Ketamine For Suicidal Ideation
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Investigating Rapid Anti-Suicidal Ideation Effects of Intravenous (IV) Ketamine in Hospitalized Patients|
- Change in Beck Scale for Suicidal Ideation (BSSI) [ Time Frame: baseline and 24 hours post infusion ]Change in BSI score at 24 hours following treatment as compared to baseline. Beck Scale is a 21-item self or clinician administered instrumentation used to measure the current intensity of patients' specific attitudes, behaviors and plans to commit suicide. Score range 0-42, with higher score indicating higher intensity.
- Change in Beck Scale for Suicidal Ideation (BSSI) [ Time Frame: baseline and 48 hours post infusion ]Change in BSI score at 48 hours following treatment as compared to baseline. Beck Scale is a 21-item self or clinician administered instrumentation used to measure the current intensity of patients' specific attitudes, behaviors and plans to commit suicide. Score range 0-42, with higher score indicating higher intensity.
- Montgomery-Asberg Depression Rating Scale (MADRS) [ Time Frame: up to 7 days post infusion ]The MADRS is a 10-item instrument used for the evaluation of depressive symptoms in adults and for the assessment of any changes to those symptoms. Higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60.
- Suicidality Item of the MADRS (MADRS-SI) [ Time Frame: 24 hours post infusion ]The MADRS-SI ranges from 0 to 6; a score of 2 corresponds to fleeting, passive SI; a score of 4 indicates that SI is frequent with at least moderate intensity but without specific plans or intention; a score of 6 corresponds to active intention and planning for suicide.
- The Young Mania Rating Scale (YMRS) [ Time Frame: baseline, 40 minutes post infusion, 240 minutes post infusion ]An 11-item questionnaire, used to assess manic symptoms based on the patient's subjective report of his or her clinical condition. There are four items that are graded on a 0 to 8 scale (irritability, speech, thought content, and disruptive/aggressive behavior), while the remaining seven items are graded on a 0 to 4 scale. The scores from each question are added together to form a total score ranging from 0 to 60, with higher scores indicating a greater severity of symptoms.
- The Brief Psychiatric Rating Scale (BPRS) [ Time Frame: baseline, 40 minutes post infusion, and 240 minutes post infusion ]The BPRS measures psychomimetic effects with higher scores indicating more severe symptoms (scale range 7 - 49).
- The Clinician-Administered Dissociative States Scale (CADSS) [ Time Frame: baseline, 40 minutes post infusion and 240 minutes post infusion ]The CADSS measures dissociation with higher scores indicating more severe symptoms (scale range 0 - 92).
- Patient Rated Inventory of Side Effects (PRISE) [ Time Frame: duration of study ]The PRISE assesses the presence of treatment side effects in nine organ/function systems (gastrointestinal, nervous system, heart, eyes/ears, skin, genital/urinary, sleep, sexual functioning, and other). Data reported in in Adverse Events section.
|Study Start Date:||January 2012|
|Study Completion Date:||September 2014|
|Primary Completion Date:||September 2014 (Final data collection date for primary outcome measure)|
single dose IV ketamine, .5mg/kg
single dose IV ketamine, .5mg/kg infused over 40 minutes
Other Name: N-methyl-D-aspartate (NMDA) glutamate receptor antagonist
Placebo Comparator: Midazolam
single dose IV midazolam, .45mg/kg
single dose IV midazolam, .45mg/kg infused over 40 minutes
Depression is a debilitating disorder that affects 12-20% of population and is among the top five leading causes of burden of disease worldwide (Kruijshaar ME 2005). Suicide associated with depression and other psychiatric disorders is a pervasive public health problem and results in almost one million deaths per year. Unfortunately, current treatments for severe depression have limited efficacy for suicidality, specifically due to the slow time course of change in suicidal thoughts. Recently ketamine, a glutamate-modulating agent, was shown to have antidepressant and anti-suicidal effect in outpatient depressed patients. The proposed study will test the ability of a single sub-anesthetic intravenous (IV) dose of the glutamate NMDA receptor antagonist, ketamine, to provide rapid decrease in suicidal ideation (SI) in patients hospitalized with SI. In this randomized parallel-arm placebo controlled trial, ketamine is compared to midazolam, which is expected to mimic some of the acute subjective effects of ketamine but not have any sustained antidepressant effects.
Specific Aim 1: To determine feasibility and tolerability of a single low-dose IV infusion of ketamine in patients with prominent SI and elevated risk for suicide.
Hypothesis 1: Ketamine administration will be feasible and well tolerated in patients admitted to a psychiatric hospital with SI.
Specific Aim 2: To test the efficacy of a single IV dose of ketamine, compared to an anesthetic control condition (midazolam), to rapidly reduce SI in a controlled hospital setting.
Hypothesis 2: Ketamine will be associated with significant and rapid reductions in SI and depressive symptoms within 24 hours.
This study will test the rapid anti-suicidal effect of a single IV dose of the N-methyl-D-aspartate (NMDA) glutamate receptor antagonist ketamine in suicidality compared with the clinical response to a single IV dose of the short-acting benzodiazepine midazolam. Midazolam is able to induce transient neuropsychiatric effects mimicking ketamine and therefore is expected to protect the integrity of the blind. Participants will continue to receive standard treatment for their psychiatric condition throughout the trial. This unique "proof-of-concept" study in suicidal patients will be conducted over three-year period.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01507181
|United States, New York|
|Icahn School of Medicine at Mount Sinai|
|New York, New York, United States, 10027|
|Principal Investigator:||James Murrough, MD||Icahn School of Medicine at Mount Sinai|