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

Phase 2

Terminated

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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Sugar pill	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.
Duloxetine	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.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.