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Electroconvulsive therapy amplitude titration for improved clinical outcomes in late-life depression

Award Number: R33MH125126
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/04/2021
PERIOD OF PERFORMANCE END DATE: 01/31/2027

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Electroconvulsive therapy amplitude titration for improved clinical outcomes in late-life depression - Electroconvulsive therapy (ECT) stimulation parameter selection reflects a balance between efficacy and cognitive adverse effects. ECT stimulation parameters associated with more antidepressant efficacy (non-focal electrode placement, longer pulse width) are associated with increased risk of cognitive adverse effects. Amplitude is currently fixed at 800 or 900 milliamperes (mA) in standard clinical practice with no clinical or scientific basis. Amplitude determines the intensity of the spatial distribution of the electric field (E-field). With a fixed extracranial amplitude, the ECT “dose” as represented by the E-field is highly variable due to anatomic differences in skin, skull, fluid, and brain tissue. This anatomic variability is prominent in older (age 50+) depressed patients and can compromise both antidepressant efficacy (insufficient stimulation of mood-related circuitry) and safety (inducing cognitive impairment due to excessive stimulation of cognitive related circuitry). Amplitude titration, as proposed in this current proposal, can reduce the variability related to fixed amplitude dosing and optimize clinical and cognitive outcomes. The goal of this project is to change standard ECT parameter selection from a fixed amplitude to an individualized and empirically determined amplitude. To achieve this goal, we will focus on the relationship between amplitude titration and treatment-responsive changes in hippocampal neuroplasticity with RUL fixed amplitude ECT. Fixed amplitude ECT results in variable E-field or ECT dose. Over the course of an ECT series, the variable ECT dose will result in inconsistent changes in hippocampal neuroplasticity. In contrast, pre-translational investigations have demonstrated that amplitude titration results in a consistent E-field or ECT “dose”. Seizure titration amplitudes (based on historic data, 233 to 544 mA) are below the amplitude range of FDA-approved ECT devices (500 to 900 mA) and will require an adaptor to reduce the output amplitude (Investigational Device Exemption). Amplitude titration will also be below the hippocampal neuroplasticity threshold and insufficient for antidepressant response. The difference between RUL amplitude titration and RUL fixed amplitude (800 mA) ECT will determine the degree of target engagement with the hippocampus. To illustrate, subjects with low amplitude titration of ~250 mA (800/250, high fixed/titration amplitude ratio) will have significant changes in hippocampal neuroplasticity. Subjects with high amplitude titration ~500 mA (800/500, low fixed/titration ratio) will have minimal changes in hippocampal neuroplasticity. The relationship between amplitude titration and fixed amplitude hippocampal neuroplasticity will be used to develop the amplitude multiplier required for consistent and clinically effective ECT dosing. A randomized controlled trial will then compare hippocampal neuroplasticity, antidepressant, and cognitive outcomes between amplitude titration with neuroplasticity multiplier (fixed pulse number) and traditional fixed amplitude ECT (800 mA, variable pulse number) in older depressed subjects.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $0 )
2026	2025	UNIVERSITY OF NEW MEXICO	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Mental Health Research Grants	000	5	12/15/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $549,610 )
2025	2025	UNIVERSITY OF NEW MEXICO	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Mental Health Research Grants	000	5	3/14/2025	NON-COMPETING CONTINUATION	$549,610
														Subtotal = $549,610

Issue Date FY: 2024 ( Subtotal = $1,046,159 )
2024	2024	UNIVERSITY OF NEW MEXICO	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Mental Health Research Grants	002	4	5/13/2024	NON-COMPETING CONTINUATION	$68,862
2024	2024	UNIVERSITY OF NEW MEXICO	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Mental Health Research Grants	001	4	1/12/2024	NON-COMPETING CONTINUATION	$619,767
2024	2023	UNIVERSITY OF NEW MEXICO	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Mental Health Research Grants	000	3	12/12/2023	EXTENSION WITH OR WITHOUT FUNDS	$357,530
														Subtotal = $1,046,159

Issue Date FY: 2023 ( Subtotal = $738,068 )
2023	2023	UNIVERSITY OF NEW MEXICO	1 UNIVERSITY OF NEW MEXICO	ALBUQUERQUE	NM	87131	BERNALILLO	USA	Mental Health Research Grants	000	3	1/30/2023	EXTENSION WITH OR WITHOUT FUNDS	$738,068
														Subtotal = $738,068

Grand Total All Awards = $2,333,837

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Electroconvulsive therapy amplitude titration for improved clinical outcomes in late-life depression

Award Number: R33MH125126

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 02/04/2021

PERIOD OF PERFORMANCE END DATE: 01/31/2027

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