AzTrials
AzTrials

Treatment Resistant Depression (TRD)KetSetNCT07824973

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

A study testing Psychedelic framing and Biomedical framing in people with Treatment Resistant Depression (TRD), run by Valdemar Landgren at 1 site in Sweden.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Treatment Resistant Depression (TRD)
What is being tested?
Psychedelic framing and Biomedical framing
Could I receive a placebo?
No, everyone receives an active treatment
How many people
120 participants
Where
1 siteSweden
Study dates
Sep 2026to Aug 2030
Phase
Interventional
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

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

Who cannot join

  • Patients who do not meet the inclusion criteria

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Alexandra Leinonen, MD contact

+46706371348

alexandra.leinonen@gu.se

Sweden1 site
  • Brain Stimulation Clinic, Skaraborg's Hospital

    Skövde, Västra Götaland County, 54160

    Alexandra Leinonen, MD, +46706371348, alexandra.leinonen@gu.se

Other trials in Sweden

About this study

Official title: A Single-center Open-label Randomized Parallel-group Superiority Trial to Compare the Efficacy of Psychedelic and Biomedical Framing of Intravenous Ketamine for Treatment-resistant Depression - the KetSet Trial

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.

Read the detailed description

Ketamine is increasingly used in the treatment of treatment-resistant depression. In this study, ketamine is administered in the same clinical manner in both groups, but the treatment context differs. One group receives a psychedelic framing that presents subjective ketamine experiences as potentially meaningful and therapeutically relevant, while the other group receives a biomedical framing that presents ketamine as a pharmacological treatment and subjective effects as side effects. The study compares the effects of these two framings on depressive symptoms, treatment experience, tolerability, and selected longer-term outcomes measured through follow-up assessments and national registers.

Being tested
Psychedelic framing, Biomedical framing
Keywords
ketamine, psychological framing, psychedelic
Medical subject headings
Depressive Disorder, Treatment-Resistant

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Psychedelic framingBehavioural

    Also called Contextual framing, Treatment setting

    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
  • Biomedical framingBehavioural

    Also called Contextual framing, Treatment setting

    The intervention includes:

    • Biomedically framed patient information (video)
    • Psychological support provided during the infuion towards alleviating side effects such as dissociation
    • CADSS and BPRS
Study groups in NCT07824973
Study groupRoleWhat they receive
Biomedical framing of ketamine treatmentActive comparatorParticipants 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.
Receives: Behavioral: Biomedical framing
Psychedelic framing of ketamine treatmentExperimentalParticipants 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.
Receives: Behavioral: Psychedelic framing

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Baseline to week 12

Secondary outcomes (28)
  1. MADRS response and remission

    Proportion of participants achieving response and remission at week 12 based on MADRS total score. Response is defined as ≥50% reduction from baseline. Remission is defined as MADRS <11.

    Measured: Week 12

  2. Self-reported depressive symptoms (MADRS-S)

    Change over time in self-reported depressive symptoms measured with the Montgomery-Åsberg Depression Rating Scale - Self-rated (MADRS-S). The MADRS-S is a 9-item scale (0-6 per item; total score range 0-54), with higher scores indicating more severe depression.

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

  3. Suicidal ideation (MADRS-S item 9)

    Change over time in self-reported suicidal ideation measured by item 9 of the MADRS-S (score 0-6; higher scores indicate greater severity).

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

  4. Time to hospitalization

    Time from baseline to first hospitalization due to depression during follow-up

    Measured: Baseline to 12 months

  5. Adverse events and treatment discontinuation

    Incidence of adverse events (mild, moderate, severe) and time to treatment discontinuation for any reason.

    Measured: Baseline to week 12

  6. Ketamine-related adverse effects (Modified KSET)

    Ketamine-related adverse effects measured with a modified version of the Ketamine Side Effect Tool (KSET), a 20-item patient-rated scale (0-3 per item; higher scores indicate greater side effect burden).

    Measured: Week 1 and week 4

  7. Quality of life and health (VAS)

    Change in self-rated quality of life and health measured with a visual analogue scale from 0 to 100, where higher scores indicate better perceived quality of life and health.

    Measured: Baseline, weeks 2, 3, 4, 5, 8, 12, and months 6 and 12

  8. Satisfaction with life

    Life satisfaction measured with the Satisfaction With Life Scale (SWLS). The SWLS has 5 items rated on a 7-point scale, with total scores ranging from 5 to 35. Higher scores indicate greater life satisfaction.

    Measured: Baseline to week 12

  9. Subjective sleep quality

    Subjective sleep quality measured with the Brief Pittsburgh Sleep Quality Index (B-PSQI). The questionnaire asks about sleep habits during the previous month and includes bedtime, sleep latency, wake time, sleep duration, nighttime sleep problems, overall sleep quality, and use of sleep medication. Higher scores indicate worse sleep quality.

    Measured: Baseline to week 12

  10. Perceived social support

    Perceived social support measured with the Social Provisions Scale-5 (SPS-5). The scale has 5 items rated on a 4-point scale from 1 to 4, with total scores ranging from 5 to 20. Higher scores indicate greater perceived social support.

    Measured: Baseline to week 12

  11. Loneliness

    Loneliness measured with the UCLA Loneliness Scale, 3-item version. The scale has 3 items rated from 1 to 3, with total scores ranging from 3 to 9. Higher scores indicate greater loneliness.

    Measured: Baseline to week 12

  12. Screen time

    Screen time measured with the Screen Time questionnaire (ScrT), which assesses average daily time spent on social media, gaming, TV/streaming, and background TV/streaming use. Higher response categories indicate more screen exposure.

    Measured: Baseline to week 12

  13. Absorption

    Trait absorption measured with the Modified Tellegen Absorption Questionnaire (MODTAS). The questionnaire assesses tendency to become fully absorbed in sensory, imaginative, or experiential activities; higher scores indicate greater absorption.

    Measured: Baseline to week 12

  14. Trait anxiety

    Trait anxiety measured with the State-Trait Anxiety Inventory short form (STAI-SF). Higher scores indicate greater anxiety-proneness.

    Measured: Baseline to week 12

  15. Cognitive fusion

    Cognitive fusion measured with the Cognitive Fusion Questionnaire (CFQ-7). The questionnaire has 7 items rated on a 7-point scale; total scores range from 7 to 49. Higher scores indicate greater cognitive fusion, meaning more entanglement with thoughts and less psychological flexibility.

    Measured: Baseline to week 12

  16. Goal attainment for behavioral activation

    Goal attainment measured with the Goal Attainment Scale for Depression (GAS-D). Individual goals are rated on a 5-point scale from -2 to +2, where 0 reflects expected goal attainment and higher scores indicate better-than-expected attainment.

    Measured: Week 1, 2, 3, 4, 5, 6, 8 and 12

  17. Therapeutic alliance

    Therapeutic alliance measured with the Working Alliance Inventory - Short Revised (WAI-SR) completed by participants and the Working Alliance Inventory - Short form (WAI-SRT) completed by clinicians. The instruments assess the quality of the working relationship across goal agreement, task agreement, and bond. Higher scores indicate a stronger therapeutic alliance.

    Measured: baseline, week 2, 6 and 12

  18. Acute mystical and challenging experiences

    Acute ketamine-related subjective experiences measured after each infusion with the Mystical Experience Questionnaire short form (MEQ-4) and the Challenging Experience Questionnaire short form (CEQ-7). The MEQ-4 is a 4-item self-report measure of mystical-type experience, scored 0 to 5 per item, with higher scores indicating a stronger mystical experience. The CEQ-7 is a 7-item self-report measure of challenging experience, scored 0 to 5 per item, with higher scores indicating a more difficult or distressing experience.

    Measured: Immediately after each of 6 infusions during weeks 1 to 4

  19. Mystical experience

    Mystical experience measured with the Mystical Experience Questionnaire (MEQ-30). The MEQ-30 is a 30-item self-report questionnaire scored on a 0 to 5 scale and assesses mystical-type experience across domains such as unity, sacredness, positive mood, transcendence of time and space, and ineffability. Higher scores indicate a stronger mystical experience.

    Measured: Week 5

  20. Expectancy

    Treatment expectation measured with patient- and clinician-rated treatment expectation questionnaires. The patient questionnaire and clinician questionnaire assess expected benefit from treatment and perceived treatment credibility. Higher scores indicate greater treatment expectancy.

    Measured: Baseline, week 1 and 2

  21. Drug liking and perceived drug effects

    Acute drug effects measured with the Drug Effect Questionnaire (DEQ). The DEQ uses 0 to 100 visual analogue ratings to assess perceived drug effect, feeling high, liking and disliking effects, and desire for more drug. Higher scores indicate stronger perceived drug effects and greater drug liking or desire for more drug, depending on the item.

    Measured: Immediately after infusion 2 and infusion 6 during weeks 1 and 4

  22. Altered states of consciousness

    Altered states of consciousness measured with the 5-Dimensional Altered States of Consciousness Scale (5D-ASC). The 5D-ASC assesses five dimensions of altered consciousness; higher scores indicate a more intense altered state in the relevant dimension.

    Measured: Week 5

  23. Psychological insight

    Psychological insight measured with the Psychological Insight Scale (PIS). The PIS contains 7 items rated from 0 to 100 and assesses new insight into one's past, self, lifestyle, and behavior change. Higher scores indicate greater psychological insight.

    Measured: Week 5

  24. Treatment evaluation

    Treatment evaluation measured with patient- and clinician-rated treatment evaluation questionnaires. These questionnaires assess overall appraisal of the treatment experience and perceived usefulness of the intervention. Higher scores indicate a more positive treatment evaluation.

    Measured: Week 6

  25. Personality traits

    Personality measured with the Ten-Item Personality Inventory (TIPI). The TIPI is a 10-item self-report measure of the Big Five personality traits: extraversion, emotional stability, agreeableness, conscientiousness, and openness to experience. It is administered as a baseline covariate; higher trait scores indicate more of the relevant personality dimension.

    Measured: Baseline

  26. Substance-related convictions or diagnoses

    Occurrence of a drug-related conviction or substance use disorder diagnosis during follow-up.

    Measured: 12 months

  27. Work ability and social transfers

    Employment-related income and social transfer dependence during follow-up, assessed as income net of social transfers.

    Measured: 12 months

  28. Psychotropic medication use

    Average daily defined dose of prescribed psychotropic medication during follow-up.

    Measured: 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Sep 2026
  2. Study startSep 2026 (estimated)
  3. Primary completionDec 2029 (estimated)
  4. Study completionAug 2030 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
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.
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
120 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07824973
Sponsor's protocol ID
2025-07756-01
Other IDs
2025
Acronym
KetSet
Status last verified
Sep 2026
First submitted
11 Sep 2026
Last updated
17 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: De-identified individual participant data will be shared after publication of the main results. Data will include participant-level clinical and outcome data used in the analyses. Supporting documentation such as the study protocol, statistical analysis plan, and analytic code will also be shared.

Questions about this trial

What is this clinical trial studying?

A study testing Psychedelic framing and Biomedical framing in people with Treatment Resistant Depression (TRD), run by Valdemar Landgren at 1 site in Sweden.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 17 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Alexandra Leinonen, MD (+46706371348, alexandra.leinonen@gu.se), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in depressive symptoms (MADRS total score) (time frame: Baseline to week 12). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Sep 2026.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in