Feasibility Study of Duloxetine in the Treatment of Depression in Patients With Traumatic Brain Injury

Study Overview
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Brief Summary
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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
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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.

Official Title
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Prevention of Depression and Enhancement of Cognitive Recovery Following Traumatic Brain Injury With Duloxetine

Conditions
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Traumatic Brain Injury, Depression

Intervention / Treatment
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* Drug: Duloxetine
* Drug: Sugar pill


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Duloxetine<br>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. | Drug: Duloxetine<br>* 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.<br>* Other names: Cymbalta;|
| Placebo Comparator: Sugar pill<br>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. | Drug: Sugar pill<br>* 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.<br>* Other names: Lactose;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 9 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 9 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Depression, Traumatic brain injury, Duloxetine, Cymbalta, impaired cognitive function