Ketamine for Suicidality in Bipolar Depression

• Sponsor: New York State Psychiatric Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT01944293
• Collaborator: Brain & Behavior Research Foundation (Other)
• Enrollment: 16
• Location: 1
• Arms: 2
• Duration (Months): 61
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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 bipolar 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 or Disease	Intervention/Treatment	Phase
Bipolar Disorder; Major Depressive Episode; Suicidal Ideation	Drug: Ketamine; Drug: Midazolam	Phase 1/Phase 2

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.

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

After post-infusion research measures are completed, all subjects will receive open clinical treatment. During open clinical treatment, medication will be changed for those patients who don't respond or whose response is transient.

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 combining inpatient and outpatient treatment. At the end of the 6 months of treatment patients will be referred for ongoing care.

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Ketamine vs. Midazolam in Bipolar Depression
• Study Start Date: Sep 1, 2013
• Actual Primary Completion Date: Sep 1, 2017
• Actual Study Completion Date: Oct 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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
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

Outcome Measures

Primary Outcome Measures

1. Change in Suicidal Ideation Measured With the Beck Scale for Suicidal Ideation [At 24 hours post-Infusion]

   Change in suicidal ideation in Bipolar Disorder during a Major Depressive Episode (MDE), with moderate to severe suicidal thoughts, from the pre-infusion baseline to 24 hours after the infusion of Ketamine (study drug) or Midazolam (active control).

Secondary Outcome Measures

1. Change in Systolic Blood Pressure [During study infusion]

   Blood pressure is measured in millimeters of mercury.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

INCLUSION CRITERIA:

• Bipolar 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.

• Moderate to severe suicidal ideation

• 18-65 years old

• Patients will only be enrolled if they agree to voluntary admission to an inpatient research unit at the New York State Psychiatric Institute (NYSPI) for infusion phase of treatment.

• 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, oral contraceptive pills

• Able to provide informed consent

• Subjects 61-65 years old must score 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

• Pregnancy and/or lactation

• Current psychotic symptoms

• Contraindication to any study treatment

• Current or past ketamine abuse or dependence ever (lifetime); any other drug or alcohol dependence within past 6 months; suicidality only due to binge substance use or withdrawal

• 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Columbia University/New York State Psychiatric Institute	New York	New York	United States	10032

Sponsors and Collaborators

• New York State Psychiatric Institute
• Brain & Behavior Research Foundation

Investigators

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

Study Documents (Full-Text)

• Statistical Analysis Plan - May 14, 2019
• Study Protocol - Jul 1, 2019

More Information

Additional Information:

• MIND Clinic for Mood and Personality Disorders
• Channel 7 NYC Story about Ketamine Research at Columbia University Medical Center

Publications

None provided.

• Responsible Party: Michael Grunebaum, MD, Clinical Psychiatrist, New York State Psychiatric Institute
• ClinicalTrials.gov Identifier: NCT01944293
• Other Study ID Numbers: #6785
• First Posted: Sep 17, 2013
• Last Update Posted: Mar 11, 2020
• Last Verified: Feb 1, 2020

• Keywords provided by Michael Grunebaum, MD, Clinical Psychiatrist, New York State Psychiatric Institute: Ketamine; Midazolam; Bipolar Disorder; Major Depressive Episode; Suicidal Ideation; Suicide; Depression; Treatment; Ketamine Treatment
• Additional relevant MeSH terms: Depression; Bipolar Disorder; Suicidal Ideation; Midazolam; Ketamine

Study Results

Participant Flow

Arm/Group Title	Ketamine	Midazolam
Arm/Group Description	0.5 mg/kg, I.V. (in the vein) Ketamine: Single dose of 0.5 mg/kg of Ketamine given intravenously (in the vein) over 40 minutes	0.02 mg/kg, I.V. (in the vein) Ketamine: Single dose of 0.5 mg/kg of Ketamine given intravenously (in the vein) over 40 minutes Midazolam: Single dose of 0.02 mg/kg of Midazolam given intravenously (in the vein) over 40 minutes
Period Title: Overall Study
STARTED	7	9
COMPLETED	7	9
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Ketamine	Midazolam	Total
Arm/Group Description	0.5 mg/kg, I.V. (in the vein) Ketamine: Single dose of 0.5 mg/kg of Ketamine given intravenously (in the vein) over 40 minutes	0.02 mg/kg, I.V. (in the vein) Ketamine: Single dose of 0.5 mg/kg of Ketamine given intravenously (in the vein) over 40 minutes Midazolam: Single dose of 0.02 mg/kg of Midazolam given intravenously (in the vein) over 40 minutes	Total of all reporting groups
Overall Participants	7	9	16
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	39 (10.2)	43 (13.9)	40.5 (12.4)
Sex: Female, Male (Count of Participants)
Female	3 42.9%	7 77.8%	10 62.5%
Male	4 57.1%	2 22.2%	6 37.5%
Race/Ethnicity, Customized (Count of Participants)
More than one race	1 14.3%	0 0%	1 6.3%
White race	6 85.7%	8 88.9%	14 87.5%
Not Hispanic	7 100%	8 88.9%	15 93.8%
Hispanic	0 0%	1 11.1%	1 6.3%
Asian	0 0%	1 11.1%	1 6.3%
Beck Scale for Suicidal Ideation (Clinician-rated) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	16.7 (8.4)	16.8 (6.0)	16.8 (6.9)

Outcome Measures

1. Primary Outcome

Title	Change in Suicidal Ideation Measured With the Beck Scale for Suicidal Ideation
Description	Change in suicidal ideation in Bipolar Disorder during a Major Depressive Episode (MDE), with moderate to severe suicidal thoughts, from the pre-infusion baseline to 24 hours after the infusion of Ketamine (study drug) or Midazolam (active control).
Time Frame	At 24 hours post-Infusion

Outcome Measure Data

Analysis Population Description

Bipolar depression with suicidal ideation.

Arm/Group Title	Ketamine	Midazolam
Arm/Group Description	0.5 mg/kg, I.V. (in the vein) Ketamine: Single dose of 0.5 mg/kg of Ketamine given intravenously (in the vein) over 40 minutes	0.02 mg/kg, I.V. (in the vein) Ketamine: Single dose of 0.5 mg/kg of Ketamine given intravenously (in the vein) over 40 minutes Midazolam: Single dose of 0.02 mg/kg of Midazolam given intravenously (in the vein) over 40 minutes
Measure Participants	7	9
Mean (Standard Deviation) [units on a scale]	-12.4 (11.6)	-6.7 (7.4)

2. Secondary Outcome

Title	Change in Systolic Blood Pressure
Description	Blood pressure is measured in millimeters of mercury.
Time Frame	During study infusion

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ketamine	Midazolam
Arm/Group Description	0.5 mg/kg, I.V. (in the vein) Ketamine: Single dose of 0.5 mg/kg of Ketamine given intravenously (in the vein) over 40 minutes	0.02 mg/kg, I.V. (in the vein) Ketamine: Single dose of 0.5 mg/kg of Ketamine given intravenously (in the vein) over 40 minutes Midazolam: Single dose of 0.02 mg/kg of Midazolam given intravenously (in the vein) over 40 minutes
Measure Participants	7	9
Mean (Standard Deviation) [mm Hg]	23 (12.8)	3 (10.2)

Adverse Events

Time Frame	6 months
Arm/Group Title	Ketamine		Midazolam
Arm/Group Description	0.5 mg/kg, I.V. (in the vein) Ketamine: Single dose of 0.5 mg/kg of Ketamine given intravenously (in the vein) over 40 minutes		0.02 mg/kg, I.V. (in the vein) Ketamine: Single dose of 0.5 mg/kg of Ketamine given intravenously (in the vein) over 40 minutes Midazolam: Single dose of 0.02 mg/kg of Midazolam given intravenously (in the vein) over 40 minutes
All Cause Mortality
	Ketamine		Midazolam
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/7 (0%)		0/9 (0%)
Serious Adverse Events
	Ketamine		Midazolam
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/7 (57.1%)		0/9 (0%)
Psychiatric disorders
Increased suicidal thoughts requiring hospitalization	2/7 (28.6%)	4	0/9 (0%)	0
suicide attempt	1/7 (14.3%)	1	0/9 (0%)	0
Preparatory suicidal behavior	1/7 (14.3%)	1	0/9 (0%)	0
Other (Not Including Serious) Adverse Events
	Ketamine		Midazolam
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/7 (0%)		0/9 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.