Ketamine-Assisted Psychotherapy for Treatment-Resistant Depression

(KAP for TRD Trial)

Overseen By Pain and Perception Lab

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Rochester

Must not be taking: Stimulants, Antipsychotics, Antihistamines, Antidepressants

Disqualifiers: Hypertension, Cardiac issues, Obesity, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 9

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how ketamine, combined with therapy, can assist people with treatment-resistant depression (TRD). TRD is a challenging form of depression that does not improve with standard treatments and is associated with higher suicide rates. The study examines whether ketamine can enhance brain flexibility and openness, potentially improving mental health and reducing suicide risk. People with TRD who have tried at least two antidepressants without success in the past two years may be suitable candidates for this trial. Participants will undergo brain scans, attend therapy sessions, and receive doses of ketamine. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to potentially benefit from an innovative approach.

Is there any evidence suggesting that ketamine-assisted psychotherapy is likely to be safe for humans?

Research has shown that ketamine is generally safe and well-tolerated for people with treatment-resistant depression (TRD). In studies involving many patients, ketamine proved both safe and effective. However, like any treatment, side effects can occur.

Some individuals may experience a dissociative state, feeling disconnected from reality. This can include vivid dreams or a sensation of time slowing down. These effects typically do not last long and cease after treatment ends.

The treatment under consideration combines ketamine with therapy, which has been shown to reduce depressive symptoms more effectively than ketamine alone. Notably, the FDA has approved a form of ketamine, called esketamine, for treating TRD, supporting its safety.

For any concerns, consult the study team or your doctor. They can help determine if this treatment is suitable for you. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for depression?

Ketamine-Assisted Psychotherapy is unique because it targets treatment-resistant depression through a novel mechanism of action. Unlike standard treatments such as SSRIs or cognitive behavioral therapy, which can take weeks to show results, ketamine acts rapidly, potentially offering relief within hours. Researchers are excited about this treatment because ketamine is believed to modulate glutamate, a neurotransmitter in the brain, offering a new pathway for alleviating depressive symptoms for those who haven't responded to traditional therapies.

What evidence suggests that ketamine-assisted psychotherapy might be an effective treatment for treatment-resistant depression?

Research has shown that ketamine-assisted therapy, which participants in this trial will receive, can significantly benefit individuals with treatment-resistant depression. Studies have found that ketamine can reduce depression symptoms by about 49% in these patients. It acts quickly, offering fast relief, which is crucial for those with severe depression. This therapy also promotes brain adaptation and change in areas related to depression, potentially enhancing emotional processing. Furthermore, when combined with talk therapy, ketamine's positive effects can last longer, improving mental health and reducing anxiety and depression symptoms. ^{1 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for individuals with treatment-resistant depression, which means their depression hasn't improved after trying other treatments. Participants will need to visit the facility multiple times and undergo MRI brain scans, psychotherapy sessions, ketamine doses, and complete online surveys.

Inclusion Criteria

My depression hasn't improved after trying two different antidepressants in the last two years.

I am 18 years old or older.

Able to speak, read, and understand English

Exclusion Criteria

I don't have metal implants, large tattoos, or fear of tight spaces, and my brain and skull are normal.

My high blood pressure is not under control.

My recent heart test (ECG) was abnormal.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Baseline Assessment

Participants undergo baseline assessments including MRI scans and questionnaires

1 week

1 visit (in-person)

Psychotherapy Preparation

Participants attend psychotherapy sessions to prepare for ketamine treatment

2 weeks

2 visits (in-person)

Ketamine Treatment

Participants receive 1-2 doses of ketamine with monitoring and support

2 weeks

2 visits (in-person)

Post-Ketamine Psychotherapy

Participants attend follow-up psychotherapy sessions to process ketamine experiences

2 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including follow-up MRI scans and questionnaires

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Ketamine-Assisted Psychotherapy

Trial Overview The study tests if ketamine can improve brain plasticity in the frontolimbic region (linked to depression) and increase psychological flexibility. It combines ketamine injections with psychotherapy to see if this approach effectively treats TRD over a two-month period.

How Is the Trial Designed?

Group I: TRD group Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

University of Rochester

Lead Sponsor

Trials

883

Recruited

555,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07247006

Ketamine-Assisted Psychotherapy for Treatment-Resistant ... The goal of this clinical trial is to understand the effect of ketamine on the brain in people with treatment-resistant depression (TRD).

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40051583/

Ketamine-Assisted Psychotherapy Provides Lasting and ... KAP produced sustained reductions in anxiety, depression, and PTSD, with symptom improvement lasting well beyond the duration of dosing and integration ...

3. link.springer.com link.springer.com/article/10.1007/s40501-025-00346-z

Ketamine-Assisted Psychotherapy for Treatment-Resistant ... This systematic review evaluates the effectiveness of KAP in reducing depressive symptoms in TRD compared to ketamine monotherapy.

4. massgeneralbrigham.org massgeneralbrigham.org/en/about/newsroom/press-releases/ketamine-esketamine-comparison-study

Study Finds Two Forms of Ketamine Therapy Can Reduce ... ... Ketamine Therapy Can Reduce Symptom Severity in Patients with Treatment-Resistant Depression ... efficacy, with a 49.22% reduction in depression ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0165032725019172

Efficacy and safety of ketamine maintenance therapy in ... Preliminary findings from the current literature propose that single ketamine infusions can produce significant reductions in depressive ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S016517812400619X

Safety outcomes of ketamine for treatment-resistant ... Ketamine can give rise to acute, cumulative and longer-term side effects (SEs) across a treatment course. The Ketamine Side Effect Tool (KSET) examines adverse ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/25271445/

Ketamine safety and tolerability in clinical trials for treatment ... Conclusions: In this relatively large group of patients with TRD, ketamine was safe and well tolerated. Further research investigating the safety of ketamine in ...

8. jamanetwork.com jamanetwork.com/journals/jamapsychiatry/fullarticle/2840552

Serial Ketamine Infusions as Adjunctive Therapy to ... This randomized clinical trial evaluates outcomes following adjunctive ketamine infusions vs midazolam for depression.