Antidepressant effects of ketamine in depressed patients.
R M Berman, A Cappiello, A Anand...
https://pubmed.ncbi.nlm.nih.gov/10686270Actively Recruiting
Phase 2
Age: 18Years - 55Years
All Genders
ID02122562
Functional Neuroimaging of Ketamine's Enhanced Antidepressant Effects in Treatment-Resistant Major Depression
Led by Mark Niciu · Updated on 2026-05-01
60
Participants Needed
1
Research Sites
N/A
Total Duration
On this page
Sponsors
M
Mark Niciu
Lead Sponsor
N
National Institute of Mental Health (NIMH)
Collaborating Sponsor
AI-Summary
What this Trial Is About
Researchers are investigating the antidepressant effects of a single subanesthetic dose of ketamine in adults aged 18 to 55 years with treatment-resistant major depressive disorder (TRD). The study focuses on how a family history of alcohol use disorder (FHP) may influence ketamine's antidepressant response compared to those without such a history (FHN). Ketamine and alcohol both act on NMDA receptors, and the study aims to understand ketamine's improved efficacy in patients with FHP by measuring glutamate release in the brain. The study has two phases: an initial medication taper and a psychotropic medication-free period lasting at least two weeks, followed by a ketamine infusion phase. Participants receive one ketamine infusion at a dose of 0.5 mg/kg over 40 minutes during 7T magnetic resonance imaging (MRI), including resting-state functional MRI and magnetic resonance spectroscopy to observe glutamate levels in specific brain regions. The study includes 50 subjects divided equally between those with and without a family history of alcohol use disorder. During the study, participants undergo clinical assessments such as the Montgomery-Åsberg Depression Rating Scale (MADRS) to measure depression severity before and one week after ketamine infusion. Additional evaluations include various psychiatric rating scales and monitoring of glutamate changes and brain connectivity via MRI. The study's primary goal is to compare antidepressant effects and brain glutamate responses between the two groups, contributing to more personalized treatments for major depression. Total participation includes the medication taper, drug-free period, ketamine infusion, and follow-up assessments.
CONDITIONS
Brief Title
Ketamine Alcohol (in Treatment-Resistant Depression)
Who Can Participate
Age: 18Years - 55Years
All Genders
Eligibility Criteria
You may qualify if you...
- Age 18 to 55 years
- Ability to understand and consent to the study with a passing score on a consent quiz
- Diagnosis of major depressive disorder without psychotic features, currently in a major depressive episode lasting at least 2 weeks
- History of failure of at least one standard antidepressant treatment
- Montgomery-Åsberg Depression Rating Scale (MADRS) score of 20 or higher at baseline and on the day of ketamine infusion
You will not qualify if you...
- Inadequate knowledge of family mental and substance use history
- Current psychotic features or diagnosis of psychotic spectrum disorders
- Current substance use disorder (except caffeine or nicotine dependence)
- Pregnancy, nursing, or women of childbearing potential not using accepted contraception
- Serious or unstable medical conditions affecting major organ systems
- Medical illnesses likely to alter brain structure or function
- Abnormal laboratory test results
- History of seizures or significant head injury
- Treatment with psychiatric medications within two weeks before ketamine infusion
- Recent treatment with fluoxetine, device-based treatments for depression, or deep brain stimulation
- Use of disallowed concomitant medications
- Positive HIV test
- Presence of ferromagnetic implants or MRI contraindications
- Anatomical brain abnormalities on MRI
- High suicidal or homicidal risk
- Current employees or immediate family of NIMH
- Engagement in structured psychotherapy for mood or anxiety disorders
- Other clinical reasons as determined by investigators
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
1
2
3
Your Study Journey
Screening
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person) for eligibility assessment and consent
Run-in Period
Duration - At least 2 weeks
Participants undergo a medication taper if needed and maintain a drug-free period for at least two weeks before receiving ketamine.
Visits as needed for medication taper and monitoring
Treatment
Duration - Single infusion with assessments up to 1 week post-infusion
Participants receive a subanesthetic dose of ketamine through an intravenous infusion during 7T-MRI scanning to evaluate antidepressant effects.
1 infusion visit plus follow-up visits over 7 days
Trial Site Locations
Total: 1 location
1
University of Iowa Health Care
Iowa City, Iowa, United States, 52242
Actively Recruiting
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Research Team
O
Osura R Amarajeewa, M.B.B.S.
M
Mark J Niciu, M.D. Ph.D.
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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Published Research Related To This Trial
A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression.
Carlos A Zarate, Jaskaran B Singh, Paul J Carlson...
https://pubmed.ncbi.nlm.nih.gov/16894061The antidepressant effect of ketamine is not associated with changes in occipital amino acid neurotransmitter content as measured by [(1)H]-MRS.
Gerald W Valentine, Graeme F Mason, Rosane Gomez...
https://pubmed.ncbi.nlm.nih.gov/21232924