Low Dose Intravenous Ketamine in Treatment Resistant Depression Patients

2016-10-18 02:08:21 | BioPortfolio


The present proposal aims to combine state-of-the-art integrated transcranial brain stimulation, electroencephalographic recording techniques with genetics and computational modeling to unveil the mechanisms underlying a fundamental cortical network process - synchronization of neuronal activity in the gamma band (30-80 Hz) - and the sources of its intersubject variability. By measuring the entrainment of prefrontal cortex produced by weak oscillatory currents, the study team will provide a new non-invasive strategy to derive robust estimates of the cortical ability to support gamma oscillations, critically overcoming limitations associated with current approaches and allowing measures solely dependent on intrinsic regional cortico-thalamic properties. Consistent with molecular evidence and the investigators biophysical models of gamma oscillations, the study team expects that such unambiguous measurement of cortical capabilities will straightforwardly map onto key genetic underpinnings related to the dopamine and neuregulin signaling pathways. These computational models will be used to offer critical mechanistic insights linking genetic variations to variability in emergent circuit-level activity in the form of cortical gamma oscillations.


The primary goal of the project is to study the effect of Ketamine on cortical neurophysiological function in Treatment Resistant Depression(TRD) patients. There are three key preclinical findings regarding Ketamine antidepressant effects that motivate the current study: a) low dose Ketamine causes early increase in glutamate neurotransmission; b) Ketamine initiates synaptic plasticity; c) ketamine infusion leads to rapid improvement in depression symptoms; d) specific expression and/or methylation markers measured in blood cells isolated treated ex vivo with ketamine will significantly correlate with the clinical response to treatment in patients with treatment-resistant depression; The proposal essentially employs robust and non-invasive neurophysiological techniques, Auditory Steady State Response(ASSR)-gamma oscillatory response and Transcranial Magnetic Stimulation(TMS) cortical excitability to investigate the above findings in patients with treatment resistant depression.


In the first session, one group of TRD patients receive low dose Ketamine (0.5 mg/kg) over 40 minutes while the other group of TRD patients receive placebo-saline infusion. In the second visit, the patients who received ketamine in the first visit will receive placebo-saline infusion and the patients who received placebo-saline infusion will receive a ketamine infusion. The study will be randomized such that in the first session, 5 patients will receive ketamine infusion and 5 patients will receive placebo. The randomization will be broken and the data analyzed. The study will then continue with the remaining 10 patients, where 5 of them will receive ketamine infusion and 5 patients will receive placebo infusion in the first session.

Ketamine Infusion:

The study team will use slow infusions of ketamine/placebo-saline solution over a time period of 40 minutes. Study drug will be provided in identical syringes, containing clear solutions of 1 mL of ketamine, e.g. 100 mg/mL with 9 mL of normal saline or just 1 ml saline solution.

Cortical Excitability:

TMS stimulation will be applied to the corresponding region of the contralateral primary motor cortex to determine motor threshold and to examine the motor cortical excitability measures after Ketamine. The optimal coil position will be determined by moving the TMS coil in 1-cm increments over the motor cortical area while delivering single or paired magnetic pulses and by observing maximal contraction of the contralateral abductor pollicis brevis (APB). Electromyography readings will be obtained from the APB muscle. TMS stimulation will then be applied to Left DLPFC or Left Brodmann Area 6 to investigate cortical excitability changes after ketamine. Electroencephalography(EEG) recordings will be concurrent with TMS procedure.

ASSR/EEG paradigm:

Participants may engage in the auditory steady state response task where click trains of 500-ms duration will be presented binaurally at 65 ± 5 decibel(dB). The click train repetition frequencies will be 40 Hz and presented in the context of an auditory oddball paradigm to ensure participant attention to the stimuli. This task will be done while participants undergo EEG recordings.

Blood Tests:

Gene Expression and Methylation:

To identify alterations in gene expression and methylation markers induced by the ex vivo treatment of peripheral blood mononuclear cells from symptomatic patients with treatment-resistant depression with ketamine and assess their correlations with clinical response (as measured by the reduction in the Hamilton Depression Rating Scale - HDRS). For that end blood samples will be collected from all subjects immediately before the first administration of ketamine.

Brain-derived neurotrophic factor,(BDNF):

Serum BDNF tests will be performed. For that end blood samples will be collected from all subjects.

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Crossover Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment


Treatment Resistant Depression


Ketamine, Saline solution


Harris County Psychiatric Center
United States


Enrolling by invitation


The University of Texas Health Science Center, Houston

Results (where available)

View Results


Published on BioPortfolio: 2016-10-18T02:08:21-0400

Clinical Trials [2227 Associated Clinical Trials listed on BioPortfolio]

Administration of Subanesthetic Dose of Ketamine and Electroconvulsive Treatment for Treatment Resistant Depression

In this proof of concept study, the investigators plan to administer iv ketamine interleaved with ECT days. Patients with treatment resistant depression who are deemed to be eligible for ...

Ketamine for Treatment Resistant Late-Life Depression

The purpose of this study is to examine the effectiveness of a single infusion of ketamine, to determine which dose is optimal and lasts the longest, and to learn about how ketamine works ...

Clinical Trial of the Use of Ketamine in Treatment Resistant Depression

The purpose of this study is to determine the efficacy of the use of intravenous low-dose ketamine in the treatment of treatment-resistant depression (TRD), as well as the changes in Gluta...

Ketamine Plus Lithium in Treatment-Resistant Depression

The purpose of this study is to test the antidepressant effect of ketamine when given repeatedly over a period of 1 week, as well as the use of Lithium as a relapse-prevention strategy for...

D-cycloserine for Relapse Prevention Following Intravenous Ketamine in Treatment-resistant Depression

This is a two-stage experiment; the first stage is an open label trial in which participants receive six intravenous (IV) treatments of ketamine. The second stage includes participants tha...

PubMed Articles [26484 Associated PubMed Articles listed on BioPortfolio]

Mood and neuropsychological effects of different doses of ketamine in electroconvulsive therapy for treatment-resistant depression.

Treatment-resistant depression (TRD) is a growing clinical challenge. Electroconvulsive therapy (ECT) is an effective tool for TRD treatment. However, there remains a subset of patients who do not res...

Spontaneous Remission of Ketamine Withdrawal-Related Depression.

Ketamine, an antagonist of the N-methyl-D-aspartate receptor, has a rapid antidepressant effect, and its withdrawal may induce depression. However, the duration of depression and possibility of sponta...

Rapid and sustained reductions in current suicidal ideation following repeated doses of intravenous ketamine: secondary analysis of an open-label study.

Ketamine rapidly reduces thoughts of suicide in patients with treatment-resistant depression who are at low risk for suicide. However, the extent to which ketamine reduces thoughts of suicide in depre...

Change in cytokine levels is not associated with rapid antidepressant response to ketamine in treatment-resistant depression.

Several pro-inflammatory cytokines have been implicated in depression and in antidepressant response. This exploratory analysis assessed: 1) the extent to which baseline cytokine levels predicted posi...

Assessing the risk factors for difficult-to-treat depression and treatment-resistant depression.

Depression is the leading cause of disability among people across the globe, according to the World Health Organization. Among those who have been diagnosed, many fail to achieve remission after follo...

Medical and Biotech [MESH] Definitions

Hypertonic sodium chloride solution. A solution having an osmotic pressure greater than that of physiologic salt solution (0.9 g NaCl in 100 ml purified water).

A cyclohexanone derivative used for induction of anesthesia. Its mechanism of action is not well understood, but ketamine can block NMDA receptors (RECEPTORS, N-METHYL-D-ASPARTATE) and may interact with sigma receptors.

An MAO inhibitor that is effective in the treatment of major depression, dysthymic disorder, and atypical depression. It also is useful in the treatment of panic disorder and the phobic disorders. (From AMA, Drug Evaluations Annual, 1994, p311)

A hallucinogen formerly used as a veterinary anesthetic, and briefly as a general anesthetic for humans. Phencyclidine is similar to KETAMINE in structure and in many of its effects. Like ketamine, it can produce a dissociative state. It exerts its pharmacological action through inhibition of NMDA receptors (RECEPTORS, N-METHYL-D-ASPARTATE). As a drug of abuse, it is known as PCP and Angel Dust.

Decompression external to the body, most often the slow lessening of external pressure on the whole body (especially in caisson workers, deep sea divers, and persons who ascend to great heights) to prevent DECOMPRESSION SICKNESS. It includes also sudden accidental decompression, but not surgical (local) decompression or decompression applied through body openings.

More From BioPortfolio on "Low Dose Intravenous Ketamine in Treatment Resistant Depression Patients"

Quick Search

Relevant Topics

Antiretroviral therapy
Standard antiretroviral therapy (ART) consists of the combination of at least three antiretroviral (ARV) drugs to maximally suppress the HIV virus and stop the progression of HIV disease. Huge reductions have been seen in rates of death and suffering whe...

Psychiatry is the study of mental disorders and their diagnosis, management and prevention.  Conditions include schizophrenia, severe depression and panic disorders among others. There are pharmaceutical treatments as well as other therapies to help...

Mental Health
Adhd Anorexia Depression Dyslexia Mental Health Psychiatry Schizophrenia Stress Mental health, although not being as obvious as physical health, is very important, causing great unhappiness to those affected, causing add...

Searches Linking to this Trial