Ketamine-Assisted Psychotherapy (KAP) Compared to Ketamine Alone for the Treatment of Depression

NCT06559826 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: STUDY-23-00661PD23-03701
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

The proposed study is a single-site, randomized, controlled clinical trial (RCT) comparing ketamine-assisted psychotherapy (KAP) to a standard evidence-based regimen of ketamine administered in a medical model without psychotherapy (KET). Eligible study participants will be adults with major depressive disorder (MDD). Adults with MDD will be randomized to KAP or KET in a 1:1 allocation. Each treatment group will receive KAP or KET over a period of four weeks. Measurement of depression severity, wellness, neurocognitive functioning and other parameters will occur at baseline prior to treatment, immediately following the end of the acute treatment period, and over an 8-week (two month) treatment follow-up period.

Conditions

Major Depressive Disorder

Keywords

Ketamine; Major Depressive Disorder; Ketamine Assisted Psychotherapy

Outcome Measures

Primary Outcomes (1)

• Montgomery-Asberg Depression Rating Scale (MADRS)

  MADRS: The Montgomery-Asberg Depression Rating Scale (MADRS) is a 10-item instrument used for the evaluation of depressive symptoms in adults and for the assessment of any changes to those symptoms. Each of the 10 items is rated on a scale of 0 to 6, with differing descriptors for each item. These individual item scores are added together to form a total score, which can range between 0 and 60 points, with higher scores indicating more severe depressive symptoms.

  9 weeks from baseline assessment

Study Arms (2)

Ketamine Assisted Psychotherapy (KAP)

EXPERIMENTAL

KAP sessions will occur once a week for a total of 4 weeks with the potential for a second session the first week for dose-finding purposes. Participants will have a ketamine exposure of at least 0.3 mg/kg and a maximum of 1.0mg/kg, at each treatment session, personalizing dose to patient experience. Each of the treatment sessions will last 120-180 min and will be conducted by a single therapist who has completed the KAP training as specified in the standard operating procedures.

Drug: Ketamine; Behavioral: Psychotherapy

Ketamine (KET)

ACTIVE COMPARATOR

Standard medicalized ketamine administration consisting of twice weekly treatment for 3 weeks, followed by a 4th week with a single ketamine infusion serving as a down-titration period before discontinuation. Participants will have a ketamine exposure of at least 0.3 mg/kg administered via intravenous infusion at each treatment session. Patients may be up-titrated over the course of subsequent treatment sessions, as indicated clinically up to 1.0 mg/kg25. No formal psychotherapy will be provided in the KET arm, though study participants will have matched basic psychoeducation related to depression and treatment with ketamine prior to the first dosing session, during the ketamine treatment period, and post-treatment, in order to match the KAP arm. All individuals will be followed over an eight week follow up period and undergo clinical study assessments.

Drug: Ketamine

Interventions

Ketamine DRUG

Following screening and baseline assessments, individuals randomized to KAP will undergo a preparatory session prior to the first day of dosing. Participants will complete a sequence of four to five intramuscular (IM) ketamine assisted therapy sessions.

Ketamine (KET); Ketamine Assisted Psychotherapy (KAP)

Psychotherapy BEHAVIORAL

Each week following KAP, there will be a separate 60-minute integration session 1-6 days afterwards. Integration sessions will focus on processing experiences and material that emerged in KAP sessions (such as assimilating challenging experiences, making meaning of experiences and imagery, working through memories and emotions, and exploring emerging relational patterns) as well as strengthening insights. Within one week of the completion of all KAP sessions, there will be one additional integration session focused on consolidating the insights and improvements gained from KAP treatment.

Ketamine Assisted Psychotherapy (KAP)

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent (and assent when applicable) obtained from subject and ability for subject to comply with the requirements of the study.
• Age 18-90 years
• Participant in good physical health
• Participants may be on medications for depression as long as they remain on a stable dose.
• A score of at least 20 on the 10 item Montgomery-Asberg Depression Scale at screening, corresponding to at least moderate current depression severity.
• Meets criteria for major depressive disorder (MDD) in current major depressive episode (MDE) according to DSM-5
• Women of child-bearing potential must have a negative pregnancy test at screening and prior to ketamine infusion

You may not qualify if:

• Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study.
• Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data.
• Any unstable medical illnesses including hepatic, renal, gastroenterological, respiratory, cardiovascular (including ischemic heart disease and uncontrolled hypertension); endocrinologic, neurologic, immunologic, or hematologic disease
• Clinically significant abnormalities of laboratories, physical examination, or ECG
• Substance drug or alcohol use disorder in the prior 12 months
• History of hypersensitivity to ketamine or esketamine
• Lifetime history of schizophrenia, schizoaffective disorder, bipolar I or II disorder
• Presence of psychotic symptoms in the current MDE, or lifetime psychotic disorder
• Recreational ketamine or phencyclidine use in the last year
• Previous non-response to clinical or research ketamine or esketamine administration
• Concurrent treatment with ECT, TMS, or VNS in the current MDE
• BMI \> 35
• Significant suicidal ideation as determined by a C-SSRS score \>2 in past 30 days
• History of suicide attempt or self harm in the prior 2 years
• SBP \> 165 or DBP \> 95 on infusion day

Sponsors & Collaborators

• Icahn School of Medicine at Mount Sinai: lead

Study Sites (1)

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

RECRUITING

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Ketamine; Psychotherapy

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Behavioral Disciplines and Activities

Study Officials

• James Murrough, MD, PhD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rachel Fremont, MD, PhD

CONTACT

212-241-6539; rachel.fremont@mssm.edu

Mackenzie Brown, MPH

CONTACT

212-241-6539; mackenzie.brown@mssm.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Psychiatry and Neuroscience

Study Record Dates

• First Submitted: August 15, 2024
• First Posted: August 19, 2024
• Study Start: January 10, 2025
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2027
• Last Updated: July 15, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)