Clinical TrialDepressive DisordersChronic PainNeuroimaging & Brain MeasuresKetamineNot yet recruiting

Ketamine-Assisted Psychotherapy for Treatment-Resistant Depression

This Phase II, open‑label, single‑group trial (n=25) will evaluate ketamine‑assisted psychotherapy in adults with treatment‑resistant depression (including participants with chronic pain) to assess feasibility, antidepressant effect and frontolimbic brain plasticity using functional MRI. The intervention is intramuscular ketamine hydrochloride (0.5–1 mg/kg IM, capped at 60 mg), given as 1–2 dosing sessions paired with psychotherapy; primary outcomes include proportion retained through 2‑month follow‑up and mean change in Hamilton Depression Rating Scale (HDRS) scores. Participants will attend 6–8 visits including two MRI scans (baseline and follow‑up), 3–4 psychotherapy sessions (two preparatory sessions before the first ketamine), and 1–2 supervised IM ketamine sessions (visit 4: 0.5 mg/kg not to exceed 60 mg; visit 6: dose may be increased but will not exceed 60 mg, determined by investigators). Supportive medications (ondansetron, lorazepam, clonidine) are available for nausea, agitation or hypertension. Key eligibility includes age ≥18, HDRS in the moderate or above range and failure of two adequate antidepressant trials in the past two years; standard MRI and medical exclusions (cardiac, uncontrolled hypertension, recent substance‑use criteria, pregnancy, etc.) apply. HDRS assessments are scheduled at baseline, within 90 minutes after dosing, daily for up to 7 days around baseline and dosing, and at the 2‑month follow‑up.

Target Enrollment
25 participants
Study Type
Phase II interventional
Design
Non-randomized

Detailed 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.

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

Study Arms & Interventions

TRD group

experimental

Interventions

  • Ketamine

Participants

Ages
18 – ?
Sexes
Male & Female

Inclusion Criteria

  • The following inclusion criteria must be met for all subjects to be considered eligible to participate:
  • 1. 18 years old or older
  • 2. Able to speak, read, and understand English
  • 3. In generally stable health
  • 4. 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 Criteria

  • General exclusion criteria for all subjects include:
  • 1. Uncontrolled hypertension
  • 2. Impaired cardiac status
  • a. Abnormal ECG report in the last month prior to screening
  • 3. Chronic Obstructive Pulmonary Disease
  • 4. Congenital Long QT Syndrome
  • 5. ≥265lbs or 120kg
  • 6. Severe obesity (BMI ≥40)
  • 7. Increased intracranial or cerebrospinal pressure
  • 8. Pregnancy or breastfeeding
  • 9. Hyperthyroidism
  • 10. Prior adverse response to ketamine, including allergic reaction
  • 11. Symptoms of psychosis or prodromal phase
  • 12. Severe personality disorder
  • 13. Autistic Spectrum Disorders
  • 14. Bipolar disorder
  • 15. History of substance abuse, defined as a score of three or more on Drug Abuse scale (prior use of psychedelics allowed)
  • 16. Past-year suicide attempt or ongoing ideation with intent to act
  • 17. All exclusion criteria for magnetic resonance imaging safety: any metallic implants, brain or skull abnormalities, tattoos on large body parts, and claustrophobia.
  • 18. 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.

Study Details

Study Team

Sponsors & Collaborators

Locations

University of Rochester Medical Center — Rochester, New York, United States

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