Armodafinil for the treatment of excessive sleepiness associated with mild or moderate closed traumatic brain injury: a 12-week, randomized, double-blind study followed by a 12-month open-label extension.

OBJECTIVE: To evaluate the efficacy and tolerability of armodafinil in patients with excessive sleepiness following mild or moderate closed traumatic brain injury (TBI).

DESIGN: Randomized, placebo-controlled, double-blind trial followed by open-label extension.

SETTING: 40 US centers.

PATIENTS: Adults with closed TBI (N = 117), Glasgow Coma Scale score >8 at time of injury; baseline Epworth Sleepiness Scale (ESS) ≥10; sleep latency <8 minutes on multiple sleep latency test (MSLT); and Clinical Global Impression-Severity of Illness (CGI-S) score ≥4 for excessive sleepiness.

INTERVENTION: Patients received armodafinil (50, 150, or 250 mg/day) or placebo for 12 weeks followed by an optional 12-month open-label extension.

MEASUREMENTS AND RESULTS: Outcomes included MSLT, ESS, Clinical Global Impression-Change (CGI-C), TBI-Work Instability Scale (TBI-WIS), CGI-S, and tolerability. The study was terminated early due to low enrollment. Patients receiving 250 mg armodafinil showed significant improvement in sleep latency from baseline to final visit versus placebo (+7.2 minutes vs. +2.4 minutes; p = 0.0010). CGI-C ratings were much/ very much improved in approximately 50% of patients receiving 150 and 250 mg armodafinil, compared to 38% on placebo. ESS and TBI-WIS scores were not significantly different between groups. In the open-label extension (N = 49), patients demonstrated gradual improvement in ESS, TBI-WIS, and CGI-S scores up to 48 weeks post-baseline. Armodafinil was generally well tolerated, with headache the most common adverse event in both double-blind and open-label portions.

CONCLUSIONS: Armodafinil 250 mg significantly improved sleep latency in patients with excessive sleepiness associated with mild or moderate TBI. Efficacy and tolerability of armodafinil were sustained throughout the open-label extension.

TRIAL REGISTRATION: NCT00893789, NCT00983437.