KET-RO Plus RO DBT for Treatment Resistant Depression

Study Overview
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Brief Summary
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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.

Official Title
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Medication-assisted Psychotherapy: Using Ketamine-enhanced Radically Open Dialectical Behavior Therapy (RO DBT) to Target Neural and Behavioral Mechanisms of Action in Emerging Adults With Moderate to Severe Depression

Conditions
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Treatment Resistant Depression

Intervention / Treatment
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* Combination Product: Ketamine Infusion plus RO DBT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females aged 18-25 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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 26 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ketamine Infusion<br> | Combination Product: Ketamine Infusion plus RO DBT<br>* 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.<br>|
| Experimental: Radically Open Dialectical Behavior Therapy (RO DBT)<br> | Combination Product: Ketamine Infusion plus RO DBT<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Remission from Depression | Remission defined as Montgomery and Asberg Depression Rating Scale (MADRS) score ≤10. Scale ranges from 0-60 with higher scores indicating higher depression severity. | Approximately 5 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual analogue scale of depressive and anxiety symptoms | Asses daily changes in symptoms following ketamine infusions and RODBT sessions | Daily following ketamine and therapy sessions during 4 weeks of ketamine-assisted RO DBT | 
| RewP | The RewP is a neural marker of reward responding and is EEG based. It will examine change id-treatment (Post Ketamine) and post treatment | Approximately 5 months | 
| ERN | The ERN is a neural marker of error monitoring and is EEG based. It will examine mechanistic change mid-treatment (post ketamine) and post-treatment. | Approximately 5 months | 
| SCS-R and UCLA Loneliness Scale | The Social Connectedness SCale Revised (SCS-R) and the UCLA loneliness scale measure social connectedness (or lack of) via self-report. They will examine mechanistic change mid-treatment (post ketamine) and post-treatment. | Approximately 5 months |