Armodafinil for treatment of excessive sleepiness associated with shift work disorder: a randomized controlled study

Abstract

Objective: To assess the effect of armodafinil, 150 mg, on the physiologic propensity for sleep and cognitive performance during usual night shift hours in patients with excessive sleepiness associated with chronic (> or =3 months) shift work disorder (SWD) of moderate or greater severity.

Patients and methods: This 12-week, randomized controlled study was conducted at 42 sleep research facilities in North America from April 2 through December 23, 2004, and enrolled 254 permanent or rotating night shift workers with SWD. Entry criteria included excessive sleepiness during usual night shifts for 3 months or longer (corroborated by mean sleep latency of < or =6 minutes on a Multiple Sleep Latency Test), insomnia (sleep efficiency < or =87.5% during daytime sleep), and SWD that was judged clinically to be of moderate or greater severity. Patients received armodafinil, 150 mg, or placebo 30 to 60 minutes before each night shift. Physiologic sleep propensity during night shift hours, clinical impression of severity, patient-reported sleepiness, and cognitive function were assessed during laboratory night shifts at weeks 4, 8, and 12.

Results: Armodafinil significantly improved mean (SD) sleep latency from 2.3 (1.6) minutes at baseline to 5.3 (5.0) minutes at final visit, compared with a change from 2.4 (1.6) minutes to 2.8 (2.9) minutes in the placebo group (P<.001). Clinical condition ratings improved in more patients receiving armodafinil (79%) vs placebo (59%) (P=.001). As reported by patients' diaries, armodafinil significantly reduced sleepiness during laboratory nights (P<.001), night shifts at work (P<.001), and the commute home (P=.003). Armodafinil improved performance on standardized memory (P<.001) and attention (power, P=.001; continuity, P<.001) tests compared with placebo. Armodafinil was well tolerated and did not affect daytime sleep, as measured by polysomnography.

Conclusion: In patients with excessive sleepiness associated with chronic SWD of moderate or greater severity, armodafinil significantly improved wakefulness during scheduled night work, raising mean nighttime sleep latency above the level considered to indicate severe sleepiness during the daytime. Armodafinil also significantly improved measures of overall clinical condition, long-term memory, and attention.

Trial registration: clinicaltrials.gov Identifier: NCT00080288.

Figures

FIGURE 1.

Patient disposition. Screened patients include patients referred from central advertising, investigators' advertising effort, and investigators' patients. Reasons patients were not randomized include the following: sleep efficiency of more than 87.5%, n=117; consent withdrawn, n=106; met exclusion criteria, n=67; clinically significant, uncontrolled medical or psychiatric condition, n=11; diagnosis of a sleep disorder other than shift work disorder (SWD), n=20; average daily caffeine consumption >600 mg/d, n=1; use of disallowed prescription or over-the-counter medications, n=10; history of substance abuse, n=2; positive urinary drug screen result at screening, n=27; disorder that may interfere with drug absorption, distribution, metabolism, or excretion, n=1; other (undetermined), n=1; mean sleep latency time greater than 6 minutes, n=45; lost to follow-up, n=36; patient in poor health, n=23; patient unable to comply with protocol, n=18; insufficient shift work exposure, n=16; patient does not meet clinical severity criteria, n=10; patient does not meet criteria for SWD diagnosis or excessive sleepiness, n=5; presence of another medical or psychiatric disorder that could account for the excessive sleepiness, n=4; adverse event, n=2; reason not provided, n=2; and other, n=55. Randomized patients who received at least 1 dose of drug and had a baseline and at least 1 postbaseline assessment for the Multiple Sleep Latency Test and Clinical Global Impressions of Improvement were included in efficacy analyses.

FIGURE 2.

Mean sleep latency on the Multiple Sleep Latency Test (MSLT). Sleep latency by visit for the last 4 tests (2-8 am) (left) and during the final visit night shift (midnight to 8 am) (right). Error bars indicate SEM. P values are based on the change from baseline compared with placebo. *P<.001, †P<.01, and ‡P<.05.

FIGURE 3.

Mean Karolinska Sleepiness Scale (KSS) scores. Scores are by visit (A) and during the final visit night shift (midnight to 8 am) (B); for quality of episodic secondary memory by visit (C) and during the final visit night shift (midnight to 8 am) (D); for delayed word recall accuracy by visit (E) and during the final visit night shift (midnight to 8 am) (F); for power of attention by visit (G) and during the final visit night shift (midnight to 8 am) (H); and for simple reaction time by visit (I) and during the final visit night shift (midnight to 8 am) (J) compared with placebo. Data presented over time are during the final visit night shift. Error bars indicate SEM. P values are based on the change from baseline compared with placebo. *P≤.001, †P≤.01, ‡P<.05.