Ketamine in the Treatment of Suicidal Depression

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by New York State Psychiatric Institute
Sponsor:
Collaborator:
Information provided by (Responsible Party):
New York State Psychiatric Institute
ClinicalTrials.gov Identifier:
NCT01700829
First received: October 2, 2012
Last updated: July 31, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Major Depressive Disorder
Suicidal Ideation
Drug: Ketamine
Drug: Midazolam
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Ketamine vs. Midazolam: Testing Rapid Relief of Suicide Risk in Depression

Resource links provided by NLM:


Further study details as provided by New York State Psychiatric Institute:

Primary Outcome Measures:
  • Reduction of suicidal ideation [ Time Frame: At 24 hours post-Infusion ] [ Designated as safety issue: No ]
    Reduction of 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.


Secondary Outcome Measures:
  • Effects on saliva stress hormone (cortisol) [ Time Frame: 24 hours post-infusion ] [ Designated as safety issue: No ]
    Effects on levels of the stress hormone cortisol in saliva from before to 24 hours after the infusion.

  • Neuropsychological effects [ Time Frame: 24 hours post-infusion ] [ Designated as safety issue: No ]
    Effects of the infusion on neuropsychological variables including decision-making and memory.


Estimated Enrollment: 70
Study Start Date: June 2012
Estimated Study Completion Date: April 2017
Estimated Primary Completion Date: April 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  • Participants who have never received medication treatment for depression.
  • Opiate use greater than total daily dose of 20mg Oxycodone or equivalent during the 3 days pre-infusion.
  • A diagnosis of sleep apnea.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01700829

Contacts
Contact: Julia E Marver, B.A. (646) 774-7627 marverj@nyspi.columbia.edu

Locations
United States, New York
Columbia University/New York State Psychiatric Institute Recruiting
New York, New York, United States, 10032
Contact: Julia E Marver, B.A.    646-774-7627    marverj@nyspi.columbia.edu   
Principal Investigator: Michael F. Grunebaum, M.D.         
Sponsors and Collaborators
New York State Psychiatric Institute
Investigators
Principal Investigator: Michael F. Grunebaum, M.D. Columbia University/New York State Psychiatric Institute
  More Information

Additional Information:
No publications provided

Responsible Party: New York State Psychiatric Institute
ClinicalTrials.gov Identifier: NCT01700829     History of Changes
Other Study ID Numbers: #6598, R01MH096784
Study First Received: October 2, 2012
Last Updated: July 31, 2014
Health Authority: United States: Federal Government
United States: Institutional Review Board

Keywords provided by New York State Psychiatric Institute:
Ketamine
Midazolam
Major Depressive Disorder
Suicidal ideation
Suicide
Depression
Treatment
Ketamine Treatment

Additional relevant MeSH terms:
Depression
Depressive Disorder
Depressive Disorder, Major
Suicidal Ideation
Behavioral Symptoms
Mental Disorders
Mood Disorders
Self-Injurious Behavior
Suicide
Ketamine
Midazolam
Adjuvants, Anesthesia
Analgesics
Anesthetics
Anesthetics, Dissociative
Anesthetics, General
Anesthetics, Intravenous
Anti-Anxiety Agents
Central Nervous System Agents
Central Nervous System Depressants
Excitatory Amino Acid Agents
Excitatory Amino Acid Antagonists
GABA Agents
GABA Modulators
Hypnotics and Sedatives
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 29, 2014