, which can reduce the time required for symptom relief of those drugs, It is a viable alternative induction drug. However, ketamine causes short-term dissociative symptoms, which may temporarily aggravate the positive symptoms of patients with schizophrenia after Electroconvulsive therapy, but the time of aggravation of positive symptoms generally does not exceed 30 minutes.

There have been many studies in the clinic, and it has been confirmed that ketamine combine propofol can be used for electroconvulsive treatment in patients with major depression and bipolar disorder, and even better Electroconvulsive quality can be obtained. Reduce the number of Electroconvulsive treatments and reduce the duration of treatment. However, the current literature has not yet verified the clinical benefit of ketamine combine propofol as an anesthetic induction drug in patients with schizophrenia who are receiving electroconvulsive therapy, and it is worthy of further study.

In the investigator's clinical practice, the purpose of this experiment is to explore: compared with propofol base anesthesia alone, and the combine use of ketamine and propofol may reduce the threshold of seizure, improve the quality of Electroconvulsive therapy and shorten the course of treatment. The combine use and titrate the drugs helps to reduce the side effects of both ketamine and propofol (such as cardiovascular side effects and positive symptoms) , achieve better Electroconvulsive therapy and effects.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 1 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Comparison of Propofol Combine Ketamine Anesthesia and Propofol Anesthesia in Schizophrenia Electroconvulsive Therapy: A Randomized Controlled Trial
• Estimated Study Start Date: May 24, 2019
• Estimated Primary Completion Date: January 19, 2021
• Estimated Study Completion Date: April 20, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: ketamine + propofol group; use ketamine + propofol for ECT induction	Drug: Propofol; Propofol 10mg/ml IV push slowly 0.5-2mg/kg; Drug: Ketamine; Ketamine 50mg/ml IV push slowly 0.5- 1mg/kg
Active Comparator: propofol group; use propofol only for ECT induction	Drug: Propofol; Propofol 10mg/ml IV push slowly 0.5-2mg/kg

Outcome Measures

Primary Outcome Measures :

1. The therapeutic effect after completing electroconvulsive treatment course [ Time Frame: At baseline, after 3rd course treatment(average 1-2 week), after 6th course treatment(average 2-4 week), after completion of treatment course( average 4-6 weeks, up to 8 weeks) ]

   Record the change of disease illness, use The Clinical Global Impression - Improvement scale (CGI-I) and Clinical Global Impression - Severity scale (CGI-S) CGI-S(Severity) range 1-7 1: normal 7:extremely severe CGI-I(Improvement) range 1-7

   1:very much improved 7: vert much worse

Secondary Outcome Measures :

1. Change from baseline in Brief Psychiatric Rating Scale (BPRS) [ Time Frame: At baseline, after 3rd course treatment(average 1-2 week), after 6th course treatment(average 2-4 week), after completion of treatment course( average 4-6 weeks, up to 8 weeks) ]

   Brief Psychiatric Rating Scale range:18-126

   Contains the following items:

   1. Somatic concern
   2. Anxiety
   3. Depression
   4. Suicidality
   5. Guilt
   6. Hostility
   7. Elated Mood
   8. Grandiosity
   9. Suspiciousness
   10. Hallucinations
   11. Unusual thought content
   12. Bizarre behaviour
   13. Self-neglect
   14. Disorientation
   15. Conceptual disorganisation
   16. Blunted affect
   17. Emotional withdrawal
   18. Motor retardation
   19. Tension
   20. Uncooperativeness
   21. Excitement
   22. Distractibility
   23. Motor hyperactivity
   24. Mannerisms and posturing Different item scores will have different results and outcomes

   ""Different values represent is not meaning a better or worse outcome, it must compare to the patient's status before""

Eligibility Criteria

• Ages Eligible for Study: 20 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• The clinical diagnosis is consistent with the schizophrenia, and the diagnostic requirements are in accordance with the Structural Diagnostic Interview Scale (SCID for Diagnostic and Statistical Manual of Mental Disorders (DSM-5)) and are recognized by psychiatrists as needing electroconvulsive therapy
• Vision and hearing that can be operated normally or corrected
• Subject consent form signed by the patient or agent

Exclusion Criteria:

• Past or recent diagnosis of neurocognitive impairment
• Contraindications for electroacupuncture treatment within one month, such as: myocardial infarction, cerebrovascular disease, Increase Intracranial pressure, cerebral hemangioma, untreated fracture, cervical spine injury, pheochromocytoma, heart failure, severe heart valve disease, deep Venous embolism, etc
• Untreated substances abuse disorder(eg illegal drugs, alcohol)
• Unspecified mental disorder
• PattientUnable to cooperate

Contacts and Locations

No Contacts or Locations Provided

More Information

• Responsible Party: Chang Gung Memorial Hospital
• ClinicalTrials.gov Identifier: NCT03829124
• Other Study ID Numbers: 201800056A3
• First Posted: February 4, 2019
• Last Update Posted: May 29, 2019
• Last Verified: January 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by Chang Gung Memorial Hospital:

Electroconvulsive therapy; ketamine

Additional relevant MeSH terms:

Schizophrenia; Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Ketamine; Propofol; Hypnotics and Sedatives; Central Nervous System Depressants; Physiological Effects of Drugs; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Anesthetics, Dissociative; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action