Ketamine For Suicidal Ideation

December 16, 2016 updated by: James Murrough

Investigating Rapid Anti-Suicidal Ideation Effects of Intravenous (IV) Ketamine in Hospitalized Patients

This study will examine the effects of Intravenous (IV) ketamine both in an outpatient population and with subjects on the inpatient unit with suicidal ideation (SI).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Depression is a debilitating disorder that affects 12-20% of population and is among the top five leading causes of burden of disease worldwide (Kruijshaar ME 2005). Suicide associated with depression and other psychiatric disorders is a pervasive public health problem and results in almost one million deaths per year. Unfortunately, current treatments for severe depression have limited efficacy for suicidality, specifically due to the slow time course of change in suicidal thoughts. Recently ketamine, a glutamate-modulating agent, was shown to have antidepressant and anti-suicidal effect in outpatient depressed patients. The proposed study will test the ability of a single sub-anesthetic intravenous (IV) dose of the glutamate NMDA receptor antagonist, ketamine, to provide rapid decrease in suicidal ideation (SI) in patients hospitalized with SI. In this randomized parallel-arm placebo controlled trial, ketamine is compared to midazolam, which is expected to mimic some of the acute subjective effects of ketamine but not have any sustained antidepressant effects.

Specific Aim 1: To determine feasibility and tolerability of a single low-dose IV infusion of ketamine in patients with prominent SI and elevated risk for suicide.

Hypothesis 1: Ketamine administration will be feasible and well tolerated in patients admitted to a psychiatric hospital with SI.

Specific Aim 2: To test the efficacy of a single IV dose of ketamine, compared to an anesthetic control condition (midazolam), to rapidly reduce SI in a controlled hospital setting.

Hypothesis 2: Ketamine will be associated with significant and rapid reductions in SI and depressive symptoms within 24 hours.

This study will test the rapid anti-suicidal effect of a single IV dose of the N-methyl-D-aspartate (NMDA) glutamate receptor antagonist ketamine in suicidality compared with the clinical response to a single IV dose of the short-acting benzodiazepine midazolam. Midazolam is able to induce transient neuropsychiatric effects mimicking ketamine and therefore is expected to protect the integrity of the blind. Participants will continue to receive standard treatment for their psychiatric condition throughout the trial. This unique "proof-of-concept" study in suicidal patients will be conducted over three-year period.

Study Type

Interventional

Enrollment (Actual)

24

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, 10027
        • Icahn School of Medicine at Mount Sinaï

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

14 years to 76 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • English speaking Male or female patients, 18-80 years
  • Patients have voluntarily admitted themselves to an inpatient psychiatric unit at MSH or, regarding the outpatient population, have clinically significant suicidal ideation without intent to harm themselves
  • Women of childbearing potential must have a negative pregnancy test
  • Clinically significant suicidal ideation and score of ≥4 on MADRS item 10 for suicidality
  • Each subject must have a level of understanding sufficient to agree to all tests and examinations required by the protocol and must sign an informed consent document

Exclusion Criteria:

  • Lifetime history of schizophrenia or other primary psychotic disorder
  • Current presence of psychotic symptoms
  • Lifetime history of a clearly established psychotic episode
  • Established diagnosis of Schizoid, Schizotypal or Paranoid personality disorder
  • Urine toxicology screen positive for drugs of abuse on admission
  • Substance abuse or dependence within the preceding 1 month
  • Anticipated discharge within 7 days of study enrollment (for patients in the inpatient arm)
  • Women who plan to become pregnant, are pregnant or are breast-feeding
  • Concurrent course of electroconvulsive therapy (ECT)
  • Any unstable medical illness including hepatic, renal, gastro-enterologic, respiratory, cardiovascular, endocrinologic, neurologic, immunologic, or hematologic disease
  • Clinically significant abnormal findings of laboratory parameters, physical examination, or ECG
  • The presence of any known or suspected contraindications to midazolam or ketamine including, but not limited to, known allergic reactions to these agents or acute intermittent porphyria
  • Uncontrolled hypertension, defined as BP systolic >160 or BP diastolic >100 on medications
  • Arrhythmia requiring medication
  • Severe coronary artery disease, defined as Canadian Cardiovascular Status III or IV

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
Experimental: Ketamine
single dose IV ketamine, .5mg/kg
Drug: Ketamine
single dose IV ketamine, .5mg/kg infused over 40 minutes
Other Names:
  • N-methyl-D-aspartate (NMDA) glutamate receptor antagonist
Placebo Comparator: Midazolam
single dose IV midazolam, .45mg/kg
Drug: Midazolam
single dose IV midazolam, .45mg/kg infused over 40 minutes

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Beck Scale for Suicidal Ideation (BSSI)
Time Frame: baseline and 24 hours post infusion
Change in BSI score at 24 hours following treatment as compared to baseline. Beck Scale is a 21-item self or clinician administered instrumentation used to measure the current intensity of patients' specific attitudes, behaviors and plans to commit suicide. Score range 0-42, with higher score indicating higher intensity.
baseline and 24 hours post infusion
Change in Beck Scale for Suicidal Ideation (BSSI)
Time Frame: baseline and 48 hours post infusion
Change in BSI score at 48 hours following treatment as compared to baseline. Beck Scale is a 21-item self or clinician administered instrumentation used to measure the current intensity of patients' specific attitudes, behaviors and plans to commit suicide. Score range 0-42, with higher score indicating higher intensity.
baseline and 48 hours post infusion

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Montgomery-Asberg Depression Rating Scale (MADRS)
Time Frame: up to 7 days post infusion
The MADRS is a 10-item instrument used for the evaluation of depressive symptoms in adults and for the assessment of any changes to those symptoms. Higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60.
up to 7 days post infusion
Suicidality Item of the MADRS (MADRS-SI)
Time Frame: 24 hours post infusion
The MADRS-SI ranges from 0 to 6; a score of 2 corresponds to fleeting, passive SI; a score of 4 indicates that SI is frequent with at least moderate intensity but without specific plans or intention; a score of 6 corresponds to active intention and planning for suicide.
24 hours post infusion
The Young Mania Rating Scale (YMRS)
Time Frame: baseline, 40 minutes post infusion, 240 minutes post infusion
An 11-item questionnaire, used to assess manic symptoms based on the patient's subjective report of his or her clinical condition. There are four items that are graded on a 0 to 8 scale (irritability, speech, thought content, and disruptive/aggressive behavior), while the remaining seven items are graded on a 0 to 4 scale. The scores from each question are added together to form a total score ranging from 0 to 60, with higher scores indicating a greater severity of symptoms.
baseline, 40 minutes post infusion, 240 minutes post infusion
The Brief Psychiatric Rating Scale (BPRS)
Time Frame: baseline, 40 minutes post infusion, and 240 minutes post infusion
The BPRS measures psychomimetic effects with higher scores indicating more severe symptoms (scale range 7 - 49).
baseline, 40 minutes post infusion, and 240 minutes post infusion
The Clinician-Administered Dissociative States Scale (CADSS)
Time Frame: baseline, 40 minutes post infusion and 240 minutes post infusion
The CADSS measures dissociation with higher scores indicating more severe symptoms (scale range 0 - 92).
baseline, 40 minutes post infusion and 240 minutes post infusion
Patient Rated Inventory of Side Effects (PRISE)
Time Frame: duration of study
The PRISE assesses the presence of treatment side effects in nine organ/function systems (gastrointestinal, nervous system, heart, eyes/ears, skin, genital/urinary, sleep, sexual functioning, and other). Data reported in in Adverse Events section.
duration of study

Collaborators and Investigators

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

Sponsor

James Murrough

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

January 1, 2012

Primary Completion (Actual)

September 1, 2014

Study Completion (Actual)

September 1, 2014

Study Registration Dates

First Submitted

January 6, 2012

First Submitted That Met QC Criteria

January 9, 2012

First Posted (Estimate)

January 10, 2012

Study Record Updates

Last Update Posted (Estimate)

February 8, 2017

Last Update Submitted That Met QC Criteria

December 16, 2016

Last Verified

December 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GCO 10-1589

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.

Clinical Trials on Suicidal Ideation

Clinical Trials on Ketamine

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Congo, DR of

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe