KAP for Depression in Abstinent Opioid Users

Study Overview
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Brief Summary
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The purpose of the study is to examine whether an investigational medication called ketamine along with psychotherapy is an effective treatment for depression in participants with a history of opioid addiction who have not abused opioids in at least 3 months. Participants will receive ketamine through intramuscular injection along with psychotherapy weekly for 8 weeks. Participation for eligible subjects who decide to enroll (including post-medication follow-up visits) will last about 16 weeks or 4 months.

Official Title
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Ketamine-assisted Psychotherapy for the Treatment of Persistent Depression in Abstinent Opioid Users

Conditions
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Opioid Use Disorder, Severe, in Sustained Remission, Opioid Use Disorder, Severe, in Early Remission, Major Depressive Disorder

Intervention / Treatment
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* Drug: Ketamine-assisted psychotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria A subject may be eligible for enrollment if all the following inclusion criteria apply within the thirty days prior to first experimental session: Between the ages of 18 to 64 years old. Able to provide informed consent. Meet DSM-5 criteria for Major Depressive Disorder, without psychotic features based on clinical interview. Score at least 20 on the Montgomery-Asberg Depression Rating Scale (MADRS, moderate or severe depression). Must meet criteria for opioid use disorder in early or sustained remission criteria by DSM-5 based on clinical interview. Subjects taking other psychotropic medications (e.g. anti-depressants, anxiolytics, methadone, buprenorphine, naltrexone) must be maintained on a stable dose for at least four weeks before study initiation. Exclusion Criteria Subjects will be excluded from the study if any of the following criteria apply: They are considered an immediate suicide risk by clinician assessment, self-reports a suicide attempt within the past year, or felt to be likely to require hospitalization during the study. Subjects who meet DSM-5 criteria for current bipolar disorder based on clinical interview. Subjects who meet DSM-5 criteria for current or history of psychotic spectrum disorders based on clinical interview. Subjects meeting DSM-5 criteria for current substance use disorder (i.e., not in early or sustained remission) other than tobacco use disorder. Subjects who report use of ketamine >20 times in the past or who meet DSM-5 criteria for Other Hallucinogen Use Disorder due to ketamine use including subjects who are currently in early or sustained remission. Women who are pregnant or nursing, and women who do not consent to use methods of highly effective birth control during the interventional phase of the study. Subjects with hypertension as defined by a baseline visit systolic blood pressure (SBP) >140 mmHg or a diastolic blood pressure (DBP) >90 mmHg. A history of allergic or other adverse reaction to ketamine (or its excipients). Clinically significant physical exam findings or self-reported medical conditions for which a transient increase in blood pressure could be significantly detrimental (e.g. glaucoma, aneurysmal disease, cardiovascular disease, or end-stage renal disease). QTc will be measured in all subjects and those with QTc 450ms or longer will be excluded. Subjects who live greater than 20 miles from the study site and cannot arrange their own transportation will be excluded from the study. Subjects with kidney or liver impairment.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ketamine-assisted psychotherapy<br>Subjects will receive 8 weekly intramuscular injections of ketamine hydrochloride starting at 0.5 mg/kg and increasing to a maximum dose of 1.5 mg/kg or a total dose of 60 mg, whichever is lower. Ketamine administration will be accompanied by psychotherapy before, after and during the session. | Drug: Ketamine-assisted psychotherapy<br>* Subjects will receive 8 weekly intramuscular injections of ketamine hydrochloride starting at 0.5 mg/kg and increasing to a maximum dose of 1.5 mg/kg or a total dose of 60 mg, whichever is lower. Ketamine administration will be accompanied by psychotherapy before, after and during the session.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Montgomery Asberg Depression Rating Scale | Clinician-administered rating of depressive symptoms; minimum score of 0, maximum score of 60; a decrease in score means a better outcome (less depressed) | Change from baseline measured at week 9 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Beck Depression Inventory | Self-rated depression inventory; minimum score of 0 maximum score of 63 with lower scores being a better outcome (less depressed) | Change from baseline measured at week 1-9, 10, 12, and 16 | 
| Visual Analog Scale (VAS) | Measure of subjective level of opioid craving; maximum score of 100 and minumum score of 0 with higher scores meaning worse outcome (more cravings) | Measured at week 1-9, 10, 12, and 16 | 
| Generalized Anxiety Disorder-7 (GAD-7) | Self-report of anxiety symptom severity; minimum score of 0 and maximum score of 21 with higher scores meaning worse outcome (more anxious) | Measured at week 1-9, 10, 12, and 16 | 
| Mystical Experience Questionnaire (MEQ) | Measure of perceptual experiences; multiple items rated on a 5 point scale with higher scores indicating more intense experience | Measured at week 1-8 | 
| Brief Pain Inventory (BPI) | Measure of pain and quality of life; maximum score of 10 and minimum of 1 with higher scores indicating worse outcome (more pain) | Measured at week 1-9, 10, 12, and 16 | 
| Insomnia Severity Index (ISI) | Assesses insomnia and sleep quality; maximum score of 28 and minimum score of 0 with higher score indicating worse outcome (worse sleep) | Measured at week 1-9, 10, 12, and 16 | 
| Five Facets of Mindfulness Questionnaire (FFMQ) | Assesses aspects of mindfulness; maximum score of 40 and minimum score of 8 with higher scores indicating better outcome (more mindfulness) | Measured at week 1-9, 10, 12, and 16 | 
| PTSD Checklist (PCL-5; PTSD checklist 5) | Measure of PTSD symptoms; maximum score 80 and minimum score of 0 with higher scores indicating worse outcome (more PTSD symptoms) | Measured at week 1-9, 10, 12, and 16 | 
| Timeline Follow-back (TLFB) | Measure of Substance Use; maximum number of substance use days per week is 7 and minimum is 0 with higher number indicating worse outcomes (more substance use) | Measured at week 1-9, 10, 12, and 16 | 
| Montgomery Asberg Depression Rating Scale | Clinician-administered rating of depressive symptoms; minimum score of 0, maximum score of 60; a decrease in score means a better outcome (less depressed) | Change from baseline measured at week 2-8, 10, 12, and 16 |