# Ketamine for The Rapid Treatment of Major Depression and Alcohol Use Disorder

> **NIH VA I01** · VA CONNECTICUT HEALTHCARE SYSTEM · 2022 · —

## Abstract

Major depressive disorder (MDD) and alcohol use disorder (AUD) are serious mental illnesses and
commonly co-occur among Veterans. Adequate treatment of depression and comorbid AUD is of major clinical
importance at the VA, yet the efficacy of current pharmacotherapy for depression is only modest and remission
rates are particularly low in depressed patients with AUD. The delay of weeks or months before the onset of
antidepressant effects of traditional antidepressants is also problematic, particularly given the elevated risk for
suicide in this population. Furthermore, despite the fact that 40% of patients with MDD have comorbid AUD in
their lifetime, AUD patients have been excluded from most antidepressant trials for depression. Thus, there is a
critical need to develop effective pharmacotherapy for MDD and AUD.
 There is a growing body of literature showing that a subanesthetic single intravenous (IV) infusion of
ketamine has rapid and robust antidepressant effects. Ketamine was also associated with a rapid reduction in
suicidal thoughts in randomized controlled trials. In addition to treating MDD, emerging evidence indicates that
ketamine, an NMDA receptor antagonist, might be an effective treatment for AUD by stabilizing glutamatergic
system. Building on this evidence, we recently tested ketamine in patients with comorbid MDD and AUD. Our
pilot data showed that ketamine may be safe and effective in reducing depression and alcohol consumption.
 The primary goal of this proposal is to test repeated intravenous ketamine (0.5 mg/kg; once a week; a
total of 4 ketamine infusions) as a treatment for MDD and AUD in a total of 60 Veterans. We propose an 8-
week, randomized, double-blind, placebo-controlled trial. The study will have two phases: 1) a 4-week
treatment phase and 2) a 4-week follow-up phase. All patients will be evaluated daily by using ecological
momentary assessment and will receive usual standard care during this trial.
 There are five objectives.
Aim #1: To evaluate whether ketamine is superior to active placebo (midazolam) in treating depression in
Veterans with comorbid MDD and AUD. We hypothesize that ketamine is superior to active placebo in clinical
response for treating depression. The clinical response will be defined as a ≥ 50% improvement from baseline
in Montgomery-Åsberg Depression Rating Scale (MADRS) score.
Aim #2: To evaluate whether ketamine is superior to active placebo (midazolam) in reducing alcohol use in
Veterans with comorbid MDD and AUD. We hypothesize that ketamine is superior to active placebo in
reducing drinking as measured by the Time Line Follow Back (TLFB).
Aim #3: To evaluate whether ketamine is superior to active placebo (midazolam) in reducing alcohol craving
during the 8-week study period. We hypothesize that ketamine is superior to active placebo (midazolam) in
reducing alcohol craving as measured by the Alcohol Urges Questionnaire (AUQ).
Aim #4: To evaluate whether ketamine is superior to active plac...

## Key facts

- **NIH application ID:** 10683073
- **Project number:** 5I01CX001379-06
- **Recipient organization:** VA CONNECTICUT HEALTHCARE SYSTEM
- **Principal Investigator:** Gihyun Yoon
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2022
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2017-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10683073

## Citation

> US National Institutes of Health, RePORTER application 10683073, Ketamine for The Rapid Treatment of Major Depression and Alcohol Use Disorder (5I01CX001379-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10683073. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*