Mechanism of Action Underlying Ketamine's Antidepressant Effects: The AMPA Throughput Theory in Patients With Treatment-Resistant Major Depression

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.

Conditions

• Depression
• Major Depressive Disorder
• Major Depression

Interventions

DEVICE

Arm 1, 2, 3 device interventions

MagPro 100 TMS Therapy System

OTHER

Arm 2 Interventions

Placebo

DRUG

Arm 1, 2, 3 drug Interventions

Ketamine

DRUG

Arm 1 and 2 Interventions

Perampanel

Sponsors & Collaborators

• National Institute of Mental Health (NIMH)

  lead NIH

Principal Investigators

• Carlos A Zarate, M.D. · National Institute of Mental Health (NIMH)

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

70 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2020-01-21

Primary Completion

2027-02-01

Completion

2027-02-01

FDA Device

Yes

Countries

• United States

Study Locations