A Phase 2 interventional study of Ketamine hydrochloride injection in Treatment Resistant Depression (TRD) and Chronic Pain, sponsored by University of Rochester. Not yet recruiting at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-24.
Sponsored by University of Rochester · Phase 2, Interventional, and Treatment
Help build ClinicalTrials.gg — short surveys, remote interviews or testing, in your language. Take part →
Among 42 studies testing ketamine in Depressive Disorder, Treatment-Resistant — 8 open to participants now, 11 under way, 3 of them phase 3. Ketamine · Depressive Disorder, Treatment-Resistant.
Among the 42 studies testing ketamine in Depressive Disorder, Treatment-Resistant, this one is the 29th largest by planned enrollment, is one of 3 that started in 2026, is one of 11 in phase 2, reaches primary completion later than 7 of the 10 other live ones, and was the 39th registered.
448 studies on the registry are indexed under Depressive Disorder, Treatment-Resistant; 147 are open to participants now.
Browse Depressive Disorder, Treatment-Resistant studies →8 of the 42 studies testing ketamine in Depressive Disorder, Treatment-Resistant are open now, in 8 countries. Recruiting first, the newest first:
Weill Medical College of Cornell University · Sites in United States
Ages 18–70
Joshua Rosenblat · Sites in Canada
Ages 18–70
Università Vita-Salute San Raffaele · Sites in Italy
Ages 18–70
Mayo Clinic · Sites in United States
Ages 18–65
Dr. Inge Winter · Sites in Austria, Germany, Greece and 3 more countries
Ages 18–65
By country, each count listing its studies:
Ketamine: first FDA approval 1970 (KETALAR). What it is approved for, and how studies give it, is on its page →
Of the 114 Depressive Disorder, Treatment-Resistant studies recruiting now, 26 (23%) set no upper age limit and 76 (67%) stop at 75 or younger; 1 takes children under 18; 13 take healthy volunteers.
This study: 18 Years and older · all sexes · no healthy volunteers.
The full table on the hub →This tab as a report to print or save as PDF → With an account.
42 studies; the count open now beside each. This study's row is marked.
A study in two phases is counted once above. Listed by phase, each with its combined phases: Phase 1 7 · Phase 2 14 · Phase 3 8 · Phase 4 8
First in 2008; this study’s year is marked. 3 started in 2026.
By drug class, each counting the studies that test any of its medicines:
This study's planned enrollment of 25 is below the median of 59 across 372 interventional studies indexed under Depressive Disorder, Treatment-Resistant.
Median enrollment 35 across the 42 interventional studies. Of the 21 that completed or were terminated, 11 (52%) have results posted.
This tab as a report to print or save as PDF → With an account.
2 of 42 have an industry lead sponsor. The 10 most frequent:
University of Rochester is the lead sponsor of 729 studies on the registry; 116 are open to participants now.
Of its 56 completed or terminated interventional studies of FDA-regulated products, 44 (79%) have results posted.
University of Rochester has 1 study filed under Depressive Disorder, Treatment-Resistant — fewer than ten, so there is no comparison to draw.
3 of the studies testing ketamine in Depressive Disorder, Treatment-Resistant that are under way reach primary completion within a year, 0 of them phase 3. Phase 3 first, then by date:
| Study | Primary completion |
|---|---|
| NCT03573349Mayo ClinicKetamine Associated ACC GABA and Glutamate Change and Depression Remission: | 2026-12 |
| NCT06480201Texas A&M UniversityGamma Oscillations as a Prognostic Marker for Ketamine Therapy in Treatment Resistant Depression | 2026-12-31 |
| NCT06480500University Health Network, Torontoi-CBT and IV Ketamine for Suicidality in Treatment-Resistant Depression: A Randomized, Midazolam-Controlled Clinical Trial | 2027-03-31 |
Add all 3 to your calendar (.ics) → With an account.
Among the 42 studies testing ketamine in Depressive Disorder, Treatment-Resistant, from their registry updates:
This tab as a report to print or save as PDF → With an account.
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:
Participants will:
The proposed study is a single center study investigating the effect of ketamine modulation on the brain signature of treatment resistant depression (TRD). The patients will undergo 2 scanning visits (baseline and follow-up). They will also receive 1-2 treatments of ketamine IM injection and 3-4 psychotherapy sessions.
Patients with TRD will be asked to come to the PI's lab for 2 visits, and 6 in the Department of Psychiatry. On visit 1, after consenting and doing the drug screen, the subjects will be asked questions on their depression experience. Subjects will then fill out demographic and clinical questionnaire to assess mood, anxiety, pain, history of early trauma, and stress. Patients will be asked to rate their depression and pain level using a visual analogue scale (VAS).
During visit 1, Drs. Geha and Swogger will interview the patients to inquire about any prior drug allergies including allergies to medications that could be possibly used in this study (ketamine/ondansetron/lorazepam/clonidine). Possible side effects will be explained to the patients. They will then undergo 60 minutes of functional and structural brain scanning, which will serve as a baseline scan.
Visits 2 and 3 will be psychotherapy sessions with Dr. Swogger to prepare for the ketamine session and focus on their difficulties and goals for the medicine session. Strategies for working with ketamine will be reviewed.
Visits 4 and 6 will be the ketamine IM injection sessions. Visit 4 they will receive 0.5 mg/kg but will not exceed 60 mg regardless of weight. Visit 6 may be a higher dose, but will not exceed 60 mg. The dose will be determined by Drs. Geha and Swogger based on the patients' experience and response in visit 4. Ondansetron will be available for nausea, lorazepam for uncontrolled agitation, and clonidine for uncontrolled hypertension. Throughout the visits members of the study team will be present to ensure patient comfort and offer reassurance, redirection, etc. They will also take notes for later processing in psychotherapy visits. When the patient emerges from non-ordinary state of consciousness, they will complete the MEQ, and the study team will complete CADSS-6 and record any other pertinent information about the experience. Once it is deemed safe, the patient may leave via someone driving them home after the visit and will be instructed on safety measures for the rest of the day.
Visits 5 and 7 will be follow up psychotherapy visits the day after the ketamine treatment. They will discuss and process the experience. If the patient wishes not to receive another dosage, then visit 7 will not occur and they will proceed with visit 8 after visit 5.
Visit 8 is conducted in the PI's lab about 4 weeks after visit 5 (one dose) or 7 (two doses). This will include answering similar questionnaires from the baseline visit to assess depression, pain, anxiety, mood, trauma, and personality. The patient will discuss the accessibility and feasibility of the study with Dr. Swogger or a member of the study team. Then they will conduct a follow up functional and structural brain imagining scan, lasting for 60 minutes.
For 7 days after visit 1, 7 days after each ketamine session, and 7 days before visit 8, the patient will complete quick at home surveys to assess depression and pain.
Throughout the study the investigators will assess depression, mood, pain, and Openness to Experience using the questionnaires below:
The trial acceptability and ketamine experience will be assessed using the questionnaires below:
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
The following inclusion criteria must be met for all subjects to be considered eligible to participate:
Exclusion Criteria
General exclusion criteria for all subjects include:
Impaired cardiac status
a. Abnormal report in the last month prior to screening
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Chronic obstructive pulmonary disease: long-term lung disease that makes it hard to breathe out, including emphysema and chronic bronchitis.
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
ECG (electrocardiogram)
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
COPD
Chronic obstructive pulmonary disease: long-term lung disease that makes it hard to breathe out, including emphysema and chronic bronchitis.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
QT and QTc
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Drug: Ketamine hydrochloride injection
0.5-1mg/kg intramuscular (IM) injection of ketamine
Also known as: ketamine, ketalar
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.
Time frame: 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.
Time frame: 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 Numerical Pain Rating Scale Score
Pain intensity will be assessed using an 11-point Numeric Rating Scale (0 = no pain, 10 = worst imaginable pain). A single value is derived by averaging participant ratings at each time point. Higher scores indicate worse pain; lower scores indicate reduced pain. Mean change is calculated as follow-up score minus baseline score.
Time frame: 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
Openness will be measured using the NEO-FFI-3 Openness subscale (12 items scored 0-4; total score range 0-48). A single value is derived by summing the 12 item scores. Higher scores indicate greater openness; lower scores indicate reduced openness. Mean change is calculated as follow-up score minus baseline score.
Time frame: Baseline and 2-month follow-up.
Mean Acceptability Rating of Ketamine-Assisted Psychotherapy
Acceptability will be assessed using a 5-point Likert scale (1 = low acceptability, 5 = high acceptability). A single value is derived by averaging scores across participants. Higher scores indicate greater acceptability; lower scores indicate lower acceptability.
Time frame: At 2 month follow-up
Proportion of Participants Reporting Adverse Events (AEs)
Adverse events will be graded using the Common Terminology Criteria for Adverse Events (CTCAE v5.0; 0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal). A single value is derived for each participant as the highest AE grade experienced. Higher values indicate more severe AEs; lower values indicate milder or no AEs.
Time frame: Throughout the 8-week study.
Mean Mystical Experience Questionnaire (MEQ-30) Total Score
Mystical experiences will be measured using the MEQ-30 (30 items scored 0-5; total score range 0-150). A single value is derived by summing item scores. Higher scores indicate more intense mystical experiences; lower scores indicate fewer or weaker mystical experiences.
Time frame: within 1-2 days after each ketamine dosing session
8. Mean Change in Resting-State fMRI Whole Brain Functional Connectivity
Functional connectivity will be measured using resting-state fMRI. Correlations between 400 cortical ROIs (Schaefer atlas) and subcortical ROIs (Harvard-Oxford atlas) will be calculated. A single value per participant is derived as the mean Fisher-Z transformed correlation coefficient across all ROI pairs. Higher values indicate stronger connectivity; lower values indicate weaker connectivity. Mean change is calculated as post-treatment value minus baseline value.
Time frame: Baseline and at 2 month follow-up
Mean Change in Subcortical Brain Volume
Volumes of subcortical structures will be calculated from MRI scans using FSL-FIRST and FreeSurfer. A single value per participant is derived by summing the volumes of predefined structures (mm³). Higher values indicate larger volumes; lower values indicate smaller volumes. Mean change is calculated as post-treatment volume minus baseline volume.
Time frame: Baseline and at 2 month follow up
Clinician-Administered Dissociative States Scale (CADSS-6) Total Score
Dissociation will be measured using the CADSS-6 (6 items scored 0-4; total score range 0-24). A single value is derived by summing item scores. Higher scores indicate greater dissociation; lower scores indicate less dissociation.
Time frame: within 90 minutes after each ketamine dosing session
Plan to share: No
No publications or documents are linked to this record.
Start is estimated for Dec 2026; primary completion for Mar 2028, 15 months later.
Of 50 phase 2 interventional studies under Depressive Disorder, Treatment-Resistant, half reached primary completion within 31 months of starting (the median), counting those still running; a quarter within 17 and three quarters within 41. This study's planned 15 months is below that.
How these figures are worked out, and which studies are left out of them.
This study is not yet recruiting, as verified in Apr 2026. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Studies of the drug tested here: Ketamine
Depressive Disorder, Treatment-Resistant →