i-CBT a IV ketamin pro sebevraždu u deprese rezistentní na léčbu: Randomizovaná klinická studie kontrolovaná midazolamem (Ket-CBT)

Participants will receive internet-based cognitive therapy (i-CBT) for 13 weeks. During the first 4 weeks of i-CBT, participants will also be administered 6 infusions of ketamine intravenously. The first two infusions will be dosed at 0.5 mg/kg over a period of 40 mins. For infusions 3 and 4, patients will be flexibly-dosed between 0.5 mg/kg to 0.75 mg/kg, depending on clinical response to first two infusions. For infusions 5 and 6, patients will be flexibly-dosed between 0.5-0.85 mg/kg, depending on the clinical response to the first 4 infusions.

38 patients will receive ketamine hydrochloride, over six infusions, flexibly dosed between 0.5 mg/kg to 0.85 mg/kg.

Each week for 13 weeks, participants will watch an online module that last approximately 45-50 mins each, with homework at the end of each module. Homework is submitted and reviewed by a therapist, who will provide personalized feedback before progression to the next module.

Participants will receive internet-based cognitive therapy (i-CBT) for 13 weeks. During the first 4 weeks of i-CBT, participants will also be administered 6 infusions of midazolam intravenously. The first two infusions will be dosed at 0.02 mg/kg over a period of 40 mins. For infusions 3 and 4, patients will be flexibly-dosed between 0.02 mg/kg to 0.03 mg/kg, depending on clinical response to first two infusions. For infusions 5 and 6, patients will be flexibly-dosed between 0.02 mg/kg to 0.035 mg/kg, depending on the clinical response to the first 4 infusions.

Each week for 13 weeks, participants will watch an online module that last approximately 45-50 mins each, with homework at the end of each module. Homework is submitted and reviewed by a therapist, who will provide personalized feedback before progression to the next module.

38 patients will receive midazolam hydrochloride, over six infusions, flexibly dosed between 0.02 mg/kg to 0.035 mg/kg.

The CSSRS evaluates suicidal ideation and behaviour. The CSSRS evaluates suicidal ideation and behaviour. The suicidal ideation score ranges from 0 (no ideation) to 5 (active suicidal ideation with specific plan and intent). Suicidal ideation intensity score ranges from 0 (no ideation) to 25 (most severe). The presence of suicidal behaviour is rated as a binary response; the lethality of actual attempts are rated on a scale of 0 (no or very minor physical damage) to 5 (death) and the potential lethality of actual attempts are rated on a scale of 0 (behaviour not likely to result in injury) to 2 (behaviour likely to result in death despite available medical care).

The MADRS is a scale measuring objective depression severity, consisting of 10 items, each scored from 0 (normal) to 6 (severe), for a total possible score of 60; higher scores denote greater severity.

The MARRRS is a self-reported 14-item self-report measure of depressive symptoms present during the past 72 hours. Total score ranges from 0 to 42; a higher score indicates greater symptom severity.

The QIDS-SR-16 total score ranges from 0 to 27 with 0 representing no depression and 27 representing severe depression.

The CGI severity module assesses the severity of a person's depressive illness using a seven-point Likert scale, ranging from "Normal, not at all depressed" to "Among the most extremely depressed patients". The CGI improvement module evaluates the global improvement of a person's condition since their last visit on a seven-point Likert scale, ranging from "Very much improved" to "Very much worse".

The CADSS measures objective dissociative symptom severity post infusion. Total scores on the 23-item CADSS range from 0 to 92; a higher score denotes greater dissociative symptom severity.

The BPRS rating scale has 18 items, each item rated on a severity scale of 1 (not present) to 7 (extremely severe). 0 is entered if the item is not assessed.

The Young Mania Rating Scale (YMRS) is a clinical interview scale to assess the severity of manic states and in this study to look at treatment-emergent mania. Total scores range from 0 to 60, with higher scores indicative of greater symptom severity.

The MEQ consists of 30 items, each item rated on a Likert scale (0-None/not at all to 5-Extreme, more than any other time in my life). The MEQ total score is computed by taking the average response to all items.

The WHO-5 is a measure of overall well-being, rated on a scale of 0 to 25, with higher scores denoting higher quality of life.

The WPAI is a six-item self-administered rating scale measuring work absenteeism, presenteeism, and productivity loss and daily activity impairment. Individuals are asked to rate to what extent health problems affected their ability to do regular daily activities other than work at a job (0-No effect on daily activities to 10-Completely prevented me from doing my daily activities). Respondents who are currently employed are additionally asked to rate the number of hours missed from work due to health problems, the number of hours missed due to other reasons (e.g., vacation, time off to participate in this study), and the number of hours worked in the past seven days, as well as to what extent health problems affected productivity while working (0-No effect on my work to 10-Completely prevented me from working). Responses to each question are scaled to an overall percentage score (0 to 100), with higher values denoting greater impairment

The PDQ-5-D total scores range from 0 to 20, with greater scores indicative of greater subjective cognitive impairment.

The DSST assesses relative contributions of speed, memory, executive function and visual scanning. Participants are required to copy symbols that are paired with simple geometric shapes or numbers within 90 seconds for a total possible score of 0 to 90. A higher score reflects greater performance.

The TMT is a two-part cognitive test. TMT-A assesses cognitive processing speed and consists of 25 circles distributed over a sheet of paper. Participants are asked to connect circles in numerical sequence. If a participant makes a mistake, the administrator points out the error, and the participant must return to the last correct circle and continue the task. Lower scores represent better performance.

The TMT is a two-part cognitive test. TMT-B assesses executive functioning and consists of 25 circles distributed over a sheet of paper. Participants are asked to connect circles in alternating numerical and alphabetical sequence (e.g., 1-A-2-B). If a participant makes a mistake, the administrator points out the error, and the participant must return to the last correct circle and continue the task. Lower scores represent better performance.

Total score ranges from 0 to 21; a higher score denotes greater symptom severity.

The SHAPS total score ranges from 14 to 56, wherein a higher score indicates greater hedonic capacity (lower anhedonic severity).

For the CRT, 4 boxes are presented on the screen in a horizontal array. Each box has an assigned response key (by default, the response keys are matched spatially to the position of their assigned boxes: DFJK).

After a fixed amount of time, one of the boxes turns red and participants are asked to press the corresponding response key as fast as possible. The response time for correct responses is recorded, with larger numbers representing slower reaction time.

The CORE is an observer-rated instrument evaluating cognitive processing disorders (non-interactiveness), agitation, and motor retardation. Scores range from 0 to 54, with higher scores representing more psychomotor signs of depression.

The F-A-S Test assesses phonemic verbal fluency by requesting an individual to orally produce words that begin with the letters F, A and S. High scores indicate better phonemic verbal fluency.

In the CVLT-II, a participant listens to series of words and is then asked to recall the terms and the category to which they belong. Higher total scores for words recognized on recognition trial indicate better verbal memory.

The UCLA assesses subjective measures of loneliness and social isolation. Scores range from 0-60 with higher scores indicating more subjective loneliness

The ESAS-r assesses 10 common symptoms: pain, tiredness, drowsiness, nausea, lack of appetite, shortness of breath, depression, anxiety, well-being and constipation. It conveys the individual's description of the severity of a symptom based on a scale ranging from 0 to 10. With higher scores indicating higher symptom severity

The PCL-5 is a 20-item self-administered measure that assesses the 20 DSM-5 symptoms of PTSD. The total scores range from 0-80, with higher scores indicating more symptom severity for PTSD.

The BSL-23 is a 23-item self-rating instrument for specific assessment of borderline personality disorder (BPD) symptomatology. The average score of items (range 0 to 4, sum of scores divided by 23) is calculated, with a higher score indicating more impairment.

The PSQI is a self-rated questionnaire which assesses sleep quality and disturbances over a 1-month time interval. The global PSQI score ranges from 0-21, with higher scores indicating poorer sleep quality

The Depression IAT measures the strength of automatic (implicit) associations between concepts (SAD and HAPPY) in people's minds relying on latency measures in a simple sorting task. Scores range from -1 to 1, with positive scores indicating a stronger association between 'ME-SAD' and 'NOT ME-HAPPY' and negative scores indicating a stronger association between 'ME-HAPPY' and 'NOT ME-SAD'.

Severity of Depression Rumination is measured using the RRS-10. Scores range from 10 to 40, with higher scores indicating more severe depression rumination.

Number of logins per day into the i-CBT platform is measured to assess i-CBT engagement.

Amount of time logged in on the i-CBT platform (in minutes) is measured to assess i-CBT engagement.

Time spent on each i-CBT session is measured to assess i-CBT engagement.

Number of logins per day, amount of time logged in, time spent on each session, time of day logged in, and time spent in each section of the module of the internet-based CBT will be measured to assess i-CBT engagement.

The likeability and craving for the study drug is assessed using the DLCQ. Likeability scores range from 0-10, with higher scores indicating more likeability. How much the participant is craving the study drug is rated on a scale of 0-10, with higher scores indicating more cravings. Craving for using greater amounts ranges from 0 to 10, with higher scores indicating more craving for greater amounts of study drug.