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 siginficant 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.