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

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.

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.

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.

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

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

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).

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.

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 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 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 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 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.

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

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 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 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 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 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.

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.

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 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 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 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 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.

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

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

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

Subjective ketamine experience assessed with a semi-structured post-infusion interview in the psychedelic treatment group only. The interview explores sensory experiences, emotions, thought control, self-body experience, space, time, mystical or spiritual experiences, changes in meaning, and post-session insight. Interview reports will be transcribed and content-analyzed to derive quantitative and thematic results.

Dissociative symptoms measured with the Clinician Administered Dissociative States Scale (CADSS) in the biomedical treatment group only. The CADSS is a clinician-administered scale with 23 items rated 0 to 4, assessing experiences such as depersonalization, derealization, altered body perception, altered sense of time, and memory gaps. Higher scores indicate greater dissociation.

Acute psychiatric symptoms measured with the Brief Psychiatric Rating Scale (BPRS) in the biomedical treatment group only. The BPRS is a clinician-rated interview scale assessing symptoms such as anxiety, depression, hostility, unusual thought content, hallucinations, and disorganization. Higher scores indicate greater psychiatric symptom severity.

Incremental intervention-related and healthcare costs associated with psychedelic framing compared with biomedical framing.