Mechanism of Action Underlying Ketamine's Antidepressant Effects: The AMPA Throughput Theory in Patients With Treatment-Resistant Major Depression
Recruiting · Bethesda, Maryland
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Legal status usually isn't required; we'll tell you each study's requirements
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Your choice
Voluntary — you can stop anytime
What is this study?
Background: Most drugs that treat mood disorders take a long time to work. Ketamine works within hours.
It is , overseen by an independent and licensed medical staff.
Read the full clinical description
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.
Who this study is looking for
In plain language, from the study's own rules. The study team confirms the full details with you — this isn't a final yes or no.
✅ You may be able to join if…
- •Adults ages 18 to 70 with major depression without psychotic features
- •Must have an initial MADRS score ≥ 22 and a YMRS score < 12 within one week of study entry and upon entry into Phase II
- •Must not have responded to two adequate antidepressant trials (and an ECT or TMS failure can count as an adequate trial)
- •Must have a current major depressive episode lasting at least 4 weeks
- •Must agree to be hospitalized
🚫 You may not be able to join if…
- •Current psychotic features, schizophrenia, or any other psychotic disorder
- •Substance abuse/dependence in the past 3 months, or illicit/drug use shortly before screening (with exceptions for caffeine/nicotine), or a positive alcohol/drug urine test (with exceptions for prescribed benzodiazepines or stimulants)
- •Pregnant or nursing, or unable/unwilling to use effective birth control or stay abstinent (and for those able to become pregnant, must have a negative urine pregnancy test close to study drug dosing)
- •Seizure history (including epilepsy in self or first-degree relatives), stroke, brain surgery, head injury, or certain brain lesions; also excludes current seizure-reducing medications
- •Too heavy (>119 kg) or cannot safely do MRI/MEG (claustrophobia or cannot lie comfortably for up to 90 minutes)
Are you a good fit?
Simplified highlights. The study team always confirms the full details with you.
- ✓Adults roughly 18–70
- ✓Have Depression or Anxiety
- !Some conditions may not be a fit: Heart / cardiovascular disease, High blood pressure
- !Not for people who are pregnant or breastfeeding
What to expect, step by step
- 1
Usually a few weeks
The study team checks whether the study is a good fit for you, with a visit and sometimes lab tests. You can ask any questions before deciding.
- 2
Treatment
If you join and choose to continue, you receive the study treatment and are watched closely by medical staff.
- 3
Follow-up
After treatment, the team checks on your health and confirms the visit schedule with you. You can leave the study at any point.
Has this treatment been tested before?
This is an early-stage study. The treatment has gone through laboratory and preliminary testing before being studied in people here.
What you need to know before you apply
What is this study testing?+
Background: Most drugs that treat mood disorders take a long time to work. Ketamine works within hours.
Is it safe? Who makes sure of that?+
This is an early study (Phase 1), focused mostly on safety. Every study is reviewed and monitored by an independent ethics board (called an IRB) whose job is to protect participants, and care is overseen by licensed medical staff. You'll be told the known risks before you agree to anything, and you can stop at any time.
Will I get a placebo instead of the real treatment?+
Some studies compare a treatment against a placebo (an inactive version), and some don't. If this one does, the study team will explain your chances of receiving the active treatment before you decide. Nothing is hidden from you.
Do I have to stop taking my current medications?+
It depends on the study. Some let you stay on your current medications and some ask you to adjust them. Never stop a medication on your own — the study team will review everything with you first.
Does it cost anything? Will I be paid?+
The study treatment and study-related visits are provided at no cost to you. Some studies also pay for your time; the coordinator can tell you if this one does. You should never be asked to pay to take part.
Do I need insurance? Will anyone ask about my immigration status?+
No. You do not need health insurance to take part in a research study, and you will not be asked about your immigration status to join. Taking part is about whether you're a medical fit for the study.
What if English isn't my first language?+
You have the right to understand everything before you agree. Study sites can often provide materials or an interpreter in your language — you can ask the coordinator for one.
Is my information private?+
Yes. Your health information is only shared with the study sites you choose to be contacted by, and only to help match and enroll you. It is never sold, and you can ask us to delete it at any time.
Some requirements (like specific lab values or timing) are confirmed directly by the study team, not by us.
Source: ClinicalTrials.gov · NCT03973268 · Locations: Maryland