Ketamine Alcohol (in Treatment-Resistant Depression)

The MADRS contains 10 items, and each item is scored 0-6. These item scores are summed to create a scale score; thus, scale scores range from 0 to 60. A scale score of 0 indicates the absence of depressive symptoms, while a score of 60 indicates severe depression. The primary outcome is the mean change in total MADRS score. A decrease in the mean MADRS score indicates a decrease (or improvement) in depressive symptoms, whereas an increase in the mean MADRS score indicates an increase (or worsening) in depressive symptoms.

High-magnetic field strength (7T) proton magnetic resonance spectroscopy (1H-MRS) detectable glutamate and other neurometabolites, e.g. N-acetylaspartate and creatine

Task-free ("resting state") functional magnetic resonance imaging (rs-FMRI) to detect changes in blood oxygen-level dependent (BOLD) signal

The HDRS is a clinician-administered depression rating scale that contains 21 items. The first 17 items are summed to create a total scale score. Score ranges indicate depression severity: 0-7 indicates the absence of depression, 8-13 indicates mild depression, 14-18 indicates moderate depression, 19-22 indicates severe depression, and >22 indicates very severe depression.

The BDI is a self-administered 21-item measure of depression severity. Each item is scored (in increasing severity) on a scale from 0-3. Total scores range from 0-63: 0-9 indicates no depression, 10-18 indicates mild depression, 19-29 indicates moderate depression, >29 indicates severe depression.

The HAM-A is a clinician-administered scale of anxiety severity that comprises 14 items rated on a scale of 0-4. The HAM-A total score is the sum of 14 items with a score range from 0-56, with lower scores indicating low levels of anxiety and higher scores indicating greater anxiety severity.

The YMRS scale is an 11-item clinician-administered rating scale to assess hypo/manic symptoms. Items 5, 6, 8, and 9 (irritability, speech, content and disruptive-aggressive behavior) are rated on a scale from 0 (symptom not present) to 8 (symptom extremely severe). The remaining items are rated on a scale from 0 (symptom not present) to 4 (symptom extremely severe). Items 5, 6, 8, and 9 are given twice the weight of the remaining 7 items. The YMRS total score ranges from 0 to 60. Lower scores indicate absence of manic-like symptoms while higher scores indicate increasingly severe manic-like symptoms.

The SHAPS scale is a 14-item self-reported instrument to measure anhedonia. Scale scores are created by summing each item. Higher scale scores indicate more anhedonia, and lower scale scores indicate increased hedonic value.

The TEPS scale is an 18-item self-reported questionnaire that measures pleasure associated with the consumption and anticipation of rewards. Lower scores indicate less pleasure while higher scores indicate greater hedonic value.

The SSI is a 19-item clinician-administered instrument designed to quantify the intensity of current conscious suicidal ideation in various dimensions of self-destructive thoughts or wishes: the extent of the wish to die, the desire to make an actual suicide attempt, and details of any plans; also, internal deterrents to an active attempt, and subjective feelings of control and/or courage regarding a proposed attempt. We will administer both the full and a short (5-item) version to assess rapid change in suicidal thinking. Scale scores are calculated by summing item scores and range from 0-38. Lower scores indicate less suicidal ideation and higher scores indicate escalating severity of suicidal thinking.

The C-SSRS is a clinician-administered instrument designed to measures suicidal ideation/behaviors with both "Lifetime/Recent" and "Since Last Visit" versions. There are four subscales. Severity of ideation subscale is measured on a 5-point ordinal scale in which 1=wish to be dead, 2=nonspecific active suicidal thoughts, 3=suicidal thoughts with methods, 4=suicidal intent, and 5=suicidal intent with plan. The intensity of ideation subscale has 5 items: frequency, duration, controllability, deterrents, and reason for ideation, which is rated on a 5 point scale. The suicidal behavior subscale is rated on attempts, preparatory behavior, and nonsuicidal self-injury. The lethality subscale measures lethalities of actual attempts, which is rated on a 6 point scale.

The AUQ is an 8-item self-report scale to assess acute alcohol cravings. It utilizes a 7 point Likert scale, and items are summed for a total scale score, where higher scores indicate greater cravings/urges to drink alcohol. This measure will be used to assess alcohol-related expectancies with both alcohol and ketamine.

The OCDS is a self-administered instrument that consists of 14 items that has been shown to be sensitive and specific for the obsessive and compulsive characteristics of alcohol misuse: drinking-related preoccupations, urges to drink, and the ability to desist these thoughts/urges. This measure will also be used to assess alcohol-related expectancies related to both alcohol and ketamine infusions. Items are rated on a 5 point Likert scale. Higher scores indicate more preoccupation, urges, or difficulty controlling urges to drink/consume alcohol.

The BPRS is a clinician-administered instrument with 4 key items will be used as an index of positive symptoms of schizophrenia. These 4 key positive domains are conceptual disorganization, hallucinatory behavior, suspiciousness and unusual thought content. 3 additional BPRS items - blunted affect, emotional withdrawal and motor retardation - are selected as a measure of negative schizophrenia symptoms. Each item is scored on a 7 point Likert scale, with 1 indicating absence of a given symptom and 7 indicating highest measured severity. Individual item are added to form a total scale score.

The VAS is a 7-item self-administered Likert-type measure with individual items scored between 0-10. This instrument rates 7 domains: happy/euphoric, restless, sad, anxious, irritated/angry, drowsy and alert. A score of 0 is described as "none", 1-3 is "mild", 4-6 is "moderate", 7-9 is "marked" and 10 is "extreme" for each given item.

The CADSS is a measure of perceptual, behavioral and attentional changes occurring during dissociative experiences that has been tested in healthy subjects and post-traumatic stress disorder (PTSD). This scale involves 19 self-reported questions and 8 observer ratings scored from 0 (not at all) - 4 (extremely). Greater scores indicate greater ketamine-induced dissociation.

The CGI is a clinician-measured scale of 3 items: Severity of Illness (item 1), Global Improvement (item 2), and Efficacy Index (item 3). Items 1 and 2 are rated on a 7-point Likert scale (1=normal, 7=among the most extremely ill patients) with a possible response of "not assessed." Item 3 is rated on a 4-point Likert scale from "none" to "outweighs therapeutic effect." Items 1 and 3 are assessed in relation to last clinical encounter (if possible).

This clinician-collected form collects information over 100 symptoms/signs across multiple organ systems. The "Specific" form is for tracking side effects that are often seen during the infusion at multiple time points. The "Regular" form is for the baseline (-60 minutes), +230 minute post-ketamine infusion (final time point on the day of ketamine infusion) and other daily time points post-ketamine infusion.

The PANAS is a self-report questionnaire comprised of 2 mood scales, one that measures positive affect and one that measures negative affect. Used as a psychometric scale, the PANAS can show relations between positive and negative affect with personality states and traits. 10 descriptors are used for each positive and negative affect scale to define their meanings. Participants are asked to respond to a 20-item test, and each individual item is scored on a a 5-point Likert scale that ranges from very slightly or not at all (1) to extremely (5).