Clinical trial NCT02752724: Ketamine Anesthesia for Improvement of Depression in ECT
Official title: Ketamine vs. Methohexital Anesthesia for Improvement of Major Depressive Disorder in Electroconvulsive Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Major Depressive Disorder
Keywords: major depressive disorder
electroconvulsive therapy
metabolomics
treatment resistant depression
anesthesiology
ketamine
prospective randomized clinical trial
Lead sponsor: VA Puget Sound Health Care System
Sponsor class: FED
First posted: 2016-04-27
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this prospective randomized clinical trial is to determine if patients receiving ketamine as a part of general anesthesia during electroconvulsive therapy (ECT) rather than standard of care will have improvement in symptoms of depression after a course of ECT treatments. The investigators hypothesize that utilization of ketamine for induction of general anesthesia during ECT treatments will improve symptoms of depression better than standard care.

This study is ONLY open to patients eligible to receive healthcare services through the Department of Veterans Affairs at the VA Puget Sound, which means service in the active military, naval or air service or separation under any condition other than dishonorable. Qualifications for VA health care benefits can be found at va.gov.

Detailed description: The purpose of this prospective randomized clinical trial is to determine if patients receiving ketamine as a part of general anesthesia during electroconvulsive therapy (ECT) rather than standard of care will have improvement in symptoms of depression after a course of ECT treatments. The investigators hypothesize that utilization of ketamine for induction of general anesthesia during ECT treatments will improve symptoms of depression better than standard care.

For induction of general anesthesia for ECT, patients will receive either 1mg/kg of methohexital (standard arm) or 1.0 mg/kg IV ketamine (experimental arm) intravenously (IV) for the duration of their ECT index course over 2-3 weeks. The primary outcome in this trial is change in symptoms of depression assessed by standard questionnaires: Patient Health Questionnaire 9 (PHQ9) and Hamilton Depression Rating Scale (HAM-D) score changes from baseline and final ECT administration. Secondary outcomes are changes in cognitive status as assessed by the Montreal Cognitive Assessment (MoCA) scale, quality of seizures and after seizure, changes in serum metabolites (including kynurenine, D/L-serine and other glutamate intermediates) after treatment and need for further ECT courses (relapse) within 1 year after initial course.

Approximately 50 veterans with the diagnosis of major depressive disorder older than 18 years of age undergoing ECT will be randomized and blinded to the intervention. Operative ECT clinicians will not be blinded; clinicians evaluating patients will be blinded. Exclusion criteria for this study include uncontrolled hypertension, blood pressure \> 180/90 mmHg at the pre-anesthesia clinic visit, renal failure, neurologic disorders (e.g. epilepsy, space occupying lesions, traumatic brain injuries in the past 6 months), myocardial infarction in the past 6 months, known allergies or adverse reactions to ketamine, American Society of Anesthesiology Physical Class greater than 3, concomitant psychosis, schizophrenia or current abuse of alcohol or illicit substances and pregnancy.

The long term objective of this trial is to systematically characterize ketamine's effect on depression outcomes utilizing validated scoring tools, its safety profile throughout an ECT index course, ketamine's effect on seizure quality and changes in novel translational endpoints to better understand mechanisms of action of ketamine and its potential role in treatment of psychiatric disorders.

Eligibility criteria: Inclusion Criteria:

* outpatients or inpatients at the Puget Sound VA with diagnosis of major depressive disorder or bipolar 1 or 2 over the age of 18 undergoing index course ECT

Exclusion Criteria:

* uncontrolled hypertension (blood pressure \> 180/90 mmHg at the pre-anesthesia clinic visit)
* renal failure
* neurologic disorders (e.g. epilepsy, space occupying lesions, traumatic brain injuries in the past 6 months)
* myocardial infarction in the past 6 months
* known allergies or adverse reactions to ketamine
* American Society of Anesthesiology Physical Class greater than 3
* concomitant psychosis
* schizophrenia or current abuse of alcohol or illicit substances and pregnancy (any trimester)

Primary outcomes:
measure: Change in Depression Patient Health Questionnaire 9 (PHQ9) Scoring
timeFrame: Change from Baseline Score 24 hours prior to starting ECT to PHQ9 score 72 hours following last ECT session
Secondary outcomes:
measure: Soluble Amino Acid Metabolomic Biomarkers
timeFrame: 30 minutes prior to first ECT session and within 30 minutes after final ECT session
measure: ECT Seizure Duration
timeFrame: Length of each intraoperative ECT seizure during an index course typically 6-12 individual seizures measure from start of seizure in operating room to end of seizure in operating room.
measure: Change in Montreal Cognitive Assessment (MoCA) Scoring
timeFrame: Change from Baseline Score 24 hours prior to starting ECT to MoCA score 72 hours following last ECT session
Other outcomes:
Locations:
city: Seattle
country: United States
facility: VA Puget Sound Health Care System
state: Washington
Study officials:
affiliation: Puget Sound VA Medical Center, Dept of Psychiatry
name: Anna Borisovskaya, MD
role: STUDY_DIRECTOR
affiliation: Puget Sound VA Medical Center, Dept of Anesthesiology
name: Irene Rozet, MD
role: PRINCIPAL_INVESTIGATOR
References: