Clinical trial NCT01700829: Ketamine in the Treatment of Suicidal Depression
Official title: Ketamine vs. Midazolam: Testing Rapid Relief of Suicide Risk in Depression
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Major Depressive Disorder
Suicidal Ideation
Keywords: Ketamine
Midazolam
Major Depressive Disorder
Suicidal ideation
Suicide
Depression
Treatment
Ketamine Treatment
Lead sponsor: New York State Psychiatric Institute
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2012-10-04
Enrollment: 82
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is designed to compare the effectiveness of two medications, Ketamine and Midazolam, for rapidly relieving suicidal thoughts in people suffering from depression.

The first drug, Ketamine, is an experimental antidepressant that early studies have shown may quickly reduce suicidal thoughts, but we are not sure how well it may work. Midazolam, the comparison drug, is not thought to reduce depression or suicidal thoughts.

Detailed description: Patients currently taking psychiatric medications may continue them during the study. However, if a patient is taking a benzodiazepine (such as Ativan, Klonopin, or Xanax), they will be able to take up to 2mg per day of Lorazepam during the week before the infusion, but none will be permitted in the 24 hours pre-infusion. Also, Zolpidem (Ambien) will not be permitted in the 24 hours pre-infusion. If a person chooses to participate, their dose of benzodiazepine may need to be reduced so that they can do without it during the 24 hours pre-infusion.

Depressed participants are randomly assigned to receive a single dose of Ketamine(0.5 mg/kg) or Midazolam (0.02 mg/kg), which is given slowly, in a vein, over about 40 minutes. The study is "double-blind," meaning patients and study staff will not know which medication is in the infusion.

If a patient does not respond to the first infusion, and s/he received Midazolam, then s/he will be offered the option of a second infusion, this time with Ketamine (0.5 mg/kg). S/he will then start treatment with a standard antidepressant, unless s/he is not already taking one.

After the infusion(s), participants will have weekly research interviews for 6 weeks to monitor response.

If a patient does have a sufficient infusion response, and s/he is not already taking an antidepressant, then s/he will receive 6-weeks antidepressant research treatment with Sertraline, Fluoxetine, Paroxetine, or Escitalopram, followed by open clinical treatment. However, if s/he is already taking an antidepressant, then s/he will receive open treatment. If s/he does not have a sufficient infusion response, then s/he will receive open treatment.

Participation in this study requires a brief inpatient stay, at no cost, at the New York State Psychiatric Institute (NYSPI).

Eligible participants enrolled in this study will be offered medication management visits at no cost for a total of up to 6 months from the date of enrollment combining inpatient and outpatient treatment. Study medications (Sertraline, Fluoxetine, Paroxetine, Escitalopram, Lorazepam, Zolpidem) will be at no cost during the 6 months. The study will not provide other medications at no cost.

Eligibility criteria: INCLUSION CRITERIA:

* Unipolar depression with current major depressive episode (MDE). Participants may be psychiatric medication-free, or if on psychiatric medication, not responding adequately given current MDE with suicidal ideation (See 2).
* Moderate to severe suicidal ideation
* 18-65 years old
* Participants must agree to a voluntary admission to an inpatient research unit at the New York State Psychiatric Institute (NYSPI)for the infusion(s), for a brief stay, or longer if clinically necessary.
* Pre-menopausal female participants of child-bearing potential must be willing to use an acceptable form of birth control during study participation such as condoms, diaphragm, or oral contraceptive pills.
* Able to provide informed consent
* Participants 61-65 years old must score a 25 or higher on the Mini-Mental State Examination (MMSE) at screening.

EXCLUSION CRITERIA:

* Unstable medical condition or neurological illness, including baseline hypertension (BP\>140/90) or significant history of cardiovascular illness.
* Significant ECG abnormality
* Pregnant or lactating
* Diagnosis of bipolar disorder or psychotic disorder
* Contraindication to any study treatment.
* Inadequate understanding of English.
* Prior ineffective trial of or adverse reaction to Ketamine or Midazolam.
* Opiate use greater than total daily dose of 20mg Oxycodone or equivalent during the 3 days pre-infusion.
* A diagnosis of sleep apnea.

Primary outcomes:
measure: Change in Scale for Suicidal Ideation
timeFrame: Day 1 (24 hours) post-treatment
Secondary outcomes:
measure: Saliva Cortisol Awakening Response (CAR).
timeFrame: Cort2 - Cort1 = (Day 1 30-mins post-awakening cortisol) - (Day 1 awakening cortisol)
measure: Neuropsychological Effects
timeFrame: Baseline and Day 1
Other outcomes:
Locations:
city: New York
country: United States
facility: Columbia University/New York State Psychiatric Institute
state: New York
Study officials:
affiliation: Columbia University/New York State Psychiatric Institute
name: Michael F. Grunebaum, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hochschild A, Keilp JG, Madden SP, Burke AK, Mann JJ, Grunebaum MF. Ketamine vs midazolam: Mood improvement reduces suicidal ideation in depression. J Affect Disord. 2022 Mar 1;300:10-16. doi: 10.1016/j.jad.2021.12.055. Epub 2021 Dec 22.
citation: Keilp JG, Madden SP, Marver JE, Frawley A, Burke AK, Herzallah MM, Gluck M, Mann JJ, Grunebaum MF. Effects of Ketamine Versus Midazolam on Neurocognition at 24 Hours in Depressed Patients With Suicidal Ideation. J Clin Psychiatry. 2021 Nov 2;82(6):21m13921. doi: 10.4088/JCP.21m13921.
citation: Grunebaum MF, Mann JJ, Galfalvy HC, Gibbons RD. Computerized-Adaptive vs. Traditional Ratings of Depression and Suicidal Thoughts: An Assay Sensitivity Pilot Study in a Ketamine Clinical Trial. Front Psychiatry. 2021 Apr 7;12:602976. doi: 10.3389/fpsyt.2021.602976. eCollection 2021.
citation: Grunebaum MF, Galfalvy HC, Choo TH, Keilp JG, Moitra VK, Parris MS, Marver JE, Burke AK, Milak MS, Sublette ME, Oquendo MA, Mann JJ. Ketamine for Rapid Reduction of Suicidal Thoughts in Major Depression: A Midazolam-Controlled Randomized Clinical Trial. Am J Psychiatry. 2018 Apr 1;175(4):327-335. doi: 10.1176/appi.ajp.2017.17060647. Epub 2017 Dec 5.