Geriatric Depression, Late Life Depression, Refractory Depression, Therapy-Resistant Depression, Treatment Resistant Depression
Conditions
Keywords
ketamine
Brief summary
This pilot study will assess the safety and feasibility of intravenous (IV) ketamine in older adults with Treatment-Resistant Depression (TRD). In addition, this study will develop and utilize innovative methodological approaches to demonstrate the feasibility of precision medicine and mobile health approaches in depression treatment.
Detailed description
Participants in this study will receive ketamine infusions twice a week for 4 weeks (acute phase). Participants who respond or remit will continue with an additional 4 weeks of weekly ketamine infusions (continuation phase). Participants will be assessed at baseline, end of acute phase, and end of continuation phase for effectiveness, safety, and executive functioning. Participants will be asked to complete daily surveys of their depression symptoms during their participation.
Interventions
DRUGKetamine
ketamine will be infused using an IV infusion pump at a rate of 0.5 mg/kg of body weight over 40 minutes
Sponsors
Washington University School of Medicine
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Community-living men and women age 65 years and older; 2. Treatment-resistant depression: defined as unipolar major depressive disorder, non-delusional (diagnosed by SCID-5) that persists despite ≥ 2 adequate antidepressant trials of different classes in the current episode; including at least one evidence-based second-line treatment in the current episode (including serotonin norepinephrine reuptake inhibitors, bupropion, tricyclics, monoamine oxidase inhibitors, or augmentation with an atypical antipsychotic, stimulant, bupropion, lithium, or triiodothyronine 3. Persistent moderate to severe depressive symptoms determined by Patient Health Questionnaire 9-item (PHQ-9)26 score ≥15 at baseline 4. Able to provide informed consent.
Exclusion criteria
1. Dementia per history, score \< 24 on the Montreal Cognitive Assessment (MoCA), or determined by clinical interview with geriatric psychiatrist to have high likelihood of dementia; 2. Psychotic spectrum or bipolar disorder or severe personality disorder that at the PIs discretion would interfere with safe participation. Anxiety disorders are not an exclusion. 3. Unstable medical conditions such that IV ketamine is not safe or tolerated or that would interfere with participation in a long-term study (i.e., poorly controlled hypertension, life expectancy \< 1 year because of terminal illness, unstable angina). 4. Baseline systolic BP \> 165 systolic or 100 diastolic at evaluation. 5. Current alcohol or substance use disorder or lifetime recreational ketamine use or other dissociative agent (e.g., PCP). 6. Use of naltrexone, memantine, or any medication that could be considered contraindicated with ketamine. 7. Taking more than 2 adequately-dosed oral antidepressants. 8. High acute risk for suicide and unable to be managed safely in the clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Remission From Depression | 4 weeks for acute phase, 8 weeks for continuation phase | Remission defined as Montgomery Asberg Depression Rating Scale score ≤10. Scale ranges from 0-60 with higher scores indicating higher depression severity. |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Acute Infusion Acute phase: ketamine infusions twice a week for 4 weeks
Ketamine: ketamine will be infused using an IV infusion pump at a rate of 0.5 mg/kg of body weight over 40 minutes | 23 |
| Total | 23 |
Baseline characteristics
| Characteristic | Acute Infusion |
|---|---|
| Age, Continuous | 71.5 years STANDARD_DEVIATION 4.9 |
| CIRS-G Total | 8.1 units on a scale STANDARD_DEVIATION 5.4 |
| DCCS | 98.2 Z-score STANDARD_DEVIATION 13.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 22 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Flanker | 82.7 Z-score STANDARD_DEVIATION 9 |
| Fluid Cognition Composite | 92.4 t-score STANDARD_DEVIATION 13.7 |
| List Sorting | 101.0 Z-score STANDARD_DEVIATION 15.6 |
| MADRS Total | 24.4 units on a scale STANDARD_DEVIATION 7.9 |
| Pattern Processing Speed | 87.7 units on a scale STANDARD_DEVIATION 17.7 |
| Picture Sequence Memory | 102.5 Z-score STANDARD_DEVIATION 13.2 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 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 | 0 Participants |
| Race (NIH/OMB) White | 23 Participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 11 Participants |
| Years of education | 16.2 years STANDARD_DEVIATION 1.9 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 23 | 0 / 15 |
| other Total, other adverse events | 4 / 23 | 0 / 15 |
| serious Total, serious adverse events | 0 / 23 | 0 / 15 |
Outcome results
Primary
Remission From Depression
Remission defined as Montgomery Asberg Depression Rating Scale score ≤10. Scale ranges from 0-60 with higher scores indicating higher depression severity.
Time frame: 4 weeks for acute phase, 8 weeks for continuation phase
Population: 25 adults ages 60 years or over with Treatment-Resistant Depression (TRD) received IV ketamine infusion twice a week for 4 weeks (the acute phase); people who responded to the infusion at the end of the acute phase went to receive weekly infusions for 4 more weeks in a continuation phase.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Acute Infusion | Remission From Depression | Acute phase | 6 Participants |
| Acute Infusion | Remission From Depression | Continuation phase | 4 Participants |