Ketamine for Depression: An MRI Study

Study Overview
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Brief Summary
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Ketamine has been shown to decrease symptoms of anxious depression quickly. This decrease has been shown to last for up to one month. MRI technology will be used before and after ketamine for patients with depression to examine the extent to which certain brain areas predict ketamine's antidepressant effects.

Detailed Description
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Ketamine's antidepressant effects were measured with Hamilton Depression Rating Scale (HDRS). MRI data will also be analyzed to examine the extent to which certain brain areas predict ketamine's antidepressant effects.

Official Title
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Baseline Insular Dysfunction as a Predictor of Ketamine's Antidepressant Effects in Anxious Depression

Conditions
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Depression, Anxious Depression, Major Depressive Disorder

Intervention / Treatment
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* Drug: Ketamine
* Other: Magnetic Resonance Imaging (MRI)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with Depression Patients will: be 18-64 years old, read, understand, and provide written informed consent in English, meet criteria for a primary psychiatric diagnosis of major depressive disorder for ≥ 4 weeks, have a history of ≥1 failed medication trial during the current depression be on a stable antidepressant and psychotherapy regimen for ≥28 days, maintain a treating doctor who is in agreement with study participation, have a reliable chaperone accompany them home following the completion of the ketamine infusion day, be generally healthy, as assessed by medical history, physical examination (including vital signs), clinical laboratory evaluations, and electrocardiogram (EKG), be of non-childbearing potential or use of an acceptable form of birth control (females only), be right handed. Exclusion Criteria: Patients with Depression Patients will be excluded if any of the following criteria are met: 1) delirium or dementia diagnosis, 2) unstable medical illness or clinically significant laboratory results, 3) history of clinically significant cardiovascular disease or electrocardiogram (EKG) findings, or medical conditions that put the patient at risk for possible cardiac side effects or alter brain morphology (e.g., traumatic brain injury), 4) history of multiple adverse drug reactions, 5) current/past history of psychotic disorders, 6) active substance use disorders (except nicotine and caffeine) within the past six months or past history of ketamine/PCP abuse, 7) requirement of excluded medications that may interact with ketamine, 8) weigh >250 lbs., 9) pregnancy, breastfeeding, or unacceptable means of birth control (females only) 10) presence of MRI contraindications (e.g., presence of metallic (ferromagnetic) implants (e.g., heart pacemaker, aneurysm clips)), 11) current serious suicidal or homicidal risk, or 12) concurrent participation in other research studies. --------------------------------------------------------------------------------------- Inclusion Criteria: Healthy Controls Healthy Controls will: be 18-64 years old, read, understand, and provide written informed consent in English, have a reliable chaperone accompany them home following the completion of the ketamine infusion day, be generally healthy, as assessed by medical history, physical examination (including vital signs), clinical laboratory evaluations, and electrocardiogram (EKG), be of non-childbearing potential or use of an acceptable form of birth control (females only), and be right handed. Exclusion Criteria: Healthy Controls Healthy controls will be excluded if any of the following criteria are met: current or past psychiatric diagnosis (excluding phobias), including alcohol or substance abuse or dependence diagnosis (except for nicotine or caffeine), presence of MRI contraindications (e.g., presence of metallic (ferromagnetic) implants (e.g., heart pacemaker, aneurysm clips)), presence of medical illness likely to alter brain morphology and/or physiology (e.g., traumatic brain injury), requirement of excluded medications that may interact with ketamine, presence of psychiatric disorders in first-degree relatives, pregnancy, breastfeeding, or unacceptable means of birth control (females only), or weight >250 lbs.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ketamine + MRI<br>All eligible participants will receive open label ketamine and undergo Magnetic Resonance Imaging (MRI). | Drug: Ketamine<br>* Ketamine 0.5mg/kg over 40 minutes IV<br>* Other names: Ketamine Hydrochloride;Other: Magnetic Resonance Imaging (MRI)<br>* MRI technology will be used before and after ketamine for patients with depression<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Hamilton Depression Rating Scale (HDRS) From Baseline/Minute 0 to 4 Hours Post-infusion. | Hamilton Depression Rating Scale; possible scores range from 0 to 81 with higher scores indicating higher depression symptoms Change will be calculated by difference between HDRS from Minute 0 to Minute 240. | 4 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change in Tissue Fractional Anisotropy Quantification (Left Inferior Longitudinal Fasciculus) | Free-water imaging, a two-compartment diffusion model, was employed to quantify tissue fractional anisotropy (FAt) pre- and post-infusion | 4 hours | 
| Percent Change in Tissue Fractional Anisotropy Quantification (Right Inferior Longitudinal Fasciculus) | Free-water imaging, a two-compartment diffusion model, was employed to quantify tissue fractional anisotropy (FAt) pre- and post-infusion | 4 hours | 
| Percent Change in Tissue Fractional Anisotropy Quantification (Left Superior Longitudinal Fasciculus) | Free-water imaging, a two-compartment diffusion model, was employed to quantify tissue fractional anisotropy (FAt) pre- and post-infusion | 4 hours | 
| Percent Change in Tissue Fractional Anisotropy Quantification (Right Uncinate Fasciculus) | Free-water imaging, a two-compartment diffusion model, was employed to quantify tissue fractional anisotropy (FAt) pre- and post-infusion | 4 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MRI, Ketamine, Depression, Anxious Depression