Major Depressive Disorder
Conditions
Keywords
ketamine, depression, treatment resistance, intranasal, antidepressant, glutamate, NMDA receptor
Brief summary
The objective of the current study is to investigate the safety and efficacy of a single dose of intranasal (IN) ketamine in treatment-resistant depression (TRD).
Interventions
DRUGKetamine
A single dose of intranasal ketamine up to 50 mg
DRUGplacebo
Single dose of saline intranasal
Sponsors
James Murrough
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female patients, 21-65 years; 2. Women of childbearing potential must agree to use a medically accepted means of contraception for the duration of the study; 3. Primary diagnosis of major depressive disorder as assessed by the SCID-P; 4. Current depressive episode; 5. History of a failure to respond to at least one (1) adequate pharmacotherapy trials in the current major depressive episode; 6. Subjects must have scored ≥ 30 on the IDS-C30 at Screening ≥ 24 at Treatment Day #1 and #2; 7. Each subject must have a level of understanding sufficient to agree to all tests and examinations required by the protocol and must sign an informed consent document; 8. Subjects must be able to identify a family member, physician, or friend who will participate in the Treatment Contract and serve as an emergency contact.
Exclusion criteria
1. Women who plan to become pregnant, are pregnant or are breast-feeding; 2. Any unstable medical illness including hepatic, renal, gastroenterologic, respiratory, cardiovascular, endocrinologic, neurologic, immunologic, or hematologic disease; 3. Clinically significant abnormal findings of laboratory parameters, physical examination, or ECG; 4. Lifetime history of schizophrenia, schizoaffective disorder, bipolar disorder, OCD, mental retardation, pervasive developmental disorders, or Tourette's syndrome; 5. Drug or alcohol abuse or dependence within the preceding 6 months; 6. Lifetime abuse or dependence on ketamine or phencyclidine; 7. Patients judged by study investigator to be at high risk for suicide. 8. Previous participation in a ketamine study at Mount Sinai
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Montgomery-Asberg Depression Rating Scale (MADRS) | 24 hours | Number of patients meeting response criteria of \>=50% decrease in MADRS score from baseline , ie, difference in depressive symptoms using MADRS instrument, 24 hours following drug administration 10-item instrument used for the evaluation of depressive symptoms in adults and for the assessment of any changes to those symptoms. Each of the 10 items is rated on a scale of 0 to 6, with differing descriptors for each item. These individual item scores are added together to form a total score, which can range between 0 and 60 points. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Systematic Assessment for Treatment Emergent Effects (SAFTEE) | 2 weeks | This is a self-report measure for systematically assessing 48 possible adverse events. It documents their severity, relationship to study drug, and the action taken. |
Countries
United States
Participant flow
Recruitment details
Study participants were recruited from physician referrals, media advertisements, and an academic outpatient psychiatric clinic. All study treatments were performed at Mount Sinai Medical Center between April 2012 and June 2013.
Participants by arm
| Arm | Count |
|---|---|
| Participants Treated | 20 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Second Intervention (7days) | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Participants Treated |
|---|---|
| Age, Continuous | 48.0 years STANDARD_DEVIATION 12.8 |
| Age of Onset | 21.4 years STANDARD_DEVIATION 12 |
| Atypical no | 18 participants |
| Atypical yes | 2 participants |
| Baseline Inventory of Depressive Symptoms- Clinician Rated (Screen) | 42.7 units on a scale STANDARD_DEVIATION 8.5 |
| Chronic no | 11 participants |
| Chronic yes | 9 participants |
| Current Anxiety Disorder no | 16 participants |
| Current Anxiety Disorder yes | 4 participants |
| Employed no | 10 participants |
| Employed yes | 10 participants |
| Failed Antidepressants Medications | 4.1 number of medications STANDARD_DEVIATION 3.9 |
| Gender Female | 10 Participants |
| Gender Male | 10 Participants |
| History of Electroconvulsive Therapy no | 16 participants |
| History of Electroconvulsive Therapy yes | 4 participants |
| History of Psychotherapy missing information | 1 participants |
| History of Psychotherapy no | 2 participants |
| History of Psychotherapy yes | 17 participants |
| History of Suicide Attempts no | 18 participants |
| History of Suicide Attempts yes | 2 participants |
| Illness Duration in Years | 27.4 years STANDARD_DEVIATION 13.7 |
| Length of Current Episode in Years | 15.2 years STANDARD_DEVIATION 17.4 |
| Married no | 14 participants |
| Married yes | 6 participants |
| Melancholic no | 11 participants |
| Melancholic yes | 9 participants |
| Past Substance Use Disorder no | 17 participants |
| Past Substance Use Disorder yes | 3 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 | 18 Participants |
| Recurrent no | 3 participants |
| Recurrent yes | 17 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 19 / 19 | 19 / 19 |
| serious Total, serious adverse events | 0 / 19 | 0 / 19 |
Outcome results
Primary
Montgomery-Asberg Depression Rating Scale (MADRS)
Number of patients meeting response criteria of \>=50% decrease in MADRS score from baseline , ie, difference in depressive symptoms using MADRS instrument, 24 hours following drug administration 10-item instrument used for the evaluation of depressive symptoms in adults and for the assessment of any changes to those symptoms. Each of the 10 items is rated on a scale of 0 to 6, with differing descriptors for each item. These individual item scores are added together to form a total score, which can range between 0 and 60 points.
Time frame: 24 hours
Population: 20 patients randomized and 18 completed both treatment periods
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ketamine | Montgomery-Asberg Depression Rating Scale (MADRS) | 8 participants |
| Placebo | Montgomery-Asberg Depression Rating Scale (MADRS) | 1 participants |
Comparison: within-subject crossover designp-value: <0.00195% CI: [3.9, 11.3]Paired t-test, 2 sided
Secondary
Systematic Assessment for Treatment Emergent Effects (SAFTEE)
This is a self-report measure for systematically assessing 48 possible adverse events. It documents their severity, relationship to study drug, and the action taken.
Time frame: 2 weeks
Population: Number of events, more detailed in adverse event section
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ketamine | Systematic Assessment for Treatment Emergent Effects (SAFTEE) | 79 events |
| Placebo | Systematic Assessment for Treatment Emergent Effects (SAFTEE) | 57 events |