# Reducing Adolescent Suicide Risk: Safety, Efficacy, and Connectome Phenotypes of Intravenous Ketamine

> **NIH NIH R01** · YALE UNIVERSITY · 2022 · $653,324

## Abstract

Project Summary (Abstract)
Suicide is the second leading cause of death in young people (10 to 34 years) and there are currently no
evidence-based pharmacologic anti-suicidal interventions for adolescents. Potent risk factors for adolescent
suicide include Major Depressive Disorder (which increases the risk 30-fold), and recent discharge from a
higher level of psychiatric care relating to suicide. These risks may be further enhanced treatment-resistant
populations. Ketamine is anti-suicidal in adult treatment resistant populations, even after controlling for its
antidepressant effects. Despite having no evidence base in pediatric psychiatry, ketamine is increasingly being
utilized off label by Child Psychiatrists, who have no evidence-based pharmacologic options beyond the
TORDIA recommendations. We have recently completed a midazolam-controlled randomized clinical trial in
adolescents with treatment resistant depression (TRD) showing rapid (1 day) antidepressant efficacy and
sound tolerability of a single ketamine dose. We have case report and pilot data suggesting tolerability and
anti-suicidal promise of repeat dosing paradigms in adolescents with TRD. Here we propose a two-phase
study to test the rapid anti-suicidal efficacy of ketamine in adolescents at high suicide risk (operationally
defined as having TRD and a suicide event within the 120 days prior to enrollment) using a conservative repeat
dosing paradigm (four intravenous infusions over two weeks). The first phase is 2-week parallel, double-blind
phase comparing ketamine to midazolam, and the second is a 4-month open phase in which midazolam-
assigned participants who remain suicidal or depressed can receive open ketamine. All participants will receive
medication management according to an adaptation of the Texas Children’s Medication Algorithm and 8 weeks
of cognitive behavioral therapy (CBT). All will be followed weekly in the open phase for efficacy and safety, with
trial design developed in consultation with the FDA. Given the need for predictive biomarkers of treatment
response, adolescents will participate in task and rest-based fMRI neuroimaging. Using our novel connectome-
based predictive modeling, which uses tasks to “tweak” brain networks across RDoC domains, we will
determine pre-treatment connectome phenotypes, or “fingerprints”, that predict treatment response. We
proposed 3 specific aims: (1) To evaluate the feasibility and safety of treating adolescents at high suicide risk
with a conservative repeat-dosing ketamine paradigm followed by standard of care treatment over 4 months.
(2) To evaluate the 48-hour impact of ketamine on suicidal ideation (measured via Columbia Suicide Rating
Scale, recent ideation subscale) compared to midazolam, and to identify connectome phenotypes predictive of
ideation post-treatment. (3) To describe the trajectory of suicidal thinking, depressive symptoms, and use of
mental health resources in both ketamine responders and non-responders over...

## Key facts

- **NIH application ID:** 10468840
- **Project number:** 5R01MH125203-03
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Michael H Bloch
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $653,324
- **Award type:** 5
- **Project period:** 2020-09-15 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10468840

## Citation

> US National Institutes of Health, RePORTER application 10468840, Reducing Adolescent Suicide Risk: Safety, Efficacy, and Connectome Phenotypes of Intravenous Ketamine (5R01MH125203-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10468840. Licensed CC0.

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