Atomoxetine for attention deficits following traumatic brain injury: results from a randomized controlled trial.

OBJECTIVE: To determine if atomoxetine would improve attention impairment following traumatic brain injury (TBI). SETTING: Outpatients from a free-standing, private, not-for-profit rehabilitation hospital. POPULATION: Fifty-five adult participants with a history of a single moderate-to-severe TBI, who were at least 1 year from injury and with self-reported complaints of attention difficulties. INTERVENTION: Atomoxetine, a selective norepinephrine re-uptake inhibitor with a primary indication for attention dosed at 40 mg twice a day for 2 weeks, compared to placebo. DESIGN: Randomized double-blind placebo controlled trial, with placebo run-in. MEASURES: Cognitive Drug Research (CDR), Computerized Cognitive Assessment System, Stroop Color and Word Test, Adult ADHD Self-Report Scale (ASRS-v1.1), Neurobehavioural Functioning Inventory (NFI). RESULTS: Atomoxetine was well-tolerated by the subject sample. The use of atomoxetine by individuals with reported attention difficulty following TBI did not significantly improve scores on measures of attention, the CDR Power of Attention domain or the Stroop Interference score. In addition, no significant relationship was found between atomoxetine use and self-reported symptoms of attention or depression. CONCLUSION: Atomoxetine did not significantly improve performance on measures of attention among individuals post-TBI with difficulties with attention. This study follows a trend of other pharmacological studies not demonstrating significant results among those with a history of TBI. Various possibilities are discussed, including the need for a more sophisticated system of classification of TBI.

A randomized trial of modafinil for the treatment of fatigue and excessive daytime sleepiness in individuals with chronic traumatic brain injury.

BACKGROUND: This study examines the efficacy of modafinil in treating fatigue and excessive daytime sleepiness in individuals with traumatic brain injury (TBI). METHODS: A single-center, double-blind, placebo-controlled cross-over trial, where 53 participants with TBI were randomly assigned to receive up to 400 mg of modafinil, or equal number of inactive placebo tablets. Main eligibility criteria were being at least 1 year post-TBI severe enough to require inpatient rehabilitation. The primary outcome measures were fatigue (Fatigue Severity Scale, FSS) and daytime sleepiness (Epworth Sleepiness Scale, ESS). RESULTS: After adjusting for baseline scores and period effects, there were no statistically significant differences between improvements seen with modafinil and placebo in the FSS at week 4 (-0.5 +/- 1.88; P = .80) or week 10 (-1.4 +/- 2.75; P = .61). For ESS, average changes were significantly greater with modafinil than placebo at week 4 (-1.2 +/- 0.49; P = .02) but not at week 10 (-0.5 +/- 0.87; P = .56). Modafinil was safe and well tolerated, although insomnia was reported significantly more often with modafinil than placebo (P = .03). CONCLUSIONS: While there were sporadic statistically significant differences identified, a clear beneficial pattern from modafinil was not seen at either week 4 or week 10 for any of the 12 outcomes. There was no consistent and persistent clinically significant difference between treatment with modafinil and placebo.

The effect of Aricept in persons with persistent memory disorder following traumatic brain injury: a pilot study.

PRIMARY OBJECTIVE: To investigate the effectiveness of donepezil hydrochloride (Aricept) in treating persistent memory deficits in people with traumatic brain injury. RESEARCH DESIGN: Single subject ABAC design was used so that each participant could serve as their own control. METHODS AND PROCEDURES: Seven TBI survivors with persistent memory dysfunction, at least 1.5 years post-injury, underwent two 6-month trials of Aricept. The following tests were used to assess memory and cognition: Brief Visual Memory Test-Revised (BVMT-R), Hopkins Verbal Learning Test, Digit Span and Letter Number Sequence sub-test of the Wechsler Adult Intelligence Scale-III, Controlled Oral Word Association Test and Memory Functioning Questionnaire. EXPERIMENTAL INTERVENTION: During the first treatment phase, participants received 5 mg/day of Aricept for 1 month, increasing to 10 mg/day of Aricept for an additional 5 months. During the second treatment phase, participants received 5 mg/day of Aricept for the entire 6 months. MAIN OUTCOMES AND RESULTS: A repeated measures analysis of variance indicated significant improvement on immediate and delayed memory portions of the BVMT-R when taking 10 mg/day of Aricept. CONCLUSIONS: Findings contribute to the growing body of research into the use of Aricept in treating memory deficits in TBI survivors and support the need for further research.