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

Mount Sinai Health System

Status and phase: Enrolling; Phase 2

Conditions: Major Depressive Disorder

Treatments: Drug: Ketamine; Behavioral: Psychotherapy

Study type: Interventional

Funder types: Other

Identifiers

NCT06559826

PD23-03701 (Other Identifier)

STUDY-23-00661

Details and patient eligibility

About

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.

Enrollment: 70 estimated patients

Sex: All

Ages: 18 to 90 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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
• MoCA score < 23

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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70 participants in 2 patient groups

Ketamine Assisted Psychotherapy (KAP)

Experimental group

Description:

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.

Treatment:

Behavioral: Psychotherapy

Drug: Ketamine

Ketamine (KET)

Active Comparator group

Description:

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.

Treatment:

Drug: Ketamine