Treatment of Post-Traumatic Brain Injury (TBI) Depression

Study Overview
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Brief Summary
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Randomized clinical trial of sertraline vs. placebo for post-TBI depression

Detailed Description
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Purpose: The purpose of this study is to document the efficacy of sertraline (Zoloft) in the treatment of depression (major depressive disorder) after TBI, including the impact on quality of life. Researchers will also explore the effects of sertraline on anxiety disorders, which often accompany post-TBI depression. Background: Major depression is experienced by many more people after TBI than prior to injury and more often than in people without a brain injury. Many studies have also shown that this higher than 'normal' incidence looms for many years post TBI. Major depression is associated with a variety of negative outcomes, including poorer functioning in basic activities, reduced employment, elevated divorce rate, reduced social and recreational activity and increased sexual dysfunction. Need for Research: Of the current drug treatments for major depression, sertraline and similar drugs (known as selective serotonin reuptake inhibitors, or selective serotonin reuptake inhibitor (SSRIs)) have few side effects in people who have experienced a brain injury and have been shown to be effective in people with no known brain injury. However, information on the impact of SSRIs on post-TBI depression, based on randomized, double-blind studies, is unavailable. Current Research Activity: Approximately 50 men and women volunteers who are post TBI and currently diagnosed with major depressive disorder are being randomly assigned to a 12-week period of taking Zoloft or a placebo. Over the period of study, participants will have the severity of their depressive symptoms assessed (as well as their symptoms of anxiety); a simple measure of the volunteer's perceived quality of life will be implemented prior to the study and at its termination. It is hypothesized that sertraline will reduce the symptoms of depression and anxiety and will increase the person's perceived quality of life to a significantly greater extent than will the placebo.

Official Title
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Treatment of Post-TBI Depression

Conditions
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Depression

Intervention / Treatment
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* Drug: Sertraline
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years or older experienced a TBI with a documented loss of consciousness or other evidence of a TBI (i.e., evidence of pathology on neuro-imaging) at least 6 months post-injury English-speaking residential telephone service living within 1.5 hours of New York City able to comprehend or answer verbal or written questionnaires willing to provide consent to participate in a 12 week drug study to treat Major Depressive Disorder (MDD); current MDD as diagnosed using Structured Clinical Interview for Diagnostic and Statistical Manual Diploma in Social Medicine (DSM) Disorders (SCID), and severity of MDD rated at least 18 on the HAM-D. Exclusion Criteria: currently taking antidepressant medication (including monamine oxidase inhibitors (MOAs) or tricyclic antidepressants (TCAs) unwilling to abstain from seeking new psychosocial or pharmacologic treatments during the course of the study currently in psychotherapy active suicidal plans and/or requiring hospitalization prior use of sertraline currently experiencing other serious medical illness currently pregnant or breast feeding mass brain lesions or other neurological diagnoses other than TBI history of current or past psychosis or mania current substance abuse history of clinically significant liver or renal disease

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sertraline<br>Daily oral sertraline in doses starting at 25mg and increasing to therapeutic levels (up to 200mg). | Drug: Sertraline<br>* Sertraline arm<br>|
| Placebo Comparator: Placebo<br>Placebo for 10 weeks. | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Depression at Baseline | The 17-item Hamilton Rating Scale for Depression (HAM-D) is a widely used clinician-rated measurement of depression severity. A score of 0-7 is considered to be normal. 8-13 = mild depression, 14-18 = moderate depression, 19-22 = severe depression, and ≥ 23 = very severe depression. Self-report of depression and DSM-IV diagnosis (HAM-D score) at baseline. | baseline | 
| Depression at End of Treatment | Self-report of depression and Diagnostic and Statistical Manual Diploma in Social Medicine (DSM-IV) diagnosis (HAM-D score) compared at end of treatment to baseline. Participants were considered treatment responders if their initial HAM-D decreased by 50% or dropped below a score of 10 at the end of the intervention. The 17-item Hamilton Rating Scale for Depression (HAM-D) is a widely used clinician-rated measurement of depression severity. A score of 0-7 is considered to be normal. 8-13 = mild depression, 14-18 = moderate depression, 19-22 = severe depression, and ≥ 23 = very severe depression. | end of treatment, average of 10 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| BAI | The Beck Anxiety Inventory (BAI) is a 21-item self-report measure that assesses subjective, somatic, or panic-related symptoms associated with anxiety rated on a scale from 0 (not at all) to 3(severely). Total score: 0-7 = minimal level of anxiety, 8-15 = mild anxiety, 16-25 = moderate anxiety, and 26-63 = severe depression | Immediately post-intervention | 
| Life-3 | Life-3 is a single-item Quality of life (QOL) measure that uses a 7-point Likert-type scale to assess satisfaction with life during the past month. It is typically administered twice during an evaluation, and the mean of the 2 obtained scores is used. Higher scores on this measure indicate higher levels of subjective QOL. Range from 1 to 7. | Immediately post-intervention at 10 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sertraline, TBI, depression, SSRI, brain injury