# Effectiveness of a Synergistic, Neuroplasticity-Based intervention for Rapid and Durable Suicide Risk Reduction

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $626,853

## Abstract

Project Summary. Intravenous ketamine, which displays rapid antidepressant and anti-suicidality properties, is posited to
reverse symptoms by rapidly enhancing neuroplasticity; but surprisingly little is known regarding its feasibility, safety,
and effectiveness for reducing suicidal outcomes among real-world, heterogenous samples at imminent risk. Furthermore,
a significant barrier to clinical adoption is the lack of evidence for durability of ketamine's effects, raising concerns about
illusory recovery and subsequent rebound of suicide risk. We posit that ketamine will rapidly decrease suicidal ideation
and rapidly increase cognitive flexibility in a real-world sample, allowing for rigid, negative biases in cognition to be
rapidly reversed. We further expect these neurocognitive changes will provide a clinical window of opportunity in which
to introduce 1) standard crisis-oriented psychiatric care; and 2) automated cognitive training (CT) techniques, which will
consolidate adaptive forms of cognitive processing (specifically, positive and life-oriented implicit representations of self)
while neuroplasticity remains high. Instantiating adaptive forms of processing (through standard care and/or automated
CT) after first 'priming' the brain with ketamine represents a potentially synergistic treatment approach that could extend
the acute effects of a single ketamine infusion beyond its typical 3-7 day window, efficiently fostering protective anti-
suicidal effects that are both rapid and enduring. In this study, 200 Medical Unit inpatients (age 18-65) will be enrolled by
referral from the psychiatric consultation/liaison service in a large Level 1 trauma hospital, following consult for a
medically serious suicide attempt (SA). Leveraging medical unit physicians who are well-accustomed to utilizing
ketamine infusion routinely in their inpatient medical settings, inpatients will be randomized in a parallel arm design to
receive a single infusion of ketamine “pre-treatment”—shortly prior to subsequent psychiatric inpatient stay—or no-
infusion. Patients will complete acute measures of explicit SI and cognitive target engagement (implicit suicide-self
associations; Aim 1). In a fully crossed (2 x 2 factorial), parallel arm design, patients will then be randomized to receive a
brief web-app-based cognitive training protocol during the post-infusion "window of opportunity," designed to implicitly
reverse negative self-representations, instilling beneficial self-representations in their place, or a sham variant of the same
training. Patients, investigators, and outcome raters will be blinded to treatment condition. Comprehensive
feasibility/safety data will be captured for both intervention components. Remote assessments and the medical record will
then be used to capture SI and SAs over a 12-month naturalistic follow-up to assess whether: ketamine followed by
standard psychiatric inpatient care has a beneficial impact over no-infusion standard-of-care (A...

## Key facts

- **NIH application ID:** 10110123
- **Project number:** 1R01MH124983-01
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Rebecca Price
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $626,853
- **Award type:** 1
- **Project period:** 2020-09-15 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10110123

## Citation

> US National Institutes of Health, RePORTER application 10110123, Effectiveness of a Synergistic, Neuroplasticity-Based intervention for Rapid and Durable Suicide Risk Reduction (1R01MH124983-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10110123. Licensed CC0.

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