Elsevier

Mayo Clinic Proceedings

Volume 84, Issue 11, November 2009, Pages 958-972
Mayo Clinic Proceedings

ORIGINAL ARTICLE
Armodafinil for Treatment of Excessive Sleepiness Associated With Shift Work Disorder: A Randomized Controlled Study

https://doi.org/10.4065/84.11.958Get rights and content

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 (ā‰„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 ā‰¤6 minutes on a Multiple Sleep Latency Test), insomnia (sleep efficiency ā‰¤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

Section snippets

PATIENTS AND METHODS

This 12-week, randomized, double-blind, placebo-controlled, parallel-group, multicenter study was conducted with a common protocol at 42 centers in the United States (37) and Canada (5) from April 2 through December 23, 2004 (a center in Australia planned to but did not enroll any patients), in compliance with the International Conference on Harmonization's Good Clinical Practice Consolidated Guidance. An independent ethics committee or institutional review board at each center approved the

RESULTS

Of the 747 adults screened, 254 met entry criteria. Of these, 245 (96%) received at least 1 dose of study medication and were included in the safety analysis (Figure 1). At baseline, the armodafinil and placebo groups were similar in demographic variables and illness severity ratings (Table 1). Overall, 138 (56%) of 245 patients were rated by the investigator as moderately ill, and 107 (44%) of 245 patients were rated as markedly, severely, or extremely ill. Most patients (212/245; 87%) were

DISCUSSION

Treatment with armodafinil, 150 mg, significantly reduced sleep propensity and subjective ratings of sleepiness and improved aspects of attention and memory in patients with SWD during usual night shift hours. These differences were associated with significantly greater improvement in the severity of patients' overall clinical condition compared with those who received placebo. Armodafinil increased nighttime mean sleep latency to greater than 5 minutes, although a proportion of individuals

CONCLUSION

Armodafinil, 150 mg, significantly improved measures of sleep propensity, subjective sleepiness, memory, and attention during scheduled night work hours in patients with excessive sleepiness associated with SWD without disturbing daytime sleep. The effects on wakefulness were apparent during the night shift and the commute home. Concurrent improvements in overall clinical condition were also found. Armodafinil was generally well tolerated. These findings support the inclusion of armodafinil as

Acknowledgments

We gratefully acknowledge Gwendolyn E. Niebler, DO, former Cephalon employee, for her contribution to the protocol design, role as medical monitor, and contribution to drafts of the manuscript; Rod J Hughes, PhD, former Cephalon employee, for contribution to the protocol design and drafts of the manuscript; Ronghua ā€œTigerā€ Yang, PhD, Cephalon employee, for statistical support during the submission and peer-review process; Mark Riotto, Cephalon employee, for editorial support; and Oxford

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    Cephalon Inc funded the study and developed the protocol in collaboration with the authors. For more information on the role of the funding source, see page 971, and for the financial disclosures of the authors, see page 969.

    This article is freely available on publication, because the authors have chosen the immediate access option, which is funded by Cephalon.

    ā€ 

    Died March 1, 2007; was an employee of Cephalon Inc.

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