Ketamine in the Treatment of Suicidal Depression
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| ClinicalTrials.gov Identifier: NCT01700829 |
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Recruitment Status :
Completed
First Posted : October 4, 2012
Results First Posted : March 11, 2020
Last Update Posted : March 11, 2020
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Major Depressive Disorder Suicidal Ideation | Drug: Ketamine Drug: Midazolam | Phase 4 |
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 Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 82 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | Ketamine vs. Midazolam: Testing Rapid Relief of Suicide Risk in Depression |
| Study Start Date : | June 2012 |
| Actual Primary Completion Date : | January 12, 2017 |
| Actual Study Completion Date : | July 31, 2017 |
| Arm | Intervention/treatment |
|---|---|
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Active Comparator: Midazolam
0.02 mg/kg, I.V. (in the vein)
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Drug: Midazolam
Single dose of 0.02 mg/kg of Midazolam given intravenously (in the vein) over 40 minutes
Other Name: Midazolam Injection |
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Active Comparator: Ketamine
0.5 mg/kg, I.V. (in the vein)
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Drug: Ketamine
Single dose of 0.5 mg/kg of ketamine given intravenously (in the vein) over 40 minutes
Other Names:
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- 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.
- Saliva Cortisol Awakening Response (CAR). [ Time Frame: Cort2 - Cort1 = (Day 1 30-mins post-awakening cortisol) - (Day 1 awakening cortisol) ]
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.
- Neuropsychological Effects [ Time Frame: Baseline and Day 1 ]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).
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years to 65 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01700829
| United States, New York | |
| Columbia University/New York State Psychiatric Institute | |
| New York, New York, United States, 10032 | |
| Principal Investigator: | Michael F. Grunebaum, M.D. | Columbia University/New York State Psychiatric Institute |
Documents provided by Michael Grunebaum, MD, New York State Psychiatric Institute:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Michael Grunebaum, MD, Assistant Professor of Clinical Psychiatry, New York State Psychiatric Institute |
| ClinicalTrials.gov Identifier: | NCT01700829 |
| Other Study ID Numbers: |
#6598 R01MH096784 ( U.S. NIH Grant/Contract ) |
| First Posted: | October 4, 2012 Key Record Dates |
| Results First Posted: | March 11, 2020 |
| Last Update Posted: | March 11, 2020 |
| Last Verified: | March 2020 |
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Ketamine Midazolam Major Depressive Disorder Suicidal ideation |
Suicide Depression Treatment Ketamine Treatment |
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Depression Depressive Disorder Depressive Disorder, Major Suicidal Ideation Behavioral Symptoms Mood Disorders Mental Disorders Suicide Self-Injurious Behavior Midazolam Ketamine Analgesics Sensory System Agents Peripheral Nervous System Agents Physiological Effects of Drugs |
Anesthetics, Dissociative Anesthetics, Intravenous Anesthetics, General Anesthetics Central Nervous System Depressants Excitatory Amino Acid Antagonists Excitatory Amino Acid Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Adjuvants, Anesthesia Hypnotics and Sedatives Anti-Anxiety Agents Tranquilizing Agents Psychotropic Drugs GABA Modulators |