Ketamine in the Treatment of Suicidal Depression

Phase 4

Completed

Conditions: Suicidal Ideation
Major Depressive Disorder

Interventions: Drug: Midazolam
Drug: Ketamine

Registration Number: NCT01700829

Lead Sponsor: New York State Psychiatric Institute

Brief Summary: This study is designed to compare the effectiveness of two medications, Ketamine and Midazolam, for rapidly relieving suicidal thoughts in people suffering from depression.

The first drug, Ketamine, is an experimental antidepressant that early studies have shown may quickly reduce suicidal thoughts, but we are not sure how well it may work. Midazolam, the comparison drug, is not thought to reduce depression or suicidal thoughts.

Detailed Description: Patients currently taking psychiatric medications may continue them during the study. However, if a patient is taking a benzodiazepine (such as Ativan, Klonopin, or Xanax), they will be able to take up to 2mg per day of Lorazepam during the week before the infusion, but none will be permitted in the 24 hours pre-infusion. Also, Zolpidem (Ambien) will not be permitted in the 24 hours pre-infusion. If a person chooses to participate, their dose of benzodiazepine may need to be reduced so that they can do without it during the 24 hours pre-infusion.

Depressed participants are randomly assigned to receive a single dose of Ketamine(0.5 mg/kg) or Midazolam (0.02 mg/kg), which is given slowly, in a vein, over about 40 minutes. The study is "double-blind," meaning patients and study staff will not know which medication is in the infusion.

If a patient does not respond to the first infusion, and s/he received Midazolam, then s/he will be offered the option of a second infusion, this time with Ketamine (0.5 mg/kg). S/he will then start treatment with a standard antidepressant, unless s/he is not already taking one.

After the infusion(s), participants will have weekly research interviews for 6 weeks to monitor response.

If a patient does have a sufficient infusion response, and s/he is not already taking an antidepressant, then s/he will receive 6-weeks antidepressant research treatment with Sertraline, Fluoxetine, Paroxetine, or Escitalopram, followed by open clinical treatment. However, if s/he is already taking an antidepressant, then s/he will receive open treatment. If s/he does not have a sufficient infusion response, then s/he will receive open treatment.

Participation in this study requires a brief inpatient stay, at no cost, at the New York State Psychiatric Institute (NYSPI).

Eligible participants enrolled in this study will be offered medication management visits at no cost for a total of up to 6 months from the date of enrollment combining inpatient and outpatient treatment. Study medications (Sertraline, Fluoxetine, Paroxetine, Escitalopram, Lorazepam, Zolpidem) will be at no cost during the 6 months. The study will not provide other medications at no cost.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 82

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Midazolam	Midazolam	0.02 mg/kg, I.V. (in the vein)
Ketamine	Ketamine	0.5 mg/kg, I.V. (in the vein)

Primary Outcome Measures

Name	Time	Method
Change in Scale for Suicidal Ideation	Day 1 (24 hours) post-treatment	Change in suicidal ideation in depressed patients with moderate to severe suicidal thoughts from the pre-infusion baseline to 24 hours after the infusion with ketamine or midazolam, a sedative not known to reduce suicidal ideation, measured with Beck Scale for Suicidal Ideation - clinician rated version. This scale has 19 items scaled 0 (least severe) to 2 (most severe) and a potential score ranging from 0 to 38, with higher score indicating greater severity.

Secondary Outcome Measures

Name	Time	Method
Saliva Cortisol Awakening Response (CAR).	Cort2 - Cort1 = (Day 1 30-mins post-awakening cortisol) - (Day 1 awakening cortisol)	On the mornings of an infusion day and on post-treatment day1, participants used salivettes (Sarstedt AG \& Co.) to provide saliva samples upon awakening (Cort1) and 30 minutes later (Cort2) to measure cortisol awakening response (CAR) = (Cort2 - Cort1). Differences between the midazolam and ketamine groups were tested using an analysis of covariance (ANCOVA) model of the change in CAR from baseline to day1, with treatment group and baseline measurement of the outcome variable as predictors. Range from 0.1 to 12.5 ng/ml and lower means less stress response, higher means greater stress response.
Neuropsychological Effects	Baseline and Day 1	The average Z-scores reported below are the average of the Z-scores for all tests administered. The Z-scores for each test were based on published normative data and normative data available in our laboratory. The population mean for a Z-score is zero, with a SD of 1, thus scores below zero would indicate performance below the population norm; a score close to zero indicates performance close to the population norm (or a normalizing of performance).