Psychedelic coaching added to ketamine treatment for treatment-resistant depression

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

This trial will test whether adding psychedelic integration coaching to ongoing ketamine or esketamine maintenance helps people with treatment-resistant depression.

Quick facts

• Phase: NA
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Massachusetts General Hospital (other)
• Locations: 2 sites (Boston, Massachusetts and 1 other locations)
• Trial ID: NCT07563868 on ClinicalTrials.gov

What this trial studies

Massachusetts General Hospital is enrolling adults with treatment-resistant depression who are already receiving maintenance IV ketamine or intranasal esketamine. Enrolled participants will receive additional psychedelic integration coaching sessions delivered via a HIPAA-compliant, MGB-approved video platform and recorded with consent. Eligible participants must have a QIDS-SR score of 11 or higher and have completed at least three prior maintenance treatments documented in their medical record. Outcomes will track depressive symptoms and related functioning during the period of added coaching to see if coaching improves or prolongs treatment benefits.

Who should consider this trial

Good fit: Adults (18+) with a lifetime depressive disorder who are currently receiving maintenance IV ketamine or intranasal esketamine at the MGH Ketamine Clinic, have QIDS-SR ≥ 11, have completed at least three maintenance treatments, speak English, and agree to recorded video coaching are ideal candidates.

Not a fit: People not receiving maintenance ketamine or esketamine, those with milder depressive symptoms (QIDS-SR < 11), or those who cannot participate in recorded English-language video sessions are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, adding coaching could increase and prolong symptom improvement and overall functioning for people receiving ketamine or esketamine for TRD.

How similar studies have performed: Therapist-led preparation and integration have shown promise in psychedelic-assisted treatments, but applying structured psychedelic coaching specifically alongside ketamine/esketamine maintenance is relatively novel and not yet widely validated.

Eligibility criteria

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.

Where this trial is running

Boston, Massachusetts and 1 other locations

• Massachusetts General Hospital's Depression and Clinical Research program — Boston, Massachusetts, United States (RECRUITING)
• Massachusetts General Hospital — Boston, Massachusetts, United States (RECRUITING)

Study contacts

• Principal investigator: Maren Nyer, PhD — Massachusetts General Hospital and Harvard Medical School
• Study coordinator: Maren Nyer, PhD

Conditions: Treatment Resistant Depression, Psychedelic Coaching, Ketamine Coaching, Depression