Ketamine as a Rapidly-Acting Antidepressant in Depressed Emergency Department Patients

August 16, 2018 updated by: NYU Langone Health

A Randomized, Double-Blinded Controlled Trial of an N-Methyl D-Aspartate Antagonist as a Rapidly-Acting Antidepressant in Depressed Emergency Department Patients

Investigators will conduct a trial to evaluate the use of Ketamine as an alternate treatment for people with Major Depressive Disorder. This study plans to explore the potential that Ketamine's rapid antidepressant action holds for improving outcomes in patients presenting to the Emergency Department with severe depression. Since this is a controlled trial we will use an IV of Ketamine or and equivalent volume of Diphenhydramine. Subjects will be randomly assigned to receive Ketamine or Benadryl. Investigators will then compare measures of mood pre- and post-infusion in the Emergency Department. To supplement self-reported measures of depressive symptoms(e.g. mood), investigators will obtain objective measures of the biological aspects of Major Depressive Disorder.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

To explore the use of ketamine as a potential rapidly-acting antidepressant (RAA) for Emergency Department (ED) patients with major depressive disorder (MDD).

Investigators will conduct a randomized controlled study to evaluate the rapidity and persistence of antidepressant effects of a single sub-anesthetic dose of intravenous (IV) ketamine (0.25mg/kg) or an equivalent volume of diphenhydramine (25mg) delivered IV over 1-2 minutes, by comparing measures of mood pre- and post-infusion in Emergency Department (ED) patients with MDD. Subjects will be randomly assigned (1:1) to receive a bolus of ketamine or diphenhydramine. To supplement self-reported measures of depressive symptoms (e.g., mood, suicidal ideation, etc.), investigators will obtain objective measures of heart rate and heart rate variability, measure serum levels of the pro- and anti-inflammatory cytokines (interleukin IL-1, IL-2, IL-6, IL-8, IL-10, IL-12, and tissue necrosis factor, TNF-α), which have been shown to play an important role in stress, depression and suicidal behavior. In addition, investigators will obtain serum levels of brain derived neurotrophic factor (BDNF) because reduced serum BDNF has been described during acute depressive episodes in patients with MDD, with reports of rescue effects following treatment with various antidepressants and with ketamine (Aydemir 2005, Gervasoni 2005, Karege 2002, Karege 2005, Duncan 2013, Shimizu 2003). Investigators will also measure serum magnesium levels, as these have been shown to correlate in a predictive manner with response to conventional antidepressants (Camardese 2012), and there are data to suggest that ketamine's efficacy in treatment-resistant depression could be related to a relative magnesium deficiency in such patients (Murck 2013).

This study will allow investigators to determine to what extent low-dose ketamine, an N-Methyl-D-Aspartate (NMDA) antagonist, achieves a rapid reduction in symptoms for severely depressed ED patients with or without suicidal ideation. For decades, much higher doses of IV ketamine (1-2mg/kg) have been used routinely in the ED as a dissociative anesthetic (Green 2011). In 2011, an open-label study was the first published of the use of low dose ketamine (0.2mg/kg), administered by rapid intravenous infusion, in the ED setting for acutely depressed patients which demonstrated its feasibility, safety, preliminary efficacy and acceptability to both ED patients and staff (Larkin 2011). One long-term goal of this research is to expand treatment options available to depressed ED patients that mitigate the need for inpatient admission and serve as a safety bridge to future out-patient treatment for major depression. As an adjunct to standard treatment, low-dose NMDA receptor antagonists have the potential to positively impact: ED waiting times; repeat visits to the ED; short-term risk of suicide attempts; length of stay on inpatient units and the need for hospital admissions for many acutely depressed patients.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
21

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

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, 10016
        • Bellevue Hospital Center
      • New York, New York, United States, 10016
        • NYU Langone Medical Center/Tisch Hospital

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Medically stable as determined by the medical physician
  • Meets criteria for Major Depressive Disorder (MDD) based on a structured clinical Interview (MINI International Neuropsychiatric Interview).
  • Reports symptoms of severe depression at the time of presentation, defined as a score of 24 or greater on the MADRS.
  • Patients for whom a psychiatric evaluation and disposition decision has been made by emergency psychiatry staff to admit to an inpatient psychiatric unit at Bellevue Hospital Center or NYU Tisch Hospital.
  • Each subject must have a level of understanding sufficient to sign an informed consent stating that the treatment being offered is not FDA approved for the treatment of depression and is being provided as an off-label option.

Exclusion Criteria:

  • Pregnancy
  • Inability to read or understand English
  • Current clinical signs of intoxication or delirium at time of study intervention
  • Overdose, within previous 24 hours, of any agent which would impair ketamine metabolism
  • Lifetime misuse/abuse of ketamine, phencyclidine (PCP),or related substances
  • Lifetime history of psychotic spectrum illness
  • First-degree relative with history of psychotic illness
  • Lifetime diagnosis of borderline personality disorder, or as confirmed by assessment using items #90-104 of the SCID-II (for DSM-IV).
  • Subjects with clinically significant abnormal findings as determined by medical history, physical examination, vital signs (blood pressure, heart rate, and respiration rate), O2 saturation measure, 12-lead ECG, clinical laboratory tests (CBC, chemistry panel, thyroid function tests), urine drug screen, and urine pregnancy test (for females of childbearing potential only).
  • Clinically unstable medical, surgical or neurological conditions at ED presentation
  • History of stroke or intracranial hypertension
  • History of glaucoma
  • Subjects with one or more seizures without a clear and resolved etiology
  • Current NMDA antagonist medications (eg. Amantadine, Rimantadine, Lamotrigine, Memantine, Dextromethorphan)
  • Known hypersensitivity to ketamine or amantadine
  • Anti-psychotic medications (Typicals or Atypicals), with the exception of low-dose quetiapine (total daily dose of 100mg or less).
  • Actively trying to commit suicide, even in a hospital setting
  • Current homicide risk
  • Unable or unwilling to give informed consent according to HIC guidelines
  • Unable or unwilling to provide 2 contact phone numbers or be followed up per study protocol.
  • Previous enrollment in this study.
  • Concurrent enrollment in a research protocol investigating experimental pharmacologic treatments for depression at this or any other institution.

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: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Ketamine
IV Ketamine .25mg/kg
Drug: Ketamine
IV of Ketamine (.25mg/kg)
Other Names:
  • Other names for ketamine: ketalar
Placebo Comparator: Diphenhydramine
25mg Diphenhydramine
Drug: Diphenhydramine
Intravenous Diphenhydramine (25mg) at the time of presentation to Emergency Department
Other Names:
  • Other names for diphenhydramine: benadryl

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Evaluate the Effects of Ketamine on Depressive Symptomatology by Measuring Change in Score on the Montgomery-Asberg Depressive Rating Scale
Time Frame: Baseline and 16 weeks

40 Minutes Post Infusion, The MADRS-S instrument has nine questions, with an overall score ranging from 0 to 54 points.

0 to 6 - normal /symptom absent 7 to 19 - mild depression 20 to 34 - moderate depression >34 - severe depression.
Baseline and 16 weeks
Beck Depression Inventory-II (BDI-II)
Time Frame: 120 min post-infusion

BDI-II items are rated on a 4-point scale ranging from 0 to 3 based on severity of each item. The maximum total score is 63.

0-13 Indicates minimal depression 14-19 Indicates mild depression 20-28 Indicates Moderate depression 29-63 Indicates Severe depression
120 min post-infusion
Hamilton Depression Scale (Ham-D)
Time Frame: 4-6 hours post-infusion

Although the HAM-D form lists 21 items, the scoring is based on the first 17. It generally takes 15-20 minutes to complete the interview and score the results. Eight items are scored on a 5-point scale, ranging from 0 = not present to 4 = severe. Nine are scored from 0-2.

Sum the scores from the first 17 items 0-7= Normal 8-13= Mild Depression 14-18= Moderate Depression 19-22= Severe Depression >23= Very Severe Depression
4-6 hours post-infusion

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in Treatment Alliance Score
Time Frame: Baseline and 16 weeks
The I-TAS is a 10-item, Likert-style rating scale designed to assess a patient's composite treatment alliance as it develops across multi-disciplinary treatment components. The I-TAS was intended to measure the primary alliance factors identified by Hatcher and Barends (1996) of bond, goals and collaboration. Each question is scored on a scale of 0 (Completely False) to 6 (Completely True). Total scores on the ITAS range from 0 to 60, with higher scores representing greater alliance with the treatment team (better outcome). The reported score is an average of each participant's total score on the ITAS.
Baseline and 16 weeks
Beck Scale for Suicidal Ideation (BSSI)
Time Frame: 40 minutes post-infusion

BDI-II items are rated on a 4-point scale ranging from 0 to 3 based on severity of each item. The maximum total score is 63.

0-13 Indicates minimal depression 14-19 Indicates mild depression 20-28 Indicates Moderate depression 29-63 Indicates Severe depression
40 minutes post-infusion
Montgomery-Åsberg Depression Rating Scale Suicide Ideation Item (MADRS-SI)
Time Frame: 40 minutes post-infusion

40 Minutes Post Infusion, The MADRS-S instrument has nine questions, with an overall score ranging from 0 to 54 points.

0 to 6 - normal /symptom absent 7 to 19 - mild depression 20 to 34 - moderate depression >34 - severe depression.
40 minutes post-infusion
Length of Inpatient Stay
Time Frame: 2 Weeks Post-infusion
2 Weeks Post-infusion
Outpatient Follow-up Compliance
Time Frame: 1 Day
Scoring System: 0= not compliant, 1=compliant
1 Day
Inpatient Treatment Alliance Scale (ITAS)
Time Frame: 7 days post-infusion
The I-TAS is a 10-item, Likert-style rating scale designed to assess a patient's composite treatment alliance as it develops across multi-disciplinary treatment components. The I-TAS was intended to measure the primary alliance factors identified by Hatcher and Barends (1996) of bond, goals and collaboration. Each question is scored on a scale of 0 (Completely False) to 6 (Completely True). Total scores on the ITAS range from 0 to 60, with higher scores representing greater alliance with the treatment team (better outcome). The reported score is an average of each participant's total score on the ITAS.
7 days post-infusion

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
NYU Langone Health

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Stephen Ross, MD, NYU Langone Health
  • Study Chair: K. Casey Paleos, MD, New York Unversity School of Medicine

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

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 1, 2013

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 1, 2016

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 1, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 12, 2013

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 3, 2014

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 8, 2014

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 14, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 16, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 13-00794

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

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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