Depression, Traumatic Brain Injury
Conditions
Keywords
Depression, Traumatic brain injury, Duloxetine, Cymbalta, impaired cognitive function
Brief summary
The primary objective of the study is to compare the efficacy of duloxetine 60 mg by mouth daily with placebo in the prevention of depression associated with mild/moderate traumatic brain injury and to enhance cognitive function.
Detailed description
The primary objective of the study is to compare the efficacy of duloxetine 60 mg by mouth daily with placebo in the prevention of depression associated with mild/moderate traumatic brain injury and to enhance cognitive function. Research exploring the use of selective serotonin reuptake inhibitors in the treatment of post-traumatic depression generally validates this approach (Horsfield et al., 2002). However, the literature suggests that serotonin/norepinephrine reuptake inhibitors such as duloxetine may be more effective in the treatment of depression.
Interventions
DRUGDuloxetine
Duloxetine 30 mg. PO daily to 120mg. PO daily for nine months in patients who have suffered a traumatic brain injury at least six months previously.
DRUGSugar pill
Sugar pills 30 mg. PO daily to 120mg. PO daily for nine months in patients who have suffered a traumatic brain injury at least six months previously.
Sponsors
Eli Lilly and Company
Rehabilitation Hospital of Indiana
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 75 Years
Healthy volunteers
No
Inclusion criteria
* Study participants will be 40 men and women between the ages of 18 and 75 who provide appropriate consent and who are agreeable to study requirements * Diagnosed with mild to moderate traumatic brain injury as defined by an initial Mayo Traumatic Brain Injury Severity Scale * Have memory impairments defined by a Hopkins Verbal Learning Test delayed recall score which falls less than or equal to 1.5 standard deviation below the mean.
Exclusion criteria
* Refusal to give informed consent * A previous Central Nervous System illness or injury, including seizure that exhibits residual symptoms. * Current post-traumatic seizure disorder * A previous diagnosis of a psychotic disorder * Current or previous (in the last 6 months) treatment history for alcohol or substance dependency * Medications affecting noradrenergic or dopaminergic systems, alpha-adrenergic antihypertensives, antidepressant, phenobarbital, Monoamine oxidase inhibitor (MAOI), scheduled benzodiazepines, psychoactive herbal supplements (including Kava, St. John's wort), or nutritional supplements or within at least 14 days of discontinuing treatment with the above medications or supplements. * A known suicide risk * A pregnant or breastfeeding woman * Uncontrolled narrow-angle glaucoma * Serious and/or unstable medical comorbidity (e.g., AIDS, cancer, history of uncontrolled hypertension or cardiovascular disease) psychological condition, or clinically significant laboratory abnormality that in the opinion of the investigator would compromise participation in the study or be likely to lead to hospitalization during the course of the study * Liver enzymes \> 1.5 times upper limit of normal * Patients with end-stage renal disease (requiring dialysis) or severe renal impairment * Known hypersensitivity to duloxetine or any of the inactive ingredients
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hamilton Rating Scale for Depression | 9 months | To compare the efficacy of duloxetine 30 mg. PO daily to 120mg. PO daily with placebo in the prevention of depression associated with mild/moderate traumatic brain injury, utilizing the Hamilton Rating Scale for Depression (Hamilton, 1960; HAM-D) as the primary efficacy measure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hopkins Verbal Learning Test | 9 months | To compare the effect of duloxetine vs. placebo on the recovery of memory functions of patients with traumatic brain injury, utilizing the 20-minute delayed recall score of the Hopkins Verbal Learning Test (Brandt, 1991) as the secondary efficacy measure. |
Countries
United States
Participant flow
Recruitment details
Subjects recruited from in-patient and medical clinic population. All subjects suffering from traumatic brain injury and loss of cognitive function.
Pre-assignment details
All subjects performed cognitive testing and assessment for depression. No subjects with seizure disorder or substance abuse issues or previous psychiatric history enrolled. Subjects excluded from the study had previously been prescribed Duloxetine.
Participants by arm
| Arm | Count |
|---|---|
| Duloxetine Duloxetine 30 mg. PO daily to 120mg. PO daily for nine months in patients who have suffered a traumatic brain injury at least six months previously. | 4 |
| Sugar Pill Sugar pills 30 mg. PO daily to 120mg. PO daily for nine months in patients who have suffered a traumatic brain injury at least six months previously. | 4 |
| Total | 8 |
Baseline characteristics
| Characteristic | Duloxetine | Sugar Pill | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 4 Participants | 8 Participants |
| Region of Enrollment United States | 4 participants | 4 participants | 8 participants |
| Sex: Female, Male Female | 0 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Male | 4 Participants | 3 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 4 | 0 / 4 |
| serious Total, serious adverse events | 0 / 4 | 0 / 4 |
Outcome results
Primary
Hamilton Rating Scale for Depression
To compare the efficacy of duloxetine 30 mg. PO daily to 120mg. PO daily with placebo in the prevention of depression associated with mild/moderate traumatic brain injury, utilizing the Hamilton Rating Scale for Depression (Hamilton, 1960; HAM-D) as the primary efficacy measure.
Time frame: 9 months
Population: Analysis was not conducted. Study was terminated before interim analysis. Raw data is stored in a secure location, but not able to be accessed.
Secondary
Hopkins Verbal Learning Test
To compare the effect of duloxetine vs. placebo on the recovery of memory functions of patients with traumatic brain injury, utilizing the 20-minute delayed recall score of the Hopkins Verbal Learning Test (Brandt, 1991) as the secondary efficacy measure.
Time frame: 9 months