Ketamine With Talk Therapy for Depression That Has Not Responded to Treatment

Trial details

Who runs it

University of Rochester

Trial code

NCT07247006

Record updated

24 September 2026

Original description

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.Read full original descriptionShow less

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

Inclusion: The following inclusion criteria must be met for all subjects to be considered eligible to participate:; 18 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.

Exclusion: Impaired cardiac status; Abnormal ECG report in the last month prior to screening; Prior adverse response to ketamine, including allergic reaction; History of substance abuse, defined as a score of three or more on Drug Abuse scale (prior use of psychedelics allowed); All exclusion criteria for magnetic resonance imaging safety: any metallic implants, brain or skull abnormalities, tattoos on large body parts, and claustrophobia; Taking medications that could interact with ketamine. Examples include but are not limited to: any types of stimulants, aripiprazole, diphenhydramine, hydromorphone, escitalopram, fluoxetine, alprazolam, and sertraline. Each subject's current medications will be evaluated for interactions with ketamine before admission into the trial; Uncontrolled hypertension; Chronic Obstructive Pulmonary Disease; Severe personality disorder; Autistic Spectrum Disorders; Bipolar disorder; Congenital Long QT Syndrome; General exclusion criteria for all subjects include:; ≥265lbs or 120kg; Severe obesity (BMI ≥40); Increased intracranial or cerebrospinal pressure; Pregnancy or breastfeeding; Hyperthyroidism; Symptoms of psychosis or prodromal phase; Past-year suicide attempt or ongoing ideation with intent to act.

ClinicalTrials.gov NCT07247006