The Mechanism of Action Underlying Ketamine's Antidepressant Effects: An Investigation of the AMPA Throughput Theory in Patients With Treatment-Resistant Major Depression
National Institute of Mental Health (NIMH)
Summary
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.
Description
Objective Work by our group and others has demonstrated that a single intravenous dose of the glutamatergic modulator ketamine consistently produces rapid (within two hours), robust, and relatively sustained (approximately one to two weeks) antidepressant effects in patients with treatment-resistant major depressive disorder (MDD) and bipolar depression. Although ketamine is an N-methyl-D-aspartate (NMDA) receptor (NMDAR) antagonist, convergent evidence from behavioral, cellular, and molecular ketamine studies supports the theory that enhanced -amino-3-hydroxy-5-methyl-4-isoxazolepropionic ac…
Eligibility
- Age range
- 18–70 years
- Sex
- All
- Healthy volunteers
- No
* INCLUSION CRITERIA: Phases I-II 1. 18 to 70 years of age. 2. Each subject must have a level of understanding sufficient to agree to all required tests and examinations and sign an informed consent document. 3. All subjects must have undergone a screening assessment under protocol 01-M-0254, "The Evaluation of Patients with Mood and Anxiety Disorders and Healthy Volunteers". 4. Subjects must fulfill DSM-IV or -5criteria for Major Depression (Major Depressive Disorder) without psychotic features, based on clinical assessment and informed by a structured diagnostic interview (SCID-P). 5. Subj…
Interventions
- DeviceArm 1, 2, 3 device interventions
MagPro 100 TMS Therapy System
- OtherArm 2 Interventions
Placebo
- DrugArm 1, 2, 3 drug Interventions
Ketamine
- DrugArm 1 and 2 Interventions
Perampanel
Location
- National Institutes of Health Clinical CenterBethesda, Maryland