Clinical trial NCT01507181: Ketamine For Suicidal Ideation
Official title: Investigating Rapid Anti-Suicidal Ideation Effects of Intravenous (IV) Ketamine in Hospitalized Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Suicidal Ideation
Keywords: suicidal ideation
major depression
treatment resistant
ketamine
glutamate
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
First posted: 2012-01-10
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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.

Eligibility criteria: 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:
measure: Change in Beck Scale for Suicidal Ideation (BSSI)
timeFrame: baseline and 24 hours post infusion
measure: Change in Beck Scale for Suicidal Ideation (BSSI)
timeFrame: baseline and 48 hours post infusion
Secondary outcomes:
measure: Montgomery-Asberg Depression Rating Scale (MADRS)
timeFrame: up to 7 days post infusion
measure: Suicidality Item of the MADRS (MADRS-SI)
timeFrame: 24 hours post infusion
measure: The Young Mania Rating Scale (YMRS)
timeFrame: baseline, 40 minutes post infusion, 240 minutes post infusion
measure: The Brief Psychiatric Rating Scale (BPRS)
timeFrame: baseline, 40 minutes post infusion, and 240 minutes post infusion
measure: The Clinician-Administered Dissociative States Scale (CADSS)
timeFrame: baseline, 40 minutes post infusion and 240 minutes post infusion
measure: Patient Rated Inventory of Side Effects (PRISE)
timeFrame: duration of study
Other outcomes:
Locations:
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: James Murrough, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Murrough JW, Soleimani L, DeWilde KE, Collins KA, Lapidus KA, Iacoviello BM, Lener M, Kautz M, Kim J, Stern JB, Price RB, Perez AM, Brallier JW, Rodriguez GJ, Goodman WK, Iosifescu DV, Charney DS. Ketamine for rapid reduction of suicidal ideation: a randomized controlled trial. Psychol Med. 2015 Dec;45(16):3571-80. doi: 10.1017/S0033291715001506. Epub 2015 Aug 12.