Talking Therapies + Esketamine for Depression

(ROSETTE Trial)

Overseen By Sina Nikayin, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Yale University

Must be taking: Esketamine

Disqualifiers: Dementia, Cognitive disorder, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 30 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how additional support, such as pre-treatment and follow-up sessions, can enhance the effectiveness of esketamine, a medication used to treat depressive episodes. One group of participants will receive these extra sessions, while another group will continue with their usual treatment. The study seeks individuals with depression who a specialist in interventional psychiatry has deemed suitable for esketamine.

As an unphased trial, this study provides a unique opportunity to contribute to understanding how support sessions can improve treatment outcomes for depression.

Do I have to stop taking my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

What prior data suggests that these presentations are safe for patients with depression?

Research has shown that esketamine has been tested in many studies for treating depression, including major depressive disorder and treatment-resistant depression. Over 100,000 patients in the U.S. have used esketamine, demonstrating its effectiveness in both the short term and the long term.

Safety data from these studies indicate that esketamine is generally well-tolerated, with most people not experiencing serious side effects. Common side effects include dizziness and nausea, but these are usually mild. Researchers have studied the safety of esketamine for up to five years, providing a clear understanding of what to expect.

In short, esketamine has a strong safety record based on extensive research. This makes it a promising option for people struggling with depression, especially when other treatments haven't worked. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for depression, which often involve medications like SSRIs and psychotherapy, this approach combines talking therapies with esketamine. Esketamine is a derivative of ketamine, known for its rapid action, offering relief in hours or days compared to the weeks traditional antidepressants may take. Additionally, this treatment includes structured presentations before and after sessions, aiming to enhance the therapeutic process and support rapid improvement. Researchers are excited because this combined approach could potentially offer faster relief and improve overall treatment effectiveness for individuals with depression.

What evidence suggests that this trial's treatments could be effective for depression?

Research has shown that esketamine effectively treats depression, particularly when other treatments fail. Studies have found that esketamine can quickly alleviate depression symptoms. For instance, one study reported a noticeable drop in depression just two days after starting treatment. Another study noted improvements in quality of life and daily activities for people using esketamine in everyday situations. This trial will compare the effectiveness of esketamine combined with talking therapies to treatment as usual (TAU). Esketamine has proven helpful even when depression does not respond to other medications. ^{1 2 4 6 7}

Who Is on the Research Team?

Sina Nikayin, MD

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for adults over 18 who are suitable for esketamine treatment as determined by a Yale Interventional Psychiatry physician. Participants must consent to the study and be able to follow the trial's schedule and requirements.

Inclusion Criteria

Written consent for the study procedures

A Yale psychiatrist has approved me for esketamine treatment.

Ability and willingness, in the investigator's judgement, to comply with the study schedule, treatment plan, and other trial requirements for the duration of the study.

Exclusion Criteria

I am unable to understand and give consent for treatment.

Any other medical or psychiatric comorbidity that the investigator judges would put the participant at additional undue risk due to study participation or would impair subject's ability to participate in the study

I have been treated with Esketamine or ketamine before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive esketamine treatment for depressive episodes, including a positive presentation before the first treatment and a follow-up session within 24 hours after the first treatment

Up to 30 days

Multiple visits including pre-treatment presentation and post-treatment follow-up

Follow-up

Participants are monitored for safety and effectiveness after treatment, with a focus on changes in MADRS and CEQ-6 scores

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Pre and Post Treatment Presentations

Trial Overview The study is testing if non-specific effects, like pretreatment presentations and post-treatment follow-ups, can boost esketamine's effectiveness in treating depression.

How Is the Trial Designed?

Group I: Intervention + TAU Experimental Treatment 1 Intervention

Participants receive a presentation prior to the first treatment and receive a "follow up" session within 24 hours after the first treatment in addition to treatment as usual

Group II: Treatment as usual (TAU) Active Control 1 Intervention

Participants receive TAU

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

National Center for Advancing Translational Sciences (NCATS)

Collaborator

Trials

394

Recruited

404,000+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39790081/

Esketamine Nasal Spray in Major Depressive Disorder The primary efficacy outcome was a reduction of the Montgomery-Asberg Depression Rating Scale, from baseline to Day 2 or Day 28 for patients ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2772598724000230

A real-world study examining the impact of esketamine ... This study describes changes in quality of life, depressive symptoms and productivity in participants treated with esketamine in real-world settings.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12450024/

Spravato for Treatment-Resistant Depression: Efficacy and ... Across multiple phase 3 trials, esketamine produced rapid and clinically meaningful improvements in depressive symptoms, with benefits emerging ...

4. jamanetwork.com jamanetwork.com/journals/jamapsychiatry/fullarticle/2836115

Esketamine Monotherapy in Adults With Treatment ... Results from this study strengthen the body of evidence for esketamine's antidepressant efficacy and inform on the monotherapy treatment ...

5. nature.com nature.com/articles/s41380-025-03320-6

Efficacy and safety of esketamine on major depression ... In conclusion, our findings demonstrate that esketamine is effective in treating MDD/TRD and preventing PPD and postoperative depression.

6. spravatohcp.com spravatohcp.com/trd-efficacy-safety/

TRD Efficacy & Safety Over 100,000 patients in the US have received treatment with SPRAVATO® as shown below in short-term (as early as 24 hours) and long-term (up to 5 years) studies ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2666144624000224

Benefits and risks of esketamine nasal spray continuation ... Intranasal esketamine is effective for short-term and long-term treatment of adult TRD. Intranasal esketamine has an established safety profile for long-term ...