Treatment Resistant Depression (TRD)
Conditions
Keywords
ketamine, psychological framing, psychedelic
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.
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.
Interventions
BEHAVIORALPsychedelic framing
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
BEHAVIORALBiomedical framing
The intervention includes: * Biomedically framed patient information (video) * Psychological support provided during the infuion towards alleviating side effects such as dissociation * CADSS and BPRS
Sponsors
Valdemar Landgren
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Prescribed ketamine treatment for depression * Able to understand study information and provide informed consent
Exclusion criteria
\- Patients who do not meet the inclusion criteria
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in depressive symptoms (MADRS total score) | Baseline to week 12 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| MADRS response and remission | Week 12 | 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. |
| Self-reported depressive symptoms (MADRS-S) | Baseline, weeks 2, 3, 4, 5, 8, 12, and month 6 | 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. |
| Suicidal ideation (MADRS-S item 9) | Baseline, weeks 2, 3, 4, 5, 8, 12, and month 6 | Change over time in self-reported suicidal ideation measured by item 9 of the MADRS-S (score 0-6; higher scores indicate greater severity). |
| Time to hospitalization | Baseline to 12 months | Time from baseline to first hospitalization due to depression during follow-up |
| Adverse events and treatment discontinuation | Baseline to week 12 | Incidence of adverse events (mild, moderate, severe) and time to treatment discontinuation for any reason. |
| Ketamine-related adverse effects (Modified KSET) | Week 1 and week 4 | 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). |
| Quality of life and health (VAS) | Baseline, weeks 2, 3, 4, 5, 8, 12, and months 6 and 12 | 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. |
| Satisfaction with life | Baseline to week 12 | 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. |
| Subjective sleep quality | Baseline to week 12 | 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. |
| Perceived social support | Baseline to week 12 | 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. |
| Loneliness | Baseline to week 12 | 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. |
| Screen time | Baseline to week 12 | 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. |
| Absorption | Baseline to week 12 | 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. |
| Trait anxiety | Baseline to week 12 | Trait anxiety measured with the State-Trait Anxiety Inventory short form (STAI-SF). Higher scores indicate greater anxiety-proneness. |
| Cognitive fusion | Baseline to week 12 | 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. |
| Goal attainment for behavioral activation | Week 1, 2, 3, 4, 5, 6, 8 and 12 | 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. |
| Therapeutic alliance | baseline, week 2, 6 and 12 | 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. |
| Acute mystical and challenging experiences | Immediately after each of 6 infusions during weeks 1 to 4 | 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. |
| Mystical experience | Week 5 | 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. |
| Expectancy | Baseline, week 1 and 2 | 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. |
| Drug liking and perceived drug effects | Immediately after infusion 2 and infusion 6 during weeks 1 and 4 | 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. |
| Altered states of consciousness | Week 5 | 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. |
| Psychological insight | Week 5 | 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. |
| Treatment evaluation | Week 6 | 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. |
| Personality traits | Baseline | 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. |
| Substance-related convictions or diagnoses | 12 months | Occurrence of a drug-related conviction or substance use disorder diagnosis during follow-up. |
| Work ability and social transfers | 12 months | Employment-related income and social transfer dependence during follow-up, assessed as income net of social transfers. |
| Psychotropic medication use | 12 months | Average daily defined dose of prescribed psychotropic medication during follow-up. |
Countries
Sweden
Contacts
CONTACTAlexandra Leinonen, MD
Outcome results
None listed