The Role of HNKs in the Antidepressant Effect of Ketamine

The objective of the proposed study is to examine the relationship between serum concentrations of HNK and changes in the Hamilton Depression Rating Scale (HDRS), Beck Depression Inventory (BDI), and the Profile of Mood States (POMS), as well as glutamatergic/GABAergic response.

To achieve these aims the investigators propose a double-blind, uncontrolled (no placebo, no healthy control subjects) study with several different doses of ketamine. The investigators will conduct MRI scans to measure Glu and GABA before and during the ketamine treatment.

Status Terminated
Results Published No
Start date 15 May 2019
End date 07 February 2020
Chance of happening 0%
Phase Phase I
Design Blinded
Type Interventional
Generation First
Participants 8
Sex All
Age 18- 65
Therapy No

Trial Details

Major depressive disorder (MDD) is a common illness, affecting over 14 million American adults each year. MDD is a leading cause of disability worldwide and is responsible for huge workplace and healthcare costs. The several week delay between onset of treatment and improvement in MDD symptoms with currently available treatments further increases the burden of the disorder. Shortening this delay is a major unmet challenge in the treatment of MDD. Studies report that a single intravenous low dose of a drug called ketamine can bring about substantial improvement in depression in hours, even in patients that have not improved with other antidepressant treatments. Certain aspects of ketamine's drug action are fairly well understood, but the question remains of how these properties relate to antidepressant effect. Preliminary data support the rapid antidepressant benefit from ketamine but do not show a relationship between clinical improvement and the amount of ketamine, norketamine or dehydronorketamine (DHNK)(two of ketamine's metabolites) in the blood. The investigators hypothesize that a different metabolite of ketamine, hydroxynorketamine (HNK), produces the antidepressant effect of ketamine. The investigators have also used a scanner to measure the effects of ketamine on two major brain chemical transmitters and found that it causes a significant increase (more than 60%) in glutamate (Glu) and gamma aminobutyric acid (GABA) levels in the front of the brain. The investigators hypothesize that this increase in Glu and GABA levels is responsible for the antidepressant action of the drug. Knowing how ketamine works could help to develop better medications that can be used orally and used for maintenance of the improvement seen with ketamine.

NCT Number NCT03977675

Sponsors & Collaborators

Columbia University
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Measures Used

Hamilton Depression Rating Scale
The Hamilton Depression Rating Scale (HDRS) is a multiple item questionnaire used to provide an indication of depression, and as a guide to evaluating recovery. The scale consists of 17 items which each item being scoring on a 3 or 5 point scale. The higher the score, the more likely a person is depressed.

Beck Depression Inventory
The Beck Depression Inventory (BDI) contains 21 self-report items, completed using a multiple-choice format. Scores range from 0-63 with higher scores associated with more severe depression.

Data attribution

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