Major Depressive DisorderPhase 4NCT01700829
Ketamine in the Treatment of Suicidal Depression
A Phase 4 study testing Ketamine and Midazolam in people with Major Depressive Disorder and Suicidal Ideation, run by New York State Psychiatric Institute at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Major Depressive Disorder, Suicidal Ideation
- What is being tested?
- Ketamine and Midazolam
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 82 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2012to 31 Jul 2017
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 9Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Columbia University/New York State Psychiatric Institute
New York, New York, 10032
About this study
Official title: Ketamine vs. Midazolam: Testing Rapid Relief of Suicide Risk in Depression
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.
Read the 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.
- Conditions
- Major Depressive Disorder, Suicidal Ideation
- Keywords
- Ketamine, Midazolam, Major Depressive Disorder, Suicidal ideation, Suicide, Depression, Treatment, Ketamine Treatment
- Medical subject headings
- Depressive Disorder, Major, Suicidal Ideation, Suicide, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KetamineDrug
Also called Ketalar, Ketamine Hydrochloride Injection
Single dose of 0.5 mg/kg of ketamine given intravenously (in the vein) over 40 minutes
MidazolamDrug
Also called Midazolam Injection
Single dose of 0.02 mg/kg of Midazolam given intravenously (in the vein) over 40 minutes
| Study group | Role | What they receive |
|---|---|---|
| Midazolam | Active comparator | 0.02 mg/kg, I.V. (in the vein) Receives: Drug: Midazolam |
| Ketamine | Active comparator | 0.5 mg/kg, I.V. (in the vein) Receives: Drug: Ketamine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Scale for Suicidal Ideation
Change in suicidal ideation in depressed patients with moderate to severe suicidal thoughts from the pre-infusion baseline to 24 hours after the infusion with ketamine or midazolam, a sedative not known to reduce suicidal ideation, measured with Beck Scale for Suicidal Ideation - clinician rated version. This scale has 19 items scaled 0 (least severe) to 2 (most severe) and a potential score ranging from 0 to 38, with higher score indicating greater severity.
Measured: Day 1 (24 hours) post-treatment
Secondary outcomes (2)
Saliva Cortisol Awakening Response (CAR).
On the mornings of an infusion day and on post-treatment day1, participants used salivettes (Sarstedt AG \& Co.) to provide saliva samples upon awakening (Cort1) and 30 minutes later (Cort2) to measure cortisol awakening response (CAR) = (Cort2 - Cort1).
Differences between the midazolam and ketamine groups were tested using an analysis of covariance (ANCOVA) model of the change in CAR from baseline to day1, with treatment group and baseline measurement of the outcome variable as predictors.
Range from 0.1 to 12.5 ng/ml and lower means less stress response, higher means greater stress response.
Measured: Cort2 - Cort1 = (Day 1 30-mins post-awakening cortisol) - (Day 1 awakening cortisol)
Neuropsychological Effects
The average Z-scores reported below are the average of the Z-scores for all tests administered. The Z-scores for each test were based on published normative data and normative data available in our laboratory. The population mean for a Z-score is zero, with a SD of 1, thus scores below zero would indicate performance below the population norm; a score close to zero indicates performance close to the population norm (or a normalizing of performance).
Measured: Baseline and Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Oct 2012 (estimated)
- Study startJun 2012
- Primary completion12 Jan 2017
- Study completion31 Jul 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 82 participants (actual)
Sponsor and investigators
- Lead sponsor
- New York State Psychiatric Institute
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Michael Grunebaum, MD, New York State Psychiatric Institute
- Investigators
- Michael F. Grunebaum, M.D., Principal investigator, Columbia University/New York State Psychiatric Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01700829
- Sponsor's protocol ID
- #6598
- Other IDs
- R01MH096784
- Status last verified
- Mar 2020
- First submitted
- 2 Oct 2012
- Last updated
- 11 Mar 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 34953926Keilp 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.
PubMed 34727422Grunebaum 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.
PubMed 33897480Grunebaum 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.
PubMed 29202655
Study at a glance
From the registry record, last updated by the sponsor on 11 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ketamine vs. Midazolam: Testing Rapid Relief of Suicide Risk in Depression
- ClinicalTrials.gov ID
- NCT01700829
- Acronym / sponsor ID
- #6598
- Conditions
- Major Depressive Disorder, Suicidal Ideation
- Keywords
- Ketamine, Midazolam, Major Depressive Disorder, Suicidal ideation, Suicide, Depression, Treatment, Ketamine Treatment
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 82 participants (actual)
- Lead sponsor
- New York State Psychiatric InstituteUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- Jun 2012
- Primary completion
- 12 Jan 2017 (actual)
- Study completion
- 31 Jul 2017 (actual)
- First posted
- 4 Oct 2012 (estimated)
- Results
- Posted 11 Mar 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Midazolam | Active comparator | Drug: Midazolam0.02 mg/kg, I.V. (in the vein) |
| Ketamine | Active comparator | Drug: Ketamine0.5 mg/kg, I.V. (in the vein) |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| KetamineAlso: Ketalar, Ketamine Hydrochloride InjectionSingle dose of 0.5 mg/kg of ketamine given intravenously (in the vein) over 40 minutes | Drug | Ketamine |
| MidazolamAlso: Midazolam InjectionSingle dose of 0.02 mg/kg of Midazolam given intravenously (in the vein) over 40 minutes | Drug | Midazolam |
Primary outcome
Change in Scale for Suicidal Ideation
Time frame: Day 1 (24 hours) post-treatment
Change in suicidal ideation in depressed patients with moderate to severe suicidal thoughts from the pre-infusion baseline to 24 hours after the infusion with ketamine or midazolam, a sedative not known to reduce suicidal ideation, measured with Beck Scale for Suicidal Ideation - clinician rated version. This scale has 19 items scaled 0 (least severe) to 2 (most severe) and a potential score ranging from 0 to 38, with higher score indicating greater severity.
2 secondary outcomes
Saliva Cortisol Awakening Response (CAR).
Time frame: Cort2 - Cort1 = (Day 1 30-mins post-awakening cortisol) - (Day 1 awakening cortisol)
Neuropsychological Effects
Time frame: Baseline and Day 1
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Mar 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34953926Hochschild 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.
- Derived from this study: PubMed 34727422Keilp 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.
- Derived from this study: PubMed 33897480Grunebaum 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.
- Derived from this study: PubMed 29202655Grunebaum 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.
- Additional InformationLink provided by the sponsor.
- MIND Clinic for Mood and Personality DisordersLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael F. Grunebaum, M.D. principal investigator
Columbia University/New York State Psychiatric Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ketamine and Midazolam in people with Major Depressive Disorder and Suicidal Ideation, run by New York State Psychiatric Institute at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Mar 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Scale for Suicidal Ideation (time frame: Day 1 (24 hours) post-treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01700829, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Mar 2020.