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NCT Number: NCT06559826

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

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.

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Key information

Conditions

Major Depressive Disorder Depressive Disorder Depressive Disorder, Major Mental Disorders Mood Disorders

Age range

18 year–90 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

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.

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.

Primary outcomes

  1. Montgomery-Asberg Depression Rating Scale (MADRS)

    Time frame: 9 weeks from baseline assessment

    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.

Study contacts

Contact information is provided by the study sponsor or research team.

Mackenzie Brown, MPH

CONTACT

[email protected]

212-241-6539

Rachel Fremont, MD, PhD

CONTACT

[email protected]

212-241-6539

Sponsors and collaborators

Lead sponsor

Icahn School of Medicine at Mount Sinai

Other

Registry information

Official study title

A Randomized-Controlled Trial of Ketamine-Assisted Psychotherapy (KAP) Compared to Ketamine Alone for the Treatment of Depression

Acronym: KAP

Important dates

Study start
2025
Primary completion
2027
Study completion
2027
First posted
Aug 19, 2024
Registry last updated
Jul 15, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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