Ketamine-Assisted Psychotherapy for Treatment-Resistant Depression

NCT07247006 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: STUDY00010828
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to understand the effect of ketamine on the brain in people with treatment-resistant depression (TRD). TRD occurs in around a third of people with depression and leads to higher suicide rates compared to those with major depressive disorder. A desperate need for a rapid acting antidepressant drug (RAAD) is needed to help improve quality of life for people with TRD. Ketamine has been shown to be a RAAD, and esketamine (a form of ketamine) was approved by the FDA to treat TRD. Ketamine has been known to cause dissociative experiences, that can lead to an increase in the "Openness to Experience" personality trait and psychological flexibility that occurs at "peak experience". This has been shown to improve mental health conditions and lower suicide risk. This study aims to further understand if there is a connection between this new change of mind and changes in brain activity. Ketamine has been shown to improve brain plasticity as well, specifically in the frontolimbic region of the brain, an area associated with depression. The investigators are analyzing the brain using functional magnetic resonance imaging (fMRI), a method used to measure brain activity. The frontolimbic region is also associated with cognitive flexibility and emotional processing, an important hurdle in treating TRD. Due to this, the investigators are pairing the ketamine treatment with psychotherapy sessions, to guide the processing experience, which can lead to higher emotional flexibility. The main questions this study aims to answer are:

• Are frontolimibic plasticity circuitry changes associated with openness to experience and peak experience?
• Is it feasible to recruit and retain people through a two-month KAP study?
• Is the structure of the study effective for treating TRD? Participants will:
• Visit the facilities 6-8 times
• Complete 2 MRI brain scans
• Complete 3-4 psychotherapy sessions
• Receive 1-2 doses of ketamine
• Complete online surveys between 3-4 visits

Conditions

Treatment Resistant Depression (TRD); Chronic Pain

Keywords

depression; fmri

Outcome Measures

Primary Outcomes (2)

• Proportion of Participants Retained in Study Through 2-Month Follow-Up

  Retention will be assessed as completion of all scheduled study assessments through the 2-month follow-up. A single value is derived for each participant, coded as 1 (retained) or 0 (not retained). Higher values indicate successful retention; lower values indicate dropout.

  2 months post-enrollment

• Mean Change in Hamilton Depression Rating Scale (HDRS) Total Score

  Depression severity will be measured using the 17-item HDRS (items scored 0-2 or 0-4; total score range 0-52). A single value is derived by summing item scores. Higher scores indicate greater depression severity (worsening); lower scores indicate reduced severity (improvement). Mean change is calculated as post-treatment score minus baseline score.

  Baseline, once a day for up to 7 days after baseline, within 90 minutes after ketamine dosing session, once a day for up to 7 days after ketamine dosing session, once a day up to 7 days before 2-month follow-up, and at 2-month follow-up

Secondary Outcomes (4)

• Mean Change in Numerical Pain Rating Scale Score

  Baseline, once a day for up to 7 days after baseline, within 90 minutes after ketamine dosing session, once a day for up to 7 days after ketamine dosing session, once a day up to 7 days before 2-month follow-up, and at 2-month follow-up

• Mean Change in NEO Five-Factor Inventory-3 (NEO-FFI-3) Openness Subscale Score

  Baseline and 2-month follow-up.

• Mean Acceptability Rating of Ketamine-Assisted Psychotherapy

  At 2 month follow-up

• Proportion of Participants Reporting Adverse Events (AEs)

  Throughout the 8-week study.

Other Outcomes (4)

• Mean Mystical Experience Questionnaire (MEQ-30) Total Score

  within 1-2 days after each ketamine dosing session

• 8. Mean Change in Resting-State fMRI Whole Brain Functional Connectivity

  Baseline and at 2 month follow-up

• Mean Change in Subcortical Brain Volume

  Baseline and at 2 month follow up

Study Arms (1)

TRD group

EXPERIMENTAL

Drug: Ketamine hydrochloride injection

Interventions

Ketamine hydrochloride injection DRUG

0.5-1mg/kg intramuscular (IM) injection of ketamine

Also known as: ketamine, ketalar

TRD group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years old or older
• Able to speak, read, and understand English
• In generally stable health
• Must have treatment resistant depression, as defined as scoring in the moderate or above range on the HDRS and having failed two adequate trials of antidepressants in the last two years.

You may not qualify if:

• Uncontrolled hypertension
• Impaired cardiac status
• a. Abnormal ECG report in the last month prior to screening
• Chronic Obstructive Pulmonary Disease
• Congenital Long QT Syndrome
• ≥265lbs or 120kg
• Severe obesity (BMI ≥40)
• Increased intracranial or cerebrospinal pressure
• Pregnancy or breastfeeding
• Hyperthyroidism
• Prior adverse response to ketamine, including allergic reaction
• Symptoms of psychosis or prodromal phase
• Severe personality disorder
• Autistic Spectrum Disorders
• Bipolar disorder

Sponsors & Collaborators

• University of Rochester: lead

Study Sites (1)

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant; Chronic Pain; Depression

Interventions

Ketamine

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Central Study Contacts

Pain and Perception Lab

CONTACT

585-275-4424; painlab@urmc.rochester.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor - Department of Psychiatry, Research (SMD)

Study Record Dates

• First Submitted: November 6, 2025
• First Posted: November 25, 2025
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): March 1, 2028
• Last Updated: April 23, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)