Ketamine in the Treatment of Suicidal Depression

March 10, 2020 updated by: Michael Grunebaum, MD, New York State Psychiatric Institute

Ketamine vs. Midazolam: Testing Rapid Relief of Suicide Risk in Depression

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

82

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10032
        • Columbia University/New York State Psychiatric Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 63 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

INCLUSION CRITERIA:

  • Unipolar depression with current major depressive episode (MDE). Participants may be psychiatric medication-free, or if on psychiatric medication, not responding adequately given current MDE with suicidal ideation (See 2).
  • Moderate to severe suicidal ideation
  • 18-65 years old
  • Participants must agree to a voluntary admission to an inpatient research unit at the New York State Psychiatric Institute (NYSPI)for the infusion(s), for a brief stay, or longer if clinically necessary.
  • Pre-menopausal female participants of child-bearing potential must be willing to use an acceptable form of birth control during study participation such as condoms, diaphragm, or oral contraceptive pills.
  • Able to provide informed consent
  • Participants 61-65 years old must score a 25 or higher on the Mini-Mental State Examination (MMSE) at screening.

EXCLUSION CRITERIA:

  • Unstable medical condition or neurological illness, including baseline hypertension (BP>140/90) or significant history of cardiovascular illness.
  • Significant ECG abnormality
  • Pregnant or lactating
  • Diagnosis of bipolar disorder or psychotic disorder
  • Contraindication to any study treatment.
  • Inadequate understanding of English.
  • Prior ineffective trial of or adverse reaction to Ketamine or Midazolam.
  • Opiate use greater than total daily dose of 20mg Oxycodone or equivalent during the 3 days pre-infusion.
  • A diagnosis of sleep apnea.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Midazolam
0.02 mg/kg, I.V. (in the vein)
Drug: Midazolam
Single dose of 0.02 mg/kg of Midazolam given intravenously (in the vein) over 40 minutes
Other Names:
  • Midazolam Injection
Active Comparator: Ketamine
0.5 mg/kg, I.V. (in the vein)
Drug: Ketamine
Single dose of 0.5 mg/kg of ketamine given intravenously (in the vein) over 40 minutes
Other Names:
  • Ketalar
  • Ketamine Hydrochloride Injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Scale for Suicidal Ideation
Time Frame: 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.
Day 1 (24 hours) post-treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Saliva Cortisol Awakening Response (CAR).
Time Frame: 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.
Cort2 - Cort1 = (Day 1 30-mins post-awakening cortisol) - (Day 1 awakening cortisol)
Neuropsychological Effects
Time Frame: 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).
Baseline and Day 1

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

New York State Psychiatric Institute

Collaborators

National Institute of Mental Health (NIMH)

Investigators

  • Principal Investigator: Michael F. Grunebaum, M.D., Columbia University/New York State Psychiatric Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2012

Primary Completion (Actual)

January 12, 2017

Study Completion (Actual)

July 31, 2017

Study Registration Dates

First Submitted

October 2, 2012

First Submitted That Met QC Criteria

October 2, 2012

First Posted (Estimate)

October 4, 2012

Study Record Updates

Last Update Posted (Actual)

March 11, 2020

Last Update Submitted That Met QC Criteria

March 10, 2020

Last Verified

March 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • #6598
  • R01MH096784 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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