Major Depression, Other Psychiatric Disorders, TBI
Conditions
Keywords
TBI, Depression, Mood, Behavior
Brief summary
This research is being done to see if a drug called escitalopram (Lexapro) is helpful to people who are suffering from depression after traumatic brain injury (TBI).
Detailed description
Despite it's high prevalence, little is known about the pharmacological treatment of depression following Traumatic Brain Injury (TBI). This is because of a lack of randomized controlled studies in the treatment of post-TBI depression. This study is designed to examine the safety and effectiveness of escitalopram in the treatment of post-TBI depression. It will also investigate metabolic changes and neural pathways associated with post-TBI depression and metabolic alterations after treatment through neuroimaging.
Interventions
DRUGEscitalopram
Escitalopram 10 mg or 20 mg daily for 12 weeks by mouth
DRUGPlacebo
Sugar pill placebo
Sponsors
Forest Laboratories
Johns Hopkins University
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 No maximum
Healthy volunteers
No
Inclusion criteria
* Closed head injury * Fulfill Diagnostic and Statistical Manual Diploma in Social Medicine (DSM) IV criteria Major Depressive Disorder * 18 years of age or older * Able to provide informed consent * Stable medical history
Exclusion criteria
* History of Stroke, Encephalitis, Seizures, or any other pre-TBI neurological diseases * History of mental retardation * Alcohol or Substance dependence in the last 1 year * Inability to undergo MRI scan * Pregnancy * Current use of any psychotropic medications including any antidepressants, antipsychotics, anxiolytics, or sedative hypnotics * Poor response to escitalopram in the past * Acutely suicidal or requiring inpatient psychiatric hospitalization, as determined by the study psychiatrist * Good medication response to another antidepressant in the past
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Montgomery-Asberg Depression Rating Scale (MADRS) at Baseline | MADRS score at baseline | This scale assesses the range of symptoms most frequently observed in patients with major depression. This measure will be used to assess the difference in Montgomery-Asberg Depression Rating Scale (MADRS) at baseline and 12 weeks. The scores range from 0-60. 0 to 6 - normal; 7 to 19 - mild depression; 20 to 34 - moderate depression; \>34 - severe depression. In this study the score was used as a continuous variable. |
| Montgomery-Asberg Depression Rating Scale (MADRS) | MADRS score at 12 weeks | This scale assesses the range of symptoms most frequently observed in patients with major depression. This measure will be used to assess the difference in Montgomery-Asberg Depression Rating Scale (MADRS) at baseline and 12 weeks. The scores range from 0-60. 0 to 6 - normal; 7 to 19 - mild depression; 20 to 34 - moderate depression; \>34 - severe depression. In this study the score was used as a continuous variable. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Anxiety Scale (CAS) | Baseline | This outcome measure is assessing the participant's anxiety as assessed by the CAS. The scores range from 0( normal; no anxiety) to 21 ( severe anxiety). It is used as a continuous variable. |
| Satisfaction With Life (SWL) | baseline | This outcome measure asses the participants overall satisfaction with life as measured by the SWL scale. The scores range from 5 ( absolutely no satisfaction ) to 35 ( very satisfied with life). It is used as continuous variable. |
| Clinical Global Impression (CGI) - Severity at Baseline | Baseline | This outcome measure is assessing the participant's overall psychiatric health based upon the CGI score as assessed by the investigator. Scores range from 1-7 1. = Normal-not at all ill 2. = Borderline mentally ill 3. = Mildly ill 4. = Moderately ill 5. = Markedly ill 6. = Severely ill 7. = Among the most extremely ill patients. |
| Disability Rating Scale (DRS) | At baseline | This scale is a measure of impairment, disability and handicap. It is intended to measure accurately general functional changes over the course of recovery and has found to be both valid and reliable. Scores range from 0 (normal) and 29 (extreme vegetative state). |
| Mini Mental Status Exam (MMSE) | At baseline | This outcome measure assess the participants Cognitive status. Scores range from 0 ( significantly impaired) -30 ( normal). A score of 23 or lower is indicative of cognitive impairment. In this study the score was used as a continuous variable. |
| Quality of Life (QWL) | At baseline | This outcome measure is assessing the participants impression of their quality of life as measured by the QWL scale. Scores range from 16 ( terrible quality of life ) to 112 (Very delighted). Used as a continuous variable. |
| Clinical Global Impression (CGI)- Improvement | at 12 weeks | This outcome measure is assessing the participant's overall psychiatric health based upon the CGI score as assessed by the investigator. The scores range from 1-7 1. = Very much improved 2. = Much improved 3. = Minimally improved 4. = No change 5. = Minimally worse 6. = Much worse 7. = Very much worse |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited from the Brain injury clinic at Johns Hopkins Bayview Medical Center, other Johns Hopkins outpatient clinics, and via advertisements in local papers.
Pre-assignment details
One admitted to active alcohol abuse before initiating medications , and therefore no longer met inclusion criteria. Another consented but failed to return for any follow-up visits.
Participants by arm
| Arm | Count |
|---|---|
| Placebo The placebo group received a pill which appeared similar to the 10 and 20 mg of escitalopram. | 6 |
| Escitalopram Escitalopram was started at 10 mg per day and increased to 20 mg if deemed clinically necessary, at week 4. No medication changes were made after week 8. | 8 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo | Escitalopram | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 1 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 7 Participants | 12 Participants |
| Region of Enrollment United States | 6 participants | 8 participants | 14 participants |
| Sex: Female, Male Female | 3 Participants | 2 Participants | 5 Participants |
| Sex: Female, Male Male | 3 Participants | 6 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 6 | 0 / 8 |
| serious Total, serious adverse events | 0 / 6 | 0 / 8 |
Outcome results
Primary
Montgomery-Asberg Depression Rating Scale (MADRS)
This scale assesses the range of symptoms most frequently observed in patients with major depression. This measure will be used to assess the difference in Montgomery-Asberg Depression Rating Scale (MADRS) at baseline and 12 weeks. The scores range from 0-60. 0 to 6 - normal; 7 to 19 - mild depression; 20 to 34 - moderate depression; \>34 - severe depression. In this study the score was used as a continuous variable.
Time frame: MADRS score at 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Group Baseline | Montgomery-Asberg Depression Rating Scale (MADRS) | 11.2 units on a scale | Standard Deviation 9.5 |
| Treatment Group Baseline | Montgomery-Asberg Depression Rating Scale (MADRS) | 7 units on a scale | Standard Deviation 5.7 |
Primary
Montgomery-Asberg Depression Rating Scale (MADRS) at Baseline
This scale assesses the range of symptoms most frequently observed in patients with major depression. This measure will be used to assess the difference in Montgomery-Asberg Depression Rating Scale (MADRS) at baseline and 12 weeks. The scores range from 0-60. 0 to 6 - normal; 7 to 19 - mild depression; 20 to 34 - moderate depression; \>34 - severe depression. In this study the score was used as a continuous variable.
Time frame: MADRS score at baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Group Baseline | Montgomery-Asberg Depression Rating Scale (MADRS) at Baseline | 29.5 units on a scale | Standard Deviation 3.9 |
| Treatment Group Baseline | Montgomery-Asberg Depression Rating Scale (MADRS) at Baseline | 33.6 units on a scale | Standard Deviation 6.9 |
Secondary
Clinical Anxiety Scale (CAS)
This outcome measure is assessing the participant's anxiety as assessed by the CAS. The scores range from 0( normal; no anxiety) to 21 ( severe anxiety). It is used as a continuous variable.
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Group Baseline | Clinical Anxiety Scale (CAS) | 9.8 units on a scale | Standard Deviation 3.8 |
| Treatment Group Baseline | Clinical Anxiety Scale (CAS) | 14.8 units on a scale | Standard Deviation 6.7 |
Secondary
Clinical Anxiety Scale (CAS)
This outcome measure is assessing the participant's anxiety as assessed by the CAS. The scores range from 0( normal; no anxiety) to 21 ( severe anxiety). It is used as a continuous variable.
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Group Baseline | Clinical Anxiety Scale (CAS) | 6.3 units on a scale | Standard Deviation 4.3 |
| Treatment Group Baseline | Clinical Anxiety Scale (CAS) | 3.9 units on a scale | Standard Deviation 5 |
Secondary
Clinical Global Impression (CGI)- Improvement
This outcome measure is assessing the participant's overall psychiatric health based upon the CGI score as assessed by the investigator. The scores range from 1-7 1. = Very much improved 2. = Much improved 3. = Minimally improved 4. = No change 5. = Minimally worse 6. = Much worse 7. = Very much worse
Time frame: at 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Group Baseline | Clinical Global Impression (CGI)- Improvement | 2.7 units on a scale | Standard Deviation 1.2 |
| Treatment Group Baseline | Clinical Global Impression (CGI)- Improvement | 2.1 units on a scale | Standard Deviation 0.6 |
Secondary
Clinical Global Impression (CGI) - Severity at Baseline
This outcome measure is assessing the participant's overall psychiatric health based upon the CGI score as assessed by the investigator. Scores range from 1-7 1. = Normal-not at all ill 2. = Borderline mentally ill 3. = Mildly ill 4. = Moderately ill 5. = Markedly ill 6. = Severely ill 7. = Among the most extremely ill patients.
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Group Baseline | Clinical Global Impression (CGI) - Severity at Baseline | 4.5 units on a scale | Standard Deviation 0.5 |
| Treatment Group Baseline | Clinical Global Impression (CGI) - Severity at Baseline | 4.8 units on a scale | Standard Deviation 0.5 |
Secondary
Disability Rating Scale (DRS)
This scale is a measure of impairment, disability and handicap. It is intended to measure accurately general functional changes over the course of recovery and has found to be both valid and reliable. Scores range from 0 (normal) and 29 (extreme vegetative state).
Time frame: At 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Group Baseline | Disability Rating Scale (DRS) | 0.7 units on a scale | Standard Deviation 1 |
| Treatment Group Baseline | Disability Rating Scale (DRS) | 0.6 units on a scale | Standard Deviation 0.3 |
Secondary
Disability Rating Scale (DRS)
This scale is a measure of impairment, disability and handicap. It is intended to measure accurately general functional changes over the course of recovery and has found to be both valid and reliable. Scores range from 0 (normal) and 29 (extreme vegetative state).
Time frame: At baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Group Baseline | Disability Rating Scale (DRS) | 1 units on a scale | Standard Deviation 1.3 |
| Treatment Group Baseline | Disability Rating Scale (DRS) | 1.4 units on a scale | Standard Deviation 1.1 |
Secondary
Mini Mental Status Exam (MMSE)
This outcome measure assess the participants Cognitive status. Scores range from 0 ( significantly impaired) -30 ( normal). A score of 23 or lower is indicative of cognitive impairment. In this study the score was used as a continuous variable.
Time frame: At 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Group Baseline | Mini Mental Status Exam (MMSE) | 29.7 units on a scale | Standard Deviation 0.5 |
| Treatment Group Baseline | Mini Mental Status Exam (MMSE) | 29.0 units on a scale | Standard Deviation 0.6 |
Secondary
Mini Mental Status Exam (MMSE)
This outcome measure assess the participants Cognitive status. Scores range from 0 ( significantly impaired) -30 ( normal). A score of 23 or lower is indicative of cognitive impairment. In this study the score was used as a continuous variable.
Time frame: At baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Group Baseline | Mini Mental Status Exam (MMSE) | 28.3 units on a scale | Standard Deviation 1.6 |
| Treatment Group Baseline | Mini Mental Status Exam (MMSE) | 27.1 units on a scale | Standard Deviation 1.03 |
Secondary
Quality of Life (QWL)
This outcome measure is assessing the participants impression of their quality of life as measured by the QWL scale. Scores range from 16 ( terrible quality of life ) to 112 (Very delighted). Used as a continuous variable.
Time frame: At baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Group Baseline | Quality of Life (QWL) | 62.8 units on a scale | Standard Deviation 22.3 |
| Treatment Group Baseline | Quality of Life (QWL) | 64.1 units on a scale | Standard Deviation 24.6 |
Secondary
Quality of Life (QWL)
This outcome measure is assessing the participants impression of their quality of life as measured by the QWL scale. Scores range from 16 ( terrible quality of life ) to 112 (Very delighted). Used as a continuous variable.
Time frame: At 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Group Baseline | Quality of Life (QWL) | 75.2 units on a scale | Standard Deviation 30.3 |
| Treatment Group Baseline | Quality of Life (QWL) | 78.7 units on a scale | Standard Deviation 17.3 |
Secondary
Satisfaction With Life (SWL)
This outcome measure asses the participants overall satisfaction with life as measured by the SWL scale. The scores range from 5 ( absolutely no satisfaction ) to 35 ( very satisfied with life). It is used as continuous variable.
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Group Baseline | Satisfaction With Life (SWL) | 21.2 units on a scale | Standard Deviation 9.2 |
| Treatment Group Baseline | Satisfaction With Life (SWL) | 22.6 units on a scale | Standard Deviation 5.7 |
Secondary
Satisfaction With Life (SWL)
This outcome measure asses the participants overall satisfaction with life as measured by the SWL scale. The scores range from 5 ( absolutely no satisfaction ) to 35 ( very satisfied with life). It is used as continuous variable.
Time frame: baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Group Baseline | Satisfaction With Life (SWL) | 13.8 units on a scale | Standard Deviation 7.7 |
| Treatment Group Baseline | Satisfaction With Life (SWL) | 15.6 units on a scale | Standard Deviation 9.3 |