Anxious Depression, Depression, Major Depressive Disorder
Conditions
Keywords
Ketamine, Depression, Anxious Depression, MRI
Brief summary
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
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.
Interventions
DRUGKetamine
Ketamine 0.5mg/kg over 40 minutes IV
OTHERMagnetic Resonance Imaging (MRI)
MRI technology will be used before and after ketamine for patients with depression
Sponsors
Brain & Behavior Research Foundation
National Institutes of Health (NIH)
Massachusetts General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
Yes
Inclusion criteria
Patients with Depression Patients will: 1. be 18-64 years old, 2. read, understand, and provide written informed consent in English, 3. meet criteria for a primary psychiatric diagnosis of major depressive disorder for ≥ 4 weeks, 4. have a history of ≥1 failed medication trial during the current depression 5. be on a stable antidepressant and psychotherapy regimen for ≥28 days, 6. maintain a treating doctor who is in agreement with study participation, 7. have a reliable chaperone accompany them home following the completion of the ketamine infusion day, 8. be generally healthy, as assessed by medical history, physical examination (including vital signs), clinical laboratory evaluations, and electrocardiogram (EKG), 9. be of non-childbearing potential or use of an acceptable form of birth control (females only), 10. 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: 1. be 18-64 years old, 2. read, understand, and provide written informed consent in English, 3. have a reliable chaperone accompany them home following the completion of the ketamine infusion day, 4. be generally healthy, as assessed by medical history, physical examination (including vital signs), clinical laboratory evaluations, and electrocardiogram (EKG), 5. be of non-childbearing potential or use of an acceptable form of birth control (females only), and 6. be right handed.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Hamilton Depression Rating Scale (HDRS) From Baseline/Minute 0 to 4 Hours Post-infusion. | 4 hours | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Tissue Fractional Anisotropy Quantification (Left Inferior Longitudinal Fasciculus) | 4 hours | Free-water imaging, a two-compartment diffusion model, was employed to quantify tissue fractional anisotropy (FAt) pre- and post-infusion |
| Percent Change in Tissue Fractional Anisotropy Quantification (Right Inferior Longitudinal Fasciculus) | 4 hours | Free-water imaging, a two-compartment diffusion model, was employed to quantify tissue fractional anisotropy (FAt) pre- and post-infusion |
| Percent Change in Tissue Fractional Anisotropy Quantification (Left Superior Longitudinal Fasciculus) | 4 hours | Free-water imaging, a two-compartment diffusion model, was employed to quantify tissue fractional anisotropy (FAt) pre- and post-infusion |
| Percent Change in Tissue Fractional Anisotropy Quantification (Right Uncinate Fasciculus) | 4 hours | Free-water imaging, a two-compartment diffusion model, was employed to quantify tissue fractional anisotropy (FAt) pre- and post-infusion |
Countries
United States
Participant flow
Recruitment details
As specified, the total number of participants enrolled are those who agreed to participate in the study following completion of the informed consent process (n=25). This number does not reflect the number of subjects who actually started treatment (n=16).
Participants by arm
| Arm | Count |
|---|---|
| Ketamine All eligible participants will receive open label ketamine
Ketamine: Ketamine 0.5mg/kg over 40 minutes IV | 16 |
| Total | 16 |
Baseline characteristics
| Characteristic | Ketamine |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 16 Participants |
| Age, Continuous | 42 years STANDARD_DEVIATION 14 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 15 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 14 Participants |
| Region of Enrollment United States | 16 participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 16 |
| other Total, other adverse events | 1 / 16 |
| serious Total, serious adverse events | 0 / 16 |
Outcome results
Primary
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.
Time frame: 4 hours
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Ketamine | Change in Hamilton Depression Rating Scale (HDRS) From Baseline/Minute 0 to 4 Hours Post-infusion. | -9.625 score on a scale |
p-value: <0.01t-test, 2 sided
Secondary
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
Time frame: 4 hours
Population: Reasons for missing data (N=3) included a scanner malfunction and participant requests to stop scanning prior to dMRI sequence acquisition.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ketamine | Percent Change in Tissue Fractional Anisotropy Quantification (Left Inferior Longitudinal Fasciculus) | .901 percent change |
p-value: 0.048t-test, 2 sided
Secondary
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
Time frame: 4 hours
Population: Reasons for missing data (N=3) included a scanner malfunction and participant requests to stop scanning prior to dMRI sequence acquisition.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ketamine | Percent Change in Tissue Fractional Anisotropy Quantification (Left Superior Longitudinal Fasciculus) | .696 percent change |
p-value: 0.0499t-test, 2 sided
Secondary
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
Time frame: 4 hours
Population: Reasons for missing data (N=3) included a scanner malfunction and participant requests to stop scanning prior to dMRI sequence acquisition.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ketamine | Percent Change in Tissue Fractional Anisotropy Quantification (Right Inferior Longitudinal Fasciculus) | 1.247 percent change |
p-value: 0.003t-test, 2 sided
Secondary
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
Time frame: 4 hours
Population: Reasons for missing data (N=3) included a scanner malfunction and participant requests to stop scanning prior to dMRI sequence acquisition.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ketamine | Percent Change in Tissue Fractional Anisotropy Quantification (Right Uncinate Fasciculus) | 1.158 percent change |
p-value: 0.038t-test, 2 sided