Coaching as an Adjunct to Ketamine Therapy for Treatment-Resistant Depression

This study is being conducted at Massachusetts General Hospital (MGH) to explore whether adding psychedelic coaching can enhance the effects of ketamine or esketamine maintenance treatment in individuals with treatment-resistant depression (TRD). The investigators are currently enrolling participants who are receiving ongoing maintenance intravenous (IV) ketamine or intranasal esketamine (Spravato) treatment at the MGH Ketamine Clinic. Participation in the study will involve adding coaching sessions to your existing ketamine maintenance treatment.

Study Overview

• Status: Recruiting
• Conditions: Treatment Resistant Depression (TRD)
• Intervention / Treatment: Behavioral: Psychedelic Integration Coaching

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Maren Nyer, PhD; Phone Number: 6176434897; Email: mnyer@mgh.harvard.edu
• Study Contact Backup: Name: Franklin King, MD; Email: fking@mgh.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
      • Principal Investigator: Maren Nyer, PhD
      • Contact: Maren Nyer, PhD; Phone Number: 6176434897; Email: mnyer@mgh.harvard.edu
      • Contact: Minna Behnan, BA; Phone Number: 6177247963; Email: mbehnan@mgh.harvard.edu
      • Principal Investigator: Franklin King, MD
      • Principal Investigator: David Mischoulon, MD, PhD
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital's Depression and Clinical Research program

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age 18 years or older at the time of informed consent/study enrollment.
2. Ability to understand and provide informed consent.
3. Fluent in English (spoken and written).
4. Willingness to have coaching sessions recorded via HIPAA-compliant MGB approved video-based platform.
5. Has a QIDS-SR score ≥ 11, indicating at least moderate depressive symptom severity at screening visit.
6. Lifetime diagnosis of a depressive disorder according to the MINI.
7. In the maintenance phase of ketamine or esketamine treatment, defined as the period following the initial acute treatment series (typically 2 treatments per week for 3 weeks).
8. Patients must have completed at least 3 maintenance treatments prior to screening visit with a QIDS-SR score ≥ 11 noted from EPIC medical records from the 3 most recent maintenance treatments.
9. Currently receiving maintenance IV ketamine or intranasal esketamine at the MGH Ketamine Clinic, with at least one treatment administered within the past 8 weeks, and planning to continue to be an active patient at the MGH Ketamine Clinic for the duration of the study.
10. Has established care with a mental health provider (e.g., psychiatrist, therapist, or other licensed mental health clinician), and, if outside the MGB-healthcare system, agrees to sign a Release of Information form (ROI) with the study team.

Exclusion Criteria:

1. Presence of an unstable medical condition, as determined by the study clinician.
2. Significant neurocognitive impairment that impairs with individual's ability to maintain ADLs and would interfere with study participation, per study clinician judgment.
3. Newly initiated psychotherapy within the past 3 months.
4. Any condition or circumstance that, in the judgment of the Principal Investigator, makes participation unsafe or unsuitable.
5. Any psychiatric condition that is currently primary, clinically predominant to their depression, or insufficiently stable such that it would interfere with study participation, per clinician judgment.
6. Plan to switch from IV ketamine treatment to intranasal esketamine or plan to switch from intranasal esketamine to IV ketamine treatment at any point during study.
7. Suicidality determined by the judgment of the study clinicians at screen, with a plan to act in next 6 months.
8. A ≥25% reduction in QIDS total score from screen to baseline visit.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Psychedelic Coaching

Behavioral: Psychedelic Integration Coaching; Participation in the study will involve adding coaching sessions to existing ketamine maintenance treatment for patients receiving ongoing maintenance IV ketamine or IN esketamine treatment at MGH's Ketamine Clinic. If participants are eligible, they will be invited to participate in 12 weekly, 50-minute one-on-one coaching sessions conducted via Zoom. These sessions are designed to help participants process and integrate their experiences with ketamine treatment, to support personal growth and symptom improvement. The coaching is non-clinical, collaborative, and participant-directed, and is provided by trained psychedelic integration coaches from the Fireside Project. Throughout the 3-month coaching period and again at a 1-month follow-up, participants will complete monthly study visits that include brief remote assessments with a study clinician, along with additional self-report questionnaires. These visits will take approximately 1 to 2 hours, depending on the time point.; Other Names: Coaching; Psychedelic Coaching

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the feasibility of adjunctive coaching during ketamine/esketamine maintenance treatment.	We will assess the feasibility of coaching, as indexed by at least 80% of participants (16 of 20 participants) completing 10 out of 12 coaching sessions. The investigators will also review all assessment procedures and calculate the percentage of completed assessments at each time point. In addition, the investigators will compute the number of participants for whom an AE occurred, along with their rate of occurrence, severity, and relationship to the study procedures.	From enrollment to the end of treatment at Month 3
To assess the acceptability of adjunctive coaching during ketamine/esketamine maintenance treatment.	Acceptability will be assessed by calculating the mean and standard deviation of participant-reported net-promoter scores, which will range from 0 (would not recommend) to 10 (would definitely recommend). Additional acceptability metrics will include qualitative and quantitative responses to the post-coaching survey and the end-of-coaching survey.	From enrollment to the end of treatment at Month 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To explore whether coaching is associated with a reduction in the frequency of ketamine/esketamine maintenance treatments (measured in days) over the 3-month study period and 1-month follow-up.	Coaching will be associated with a reduction in the frequency of ketamine maintenance treatments (measured in days) assessed through chart review of patients' 3 treatments prior to enrollment in study and following completion of study.	Baseline (3 ketamine treatments prior to enrollment), through the intervention (3 months after enrollment), and follow-up (1 month post-intervention)
To explore whether coaching is associated with a change in dose (measured in mg) and/or need for anxiolytic medications prior to ketamine/esketamine treatment.	Coaching will be associated with a reduction in the dose and/or need for anxiolytic medications (measured in mg) prior to ketamine/esketamine treatment, assessed through chart review of patients' 3 treatments prior to enrollment in study and following completion of study.	Baseline (3 ketamine treatments prior to enrollment), through the intervention (3 months after enrollment), and follow-up (1 month post-intervention)
To explore whether adjunctive coaching is associated with a change in depressive symptoms, as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) total score.	Coaching will be associated with a reduction in depressive symptoms (i.e., MADRS total scores) at Month 1, Month 2, and Month 3.	Screening, Baseline, Month 1, Month 2, Month 3, and 1-Month Post Study Completion
To explore whether coaching is associated with improvements in International Trauma Questionaire (ITQ) scores.	Coaching will lead to improvements in secondary outcomes, including the as International Trauma Questionnaire (ITQ) assessed at Screening, Baseline, Month 1, Month 2, Month 3, and 1-Month Post Study Completion.	Screening, Baseline, Month 1, Month 2, Month 3, and 1-Month Post Study Completion
To explore whether coaching is associated with improvements in 5-item World Health Organization Well-Being Index (WHO-5) scores.	Coaching will lead to improvements in secondary outcomes, including the as 5-item World Health Organization Well-Being Index (WHO-5) assessed at Screening, Baseline, Month 1, Month 2, Month 3, and 1-Month Post Study Completion.	Screening, Baseline, Month 1, Month 2, Month 3, and 1-Month Post Study Completion
To explore whether coaching is associated with improvements in Quick Inventory of Depressive Symptomatology - Self Report (QIDS-SR) scores.	Coaching will lead to improvements in secondary outcomes, including the as Quick Inventory of Depressive Symptomatology - Self Report (QIDS-SR) assessed at Screening, Baseline, Month 1, Month 2, Month 3, and 1-Month Post Study Completion.	Screening, Baseline, Month 1, Month 2, Month 3, and 1-Month Post Study Completion
To explore whether coaching is associated with improvements in Patient-Reported Outcomes Measurement Information System (PROMIS-29) scores.	Coaching will lead to improvements in secondary outcomes, including the as Patient-Reported Outcomes Measurement Information System (PROMIS-29) assessed at Screening, Baseline, Month 1, Month 2, Month 3, and 1-Month Post Study Completion.	Screening, Baseline, Month 1, Month 2, Month 3, and 1-Month Post Study Completion
To explore whether coaching is associated with improvements in Perceived Stress Scale (PSS) scores.	Coaching will lead to improvements in secondary outcomes, including the as Perceived Stress Scale (PSS) assessed at Screening, Baseline, Month 1, Month 2, Month 3, and 1-Month Post Study Completion.	Screening, Baseline, Month 1, Month 2, Month 3, and 1-Month Post Study Completion
To explore whether coaching is associated with improvements in Self-Compassion Scale - Short Form (SCS-SF) scores.	Coaching will lead to improvements in secondary outcomes, including the as Self-Compassion Scale - Short Form (SCS-SF) assessed at Screening, Baseline, Month 1, Month 2, Month 3, and 1-Month Post Study Completion.	Screening, Baseline, Month 1, Month 2, Month 3, and 1-Month Post Study Completion

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: Fireside Project
• Investigators: Principal Investigator: Maren Nyer, PhD, Massachusetts General Hospital and Harvard Medical School; Principal Investigator: Franklin King, MD, Massachusetts General Hospital and Harvard Medical School; Principal Investigator: David Mischoulon, MD/PhD, Massachusetts General Hospital and Harvard Medical School

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2028

Study Registration Dates

• First Submitted: March 27, 2026
• First Submitted That Met QC Criteria: April 30, 2026
• First Posted (Actual): May 4, 2026

Study Record Updates

• Last Update Posted (Actual): May 4, 2026
• Last Update Submitted That Met QC Criteria: April 30, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Depression; Psychedelic Coaching; Ketamine Coaching
• Additional Relevant MeSH Terms: Mental Disorders; Behavioral Symptoms; Mood Disorders; Depressive Disorder; Behavior; Depression; Depressive Disorder, Treatment-Resistant
• Other Study ID Numbers: 2025P002110; GR1001602 (Other Grant/Funding Number: Fireside Project)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data (IPD) will not be shared due to the sensitive nature of the psychiatric and clinical data collected and the potential risk of participant re-identification. Study findings will be reported in aggregate form only to protect participant confidentiality.

Drug and device information, study documents

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