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


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.


CONCLUSIONS
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.


BACKGROUND
clinicaltrials.gov Identifier: NCT00080288.
Czeisler
Charles A
CA
Division of Sleep Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. charles_czeisler@hms.harvard.edu
Walsh
James K
JK
Wesnes
Keith A
KA
Arora
Sanjay
S
Roth
Thomas
T
D000046:Academic Medical Centers; D000328:Adult; D000368:Aged; D001559:Benzhydryl Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D000697:Central Nervous System Stimulants / Q000009:adverse effects / Q000627:therapeutic use*; D006970:Disorders of Excessive Somnolence / Q000188:drug therapy / Q000517:prevention & control; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004562:Electrocardiography; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008505:Medical Staff, Hospital; D008875:Middle Aged; D008910:Minnesota; D000077408:Modafinil; D017286:Polysomnography; D011336:Probability; D018570:Risk Assessment; D012720:Severity of Illness Index; D020178:Sleep Disorders, Circadian Rhythm / Q000188:drug therapy* / Q000517:prevention & control; D018709:Statistics, Nonparametric; D013647:Task Performance and Analysis; D016896:Treatment Outcome; D014940:Work Schedule Tolerance; D055815:Young Adult
D001559:Benzhydryl Compounds; D000697:Central Nervous System Stimulants; D000077408:Modafinil