Integrating Ketamine Effects on Neuronal Molecular Signatures and the Brain Functional and Structural Connectome
Massachusetts General Hospital
Summary
Subanesthetic dose of intravenous ketamine (KET) has been found to be highly effective in rapid treatment depression and associated suicidality but its exact mechanism of remains uncertain. This study will use a novel approach to elucidate KET's effects on the molecular/ gene expression pathways in living neurons obtained from the olfactory epithelium and correlate the changes to rapid improvement in depression via changes in the brain connectome. The study will identify the molecular targets and pathways involved in KET'S mechanism of rapid clinical action and pave the way for development of novel, more efficacious, and safer therapeutic agents.
Description
We propose a mechanistic clinical trial to identify molecular and imaging correlates of rapid action of intravenous subanesthetic dose of ketamine (KET). KET is a rapidly acting highly effective treatment for depression and frequently accompanying suicidality. However, its mechanism of rapid action remains unclear which has hindered development of methods to monitor its effects and development of new medications with similar efficacy but more favorable side-effects profile. A basic science bottom-up approach for identification and development of novel drug agents has a high degree of uncertain…
Eligibility
- Age range
- 18–50 years
- Sex
- All
- Healthy volunteers
- Yes
Inclusion Criteria: * 1\. Able to give voluntary informed consent; 2. Satisfy criteria for Diagnostic and Statistical Manual 5th edition (DSM-V) for Major Depression Disorder (MDD) 3. Currently in a depressive episode (MDE); 4. Montgomery and Asberg Depression Rating Scale (MADRS) score \>21 but \<32(moderate to severe depression)11; 3. Psychotropic medication-free \> 2weeks and if on fluoxetine then for \>5 weeks at time of inclusion in the study(no taper or medication washout will be done for the purpose of the study). 6. Satisfy criteria to undergo an MRI scan based on MRI screening questi…
Interventions
- Drugketamin
Participants in this study will have been diagnosed with major depressive episode (MDE) and have not received any psychiatric treatment for at least 2 weeks (5 weeks if on fluoxetine).Patients will receive intravenous ketamine as the only study drug treatment for the 2 weeks of the study. Magnetic Resonance Imaging (MRI) will be used to measure effects of ketamine on brain structure, function and chemistry, in addition to a soft-nasal brushing procedure to obtain olfactory sensory neurons which will provide the ability to profile in vivo how neurons may react to KET treatment in depressed patients.
Location
- Massachusetts General HosipitalBoston, Massachusetts