ECT Pulse Amplitude and Medial Temporal Lobe Engagement

Electroconvulsive therapy (ECT) remains the gold-standard treatment for patients with depressive episodes. During a typical four-week ECT series, most depressive episodes will respond to treatment and people will improve their level of functioning (return to work or family). Independent of the antidepressant effect of ECT, many patients experience transient memory impairment. This investigation will examine the impact of one ECT parameter (pulse amplitude or current) on brain changes (structure of connections within the brain) and clinical outcomes. The goal of this investigation is to determine the optimal parameter for an individual patient that will maintain the clinical response (reduce depression severity) and minimize side effects (eliminate memory issues related to treatment).

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Device: MECTA Spectrum 5000Q Amplitude

Detailed Description

Electroconvulsive therapy (ECT) remains the gold-standard treatment for patients with depressive episodes. During a typical four-week ECT series, most depressive episodes remit, and formerly suicidal or psychotically depressed patients will resume their premorbid levels of functioning. Independent of the antidepressant effect of ECT, many patients experience debilitating but transient cognitive effects such as attention and memory deficits. These unwanted side effects are particularly troubling for older patients who are more likely to have existing cognitive deficits. Both the stimulus delivery (electrode placement, pulse amplitude, and pulse width) and seizure induction appear to work in synergy, but the underlying mechanism of action for successful response has yet to be fully elucidated. Moreover, further work is needed to understand the relationship between clinical improvement and cognitive impairment. This investigation will examine the clinical and neurocognitive impact of targeted medial temporal lobe engagement as a function of pulse amplitude, one of several variable factors influencing the ECT charge. The ECT charge is measured in millicoulombs (mC) and derived from multiplying pulse train duration, pulse-pair frequency, pulse width, and pulse amplitude. Pulse amplitude determines the induced electric field strength in the brain and is presently fixed at 900 milliamperes (mA) with no clinical or scientific justification. The central hypothesis of this investigation is that the optimal pulse amplitude for an individual patient will enhance neuroplasticity (clinical response) while minimizing the disruption of dominant hemisphere hippocampal cognitive circuitry (resulting in cognitive stability). The preliminary data informs the dosage range between 600 and 800 mA. Pulse amplitudes outside of this range compromise efficacy (500 mA) or may increase risk of cognitive impairment (900 mA). The first aim of this investigation will identify the electric field strength and neuroplasticity associated with clinical response. Critically, this aim will establish the neuroplasticity threshold, which is defined as the electric field strength necessary to induce neuroplasticity. The second aim will detect the neural correlates of ECT-mediated cognitive changes, which may be related to disrupted dominant hemisphere long-term potentiation. The third aim will use data-driven dual regression to predict the optimal pulse amplitude for an individual patient. This contribution will be significant because the electric field, when manipulated by pulse amplitude, can subsequently maximize hippocampal neuroplasticity (efficacy) and minimize disrupted connectivity (cognitive stability) thus improving clinical outcomes.

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131-0001
      • Chris Abbott

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Diagnosis of major depressive disorder (with or without psychotic features)
2. the clinical indications for ECT including treatment resistance or a need for a rapid and definitive response
3. Hamilton Depression Rating Scale 24-item (HDRS-24) > 21
4. age range between 50 and 80 years of age
5. right-handedness

Exclusion Criteria:

1. Defined neurological or neurodegenerative disorder (e.g., history of head injury with loss of consciousness > 5 minutes, epilepsy, Alzheimer's disease)
2. other psychiatric conditions (e.g., schizophrenia, schizoaffective disorder, bipolar disorder)
3. current drug or alcohol use disorder, except for nicotine; and 4) contraindications to MRI.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 600 mA Right Unilateral ECT; MECTA Spectrum 5000Q Amplitude	Device: MECTA Spectrum 5000Q Amplitude; Current
Experimental: 700 mA Right Unilateral ECT; MECTA Spectrum 5000Q Amplitude	Device: MECTA Spectrum 5000Q Amplitude; Current
Active Comparator: 800 mA Right Unilateral ECT; MECTA Spectrum 5000Q Amplitude	Device: MECTA Spectrum 5000Q Amplitude; Current

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Depression Severity	Hamilton Depression Rating Scale - 24 item. Scores range from 0 to 76 (higher scores indicate more depression severity)	post-ECT Hamilton Depression Rating Scale -24 item. The time frame is 4 weeks after study initiation.
Cognition	Hopkins Verbal Learning Trial-Revised (percent retention score, range 0 - 100, higher is better)	post-ECT Hopkins Verbal Learning Trial-Revised (percent retention score, range 0 - 100, higher is better). The time frame is 4 weeks after study initiation.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Structural magnetic resonance imaging (MRI): Medial temporal lobe volumes	Medial temporal lobe volumes	change from pre-ECT baseline (within one week of ECT start) to post-ECT Index (within one week of finishing ECT index)
Resting state functional MRI	resting state medial temporal lobe functional connectivity	change from pre-ECT baseline (within one week of ECT start) to post-ECT Index (within one week of finishing ECT index)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Montreal Cognitive Assessment	brief cognitive screening	change from pre-ECT baseline (within one week of ECT start) to post-ECT Index (within one week of finishing ECT index)
Hopkins Verbal Learning Trials - Revised	Verbal memory test (other aspects of test not included as primary outcome)	change from pre-ECT baseline (within one week of ECT start) to post-ECT Index (within one week of finishing ECT index)
Brief Visual Memory Test-Revised	Visual memory test	change from pre-ECT baseline (within one week of ECT start) to post-ECT Index (within one week of finishing ECT index)
Delis Kaplan Executive Function System (DKEFS) Color Interference	cognitive measure	change from pre-ECT baseline (within one week of ECT start) to post-ECT Index (within one week of finishing ECT index)
Delis Kaplan Executive Function System (DKEFS) Verbal Fluency	cognitive measure	change from pre-ECT baseline (within one week of ECT start) to post-ECT Index (within one week of finishing ECT index)
Dot counting	cognitive measure	change from pre-ECT baseline (within one week of ECT start) to post-ECT Index (within one week of finishing ECT index)
Wechsler Adult Intelligence Scale-4 Digit Span	cognitive measure	change from pre-ECT baseline (within one week of ECT start) to post-ECT Index (within one week of finishing ECT index)
Autobiographical Memory	cognitive measure	change from pre-ECT baseline (within one week of ECT start) to post-ECT Index (within one week of finishing ECT index)

Collaborators and Investigators

• Sponsor: University of New Mexico
• Collaborators: National Institute of Mental Health (NIMH); University of Texas; The Mind Research Network
• Investigators: Principal Investigator: Chris Abbott, MD, University of New Mexico

Publications and helpful links

General Publications

• Abbott CC, Quinn D, Miller J, Ye E, Iqbal S, Lloyd M, Jones TR, Upston J, Deng Z, Erhardt E, McClintock SM. Electroconvulsive Therapy Pulse Amplitude and Clinical Outcomes. Am J Geriatr Psychiatry. 2021 Feb;29(2):166-178. doi: 10.1016/j.jagp.2020.06.008. Epub 2020 Jun 17.

Study record dates

Study Major Dates

• Study Start: October 1, 2016
• Primary Completion (Actual): March 23, 2020
• Study Completion (Actual): March 23, 2020

Study Registration Dates

• First Submitted: August 16, 2016
• First Submitted That Met QC Criteria: December 16, 2016
• First Posted (Estimated): December 21, 2016

Study Record Updates

• Last Update Posted (Estimated): July 24, 2023
• Last Update Submitted That Met QC Criteria: June 30, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: MRI; major depressive disorder; electroconvulsive therapy
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major
• Other Study ID Numbers: 5U01MH111826 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: National Data Archive (NDA)
• IPD Sharing Time Frame: Clinical, cognitive and MRI data was uploaded to NDA.
• IPD Sharing Access Criteria: per NDA protocol
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No