Actively Recruiting
Mechanism of Action Underlying Ketamine's Antidepressant Effects: The AMPA Throughput Theory in Patients With Treatment-Resistant Major Depression
Led by National Institute of Mental Health (NIMH) · Updated on 2026-02-24
70
Participants Needed
1
Research Sites
366 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
Background: Most drugs that treat mood disorders take a long time to work. Ketamine works within hours. A dose can last for a week or more. Certain receptors in the brain might help ketamine work. A drug that blocks these receptors might affect how it works. Objective: To see if the antidepressant response of ketamine is linked to AMPA receptors. Eligibility: Adults ages 18-70 with major depression disorder without psychotic features Design: Participants will be screened under protocol 01-M-0254. They will have blood tests and a physical exam. Participants will stay at the NIH Clinical Center for 5 weeks. Phase 1 lasts 4 weeks. For 2 weeks, participants will taper off their psychiatric medicine. Then they will have the following tests: * Blood draws * Psychological tests * MRI: Participants will lie in a machine that takes pictures of their brain. * MEG: Participants will lie down and do tasks. A cone lowered on their head will record brain activity. * Optional sleep tests: Electrodes on the scalp and body and belts around the body will monitor participants while they sleep. * Optional TMS: Participants will do tasks while a wire coil is held on their scalp. An electrical current will pass through the coil that affects brain activity. For phase 2, on day 0 participants will take the study drug or a placebo orally. While having a MEG, they will get ketamine infused into a vein in one arm while blood is drawn from a vein in the other arm. On day 1, participants will again take the study drug or a placebo orally. On days 3-7, they will repeat many of the phase 1 tests. Days 8 and 9 are optional and include an open label ketamine treatment and many of the phase 1 tests.
CONDITIONS
Official Title
Mechanism of Action Underlying Ketamine's Antidepressant Effects: The AMPA Throughput Theory in Patients With Treatment-Resistant Major Depression
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Age between 18 and 70 years
- Ability to understand and agree to all tests and sign informed consent
- Completed screening under protocol 01-M-0254
- Diagnosis of major depressive disorder without psychotic features based on clinical assessment
- Initial Montgomery-Asberg Depression Rating Scale (MADRS) score of 22 or higher and Young Mania Rating Scale (YMRS) score below 12
- Lack of response to at least two adequate antidepressant treatments, including current episode
- Current major depressive episode lasting at least four weeks
- Agree to be hospitalized during study participation
- For open-label ketamine treatment, completion of Phase II and use of effective birth control or sexual abstinence if able to become pregnant
You will not qualify if you...
- Current psychotic features or diagnosis of schizophrenia or other psychotic disorders
- Substance abuse or dependence within past 3 months (except caffeine or nicotine) and negative drug/alcohol tests at screening
- Serious unstable medical illnesses including liver, kidney, heart, lung, endocrine, neurological, immune, or blood disorders
- Pregnancy, nursing, or physical ability to become pregnant without effective birth control during study
- History of seizures, epilepsy, stroke, brain surgery, head injury, or structural brain lesions
- Medical conditions likely to alter brain structure or function, even if controlled
- Significant abnormal lab tests
- Hearing loss that could worsen with imaging procedures
- Positive HIV test
- Weight over 119 kg
- Use of psychiatric or non-psychiatric medications prior to Phase II (must be tapered during Phase I)
- Use of opioid medications in past 3 months
- Use of reversible monoamine oxidase inhibitors (MAOI) prior to Phase II
- Use of fluoxetine or aripiprazole at screening
- Unwillingness to stop structured psychotherapy during Phases I and II
- Presence of metallic implants
- Claustrophobia or inability to lie still for imaging
- Serious suicidal or homicidal risk or history of aggressive behavior
- Current NIMH staff or immediate family member
- For open-label treatment, serious adverse reactions to ketamine or positive drug test before treatment
- Pregnancy or nursing during open-label treatment
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
Y
Yamila I Carmona
CONTACT
C
Carlos A Zarate, M.D.
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
TRIPLE
Allocation
RANDOMIZED
Model
PARALLEL
Primary Purpose
BASIC_SCIENCE
Number of Arms
3
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