# CAP-Ketamine for antidepressant resistant PTSD

> **NIH VA I01** · VA CONNECTICUT HEALTHCARE SYSTEM · 2020 · —

## Abstract

ABSTRACT
Post-traumatic stress disorder (PTSD) is a debilitating and chronic mental illness with limited treatment
options. Currently, there are only two FDA-approved PTSD medications both of which are
monoaminergic antidepressants. Rates of non-response to these medications are high, in particular in
military PTSD. Thus, we are proposing to examine the efficacy of a novel drug, ketamine, in treating
antidepressant-resistant PTSD. Mounting evidence indicates that the N- methyl-D-aspartate (NMDA)
glutamate receptor antagonist, ketamine, produces a rapid (within 4 hours) and potent (50% to 90%
response rate) antidepressant action in patients with severe antidepressant-resistant depression. Pilot
evidence and case reports provided preliminary evidence supporting the safety and utility of investigating
the therapeutic effects of ketamine in PTSD. However, the efficacy of this drug has not yet been tested in
an active duty military or veteran population with PTSD.
As a project proposal to be funded under the DoD/VA collaborative Consortium to Alleviate PTSD
(CAP), we propose a multisite, placebo-controlled, double blind clinical trial to examine the dose-related
and multi-dose efficacy of ketamine, as compared to placebo, in producing a rapid and sustained
reduction in PTSD and depressive symptomatology in an active duty military and veteran population with
treatment-resistant PTSD. Approximately 198 eligible subjects who meet criteria for PTSD and
additional inclusion and exclusion criteria will be randomized to the study drug (i.e. ketamine 0.5 mg/kg,
ketamine 0.2 mg/kg, or placebo). The study drug will be administered intravenously twice per week for 4
weeks, followed by a 4-week follow-up period. The proposed 4-week repeat dosing study is, to our
knowledge, the first test of the therapeutic effects of ketamine in the veteran population, and the first
placebo-controlled multisite trial to determine the dose-related effects of repeated ketamine on PTSD. It will
also be the largest ketamine clinical trial, which will provide critical information about the safety of
repeated dosing and the durability of benefit following a 4-week treatment regimen approach. Blood
collection and banking at the CAP Biomarkers and Genomics Core will be performed for future CAP
spearheaded analyses.

## Key facts

- **NIH application ID:** 9856940
- **Project number:** 5I01CX001142-05
- **Recipient organization:** VA CONNECTICUT HEALTHCARE SYSTEM
- **Principal Investigator:** John H. Krystal
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2016-01-01 → 2020-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9856940

## Citation

> US National Institutes of Health, RePORTER application 9856940, CAP-Ketamine for antidepressant resistant PTSD (5I01CX001142-05). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9856940. Licensed CC0.

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