Actively Recruiting
Neuropharmacologic Imaging and Biomarker Assessments of Response to Acute and Repeated-Dosed Ketamine Infusions in Major Depressive Disorder
Led by National Institute of Mental Health (NIMH) · Updated on 2026-04-24
150
Participants Needed
1
Research Sites
553 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
Background: Most medications that treat depression take weeks or months to work. Researchers want to develop fast-acting treatments. One dose of ketamine has a rapid antidepressant effect. For most people, this lasts a week or less. Repeated doses of ketamine may help maintain this effect. Objective: Main Study: To study the effects of ketamine in treating depression. Ketamine Metabolites Substudy: To study how ketamine effects brain chemistry. To study how ketamine effects the brain. This is done by looking at metabolites, which are created when a drug is broken down. Eligibility: Main Study: People ages 18-65 with major depressive disorder and healthy volunteers Ketamine Metabolites Substudy: Healthy volunteers ages 18-65 Design: Main Study: Participants will be screened in another study, with: * Medical and psychiatric history * Psychiatric and physical exam * Blood, urine, and heart tests Participants will be inpatients at NIH for 4 phases totaling 14-20 weeks. Phase I (2-7 weeks): * Gradually stop current medications * MRI: Participants lie and perform tasks in a machine that takes pictures of the body. * Mood and thinking tests * Blood and urine tests * Sleep test: Monitors on the skin record brain waves, breathing, heart rate, and movement during sleep. * Transcranial magnetic stimulation: A coil on the scalp gives an electrical current that affects brain activity. * Stress tests: Electrodes on the skin measure reactions to loud noises or electric shocks. Phase I tests are repeated in Phases II and III and in the final visit. Phase II (4-5 weeks): * 4 weekly IV infusions of ketamine or a placebo during an MRI or MEG. For the MEG, a cone over the head records brain activity. Phase III (optional): * 8 infusions of ketamine over 4 weeks Phase IV (optional): * Symptoms monitoring for 4 weeks * Participants will have a final visit. They will be offered standard treatment at NIH for up to 2 months. Ketamine Metabolites Substudy: Participants will be screened in another study, with: * Medical and psychiatric history * Psychiatric and physical exam * Blood, urine, and heart tests Participants will be inpatients at NIH for 4 days. Study Procedures: Mood and thinking tests Blood and urine tests 1 infusion of ketamine Spinal tap and spinal catheter: Used to get samples of cerebrospinal fluid (CSF). This is a fluid that moves around and within the brain and spinal cord. Studying CSF will help us learn how ketamine effects brain chemistry
CONDITIONS
Official Title
Neuropharmacologic Imaging and Biomarker Assessments of Response to Acute and Repeated-Dosed Ketamine Infusions in Major Depressive Disorder
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Age between 18 and 65 years
- Ability to understand and agree to all required tests and sign informed consent
- Completed screening under specified protocols
- Agree to be hospitalized during the study
- For MDD patients: Diagnosed with major depressive disorder (single or recurrent episode) with current episode lasting at least 2 weeks
- For MDD patients: Baseline depression score (MADRS) of 20 or higher and mania score (YMRS) below 12 at screening and start of Phases II and III
- For MDD patients: History of lack of response to at least one adequate antidepressant trial or electroconvulsive therapy
- For healthy volunteers in substudy: Same age and consent criteria, and agreement to hospitalization
You will not qualify if you...
- Diagnosis of bipolar disorder or psychotic disorders such as schizophrenia
- History of drug or alcohol abuse or dependence within past 3 months (except caffeine or nicotine)
- Current serious suicidal or homicidal risk
- Pregnant or nursing women or planning pregnancy without effective birth control
- Serious unstable illnesses including liver, kidney, heart, lung, neurological, immune or blood diseases
- Abnormal lab test results that are clinically significant
- History of seizures, epilepsy, brain injury, or use of medications lowering seizure threshold
- Use of other medications 14 days prior to Phase II (with exceptions for fluoxetine and aripiprazole)
- Use of opioid medication within past 3 months
- Presence of metallic implants incompatible with imaging
- Claustrophobia or inability to tolerate MRI scanning
- Positive HIV test
- Weight over 119 kg
- For healthy volunteers: Any current or past DSM-IV or DSM-5 Axis I disorder confirmed by clinical interview
- For healthy volunteers substudy: Same health exclusions as above plus any recent substance abuse and medication use
AI-Screening
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Trial Site Locations
Total: 1 location
1
National Institutes of Health Clinical Center
Bethesda, Maryland, United States, 20892
Actively Recruiting
Research Team
L
Laura R Waldman, L.C.S.W.
CONTACT
C
Carlos A Zarate, M.D.
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
DOUBLE
Allocation
RANDOMIZED
Model
CROSSOVER
Primary Purpose
TREATMENT
Number of Arms
8
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