Depression
Conditions
Keywords
Sertraline, TBI, depression, SSRI, brain injury
Brief summary
Randomized clinical trial of sertraline vs. placebo for post-TBI depression
Detailed description
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.
Interventions
DRUGSertraline
Sertraline arm
DRUGPlacebo
Placebo
Sponsors
U.S. Department of Education
Icahn School of Medicine at Mount Sinai
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Depression at Baseline | 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. |
| Depression at End of Treatment | end of treatment, average of 10 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| BAI | Immediately post-intervention | 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 |
| Life-3 | Immediately post-intervention at 10 weeks | 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. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited through physician referrals and flyers posted in outpatient rehabilitation treatment areas and distributed at TBI-survivor groups. Participants from past research projects who had agreed to be contacted for future studies were contacted.
Participants by arm
| Arm | Count |
|---|---|
| Sertraline Daily oral sertraline in doses starting at 25mg and increasing to therapeutic levels (up to 200mg) | 22 |
| Placebo Placebo for 10 weeks | 19 |
| Total | 41 |
Baseline characteristics
| Characteristic | Sertraline | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 46.8 years STANDARD_DEVIATION 12.8 | 51.5 years STANDARD_DEVIATION 8.2 | 49.1 years STANDARD_DEVIATION 10.9 |
| Sex: Female, Male Female | 12 Participants | 7 Participants | 19 Participants |
| Sex: Female, Male Male | 10 Participants | 12 Participants | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 22 | 2 / 19 |
| serious Total, serious adverse events | 0 / 22 | 0 / 19 |
Outcome results
Primary
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.
Time frame: baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sertraline | Depression at Baseline | 27.5 units on a scale | Standard Deviation 7.1 |
| Placebo | Depression at Baseline | 25.2 units on a scale | Standard Deviation 8 |
Primary
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.
Time frame: end of treatment, average of 10 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sertraline | Depression at End of Treatment | 13.7 units on a scale | Standard Deviation 9.7 |
| Placebo | Depression at End of Treatment | 16.2 units on a scale | Standard Deviation 9.6 |
Secondary
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
Time frame: Immediately post-intervention
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sertraline | BAI | 11.1 units on a scale | Standard Deviation 11.9 |
| Placebo | BAI | 13.1 units on a scale | Standard Deviation 11.6 |
Secondary
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.
Time frame: Immediately post-intervention at 10 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sertraline | Life-3 | 6.3 units on a scale | Standard Deviation 8 |
| Placebo | Life-3 | 4.9 units on a scale | Standard Deviation 3.5 |