Ketamine Treatment for Treatment-Resistant Depression - the Role of Framing

NCT07824973 | Not Yet Recruiting DMC

• 2 other identifiers: 2025-07756-012025
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

Ketamine is a medicine used in psychiatry for treatment-resistant depression. This study compares two ways of framing ketamine treatment: a psychedelic framing and a biomedical framing. The study will examine whether the framing affects depressive symptoms, treatment experience, tolerability, and longer-term outcomes.

Conditions

Treatment Resistant Depression (TRD)

Keywords

ketamine; psychological framing; psychedelic

Outcome Measures

Primary Outcomes (1)

• Change in depressive symptoms (MADRS total score)

  Mean change from baseline to week 12 in depressive symptoms measured with the Montgomery-Åsberg Depression Rating Scale (MADRS). The MADRS is a clinician-rated 10-item scale (0-6 per item; total score range 0-60), with higher scores indicating more severe depression.

  Baseline to week 12

Secondary Outcomes (28)

• MADRS response and remission

  Week 12

• Self-reported depressive symptoms (MADRS-S)

  Baseline, weeks 2, 3, 4, 5, 8, 12, and month 6

• Suicidal ideation (MADRS-S item 9)

  Baseline, weeks 2, 3, 4, 5, 8, 12, and month 6

• Time to hospitalization

  Baseline to 12 months

• Adverse events and treatment discontinuation

  Baseline to week 12

Other Outcomes (4)

• Subjective ketamine experience interview

  After infusion 1, infusion 3, and infusion 6 during weeks 1, 2, and 4

• Acute dissociative symptoms

  After each of 6 infusions during weeks 1 to 4

• Acute psychiatric symptoms

  After each of 6 infusions during weeks 1 to 4

Study Arms (2)

Biomedical framing of ketamine treatment

ACTIVE COMPARATOR

Participants view a brief video presenting ketamine treatment from a biomedical perspective, emphasizing its pharmacological antidepressant effects. Potential side effects are described, and participants are informed that clinical support will be provided throughout treatment with the aim of alleviating these effects. A healthcare professional is present during all six ketamine infusions. The staff member provides psychological support, helps reduce anxiety, and assists the participant in managing or distracting from side effects such as distressing dissociation. Infusions may be paused if needed. After each infusion, participants are assessed for side effects using the Clinician-Administered Dissociative States Scale (CADSS) and the Brief Psychiatric Rating Scale (BPRS). Participants may choose to use music and/or an eye mask during the infusion if they wish, but these are not actively provided or encouraged by the treatment staff.

Behavioral: Biomedical framing

Psychedelic framing of ketamine treatment

EXPERIMENTAL

Participants view a brief video presenting ketamine treatment from a psychedelic perspective, in which the subjective psychoactive effects are described as potentially meaningful and therapeutically relevant. Participants are informed that supportive presence will be provided throughout the session. A healthcare professional is present during all six ketamine infusions. The staff member provides psychological support, encourages participants to engage with their inner experience, and offers reassurance when needed. Infusions may be paused if needed. The treatment setting includes optional supportive elements such as a short mindfulness practice, music and eye mask to facilitate inward focus. After each infusion, participants are invited to reflect on their experience through a semi-structured interview, with clinician time matched to the CADSS and BPRS assessments conducted in the comparator arm.

Behavioral: Psychedelic framing

Interventions

Psychedelic framing BEHAVIORAL

The intervention includes: * Psychedelic framed patient information (video) * Psychedelic environment during infusions (mindfulness practice, music, eye mask) and psychological support provided towards engaging in the inner experience * Interview on the ketamine-induced experience

Also known as: Contextual framing, Treatment setting

Psychedelic framing of ketamine treatment

Biomedical framing BEHAVIORAL

The intervention includes: * Biomedically framed patient information (video) * Psychological support provided during the infuion towards alleviating side effects such as dissociation * CADSS and BPRS

Also known as: Contextual framing, Treatment setting

Biomedical framing of ketamine treatment

Eligibility Criteria

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

You may qualify if:

• Prescribed ketamine treatment for depression
• Able to understand study information and provide informed consent

Sponsors & Collaborators

• Valdemar Landgren: lead

Study Sites (1)

Brain Stimulation Clinic, Skaraborg's Hospital

Skövde, Västra Götaland County, 54160, Sweden

Location

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Central Study Contacts

Alexandra Leinonen, MD

CONTACT

+46706371348; alexandra.leinonen@gu.se

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: PhD, psychiatrist

Model Details: Participants are randomized 1:1 to receive ketamine treatment with either psychedelic framing or biomedical framing. The ketamine dosing and infusion schedule are identical in both groups; only the framing and supporting context differ.

Study Record Dates

• First Submitted: September 11, 2026
• First Posted: September 17, 2026
• Study Start: September 1, 2026
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): August 1, 2030
• Last Updated: September 17, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: Available beginning 12 months after publication of the primary results and remaining available indefinitely, or for the period specified on OSF.
• Access Criteria: De-identified IPD and supporting documents will be made available via OSF. Access by request.

Locations

SE (1)