Bipolar Disorder, Major Depressive Episode, Suicidal Ideation
Conditions
Keywords
Ketamine, Midazolam, Bipolar Disorder, Major Depressive Episode, Suicidal Ideation, Suicide, Depression, Treatment, Ketamine 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 bipolar 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. 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). After the infusion(s), participants will have weekly research interviews for 6 weeks to monitor response. After post-infusion research measures are completed, all subjects will receive open clinical treatment. During open clinical treatment, medication will be changed for those patients who don't respond or whose response is transient. 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 combining inpatient and outpatient treatment. At the end of the 6 months of treatment patients will be referred for ongoing care.
Interventions
DRUGKetamine
Single dose of 0.5 mg/kg of Ketamine given intravenously (in the vein) over 40 minutes
DRUGMidazolam
Single dose of 0.02 mg/kg of Midazolam given intravenously (in the vein) over 40 minutes
Sponsors
Brain & Behavior Research Foundation
New York State Psychiatric Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Bipolar 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. * Moderate to severe suicidal ideation * 18-65 years old * Patients will only be enrolled if they agree to voluntary admission to an inpatient research unit at the New York State Psychiatric Institute (NYSPI) for infusion phase of treatment. * 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, oral contraceptive pills * Able to provide informed consent * Subjects 61-65 years old must score 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 * Pregnancy and/or lactation * Current psychotic symptoms * Contraindication to any study treatment * Current or past ketamine abuse or dependence ever (lifetime); any other drug or alcohol dependence within past 6 months; suicidality only due to binge substance use or withdrawal * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Suicidal Ideation Measured With the Beck Scale for Suicidal Ideation | At 24 hours post-Infusion | Change in suicidal ideation in Bipolar Disorder during a Major Depressive Episode (MDE), with moderate to severe suicidal thoughts, from the pre-infusion baseline to 24 hours after the infusion of Ketamine (study drug) or Midazolam (active control). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Systolic Blood Pressure | During study infusion | Blood pressure is measured in millimeters of mercury. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ketamine 0.5 mg/kg, I.V. (in the vein)
Ketamine: Single dose of 0.5 mg/kg of Ketamine given intravenously (in the vein) over 40 minutes | 7 |
| Midazolam 0.02 mg/kg, I.V. (in the vein)
Ketamine: Single dose of 0.5 mg/kg of Ketamine given intravenously (in the vein) over 40 minutes
Midazolam: Single dose of 0.02 mg/kg of Midazolam given intravenously (in the vein) over 40 minutes | 9 |
| Total | 16 |
Baseline characteristics
| Characteristic | Ketamine | Midazolam | Total |
|---|---|---|---|
| Age, Continuous | 39 years STANDARD_DEVIATION 10.2 | 43 years STANDARD_DEVIATION 13.9 | 40.5 years STANDARD_DEVIATION 12.4 |
| Beck Scale for Suicidal Ideation (Clinician-rated) | 16.7 units on a scale STANDARD_DEVIATION 8.4 | 16.8 units on a scale STANDARD_DEVIATION 6 | 16.8 units on a scale STANDARD_DEVIATION 6.9 |
| Race/Ethnicity, Customized Asian | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Hispanic | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized More than one race | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Not Hispanic | 7 Participants | 8 Participants | 15 Participants |
| Race/Ethnicity, Customized White race | 6 Participants | 8 Participants | 14 Participants |
| Sex: Female, Male Female | 3 Participants | 7 Participants | 10 Participants |
| Sex: Female, Male Male | 4 Participants | 2 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 9 |
| other Total, other adverse events | 0 / 7 | 0 / 9 |
| serious Total, serious adverse events | 4 / 7 | 0 / 9 |
Outcome results
Primary
Change in Suicidal Ideation Measured With the Beck Scale for Suicidal Ideation
Change in suicidal ideation in Bipolar Disorder during a Major Depressive Episode (MDE), with moderate to severe suicidal thoughts, from the pre-infusion baseline to 24 hours after the infusion of Ketamine (study drug) or Midazolam (active control).
Time frame: At 24 hours post-Infusion
Population: Bipolar depression with suicidal ideation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ketamine | Change in Suicidal Ideation Measured With the Beck Scale for Suicidal Ideation | -12.4 units on a scale | Standard Deviation 11.6 |
| Midazolam | Change in Suicidal Ideation Measured With the Beck Scale for Suicidal Ideation | -6.7 units on a scale | Standard Deviation 7.4 |
Secondary
Change in Systolic Blood Pressure
Blood pressure is measured in millimeters of mercury.
Time frame: During study infusion
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ketamine | Change in Systolic Blood Pressure | 23 mm Hg | Standard Deviation 12.8 |
| Midazolam | Change in Systolic Blood Pressure | 3 mm Hg | Standard Deviation 10.2 |