Working Mechanisms and Effectiveness of IV Ketamine-assisted Psychotherapy on Depression in TRD Clients

July 13, 2026 updated by: Rutger Engels, Senz

Effectiveness and Underlying Mechanisms of an Innovative Treatment Program for Persistent Mood and Anxiety Conditions

Ketamine-Assisted Psychotherapy (KAP) is an innovative treatment that combines intravenous ketamine with psychotherapy in a carefully monitored clinical setting. At Senz, this treatment is being evaluated in an open-label clinical trial for individuals with persistent depression who have not responded sufficiently to previous treatments. The combination of ketamine, psychological support, and integration sessions aims to promote emotional processing, psychological flexibility, and lasting therapeutic change.

Study Overview

Status

Recruiting

Conditions

Detailed Description

Ketamine-Assisted Psychotherapy (KAP) combines the administration of intravenous ketamine with psychotherapy in a structured and medically supervised treatment programme. At Senz, KAP is currently being offered within the context of an open-label clinical trial for adults with persistent or treatment-resistant depression who have not experienced sufficient benefit from previous pharmacological and psychological treatments. The aim of the study is to evaluate both the clinical effectiveness and the subjective therapeutic impact of KAP in routine mental healthcare.

The treatment consists of several phases, including comprehensive psychological and psychiatric assessment, medical screening, preparation sessions, ketamine administration sessions, and post-session integration therapy. Prior to participation, clients undergo a detailed evaluation of psychiatric history, previous treatments, physical health, medication use, and relevant laboratory tests. During preparation sessions, participants receive psychoeducation, explore treatment intentions, learn techniques for emotional regulation, and develop a therapeutic framework for working with the experiences that may arise during ketamine sessions.

Safety is a central component of the protocol. Ketamine is administered intravenously in a controlled clinical environment under the supervision of a psychiatrist, psychologist, and trained nursing staff. Vital signs, including blood pressure, heart rate, and oxygen saturation, are monitored throughout treatment. Participants are screened for medical and psychiatric contraindications, and clear procedures are in place for managing adverse events or unexpected reactions. Following each treatment session, participants remain under observation until clinically stable and are required to arrange supported transport home.

The study includes a comprehensive assessment programme to evaluate both outcomes and therapeutic processes. Standardised measures of depressive symptoms are collected throughout treatment, alongside questionnaires assessing subjective experiences. Integration sessions following each ketamine administration help participants reflect on their experiences, consolidate insights, and translate these into meaningful behavioural changes in daily life. By combining rigorous clinical monitoring with psychotherapy and systematic outcome assessment, the trial aims to contribute to the growing evidence base for ketamine-assisted psychotherapy while providing high-quality care for participants.

Study Type

Observational

Enrollment (Estimated)

120

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Netherlands
    • Utrecht
      • Doorn, Utrecht, Netherlands, 3941ZS
        • Recruiting
        • SENZ
        • Contact:
        • Contact:
        • Principal Investigator:
          • Rutger Engels, dr

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Clients of Senz with TRD who are eligible for IV ketamine treatment (KAP)

Description

Inclusion Criteria:

  • Adults (18 years and older)
  • TRD
  • A MADRS score above the established clinical cut-off, indicating clinically significant depressive symptoms
  • Insufficient response to at least two adequate antidepressant treatment trials and one evidence-based psychotherapy, or failure to achieve adequate improvement following at least three consecutive treatment steps in accordance with the Dutch Multidisciplinary Guideline for Depression

Exclusion Criteria:

  • Current substance use disorder or recent illicit drug use
  • Substance use disorder not in remission for at least 3 months
  • Inability to abstain from alcohol for 24 hours before and after treatment
  • Acute suicidality
  • Current or past psychotic disorder
  • Significant neurological disorders (e.g., epilepsy, elevated intracranial pressure)
  • Uncontrolled hypertension or medical conditions associated with increased cardiovascular or cerebrovascular risk (e.g., aneurysms, recent myocardial infarction or intracerebral hemorrhage)
  • Significant bladder disease (e.g., cystitis)
  • Severe hepatic impairment
  • Pregnancy, breastfeeding, or ongoing IVF treatment
  • Extreme underweight or obesity where treatment is deemed medically unsafe Inability to arrange an accompanying adult for transport and support after treatment

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
adults with treatment resistant depression
MADRS depression score above the clinical cut-off. Insufficient response to at least two antidepressant treatments and one evidence-based form of psychotherapy, or completion of at least three consecutive treatment steps according to the Dutch multidisciplinary guideline for depression.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Beck Depression Inventory
Time Frame: baseline/pre-intervention/post-intervention (end of treatment)/3months after post-intervention
depression self-report measure. Zero is equivalent to no depression and 64 indicates the highest score on depression.
baseline/pre-intervention/post-intervention (end of treatment)/3months after post-intervention

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Montgomery-Åsberg Depression Rating Scale
Time Frame: baseline/pre-intervention/post-intervention (end of treatment)/3months after post-intervention
depression clinician report. Zero is equivalent to no depression and 60 indicates the highest score on depression.
baseline/pre-intervention/post-intervention (end of treatment)/3months after post-intervention

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Senz

Collaborators

Radboud University Medical Center

Investigators

  • Principal Investigator: Rutger Engels, SENZ

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 1, 2025

Primary Completion (Estimated)

January 1, 2033

Study Completion (Estimated)

January 1, 2033

Study Registration Dates

First Submitted

June 3, 2026

First Submitted That Met QC Criteria

July 13, 2026

First Posted (Actual)

July 15, 2026

Study Record Updates

Last Update Posted (Actual)

July 15, 2026

Last Update Submitted That Met QC Criteria

July 13, 2026

Last Verified

July 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 24-343/DB/02

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

not decided yet, will be discussed in the team

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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