Clinical trial NCT02761330: Cognitive Recovery After Electroconvulsive Therapy and General Anesthesia
Official title: Cognitive Recovery After Electroconvulsive Therapy and General Anesthesia Reconstitution of Consciousness and Cognition (Phase 2)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Depression
Delirium
Seizures
Cognitive Disorders
Keywords: Anesthesia
Electroconvulsive therapy
Delirium
Electroencephalography
Seizures
Depression
Ketamine
Etomidate
Physiological Effects of Drugs
Pharmacologic Actions
Confusion
Mental Disorders
Neurobehavioral Manifestations
Signs and Symptoms
Neurologic Manifestations
Cognitive Disorders
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
Collaborators: name: James S McDonnell Foundation
First posted: 2016-05-04
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: This study is geared toward characterizing the recovery of brain activity and cognitive function following treatments of electroconvulsive therapy and ketamine general anesthesia.

Detailed description: Seizures are often associated with loss of consciousness, possibly through effects on sub-cortical arousal systems, disruption of cortical-subcortical interactions, and ultimately through depressed neocortical function. Furthermore, people are often confused in the post-ictal state even when consciousness returns after a seizure. Disrupted cognitive function during the postictal phase has not been fully characterized but presents short and long-term implications. Many experience an acute disorder of attention, consciousness, and cognition, referred to as delirium. Memory deficits are also common. The neurobiology for these phenomena are incomplete and challenging to test, as seizures are typically sporadic and vary in intensity and character. In contrast, the setting of electroconvulsive therapy (ECT) provides the opportunity to study the reconstitution of consciousness and cognition following seizures in an elective and predictable context.

There is no standard agent used to induce general anesthesia during ECT. Ketamine is receiving greater attention as an infusion for treating depression and for its potential benefits on improving ECT efficacy and expediting cognitive recovery. Further data are needed to determine whether ketamine may improve recovery of cognitive function relative to etomidate, a commonly used anesthetic for general anesthesia during ECT.

The investigators will evaluate the cognition function and electroencephalographic patterns that accompany the recovery from ECT and general anesthesia. Twenty patients with refractory depression will be randomized in this interventional single-blinded randomized crossover trial. Each patient will complete seven study visits. The first visit will be conducted during the dose-charge titration ECT treatment with etomidate anesthesia. After this session, patients will be randomized to three sessions each week for two weeks (six treatments total). Over the first week patients will be randomized in order for three treatment arms: (1) etomidate general anesthesia and ECT, (2) ketamine general anesthesia and ECT, and (3) ketamine alone. Patients will be blinded to the treatment arm for each session. Baseline and post-treatment measurements of cognition and ECT will be acquired on each of the six treatment sessions.

Patients that agree will have a MRI.

Eligibility criteria: Inclusion Criteria:

* Treatment resistant depression requiring outpatient ECT
* Planned right unilateral ECT stimulation
* English speaking
* Able to provide written informed consent

Exclusion Criteria:

* Known brain lesion or neurological illness that causes cognitive impairment
* Schizophrenia
* Schizoaffective disorder
* Blindness or deafness or motor impediments that may impair performance for cognitive testing battery
* Inadequate ECT seizure duration with etomidate

Primary outcomes:
measure: Change in Cognitive Function During Recovery: Rate of Recovery
timeFrame: 0, 30, 60, 90, 120 minutes following return of consciousness, assessed on treatment days 1-6.
measure: Change in Cognitive Function During Recovery: Initial Decrement
timeFrame: 0, 30, 60, 90, 120 minutes following return of consciousness, assessed on treatment days 1-6.
Secondary outcomes:
measure: Delirium Incidence and Severity
timeFrame: Immediately following return of consciousness (t=0) during treatment days 1-6.
measure: Suicidality
timeFrame: assessed at baseline on treatment days 1-6.
measure: ECT Seizure Duration
timeFrame: up to days 1-6
measure: ECT Electrical Dose
timeFrame: First ECT treatment session during Treatment Week 1
measure: Subjective Assessment of Whether ECT Was Performed, Determined by Asking the Patient.
timeFrame: Assessed at 120 minutes after return of responsiveness on treatment days 1-6
measure: Change in Mood Assessed Using the Mood Self-Assessment Manikin
timeFrame: baseline and 120 minutes after return of responsiveness, assessed on treatment days 1-6
measure: Average Change in Mood Based on the Depression PROMIS-CAT
timeFrame: baseline and 120 minutes after return of responsiveness, assessed on treatment days 1-6
measure: Change in Delta Band (0.5-4 Hz) Relative Power in the Scale EEG During Recovery
timeFrame: baseline, post-ECT from 0-120 minutes
measure: Change in Theta Band (4-8 Hz) Relative Power in the Scalp EEG During Recovery
timeFrame: baseline, post-ECT from 0-120 minutes
measure: Change in Alpha Band (8-13 Hz) Power in the Scalp EEG During Recovery
timeFrame: baseline, post-ECT from 0-120 minutes
measure: Change in Beta Band (13-20 Hz) Relative Power in the Scalp EEG During Recovery
timeFrame: baseline, post-ECT from 0-120 minutes
measure: Change in Anterior-Posterior Functional Connectivity in the Scalp During Recovery
timeFrame: baseline, post-ECT from 0-120 minutes
measure: Change in Anterior-Posterior Phase-lag in the Scalp EEG During Recovery
timeFrame: baseline, post-ECT from 0 -120 minutes
measure: Change in EEG Entropy in the Scalp EEG During Recovery
timeFrame: baseline, Post-ECT from 0 -120 minutes
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
References:
citation: Hickman LB, Kafashan M, Labonte AK, Chan CW, Huels ER, Guay CS, Guan MJ, Ching S, Lenze EJ, Farber NB, Avidan MS, Hogan RE, Palanca BJA. Postictal generalized electroencephalographic suppression following electroconvulsive therapy: Temporal characteristics and impact of anesthetic regimen. Clin Neurophysiol. 2021 Apr;132(4):977-983. doi: 10.1016/j.clinph.2020.12.018. Epub 2021 Jan 28.
citation: Hickman LB, Hogan RE, Labonte AK, Kafashan M, Chan CW, Huels ER, Ching S, Lenze EJ, Maccotta L, Eisenman LN, Keith Day B, Farber NB, Avidan MS, Palanca BJA. Voltage-based automated detection of postictal generalized electroencephalographic suppression: Algorithm development and validation. Clin Neurophysiol. 2020 Dec;131(12):2817-2825. doi: 10.1016/j.clinph.2020.08.015. Epub 2020 Sep 11.
citation: Palanca BJA, Maybrier HR, Mickle AM, Farber NB, Hogan RE, Trammel ER, Spencer JW, Bohnenkamp DD, Wildes TS, Ching S, Lenze E, Basner M, Kelz MB, Avidan MS. Cognitive and Neurophysiological Recovery Following Electroconvulsive Therapy: A Study Protocol. Front Psychiatry. 2018 May 14;9:171. doi: 10.3389/fpsyt.2018.00171. eCollection 2018.