Role Of Non-Specific Effects in The Treatment of Depression With Esketamine (ROSETTE)

The investigators aim to examine the magnitude of non-specific effects in the treatment of depressive episodes with esketamine, by providing patients in the intervention group with a pretreatment presentation and post-treatment follow up session, to assess whether nonspecific effects can be used effectively to improve the effectiveness of treatment with esketamine.

Study Overview

• Status: Terminated
• Conditions: Depressive Episode
• Intervention / Treatment: Behavioral: Pre and Post Treatment Presentations

Detailed Description

Primary Objective:

To determine whether a positive presentation before first treatment improves expectation of improvement from treatment in patients receiving esketamine for a depressive episode within 24 hours after the first treatment.

Secondary Objectives:

To determine whether a post-treatment follow up session to provide encouragement and reassurance improves expectation of improvement from treatment in patients receiving esketamine for a depressive episode within 24 hours after the first treatment.

To determine whether a positive presentation results in an improved response from treatment in patients receiving esketamine for a depressive episode as measured by MADRS score within 24 hours after the first treatment.

To determine whether a positive presentation before first treatment, combined with a posttreatment follow up session after first treatment, result in an improved response from treatment in patients receiving esketamine for a depressive episode as measured by MADRS score by the end of the acute course of esketamine treatment.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale Psychiatry Hospital Interventional Psychiatry Services (IPS) unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants must be either male or female and at least 18 years old
• Deemed clinically appropriate to receive esketamine by a Yale Interventional Psychiatry physician.
• Written consent for the study procedures
• 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:

• Hearing or visual impairment to the degree that would interfere with ability to view the presentation
• Difficulty in understanding spoken or written English
• Unable to provide informed consent
• Dementia or other cognitive disorder or intellectual disability that would impair the subject's ability to understand the presentation (per investigator judgment)
• 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.
• Previous Esketamine or ketamine treatment
• Unable to give informed consent
• Was previously enrolled/randomized into the trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Treatment as usual (TAU); Participants receive TAU
Experimental: Intervention + TAU; 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	Behavioral: Pre and Post Treatment Presentations; A short presentation provided to the participants within 72 hours prior to the first treatment of the acute course. The presentation will emphasize the effectiveness of the treatment, and provide notable encouragement and reassurance. The intervention group will additionally receive a follow up session within 24 hours after the first treatment to provide encouragement and reassurance

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Group Difference in Change in Question 6 Score on Treatment Credibility and Expectancy Scale (CEQ-6)	Participants' expectations will be assessed by the change in the group score of item 6 of the CEQ-6 at baseline and after the presentation (before treatment 1). Item 6 is scored from 0% (not at all) to 100% (very much). Higher scores indicates expectations have been met.	baseline and after presentation (before treatment 1), up to 30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Group Difference in Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Score	MADRS score will be used to assess whether a positive presentation results in an improved response from treatment in participants receiving esketamine for a depressive episode within 24 hours after the first treatment. MADRS is a ten-item diagnostic questionnaire used to measure the severity of depressive episodes. Each item is rated on a 0-6 scale, resulting in a maximum total score of 60 points, with higher scores indicative of greater depressive symptomology.	baseline and within 24 hours post treatment 1

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: National Center for Advancing Translational Sciences (NCATS)
• Investigators: Principal Investigator: Sina Nikayin, MD, Yale University

Study record dates

Study Major Dates

• Study Start (Actual): July 13, 2024
• Primary Completion (Actual): December 31, 2024
• Study Completion (Actual): December 31, 2024

Study Registration Dates

• First Submitted: June 6, 2023
• First Submitted That Met QC Criteria: June 6, 2023
• First Posted (Actual): June 20, 2023

Study Record Updates

• Last Update Posted (Estimated): January 14, 2026
• Last Update Submitted That Met QC Criteria: December 22, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Depression; Inorganic Chemicals; Elements; Metals; Metals, Heavy; Lead
• Other Study ID Numbers: 2000034829; 2UL1TR001863-06 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No