IM Ketamine vs Midazolam for Suicidal ER Patients

Rising US suicide rates and the increased risk of suicide among persons who visit an emergency department (ED) for suicidality make the ED an important site for interventions to prevent suicide. There is no approved treatment for rapid relief of suicidal thoughts although clinical trials, including ours, show relief of suicidal thoughts within hours of treatment with inexpensive, generic, sub-anesthetic ketamine. We propose a clinical trial of intramuscular ketamine in depressed ED patients with high-risk suicidality, which if successful would support a novel, easy-to-use, scalable intervention for busy emergency clinicians to implement.

Study Overview

• Status: Active, not recruiting
• Conditions: Suicidal Ideation; Depression, Unipolar; Depression, Bipolar
• Intervention / Treatment: Drug: Ketamine hydrochloride injection; Drug: Midazolam injection

Detailed Description

Rising US suicide rates and the increased risk of suicide among persons who visit an emergency department (ED) for suicidality make the ED an important site for interventions to prevent suicide. Clinical trials, including ours, show relief of suicidal thoughts within hours of treatment with inexpensive, generic, subanesthetic ketamine. We have received NIMH R01 funding to conduct a clinical trial of intramuscular (IM) ketamine in unipolar or bipolar depressed adults who present to the CUIMC psychiatric ED with suicidality severe enough to require inpatient hospitalization as judged by ED clinical staff. Clinical staff will ask potentially eligible patients if they would like to learn more about the study, and if so, a research assistant (RA) will describe the study to the patient and perform a basic eligibility screen. Key exclusions are unstable medical problems, substance abuse, psychosis, and further detail is provided in the Inclusion/Exclusion criteria. Participants (N=90) who enroll will undergo baseline clinical ratings, brief cognitive testing, and then be randomized, double-blind, in a 2:1 ratio to a single IM injection of ketamine (n=60) or midazolam comparator (n=30). Vital signs and clinical state will be monitored until injection effects subside (approximately 2 hrs). Blood samples will be drawn at 60 minutes and 90 minutes postinjection to assay ketamine level and a genetic sample will be stored. All participants will then be admitted to the 9GN inpatient unit for standard clinical treatment with periodic research follow-up ratings through 4 weeks post-discharge from hospital. Ongoing outpatient treatment will be arranged by the inpatient clinical team. Positive results from this trial would support a novel, easy-to-use, inexpensive, and scalable intervention for busy emergency clinicians to implement.

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Michael Grunebaum, MD; Phone Number: 646-774-7573; Email: michael.grunebaum@nyspi.columbia.edu
• Study Contact Backup: Name: Sumra Sajid, BA; Phone Number: 646-774-7564; Email: sumra.sajid@nyspi.columbia.edu

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Comprehensive Psychiatric Emergency Department of Columbia University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• DSM5 unipolar or bipolar (I, II, or Unspecified) major depressive episode
• Presenting to emergency department and assessed by psychiatrist staff as needing inpatient treatment due to suicidality
• Participant agrees to voluntary inpatient psychiatric admission
• Beck Scale for Suicidal Ideation score of 4 or higher

Exclusion Criteria:

• Substance use disorder in past 2 weeks
• Current psychosis or mania
• Intellectual disability
• Inadequate understanding of English and/or lack of capacity for informed consent
• Pregnancy or lactation
• Medical contraindication to ketamine or midazolam
• Unstable medical or neurological illness such as uncontrolled hypertension, significant cardiac arrhythmia, unstable cerebrovascular disease. Chronic, stable medical conditions such as controlled hypertension or diabetes will not be excluded.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ketamine; Ketamine hydrochloride 0.5 mg/kg IM single injection	Drug: Ketamine hydrochloride injection; single IM injection of ketamine hydrochloride 0.5 mg/kg
Active Comparator: midazolam; Midazolam 0.06 mg/kg IM single injection	Drug: Midazolam injection; single IM injection of midazolam 0.06 mg/kg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Scale for Suicidal Ideation (SSI)	Beck Scale for Suicidal Ideation clinician-rated version	24 hours post-treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Systematic Assessment for Treatment Emergent Events (SAFTEE)	Frequency of adverse events at 24 hours post-treatment	24 hours post-treatment

Collaborators and Investigators

• Sponsor: New York State Psychiatric Institute
• Collaborators: National Institute of Mental Health (NIMH)
• Investigators: Principal Investigator: Michael Grunebaum, MD, New York State Psychiatric Institute/Columbia University Irving Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): January 2, 2021
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): March 1, 2025

Study Registration Dates

• First Submitted: November 20, 2020
• First Submitted That Met QC Criteria: November 20, 2020
• First Posted (Actual): November 23, 2020

Study Record Updates

• Last Update Posted (Actual): August 9, 2023
• Last Update Submitted That Met QC Criteria: August 8, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: depression; midazolam; clinical trial; ketamine; suicidality
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Bipolar and Related Disorders; Self-Injurious Behavior; Suicide; Depression; Depressive Disorder; Bipolar Disorder; Suicidal Ideation; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Ketamine; Midazolam
• Other Study ID Numbers: 8070 (CTEP); R01MH125155-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All associated research findings published or provided to NIH, will be made readily available for research purposes to qualified individuals within the scientific community. All data will be made anonymous and available after written requests for data are submitted by such qualified individuals to the PI.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No