Ketamine + Mindfulness for Depression

In this project, the investigators will administer a single infusion of IV ketamine to depressed patients and randomize the patients to receive either a) usual/typical infusion conditions or b) mindfulness training and exercises in conjunction with the infusion. Investigators will test whether the conjunction of ketamine + mindfulness enhances the reductions in depression following a single ketamine infusion.

Study Overview

• Status: Completed
• Conditions: Depression, Unipolar
• Intervention / Treatment: Drug: Intravenous Ketamine; Behavioral: Brief Mindfulness Exercises; Behavioral: Academic Exercises

Detailed Description

NOTE: The study's target sample size was revised after beginning the study, based on a revised available budget.

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Western Psychiatric Institute And Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

All participants will:

1. be between the ages of 18 and 65 years,
2. score ≥ 14 on the Hamilton Depression Rating Scale (modified Ham-D)
3. possess a level of understanding sufficient to agree to all tests and examinations required by the protocol and must sign an informed consent document

Exclusion Criteria:

All participants:

1. Presence of lifetime bipolar, psychotic, or autism spectrum; current problematic substance use (e.g., ongoing moderate-to-severe substance use disorder);
2. Acute suicidality or other psychiatric crises requiring treatment escalation. We will use the Columbia Suicide Severity Rating Scale (CSSRS) as both an initial exclusion criteria (CSSRS "Baseline/Screening" Version for past 1month period) and as grounds for rescue/removal (CSSRS "Since Last Visit" form). The CSSRS will be administered using a paper form by an experienced and thoroughly trained clinical assessor on the study team. Subjects with CSSRS suicide ideation scores scored "yes" on items 4 (active suicidal ideation with some intent to act) and/or 5 (active suicidal ideation with specific plan and intent) will be excluded from the study, and if enrolled, will be exited from the study and referred immediately to the nearest emergency mental health facility for additional thorough assessment and appropriate treatment referral.
3. Changes made to treatment regimen within 4 weeks of baseline assessment.
4. Reading level <6th grade as per patient self-report.
5. Patients who have received ECT in the past 2 months prior to Screening.
6. Current pregnancy or breastfeeding
7. Patients must be reasonable medical candidates for ketamine infusion, as determined by a physician co-investigator. Serious, unstable medical illnesses including respiratory [obstructive sleep apnea, or history of difficulty with airway management during previous anesthetics], cardiovascular [including ischemic heart disease and uncontrolled hypertension], and neurologic [including history of severe head injury] will be exclusions.
8. Clinically significant abnormal findings of laboratory parameters [including urine toxicology screen for unreported drugs of abuse], vitals, or ECG.
9. Uncontrolled or poorly controlled hypertension, as determined by a physician co-investigator's review of vitals collected during screening and any other relevant medical history/records.
10. Patients with one or more seizures without a clear and resolved etiology.
11. Patients starting hormonal treatment (e.g., estrogen) in the 3 months prior to Screening.
12. Past intolerance or hypersensitivity to ketamine.
13. Patients taking medications with known activity at the NMDA or AMPA glutamate receptor [riluzole, amantadine, memantine, topiramate, dextromethorphan, D-cycloserine], or the mu-opioid receptor [opiate medications--morphine, oxycodone, heroin, fentanyl)]. However, lamotrigine will not be a study exclusion given that it has been shown not to impact ketamine's safety profile or its antidepressant efficacy.
14. Patients taking any of the following medications: St John's Wort, theophylline, tramadol, metrizamide.
15. Patients who report meditating with mindfulness techniques >1 hour weekly (on average) for the past 6 months or longer.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intravenous Ketamine + Mindfulness Exercises	Drug: Intravenous Ketamine; Single infusion of intravenous racemic ketamine (0.5mg/kg over 40min); Behavioral: Brief Mindfulness Exercises; 30min guided training in mindfulness meditation immediately prior to infusion
Active Comparator: Intravenous Ketamine + Academic Exercises	Drug: Intravenous Ketamine; Single infusion of intravenous racemic ketamine (0.5mg/kg over 40min); Behavioral: Academic Exercises; 30min of mental math and other academic cognitive puzzles completed silently/mentally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Montgomery-Asberg Depression Rating Scale	Clinician-rated depression (range: 0-60; higher scores = worse outcome)	24hrs post-intervention
Montgomery-Asberg Depression Rating Scale	Clinician-rated depression (range: 0-60; higher scores = worse outcome)	5 days post-intervention
Montgomery-Asberg Depression Rating Scale	Clinician-rated depression (range: 0-60; higher scores = worse outcome)	12 days post-intervention
Montgomery-Asberg Depression Rating Scale	Clinician-rated depression (range: 0-60; higher scores = worse outcome)	21 days post-intervention
Montgomery-Asberg Depression Rating Scale	Clinician-rated depression (range: 0-60; higher scores = worse outcome)	30 days post-intervention
State Mindfulness Scale	Self-reported mindfulness (range 21-105; higher scores = more mindfulness)	80min post-infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quick Inventory of Depressive Symptoms	Self-reported depression (range: 0-27; higher scores = worse outcome)	24hrs post-intervention
Quick Inventory of Depressive Symptoms	Self-reported depression (range: 0-27; higher scores = worse outcome)	5 days post-intervention
Quick Inventory of Depressive Symptoms	Self-reported depression (range: 0-27; higher scores = worse outcome)	12 days post-intervention
Quick Inventory of Depressive Symptoms	Self-reported depression (range: 0-27; higher scores = worse outcome)	21 days post-intervention
Quick Inventory of Depressive Symptoms	Self-reported depression (range: 0-27; higher scores = worse outcome)	30 days post-intervention
Mindful Attention Awareness Scale	self-reported trait mindfulness (range: 1-6; higher scores=greater mindfulness)	24hrs post-intervention
Mindful Attention Awareness Scale	self-reported trait mindfulness (range: 1-6; higher scores=greater mindfulness)	5 days post-intervention
Mindful Attention Awareness Scale	self-reported trait mindfulness (range: 1-6; higher scores=greater mindfulness)	12 days post-intervention
Mindful Attention Awareness Scale	self-reported trait mindfulness (range: 1-6; higher scores=greater mindfulness)	21 days post-intervention
Mindful Attention Awareness Scale	self-reported trait mindfulness (range: 1-6; higher scores=greater mindfulness)	30 days post-intervention
Modified Hamilton Depression Rating Scale	Clinician-rated depression (range: 0-52; higher scores = worse outcome)	24hrs post-intervention
Modified Hamilton Depression Rating Scale	Clinician-rated depression (range: 0-52; higher scores = worse outcome)	5 days post-intervention
Modified Hamilton Depression Rating Scale	Clinician-rated depression (range: 0-52; higher scores = worse outcome)	12 days post-intervention
Modified Hamilton Depression Rating Scale	Clinician-rated depression (range: 0-52; higher scores = worse outcome)	21 days post-intervention
Modified Hamilton Depression Rating Scale	Clinician-rated depression (range: 0-52; higher scores = worse outcome)	30 days post-intervention
Hood Mysticism Scale	clinician-administered to assess mystical experiences (range: -64 to +64; higher scores = greater mystical experience)	40 minutes post-intervention
Daily Spiritual Experience Scale	self-reported spiritual experiences (range: 1-6; higher scores=greater spiritual experience)	5 days post-intervention
Daily Spiritual Experience Scale	self-reported spiritual experiences (range: 1-6; higher scores=greater spiritual experience)	12 days post-intervention
Daily Spiritual Experience Scale	self-reported spiritual experiences (range: 1-6; higher scores=greater spiritual experience)	21 days post-intervention
Daily Spiritual Experience Scale	self-reported spiritual experiences (range: 1-6; higher scores=greater spiritual experience)	30 days post-intervention

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Awe Experience Scale	self-report measure of awe-inspiring experiences (range: 30-210; higher score=greater awe)	infusion +80min
Sustained Attention Response Task (SART) Omission Errors	performance-based measure of mindful attention	infusion +24 hours (1 day)
Sustained Attention Response Task (SART) Self-reported Task Focus	self-report rating of being on-task (range: 1-7; higher score=more on-task)	infusion +24 hours (1 day)
Dual Probe Video Task	attentional bias (proportion score) towards sad film clips (range: 0-1.0; higher score=greater attention bias towards sad films)	infusion +24 hours (1 day)
Pain Rating Via Quantitative Sensory Testing	Pain rating obtained from Quantitative Sensory Testing by mechanical temporal summation (range: 0-10; higher score=more pain)	1-hour post-infusion
PROMIS Pain Intensity Score	PROMIS Pain Intensity Short Form scale T-score (range=0-100; higher score=worse pain)	1-hour post-infusion
PROMIS Pain Interference Score	PROMIS Pain Interference Short Form scale T-score (range=0-100; higher score=worse pain)	1-hour post-infusion

Collaborators and Investigators

• Sponsor: Rebecca Price
• Investigators: Principal Investigator: Rebecca Price, PhD, University of Pittsburgh

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2022
• Primary Completion (Actual): August 1, 2023
• Study Completion (Actual): September 1, 2023

Study Registration Dates

• First Submitted: December 9, 2021
• First Submitted That Met QC Criteria: December 9, 2021
• First Posted (Actual): December 23, 2021

Study Record Updates

• Last Update Posted (Actual): August 20, 2024
• Last Update Submitted That Met QC Criteria: July 30, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Ketamine
• Other Study ID Numbers: STUDY21110040

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No