Trial Outcomes & Findings for Cognitive Recovery After Electroconvulsive Therapy and General Anesthesia (NCT NCT02761330)

NCT ID: NCT02761330

Last Updated: 2021-06-28

Results Overview

A cognitive test battery was administered at 0, 30, 60, 90, and 120 minutes following return of consciousness after general anesthesia on each treatment day (1-6). The data from each treatment day (1-6) were averaged for analyses. Cognition Test Battery: * Psychomotor Vigilance Task (PVT) * Digital Symbol Substitution Task (DSST) * Motor Praxis Task (MP) * Visual Object Learning Task (VOLT) * Abstract Matching (AM) Rate of Recovery for this measure is defined as the time (in inverse hours) for participants to return to their baseline performance for each task.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

17 participants

Primary outcome timeframe

0, 30, 60, 90, 120 minutes following return of consciousness, assessed on treatment days 1-6.

Results posted on

2021-06-28

Participant Flow

17 patients were enrolled for study participation between May 2016 and July 2018 at Barnes Jewish Hospital in St. Louis, MO.

14 of 17 participants were randomized. Of those not randomized, 1 participant's treatment course was canceled by clinical staff, 1 participant withdrew consent prior to any study participation, and 1 participant was deemed ineligible.

Participant milestones

Participant milestones
Measure
Ketamine +ECT, Etomidate + ECT, Ketamine Sham
Participants first received ECT treatment under Ketamine general anesthesia, then ECT treatment under Etomidate anesthesia, and finally participants received Ketamine general anesthesia with sham ECT. Ketamine+ECT: General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose. Ketamine Sham: General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, no ECT charge will be administered. Etomidate + ECT: General anesthesia for ECT will be induced with etomidate, approximately 0.2 mg/kg (0.1-0.6 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose.
Ketamine +ECT, Ketamine Sham, Etomidate + ECT
Participants first received ECT treatment under Ketamine general anesthesia, then Ketamine general anesthesia with sham ECT and finally participants received ECT treatment under Etomidate anesthesia. Ketamine+ECT: General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose. Ketamine Sham: General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, no ECT charge will be administered. Etomidate + ECT: General anesthesia for ECT will be induced with etomidate, approximately 0.2 mg/kg (0.1-0.6 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose.
Etomidate +ECT, Ketamine + ECT, Ketamine Sham
Participants first received ECT treatment under Etomidate general anesthesia, then ECT treatment under Ketamine general anesthesia and finally participants received Ketamine general anesthesia with sham ECT. Ketamine+ECT: General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose. Ketamine Sham: General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, no ECT charge will be administered. Etomidate + ECT: General anesthesia for ECT will be induced with etomidate, approximately 0.2 mg/kg (0.1-0.6 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose.
Etomidate +ECT, Ketamine Sham, Ketamine +ECT
Participants first received ECT treatment under Etomidate general anesthesia, then Ketamine general anesthesia with sham ECT and finally participants received ECT treatment under Ketamine anesthesia. Ketamine+ECT: General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose. Ketamine Sham: General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, no ECT charge will be administered. Etomidate + ECT: General anesthesia for ECT will be induced with etomidate, approximately 0.2 mg/kg (0.1-0.6 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose.
Ketamine Sham, Etomidate +ECT, Ketamine +ECT
Participants first received Ketamine general anesthesia with sham ECT, then ECT treatment under Etomidate general anesthesia and finally participants received ECT treatment under Ketamine anesthesia. Ketamine+ECT: General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose. Ketamine Sham: General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, no ECT charge will be administered. Etomidate + ECT: General anesthesia for ECT will be induced with etomidate, approximately 0.2 mg/kg (0.1-0.6 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose.
Ketamine Sham, Ketamine +ECT, Etomidate +ECT
Participants first received Ketamine general anesthesia with sham ECT, then ECT treatment under Ketamine general anesthesia and finally participants received ECT treatment under Etomidate anesthesia. Ketamine+ECT: General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose. Ketamine Sham: General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, no ECT charge will be administered. Etomidate + ECT: General anesthesia for ECT will be induced with etomidate, approximately 0.2 mg/kg (0.1-0.6 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose.
Treatment Week 1
STARTED
2
3
2
3
1
3
Treatment Week 1
COMPLETED
2
3
2
2
1
2
Treatment Week 1
NOT COMPLETED
0
0
0
1
0
1
Treatment Week 2
STARTED
2
3
2
1
1
1
Treatment Week 2
COMPLETED
2
3
2
1
1
1
Treatment Week 2
NOT COMPLETED
0
0
0
0
0
0

Reasons for withdrawal

Reasons for withdrawal
Measure
Ketamine +ECT, Etomidate + ECT, Ketamine Sham
Participants first received ECT treatment under Ketamine general anesthesia, then ECT treatment under Etomidate anesthesia, and finally participants received Ketamine general anesthesia with sham ECT. Ketamine+ECT: General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose. Ketamine Sham: General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, no ECT charge will be administered. Etomidate + ECT: General anesthesia for ECT will be induced with etomidate, approximately 0.2 mg/kg (0.1-0.6 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose.
Ketamine +ECT, Ketamine Sham, Etomidate + ECT
Participants first received ECT treatment under Ketamine general anesthesia, then Ketamine general anesthesia with sham ECT and finally participants received ECT treatment under Etomidate anesthesia. Ketamine+ECT: General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose. Ketamine Sham: General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, no ECT charge will be administered. Etomidate + ECT: General anesthesia for ECT will be induced with etomidate, approximately 0.2 mg/kg (0.1-0.6 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose.
Etomidate +ECT, Ketamine + ECT, Ketamine Sham
Participants first received ECT treatment under Etomidate general anesthesia, then ECT treatment under Ketamine general anesthesia and finally participants received Ketamine general anesthesia with sham ECT. Ketamine+ECT: General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose. Ketamine Sham: General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, no ECT charge will be administered. Etomidate + ECT: General anesthesia for ECT will be induced with etomidate, approximately 0.2 mg/kg (0.1-0.6 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose.
Etomidate +ECT, Ketamine Sham, Ketamine +ECT
Participants first received ECT treatment under Etomidate general anesthesia, then Ketamine general anesthesia with sham ECT and finally participants received ECT treatment under Ketamine anesthesia. Ketamine+ECT: General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose. Ketamine Sham: General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, no ECT charge will be administered. Etomidate + ECT: General anesthesia for ECT will be induced with etomidate, approximately 0.2 mg/kg (0.1-0.6 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose.
Ketamine Sham, Etomidate +ECT, Ketamine +ECT
Participants first received Ketamine general anesthesia with sham ECT, then ECT treatment under Etomidate general anesthesia and finally participants received ECT treatment under Ketamine anesthesia. Ketamine+ECT: General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose. Ketamine Sham: General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, no ECT charge will be administered. Etomidate + ECT: General anesthesia for ECT will be induced with etomidate, approximately 0.2 mg/kg (0.1-0.6 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose.
Ketamine Sham, Ketamine +ECT, Etomidate +ECT
Participants first received Ketamine general anesthesia with sham ECT, then ECT treatment under Ketamine general anesthesia and finally participants received ECT treatment under Etomidate anesthesia. Ketamine+ECT: General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose. Ketamine Sham: General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, no ECT charge will be administered. Etomidate + ECT: General anesthesia for ECT will be induced with etomidate, approximately 0.2 mg/kg (0.1-0.6 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose.
Treatment Week 1
Withdrawal by Subject
0
0
0
1
0
1

Baseline Characteristics

Cognitive Recovery After Electroconvulsive Therapy and General Anesthesia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
AllParticipants
n=15 Participants
All participants enrolled in study procedures.
Age, Continuous
37 years
STANDARD_DEVIATION 13.56 • n=5 Participants
Sex: Female, Male
Female
8 Participants
n=5 Participants
Sex: Female, Male
Male
7 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
0 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
15 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=5 Participants
Race (NIH/OMB)
Asian
0 Participants
n=5 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=5 Participants
Race (NIH/OMB)
Black or African American
0 Participants
n=5 Participants
Race (NIH/OMB)
White
15 Participants
n=5 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=5 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants

PRIMARY outcome

Timeframe: 0, 30, 60, 90, 120 minutes following return of consciousness, assessed on treatment days 1-6.

Population: Participants with cogntive task data complete for the majority of timepoints following return of responsiveness for more than one treatment day were included in analyses. Additional participants were excluded for individual cognitive task measures for being extreme outliers.

A cognitive test battery was administered at 0, 30, 60, 90, and 120 minutes following return of consciousness after general anesthesia on each treatment day (1-6). The data from each treatment day (1-6) were averaged for analyses. Cognition Test Battery: * Psychomotor Vigilance Task (PVT) * Digital Symbol Substitution Task (DSST) * Motor Praxis Task (MP) * Visual Object Learning Task (VOLT) * Abstract Matching (AM) Rate of Recovery for this measure is defined as the time (in inverse hours) for participants to return to their baseline performance for each task.

Outcome measures

Outcome measures
Measure
Etomidate + ECT
n=9 Participants
General anesthesia for ECT will be induced with etomidate, approximately 0.2 mg/kg (0.1-0.6 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose. Electroconvulsive Therapy: Dose of the ECT charge will be determined during titration session prior to randomization.
Ketamine + ECT
n=9 Participants
General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose. Ketamine: Ketamine will be used to induce general anesthesia with or without subsequent ECT. Within a single patient, the dose will remain consistent throughout the study and is estimated to be 2 mg/kg. Electroconvulsive Therapy: Dose of the ECT charge will be determined during titration session prior to randomization.
Ketamine Alone
n=11 Participants
General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, no ECT charge will be administered. Ketamine: Ketamine will be used to induce general anesthesia with or without subsequent ECT. Within a single patient, the dose will remain consistent throughout the study and is estimated to be 2 mg/kg.
Change in Cognitive Function During Recovery: Rate of Recovery
MP Reaction Time
3.9 inverse hours
Interval 3.5 to 4.4
2.5 inverse hours
Interval 1.4 to 3.1
2.6 inverse hours
Interval 2.6 to 2.6
Change in Cognitive Function During Recovery: Rate of Recovery
PVT Reaction Time
3.5 inverse hours
Interval 2.2 to 4.0
6.3 inverse hours
Interval 5.4 to 7.1
24.7 inverse hours
Interval 8.1 to 27.5
Change in Cognitive Function During Recovery: Rate of Recovery
DSST Reaction Time
9.7 inverse hours
Interval 6.8 to 10.0
3.0 inverse hours
Interval 2.2 to 3.1
2.9 inverse hours
Interval 2.4 to 3.7
Change in Cognitive Function During Recovery: Rate of Recovery
VOLT Reaction Time
9.2 inverse hours
Interval 8.9 to 9.3
11.6 inverse hours
Interval 5.2 to 12.8
3.1 inverse hours
Interval 2.8 to 3.3
Change in Cognitive Function During Recovery: Rate of Recovery
AM Reaction Time
4.8 inverse hours
Interval 4.8 to 4.8
1.6 inverse hours
Interval 1.6 to 1.6
2.3 inverse hours
Interval 2.2 to 2.4

PRIMARY outcome

Timeframe: 0, 30, 60, 90, 120 minutes following return of consciousness, assessed on treatment days 1-6.

Population: Participants with cogntive task data complete for the majority of timepoints following return of responsiveness for more than one treatment day were included in analyses. Additional participants were excluded for individual cognitive task measures for being extreme outliers.

A cognitive test battery was administered at 0, 30, 60, 90, and 120 minutes following return of consciousness after general anesthesia on each treatment day (1-6). The data from each treatment day (1-6) were averaged for analyses. Cognition Test Battery: * Psychomotor Vigilance Task (PVT) * Digital Symbol Substitution Task (DSST) * Motor Praxis Task (MP) * Visual Object Learning Task (VOLT) * Abstract Matching (AM) Initial Decrement for this measure is defined as the difference between response times (in seconds) at baseline and t=0 for each task.

Outcome measures

Outcome measures
Measure
Etomidate + ECT
n=9 Participants
General anesthesia for ECT will be induced with etomidate, approximately 0.2 mg/kg (0.1-0.6 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose. Electroconvulsive Therapy: Dose of the ECT charge will be determined during titration session prior to randomization.
Ketamine + ECT
n=9 Participants
General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose. Ketamine: Ketamine will be used to induce general anesthesia with or without subsequent ECT. Within a single patient, the dose will remain consistent throughout the study and is estimated to be 2 mg/kg. Electroconvulsive Therapy: Dose of the ECT charge will be determined during titration session prior to randomization.
Ketamine Alone
n=11 Participants
General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, no ECT charge will be administered. Ketamine: Ketamine will be used to induce general anesthesia with or without subsequent ECT. Within a single patient, the dose will remain consistent throughout the study and is estimated to be 2 mg/kg.
Change in Cognitive Function During Recovery: Initial Decrement
PVT Initial Decrement
0.4 seconds
Interval 0.4 to 0.4
3.5 seconds
Interval 2.4 to 5.7
6.8 seconds
Interval 1.3 to 8.2
Change in Cognitive Function During Recovery: Initial Decrement
DSST Initial Decrement
2.4 seconds
Interval 1.3 to 3.3
5.1 seconds
Interval 2.7 to 9.3
3.1 seconds
Interval 2.3 to 12.6
Change in Cognitive Function During Recovery: Initial Decrement
MP Initial Decrement
1.9 seconds
Interval 0.6 to 2.8
3.0 seconds
Interval 1.7 to 4.1
2.4 seconds
Interval 1.2 to 4.4
Change in Cognitive Function During Recovery: Initial Decrement
VOLT Initial Decrement
4.9 seconds
Interval 1.4 to 6.6
20.9 seconds
Interval 20.4 to 21.2
6.5 seconds
Interval 0.3 to 11.4
Change in Cognitive Function During Recovery: Initial Decrement
AM Initial Decrement
3.2 seconds
Interval 1.5 to 4.9
2.0 seconds
Interval 1.1 to 4.6
6.7 seconds
Interval 3.2 to 7.8

SECONDARY outcome

Timeframe: Immediately following return of consciousness (t=0) during treatment days 1-6.

Population: All participants (12) who completed both baseline and t=0 delirium assessments on at least one treatment day.

Assessed using 3D Confusion Assessment Method (CAM). The groups/arms for this outcome are separated by anesthetic regimen; however, due to the crossover design of this study all participants are included in analyses for each group.

Outcome measures

Outcome measures
Measure
Etomidate + ECT
n=42 Delirium Assessments
General anesthesia for ECT will be induced with etomidate, approximately 0.2 mg/kg (0.1-0.6 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose. Electroconvulsive Therapy: Dose of the ECT charge will be determined during titration session prior to randomization.
Ketamine + ECT
n=46 Delirium Assessments
General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose. Ketamine: Ketamine will be used to induce general anesthesia with or without subsequent ECT. Within a single patient, the dose will remain consistent throughout the study and is estimated to be 2 mg/kg. Electroconvulsive Therapy: Dose of the ECT charge will be determined during titration session prior to randomization.
Ketamine Alone
n=44 Delirium Assessments
General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, no ECT charge will be administered. Ketamine: Ketamine will be used to induce general anesthesia with or without subsequent ECT. Within a single patient, the dose will remain consistent throughout the study and is estimated to be 2 mg/kg.
Delirium Incidence and Severity
Negative Delirium at t=0
20 Delirium Assessments
23 Delirium Assessments
19 Delirium Assessments
Delirium Incidence and Severity
Positive Delirium at Baseline
1 Delirium Assessments
0 Delirium Assessments
0 Delirium Assessments
Delirium Incidence and Severity
Negative Delirium at Baseline
20 Delirium Assessments
23 Delirium Assessments
23 Delirium Assessments
Delirium Incidence and Severity
Positive Delirium at t=0
1 Delirium Assessments
0 Delirium Assessments
2 Delirium Assessments

SECONDARY outcome

Timeframe: assessed at baseline on treatment days 1-6.

Population: 114 Assessments of suicidality were completed across 13 participants on days 1-6. Data reported show the average change in suicidality from baseline to treatment 6 based on the Scale of Suicide Ideation.

The groups/arms for this outcome are combined as a whole-group analysis due to the crossover design of this study, as pre-specified by the study protocol. Breaking up the analyses into the various arms of the study would change our scientific questions and approach. All participants included in analyses completed all treatments, the various arms for the study vary only in the order in which participants received each treatment. These data show the change in suicidality from baseline to treatment 6 based on the Scale of Suicide Ideation. The measure completed was the Scale of Suicide Ideation. For this study, participants completed the following questions of the questionnaire: 1. wish to live (0 Moderate to Strong, 1 Weak, 2 None) 2. wish to die (0 None, 1 Weak, 2 Moderate to Strong) The total scores range from 0-4. Lower scores indicate high suicide ideation, and high scores indicate low suicide ideation.

Outcome measures

Outcome measures
Measure
Etomidate + ECT
n=114 Suicide Assessments
General anesthesia for ECT will be induced with etomidate, approximately 0.2 mg/kg (0.1-0.6 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose. Electroconvulsive Therapy: Dose of the ECT charge will be determined during titration session prior to randomization.
Ketamine + ECT
General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose. Ketamine: Ketamine will be used to induce general anesthesia with or without subsequent ECT. Within a single patient, the dose will remain consistent throughout the study and is estimated to be 2 mg/kg. Electroconvulsive Therapy: Dose of the ECT charge will be determined during titration session prior to randomization.
Ketamine Alone
General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, no ECT charge will be administered. Ketamine: Ketamine will be used to induce general anesthesia with or without subsequent ECT. Within a single patient, the dose will remain consistent throughout the study and is estimated to be 2 mg/kg.
Suicidality
Change in Will to live
0.077 score on a scale
Standard Deviation 0.277
Suicidality
Change in Will to die
0.077 score on a scale
Standard Deviation 0.277

SECONDARY outcome

Timeframe: up to days 1-6

Population: These data were not collected from patient ECT procedure records and therefore were not analyzed.

Duration (in seconds) of seizure induced by ECT treatment

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: First ECT treatment session during Treatment Week 1

Population: Results are shown for all 13 participants who completed at least one treatment session following the dose charge titration session.

The electrical dose necessary for seizure induction is determined during a dose-charge titration session prior to participant randomization and session 1. These results report the average electrical dose across all participants for the first treatment session during Treatment Week 1. The range for these data is 0 - 100% electrical charge.

Outcome measures

Outcome measures
Measure
Etomidate + ECT
n=13 Participants
General anesthesia for ECT will be induced with etomidate, approximately 0.2 mg/kg (0.1-0.6 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose. Electroconvulsive Therapy: Dose of the ECT charge will be determined during titration session prior to randomization.
Ketamine + ECT
General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose. Ketamine: Ketamine will be used to induce general anesthesia with or without subsequent ECT. Within a single patient, the dose will remain consistent throughout the study and is estimated to be 2 mg/kg. Electroconvulsive Therapy: Dose of the ECT charge will be determined during titration session prior to randomization.
Ketamine Alone
General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, no ECT charge will be administered. Ketamine: Ketamine will be used to induce general anesthesia with or without subsequent ECT. Within a single patient, the dose will remain consistent throughout the study and is estimated to be 2 mg/kg.
ECT Electrical Dose
32.5 percentage of electrical charge
Standard Deviation 8.66

SECONDARY outcome

Timeframe: Assessed at 120 minutes after return of responsiveness on treatment days 1-6

Population: The sample analyzed for each group consists of the total number of treatments performed with paired subjective assessments out of 12 participants.

To assess patient blinding of treatment performed, the patient will be asked: "Based on how you feel, did you have ECT today?" Results indicate participants correctly answering the subjective assessment.

Outcome measures

Outcome measures
Measure
Etomidate + ECT
n=23 Subjective Assessments w/ paired Tx
General anesthesia for ECT will be induced with etomidate, approximately 0.2 mg/kg (0.1-0.6 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose. Electroconvulsive Therapy: Dose of the ECT charge will be determined during titration session prior to randomization.
Ketamine + ECT
n=21 Subjective Assessments w/ paired Tx
General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose. Ketamine: Ketamine will be used to induce general anesthesia with or without subsequent ECT. Within a single patient, the dose will remain consistent throughout the study and is estimated to be 2 mg/kg. Electroconvulsive Therapy: Dose of the ECT charge will be determined during titration session prior to randomization.
Ketamine Alone
n=22 Subjective Assessments w/ paired Tx
General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, no ECT charge will be administered. Ketamine: Ketamine will be used to induce general anesthesia with or without subsequent ECT. Within a single patient, the dose will remain consistent throughout the study and is estimated to be 2 mg/kg.
Subjective Assessment of Whether ECT Was Performed, Determined by Asking the Patient.
18 Subjective Assessments w/ paired Tx
18 Subjective Assessments w/ paired Tx
6 Subjective Assessments w/ paired Tx

SECONDARY outcome

Timeframe: baseline and 120 minutes after return of responsiveness, assessed on treatment days 1-6

Population: The average change in SAM score from baseline to t=120 for all sessions across all participants (t=120 - baseline).

Mood Self-Assessment Manikin (SAM) Scale: 1 (very unpleasant) - 9 (very pleasant). The groups/arms for this outcome are combined as a whole-group analysis due to the Crossover design of this study, as pre-specified by the study protocol. Breaking up the analyses into the various arms of the study would change our scientific questions and approach. Further, any statistical analyses would be underpowered due to low participant numbers in each arm. Thus, the results are combined and reported as a whole group analysis. All participants included in analyses completed all treatments included in the study, the various arms for the study vary only in the order in which participants received each treatment. These data show the change in mood from baseline to treatment 6 based on the SAM. Additionally, data collected at baseline are not dependent on the study group/arm.

Outcome measures

Outcome measures
Measure
Etomidate + ECT
n=64 SAM Assessments
General anesthesia for ECT will be induced with etomidate, approximately 0.2 mg/kg (0.1-0.6 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose. Electroconvulsive Therapy: Dose of the ECT charge will be determined during titration session prior to randomization.
Ketamine + ECT
General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose. Ketamine: Ketamine will be used to induce general anesthesia with or without subsequent ECT. Within a single patient, the dose will remain consistent throughout the study and is estimated to be 2 mg/kg. Electroconvulsive Therapy: Dose of the ECT charge will be determined during titration session prior to randomization.
Ketamine Alone
General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, no ECT charge will be administered. Ketamine: Ketamine will be used to induce general anesthesia with or without subsequent ECT. Within a single patient, the dose will remain consistent throughout the study and is estimated to be 2 mg/kg.
Change in Mood Assessed Using the Mood Self-Assessment Manikin
-0.266 score on a scale
Standard Deviation 1.043

SECONDARY outcome

Timeframe: baseline and 120 minutes after return of responsiveness, assessed on treatment days 1-6

Population: All 13 participants who completed the depression PROMS-CAT both before and after treatment (baseline and 120 minutes following return of responsiveness) on at least one treatment day.

PROMIS-CAT (Patient Reported Outcomes Measurement Information System-Computer Adaptive Testing) for depression The groups/arms for this outcome are combined as a whole-group analysis due to the Crossover design of this study, as pre-specified by the study protocol. Breaking up the analyses into the various arms of the study would change our scientific questions and approach. Further, any statistical analyses would be underpowered due to low participant numbers in each arm. Thus, the results are combined and reported as a whole group analysis. All participants included in analyses completed all treatments included in the study, the various arms for the study vary only in the order in which participants received each treatment. These data show the change in mood from baseline to treatment 6 based on the PROMIS-CAT. Additionally, data collected at baseline are not dependent on the study group/arm.

Outcome measures

Outcome measures
Measure
Etomidate + ECT
n=13 Participants
General anesthesia for ECT will be induced with etomidate, approximately 0.2 mg/kg (0.1-0.6 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose. Electroconvulsive Therapy: Dose of the ECT charge will be determined during titration session prior to randomization.
Ketamine + ECT
General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose. Ketamine: Ketamine will be used to induce general anesthesia with or without subsequent ECT. Within a single patient, the dose will remain consistent throughout the study and is estimated to be 2 mg/kg. Electroconvulsive Therapy: Dose of the ECT charge will be determined during titration session prior to randomization.
Ketamine Alone
General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, no ECT charge will be administered. Ketamine: Ketamine will be used to induce general anesthesia with or without subsequent ECT. Within a single patient, the dose will remain consistent throughout the study and is estimated to be 2 mg/kg.
Average Change in Mood Based on the Depression PROMIS-CAT
-0.5108 score on a scale
Standard Deviation 1.975

SECONDARY outcome

Timeframe: baseline, post-ECT from 0-120 minutes

Population: Participants with EEG data collected at baseline at T0 post-ECT for at least 1 ECT session were included in analyses.

High-density EEG collected during 5-minute epochs of eyes-closed quiet resting at baseline and post-ECT. Results are reported as the percent of total power in the delta band over the sum of total power between 0.5 - 70Hz.

Outcome measures

Outcome measures
Measure
Etomidate + ECT
n=9 Participants
General anesthesia for ECT will be induced with etomidate, approximately 0.2 mg/kg (0.1-0.6 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose. Electroconvulsive Therapy: Dose of the ECT charge will be determined during titration session prior to randomization.
Ketamine + ECT
n=9 Participants
General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose. Ketamine: Ketamine will be used to induce general anesthesia with or without subsequent ECT. Within a single patient, the dose will remain consistent throughout the study and is estimated to be 2 mg/kg. Electroconvulsive Therapy: Dose of the ECT charge will be determined during titration session prior to randomization.
Ketamine Alone
n=10 Participants
General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, no ECT charge will be administered. Ketamine: Ketamine will be used to induce general anesthesia with or without subsequent ECT. Within a single patient, the dose will remain consistent throughout the study and is estimated to be 2 mg/kg.
Change in Delta Band (0.5-4 Hz) Relative Power in the Scale EEG During Recovery
-0.064 percent of total power
Interval -0.182 to 0.033
-0.111 percent of total power
Interval -0.16 to 0.0
-0.038 percent of total power
Interval -0.106 to 0.118

SECONDARY outcome

Timeframe: baseline, post-ECT from 0-120 minutes

Population: Participants with EEG data collected at baseline at T0 post-ECT for at least 1 ECT session were included in analyses.

High-density EEG collected during 5-minute epochs of eyes-closed quiet resting at baseline and post-ECT. Results are reported as the percent of total power in the theta band over the sum of total power between 0.5 - 70Hz.

Outcome measures

Outcome measures
Measure
Etomidate + ECT
n=9 Participants
General anesthesia for ECT will be induced with etomidate, approximately 0.2 mg/kg (0.1-0.6 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose. Electroconvulsive Therapy: Dose of the ECT charge will be determined during titration session prior to randomization.
Ketamine + ECT
n=9 Participants
General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose. Ketamine: Ketamine will be used to induce general anesthesia with or without subsequent ECT. Within a single patient, the dose will remain consistent throughout the study and is estimated to be 2 mg/kg. Electroconvulsive Therapy: Dose of the ECT charge will be determined during titration session prior to randomization.
Ketamine Alone
n=10 Participants
General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, no ECT charge will be administered. Ketamine: Ketamine will be used to induce general anesthesia with or without subsequent ECT. Within a single patient, the dose will remain consistent throughout the study and is estimated to be 2 mg/kg.
Change in Theta Band (4-8 Hz) Relative Power in the Scalp EEG During Recovery
-0.008 percent of total power
Interval -0.048 to 0.051
-0.015 percent of total power
Interval -0.038 to 0.077
0.015 percent of total power
Interval -0.04 to 0.156

SECONDARY outcome

Timeframe: baseline, post-ECT from 0-120 minutes

Population: Participants with EEG data collected at baseline at T0 post-ECT for at least 1 ECT session were included in analyses.

High-density EEG collected during 5-minute epochs of eyes-closed quiet resting at baseline and post-ECT. Results are reported as the percent of total power in the alpha band over the sum of total power between 0.5 - 70Hz.

Outcome measures

Outcome measures
Measure
Etomidate + ECT
n=9 Participants
General anesthesia for ECT will be induced with etomidate, approximately 0.2 mg/kg (0.1-0.6 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose. Electroconvulsive Therapy: Dose of the ECT charge will be determined during titration session prior to randomization.
Ketamine + ECT
n=9 Participants
General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose. Ketamine: Ketamine will be used to induce general anesthesia with or without subsequent ECT. Within a single patient, the dose will remain consistent throughout the study and is estimated to be 2 mg/kg. Electroconvulsive Therapy: Dose of the ECT charge will be determined during titration session prior to randomization.
Ketamine Alone
n=10 Participants
General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, no ECT charge will be administered. Ketamine: Ketamine will be used to induce general anesthesia with or without subsequent ECT. Within a single patient, the dose will remain consistent throughout the study and is estimated to be 2 mg/kg.
Change in Alpha Band (8-13 Hz) Power in the Scalp EEG During Recovery
0.016 percent of total power
Interval -0.001 to 0.142
0.053 percent of total power
Interval 0.016 to 0.112
0.006 percent of total power
Interval -0.026 to 0.053

SECONDARY outcome

Timeframe: baseline, post-ECT from 0-120 minutes

Population: Participants with EEG data collected at baseline at T0 post-ECT for at least 1 ECT session were included in analyses.

High-density EEG collected during 5-minute epochs of eyes-closed quiet resting at baseline and post-ECT. Results are reported as the percent of total power in the beta band over the sum of total power between 0.5 - 70Hz.

Outcome measures

Outcome measures
Measure
Etomidate + ECT
n=9 Participants
General anesthesia for ECT will be induced with etomidate, approximately 0.2 mg/kg (0.1-0.6 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose. Electroconvulsive Therapy: Dose of the ECT charge will be determined during titration session prior to randomization.
Ketamine + ECT
n=9 Participants
General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose. Ketamine: Ketamine will be used to induce general anesthesia with or without subsequent ECT. Within a single patient, the dose will remain consistent throughout the study and is estimated to be 2 mg/kg. Electroconvulsive Therapy: Dose of the ECT charge will be determined during titration session prior to randomization.
Ketamine Alone
n=10 Participants
General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, no ECT charge will be administered. Ketamine: Ketamine will be used to induce general anesthesia with or without subsequent ECT. Within a single patient, the dose will remain consistent throughout the study and is estimated to be 2 mg/kg.
Change in Beta Band (13-20 Hz) Relative Power in the Scalp EEG During Recovery
-0.001 percent of total power
Interval -0.01 to 0.029
-0.004 percent of total power
Interval -0.012 to 0.039
-0.008 percent of total power
Interval -0.019 to 0.014

SECONDARY outcome

Timeframe: baseline, post-ECT from 0-120 minutes

Population: Participants with EEG data collected at baseline at T0 post-ECT for at least 1 ECT session were included in analyses.

High-density EEG collected during 5-minute epochs of eyes-closed quiet resting at baseline and post-ECT. Results are reported as the coherence measure, which is used for tracking changes in anterior-posterior functional connectivity. Coherence is a measure of synchronization between two signals which is used to measure anterior-posterior functional connectivity. Coherence is a unitless measure between 0 and 1. High coherence between time-series of two neural populations reflects higher efficiency in communication between those populations and therefore stronger functional connectivity.

Outcome measures

Outcome measures
Measure
Etomidate + ECT
n=9 Participants
General anesthesia for ECT will be induced with etomidate, approximately 0.2 mg/kg (0.1-0.6 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose. Electroconvulsive Therapy: Dose of the ECT charge will be determined during titration session prior to randomization.
Ketamine + ECT
n=9 Participants
General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose. Ketamine: Ketamine will be used to induce general anesthesia with or without subsequent ECT. Within a single patient, the dose will remain consistent throughout the study and is estimated to be 2 mg/kg. Electroconvulsive Therapy: Dose of the ECT charge will be determined during titration session prior to randomization.
Ketamine Alone
n=10 Participants
General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, no ECT charge will be administered. Ketamine: Ketamine will be used to induce general anesthesia with or without subsequent ECT. Within a single patient, the dose will remain consistent throughout the study and is estimated to be 2 mg/kg.
Change in Anterior-Posterior Functional Connectivity in the Scalp During Recovery
-0.014 unitless
Interval -0.052 to 0.004
-0.002 unitless
Interval -0.01 to 0.014
-0.004 unitless
Interval -0.043 to 0.0023

SECONDARY outcome

Timeframe: baseline, post-ECT from 0 -120 minutes

High-density EEG collected during 5-minute epochs of eyes-closed quiet resting at baseline and post-ECT. Phase-lag was assessed using the Phase-Lag Index (PLI), a measure ranging from 0 - 1. A consistent phase-lag between two tim-series results in a PLI of 1. A time-series without coupling results in a PLI near or equaling 0. Results show the difference in anterior-posterior PLI between baseline and post-ECT.

Outcome measures

Outcome measures
Measure
Etomidate + ECT
n=9 Participants
General anesthesia for ECT will be induced with etomidate, approximately 0.2 mg/kg (0.1-0.6 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose. Electroconvulsive Therapy: Dose of the ECT charge will be determined during titration session prior to randomization.
Ketamine + ECT
n=9 Participants
General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose. Ketamine: Ketamine will be used to induce general anesthesia with or without subsequent ECT. Within a single patient, the dose will remain consistent throughout the study and is estimated to be 2 mg/kg. Electroconvulsive Therapy: Dose of the ECT charge will be determined during titration session prior to randomization.
Ketamine Alone
n=10 Participants
General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, no ECT charge will be administered. Ketamine: Ketamine will be used to induce general anesthesia with or without subsequent ECT. Within a single patient, the dose will remain consistent throughout the study and is estimated to be 2 mg/kg.
Change in Anterior-Posterior Phase-lag in the Scalp EEG During Recovery
-0.001 Phase Lag Index (PLI)
Interval -0.034 to 0.044
-0.049 Phase Lag Index (PLI)
Interval -0.089 to 0.066
-0.017 Phase Lag Index (PLI)
Interval -0.058 to -0.005

SECONDARY outcome

Timeframe: baseline, Post-ECT from 0 -120 minutes

Population: Participants with EEG data collected at baseline at T0 post-ECT for at least 1 ECT session were included in analyses.

High-density EEG collected during 5-minute epochs of eyes-closed quiet resting at baseline and post-ECT. Results are reported as permutation entropy (PE) measures in posterior regions, which we are using to track changes in scalp EEG entropy. Permutation Entropy (PE) is a measure that is used to quantify the complexity of time series signals. It is a unitless measure between 0 and 1. Lower the PE represents a more regular and more deterministic time series while higher PE represents a more complex time series.

Outcome measures

Outcome measures
Measure
Etomidate + ECT
n=9 Participants
General anesthesia for ECT will be induced with etomidate, approximately 0.2 mg/kg (0.1-0.6 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose. Electroconvulsive Therapy: Dose of the ECT charge will be determined during titration session prior to randomization.
Ketamine + ECT
n=9 Participants
General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose. Ketamine: Ketamine will be used to induce general anesthesia with or without subsequent ECT. Within a single patient, the dose will remain consistent throughout the study and is estimated to be 2 mg/kg. Electroconvulsive Therapy: Dose of the ECT charge will be determined during titration session prior to randomization.
Ketamine Alone
n=10 Participants
General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, no ECT charge will be administered. Ketamine: Ketamine will be used to induce general anesthesia with or without subsequent ECT. Within a single patient, the dose will remain consistent throughout the study and is estimated to be 2 mg/kg.
Change in EEG Entropy in the Scalp EEG During Recovery
-0.018 unitless
Interval -0.047 to -0.005
-0.003 unitless
Interval -0.039 to 0.013
-0.006 unitless
Interval -0.012 to 0.003

Adverse Events

Ketamine +ECT

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Etomidate +ECT

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Ketamine Sham

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Alyssa Labonte

Washington Universtiy School of Medicine

Phone: 314-273-7338

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place