Background: Excessive daytime sleepiness (EDS) and fatigue are common symptoms after traumatic brain injury (TBI), but there is no specific treatment for affected patients. With this pilot study, we aimed at studying the effect of daily modafinil on posttraumatic EDS and fatigue. Methods: We conducted a prospective, double-blind, randomized, placebo-controlled pilot study in 20 patients with TBI who had fatigue or EDS or both. After baseline examinations (questionnaires including the Epworth Sleepiness Scale to assess EDS and the Fatigue Severity Scale to assess fatigue, actigraphy, polysomnography, maintenance of wakefulness test, and psychomotor vigilance test), 10 patients received 100 to 200 mg modafinil every morning, and 10 patients were treated with placebo. After a 6-week treatment period, all examinations were repeated. Results: EDS improved significantly in patients with TBI who were treated with modafinil, compared with the placebo group. Similarly, the ability to stay awake on the maintenance of wakefulness test improved only in the modafinil group. Modafinil, however, had no impact on posttraumatic fatigue. Clinically relevant side effects were not observed. Conclusion: This study indicates that modafinil is effective and well tolerated in the treatment of posttraumatic EDS but not of fatigue. Classification of evidence: This study provides Class I evidence that modafinil (100-200 mg daily) improves posttraumatic EDS compared with placebo. This study provides Class I evidence that modafinil (100-200 mg daily) does not improve posttraumatic fatigue compared with placebo. Neurology (R) 2010;75:1780-1785
