Ketamine For Suicidal Ideation

Ketamine

Brief Summary

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).

Intervention / Treatment

Ketamine (DRUG)

single dose IV ketamine, .5mg/kg infused over 40 minutes
Midazolam (DRUG)

single dose IV midazolam, .45mg/kg infused over 40 minutes

Condition or Disease

Suicidal Ideation

Phase

Phase 4

Study Design

Study type:	INTERVENTIONAL
Status:	Completed
Study results:	No Results Available
Age:	18 Years to 80 Years
Enrollment:	24 (ACTUAL)
Funded by:	Other
Allocation:	Randomized
Primary Purpose:	Treatment
Masking QUADRUPLE: Participant Care Provider Investigator Outcomes Assessor

Clinical Trial Dates

Start date:	Jan 01, 2012
Primary Completion:	Sep 01, 2014	ACTUAL
Completion Date:	Sep 01, 2014	ACTUAL
Study First Posted:	Jan 10, 2012	ESTIMATED
Results First Posted:	Feb 08, 2017	ESTIMATED
Last Updated:	Dec 16, 2016

Sponsors / Collaborators

Lead Sponsor: James Murrough

Responsible Party: James Murrough

Location

New York, New York, USA

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.

Participant Groups

single dose IV ketamine, .5mg/kg
single dose IV midazolam, .45mg/kg

Eligibility Criteria

Sex:	All
Minimum Age:	18
Maximum Age:	80
Age Groups:	Adult / Older Adult
Healthy Volunteers:	Yes

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

Primary Outcomes

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.
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.

Secondary Outcomes

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.
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.
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.
The BPRS measures psychomimetic effects with higher scores indicating more severe symptoms (scale range 7 - 49).
The CADSS measures dissociation with higher scores indicating more severe symptoms (scale range 0 - 92).
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.

More Details

NCT Number:	NCT01507181
Other IDs:	GCO 10-1589
Study URL:	https://clinicaltrials.gov/study/NCT01507181

Last updated: Sep 29, 2023