Ketamine-Assisted Psychotherapy for Treatment-Resistant Depression

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

NCT Number	NCT07247006
Lead Sponsor	University of Rochester
Conditions	Treatment Resistant Depression (TRD), Chronic Pain
Enrollment	25 participants
Start Date	2026-06
Primary Completion	2028-01 (estimated)
Study Completion	2028-03 (estimated)
Updated on ClinicalTrials.gov	2026-04-23