Alcohol Abuse, Depression, Suicidal Ideation
Conditions
Keywords
Ketamine, Depression, Suicidal Ideation, Alcohol Abuse
Brief summary
This project aims to evaluate the potential rapid and sustained antisuicidal and antidepressant effects of a single intranasal dose of ketamine in inpatients during a mood episode in Major Depressive Disorder (MDD) or Bipolar Disorder (BD) with or without comorbid recent abuse of alcohol.
Detailed description
Clinicians have a limited ability to predict imminent suicidal behavior and efficacious treatments are not available to treat suicidal patients. Thus, Rapid-acting treatments for suicidal individuals are truly needed. This project aims to evaluate the potential rapid and sustained antisuicidal and antidepressant effects of a single intranasal dose of ketamine in inpatients during a mood episode (in Major Depressive Disorder, MDD or Bipolar Disorder, BD) with or without comorbid recent abuse of alcohol. These results will elucidate the antisuicidal effects of ketamine using the intranasal route along with the identification of associated mediators or moderators; this approach has the potential for enormous public health impact.
Interventions
DRUGIntranasal ketamine
Intranasal ketamine will be prepared as 100mg/ml ketamine in 0.9% saline. An mucosal atomization device will be used to provide 5 intranasal applications of solution (volume 100 μl), separated by 3 minutes, over a total of 15 minutes. Each of five ketamine applications will provide 10 mg of study drug, for a total of 50mg. The dose to be used (0.5-1mg/Kg) is 6 to 18 times lower than the sedation dose (6-9mg/Kg).
DRUGPlacebo
Saline alone. An mucosal atomization device will be used to provide 5 intranasal applications of saline (volume 100 μl), separated by 3 minutes, over a total of 15 minutes.
Sponsors
The University of Texas Health Science Center, Houston
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Randomized, Double-Blind, Placebo-Controlled
Eligibility
Sex/Gender
ALL
Age
21 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Voluntary admission to Harris County Psychiatry Center * Able to provide written informed consent * Current suicidal ideation and depressive symptoms and Diagnostic and Statistical Manual of Mental Disorders -IV- Text Revision(DSM-IV-TR) depressive episode (also MADRS greater than or equal to 12) and Young Mania Rating Scale (YMRS) score lower than 8 * DSM-IV-TR criteria for current alcohol abuse (but not intoxicated/withdrawal, abstinent from drinking for \> 5 days prior to admission). * Lifetime history of suicide attempt (patient) * Not taking any medication in the last 24hs. * Scale for Suicide Ideation (SSI) score over 4 (first five items) and Columbia scale (C-SSRS) score 4 or 5
Exclusion criteria
* Unstable medical condition or medical problem with known central nervous system (CNS) effects, e.g. uncontrolled hypertension systolic blood pressure (SBP) ≥170 and/or diastolic blood pressure (DBP) ≥100) or recent history (6 months) of alcohol-withdrawal seizures or significant abnormal laboratory tests (liver function test (LFT) 3 times higher than normal). * Prior diagnosis of a DSM-IV-TR psychotic spectrum disorder, psychotic symptoms, or personality disorder. * Currently under the acute effects of an illicit substance. * Pregnant or nursing women. * Subjects with a history of DSM-IV drug dependency or abuse (except for caffeine or nicotine dependence) within the preceding 3 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Suicidal Ideation as Assessed by the Scale for Suicide Ideation (SSI) | 24 hours | The scale contains 19 items rated on a scale from 0 to 2, allowing score range from 0 to 38, score over 4 (first five items) will be considered inclusion criteria. Higher values indicate worsening or presence of suicidal ideation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Depression as Assessed by the Montgomery-Åsberg Depression Rating Scale (MADRS) | 24 hours | It has ten items, each item yields a score of 0 to 6. Hence the overall score ranges from 0 to 60. Higher scores indicate more severe depression. |
| Snaith-Hamilton Pleasure Scale | 24 hours | The Snaith-Hamilton Pleasure Scale (SHAPS) is an assessment of anhedonia, which is the inability to experience pleasure. The SHAPS has 14 items. Each item has four possible responses: strongly disagree, disagree, agree, or strongly agree. A response of strongly disagree or disagree equals one point, and a response of strongly agree or agree equals 0 points. Thus, the final score ranges from 0 to 14. A score of 2 or less constitutes a normal score, while an abnormal score is defined as 3 or more. |
| Alcohol Urge Questionnaire (AUQ) | 24 hours | Alcohol Urge Questionnaire (AUQ) is a multi-item measure of self-reported urges to drink alcohol, predictor of drinking abuse and relapse. AUQ is an 8-item questionnaire. Each item is scored on a 1 to 7 scale (Strongly Disagree = 1 and Strongly Agree = 7). Items 2 and 7 are reverse scored. Total score ranges from 8 to 56, and a higher score reflects greater craving. |
| Manic Symptoms as Assessed by Score on the Young Mania Rating Scale (YMRS) | 24 hours | The YMRS has 11 items, and total score ranges from 0 to 88, with a higher score indicating greater mania. |
| Dissociative State as Assessed by Score on Clinician-Administered Dissociative States Scale (CADSS) | 24 hours | The CADSS consists of 23 items, and each item is rated on a scale from 0 (not at all) to 4 (severe), with the total score ranging from 0 to 92. A higher score indicates greater severity of dissociative state. |
Countries
United States
Participant flow
Pre-assignment details
5 participants who were enrolled were not randomized and did not start the study.
Participants by arm
| Arm | Count |
|---|---|
| Intranasal Ketamine Intranasal ketamine
Intranasal ketamine: Intranasal ketamine will be prepared as 100mg/ml ketamine in 0.9% saline. An mucosal atomization device will be used to provide 5 intranasal applications of solution (volume 100 μl), separated by 3 minutes, over a total of 15 minutes. Each of five ketamine applications will provide 10 mg of study drug, for a total of 50mg. The dose to be used (0.5-1mg/Kg) is 6 to 18 times lower than the sedation dose (6-9mg/Kg). | 17 |
| Placebo non-active placebo
Placebo: Saline alone. An mucosal atomization device will be used to provide 5 intranasal applications of saline (volume 100 μl), separated by 3 minutes, over a total of 15 minutes. | 11 |
| Total | 28 |
Baseline characteristics
| Characteristic | Intranasal Ketamine | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 39 years STANDARD_DEVIATION 9 | 38.8 years STANDARD_DEVIATION 11.1 | 38.5 years STANDARD_DEVIATION 13.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 3 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants | 25 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 6 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 3 Participants | 0 Participants |
| Race (NIH/OMB) White | 11 Participants | 19 Participants | 8 Participants |
| Region of Enrollment United States | 17 Participants | 28 Participants | 11 Participants |
| Sex: Female, Male Female | 5 Participants | 7 Participants | 2 Participants |
| Sex: Female, Male Male | 12 Participants | 21 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 17 | 0 / 11 |
| other Total, other adverse events | 12 / 17 | 4 / 11 |
| serious Total, serious adverse events | 0 / 17 | 0 / 11 |
Outcome results
Primary
Suicidal Ideation as Assessed by the Scale for Suicide Ideation (SSI)
The scale contains 19 items rated on a scale from 0 to 2, allowing score range from 0 to 38, score over 4 (first five items) will be considered inclusion criteria. Higher values indicate worsening or presence of suicidal ideation.
Time frame: 24 hours
Population: Data for this outcome measure were not collected for 1 participant in the placebo arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intranasal Ketamine | Suicidal Ideation as Assessed by the Scale for Suicide Ideation (SSI) | 10.8 score on a scale | Standard Deviation 8.08 |
| Placebo | Suicidal Ideation as Assessed by the Scale for Suicide Ideation (SSI) | 12.3 score on a scale | Standard Deviation 7.83 |
Secondary
Alcohol Urge Questionnaire (AUQ)
Alcohol Urge Questionnaire (AUQ) is a multi-item measure of self-reported urges to drink alcohol, predictor of drinking abuse and relapse. AUQ is an 8-item questionnaire. Each item is scored on a 1 to 7 scale (Strongly Disagree = 1 and Strongly Agree = 7). Items 2 and 7 are reverse scored. Total score ranges from 8 to 56, and a higher score reflects greater craving.
Time frame: 24 hours
Population: Data for this outcome measure were not collected for 1 participant in the ketamine arm and one participant in the placebo arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intranasal Ketamine | Alcohol Urge Questionnaire (AUQ) | 13.8 score on a scale | Standard Deviation 12.2 |
| Placebo | Alcohol Urge Questionnaire (AUQ) | 16.3 score on a scale | Standard Deviation 11.2 |
Secondary
Depression as Assessed by the Montgomery-Åsberg Depression Rating Scale (MADRS)
It has ten items, each item yields a score of 0 to 6. Hence the overall score ranges from 0 to 60. Higher scores indicate more severe depression.
Time frame: 24 hours
Population: Data for this outcome measure were not collected for 1 participant in the placebo arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intranasal Ketamine | Depression as Assessed by the Montgomery-Åsberg Depression Rating Scale (MADRS) | 16.8 score on a scale | Standard Deviation 13.7 |
| Placebo | Depression as Assessed by the Montgomery-Åsberg Depression Rating Scale (MADRS) | 22.5 score on a scale | Standard Deviation 17.7 |
Secondary
Dissociative State as Assessed by Score on Clinician-Administered Dissociative States Scale (CADSS)
The CADSS consists of 23 items, and each item is rated on a scale from 0 (not at all) to 4 (severe), with the total score ranging from 0 to 92. A higher score indicates greater severity of dissociative state.
Time frame: 24 hours
Population: Data for this outcome measure were not collected for 1 participant in the placebo arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intranasal Ketamine | Dissociative State as Assessed by Score on Clinician-Administered Dissociative States Scale (CADSS) | 0.824 score on a scale | Standard Deviation 2.9 |
| Placebo | Dissociative State as Assessed by Score on Clinician-Administered Dissociative States Scale (CADSS) | 1.60 score on a scale | Standard Deviation 3.2 |
Secondary
Manic Symptoms as Assessed by Score on the Young Mania Rating Scale (YMRS)
The YMRS has 11 items, and total score ranges from 0 to 88, with a higher score indicating greater mania.
Time frame: 24 hours
Population: Data for this outcome measure were not collected for 1 participant in the placebo arm
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intranasal Ketamine | Manic Symptoms as Assessed by Score on the Young Mania Rating Scale (YMRS) | 2.29 score on a scale | Standard Deviation 2.85 |
| Placebo | Manic Symptoms as Assessed by Score on the Young Mania Rating Scale (YMRS) | 2.40 score on a scale | Standard Deviation 2.12 |
Secondary
Snaith-Hamilton Pleasure Scale
The Snaith-Hamilton Pleasure Scale (SHAPS) is an assessment of anhedonia, which is the inability to experience pleasure. The SHAPS has 14 items. Each item has four possible responses: strongly disagree, disagree, agree, or strongly agree. A response of strongly disagree or disagree equals one point, and a response of strongly agree or agree equals 0 points. Thus, the final score ranges from 0 to 14. A score of 2 or less constitutes a normal score, while an abnormal score is defined as 3 or more.
Time frame: 24 hours
Population: Data for this outcome measure were not collected for 1 participant in the placebo arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intranasal Ketamine | Snaith-Hamilton Pleasure Scale | 4.12 score on a scale | Standard Deviation 4.81 |
| Placebo | Snaith-Hamilton Pleasure Scale | 5.00 score on a scale | Standard Deviation 4.29 |