Treatment Resistant Depression
Conditions
Brief summary
This pilot study will assess the safety and feasibility of intravenous (IV) ketamine combined with RO DBT in young adults with Treatment-Resistant Depression (TRD). In addition, this study will develop and utilize innovative methodological approaches to demonstrate the feasibility of precision medicine with this type of therapy.
Interventions
COMBINATION_PRODUCTKetamine Infusion plus RO DBT
The participant will receive 4 weeks of 0.5mg/kg intravenous ketamine given over 40 minutes, as is routinely done in ketamine treatment and four months of RO DBT treatment.
Sponsors
Washington University School of Medicine
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Males and females aged 18-65 * Moderate to severe persistent depression \[treatment resistant depression - TRD\] (exhibiting 2+ unipolar major depression episodes (non-delusional) with prior treatment non-response to antidepressant or psychosocial treatment * Treatment-resistant depression: defined as unipolar major depressive disorder, non-delusional (diagnosed by SCID-5, Structured Clinical Interview for the DSM ) 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 Triiodothyroinine) higher proportion of OC (over controlled) words endorsed compared to UC (Under controlled) words on the Word Pairs Checklist * no current or past psychosis * English speaking * Able to attend in-person behavioral sessions and ketamine/therapy visits * Willingness to have RO DBT-A as only psychosocial treatment engaged in (medication treatment may continue-but see below for exclusion)
Exclusion criteria
* Outside age range * Significant neurological condition (i.e., seizure, stroke, severe head injury) or mental retardation (IQ\<70) * Current or recent substance use disorder, actively suicidal or homicidal (e.g., requires hospitalization) * Use of naltrexone, memantine or medication considered contraindicated with ketamine * Baseline systolic BP \> 150 systolic or 90 diastolic at evaluation. Participants who initially present with elevated blood pressure may be re-assessed; and if needed, referred to their healthcare provider for hypertension management * Taking more than 2 adequately-dosed oral antidepressants * Inability to understand, speak and read English sufficiently * Not be pregnant or at risk of becoming pregnant * Medical conditions or medication usage that in the judgement of the investigators puts the patient at unreasonable safety risk * First degree relative with a psychotic diagnosis involving hallucinations, delusions, or disorganized thinking and speech (e.g. schizophrenia, schizoaffective disorder, etc)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Decrease in Depressive Symptoms | Approximately 5 months | Decrease in depressive symptoms as assessed via the Montgomery and Asberg Depression Rating Scale (MADRS), a clinician-interviewed assessment of depressive symtpoms. Scale ranges from 0-60 with higher scores indicating higher depression severity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Visual Analogue Scale (VAS) of Depressive and Anxiety Symptoms | Completed immediately following individual ketamine sessions during 4 weeks of ketamine-assisted RO DBT | Visual analogue sliding scale (0-100) of self-reported ratings of feeling "depressed" or "anxious" in the moment, with higher scores indicating higher depression or anxiety. This visual analogue scale was administered three times: pre-ketamine, 40 minutes post-ketamine and 90 minutes post-ketamine. Reported below is the average rating across all ketamine sessions across the 4 weeks at the 90 minute post-ketamine reported. Units of measure are on the 0 to 100 scale. |
| Reward Positivity (RewP) | Immediately post-treatment (approximately 5 months since baseline) | The Reward Positivity (RewP) is an electroencephalogram (EEG) based event related potential (ERP) and neural marker of reward responding. During the "Doors Task", a commonly used task to elicit the RewP, participants can win money or lose money when opening doors. The RewP is calculated as the electrical signal in response to winning at electrode Cz on the scalp minus the electrical signal in response to losing at electrode Cz between the timepoints 250-500ms. Thus, it is a difference score of win minus loss response to assess reward response and is measured via microvolts with higher scores indicating a stronger neural response to reward. It will examine change mid-treatment (Post Ketamine) and post treatment. Post-treatment RewP scores reported below. |
| Error-related Negativity (ERN) | Immediately post-treatment (approximately 5 months since baseline) | The erorr-related negativity (ERN) is an electroencephalogram (EEG) based neural marker of error monitoring measured via an event related potential (ERP). It is elicited via Go/No-go tasks where participants make 'correct' responses and 'error' responses. The ERN is calculated as the electrical signal in response to making an error response at Cz on the scalp minus the electrical signal in response to making a correct response at electrode Cz between timepoints 0-50ms. Thus, it is a difference score of error - correct neurla response to assess error or performance monitoring and is measured via microvolts with higher scores indicating a larger response to errors. It will examine change mid-treatment (post ketamine) and post-treatment. Post-treatment ERN scores reported below. |
| Social Connectedness Scale- Revised (SCS-R) | Immediately post-treatment (approximately 5 months since baseline) | The Social Connectedness Scale Revised (SCS-R) is a self-report that assesses interpersonal closeness with a range of scores from 20 to 120, with a higher total score indicating greater social connectedness. This measure will examine mechanistic change mid-treatment (post ketamine) and post-treatment; Post-treatment scores provided below. |
| UCLA Loneliness Scale | Immediately post-treatment (approximately 5 months since baseline) | The UCLA loneliness scale measure social connectedness (or lack of given it assesses perceived loneliness) via self-report with a range of 20 to 80 with higher scores indicating greater loneliness. This measure will examine mechanistic change mid-treatment (post ketamine) and post-treatment; Post-treatment scores provided below. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORKirsten Gilbert, PhD
Washington University School of Medicine
Participant flow
Pre-assignment details
16 participants were consented and enrolled. However, 3 participants were deemed ineligible at the baseline assessment and did not start treatment.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 29.32 age in years STANDARD_DEVIATION 12.47 |
| MADRS | 26.15 score on MADRS STANDARD_DEVIATION 5.61 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 1 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 | 10 Participants |
| Region of Enrollment United States | 13 Participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 13 |
| other Total, other adverse events | 0 / 13 |
| serious Total, serious adverse events | 0 / 13 |
Outcome results
None listed