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Clinical and Research News
Tactics to Boost Alertness May Benefit Night Workers
Psychiatric News
Volume 39 Number 13 page 26-58

A novel high-frequency, low-dose caffeine regimen can counteract performance decrements linked with extended bouts of wakefulness, a study in the May issue of Sleep shows.

The findings may benefit resident physicians, military personnel, emergency workers, and others who must stay awake—and highly alert—more than 16 hours at a time, said James Wyatt, Ph.D., who led the research team. Wyatt is an assistant professor of psychology at Rush University Medical Center in Chicago.

Wyatt and colleagues at Harvard Medical School studied 16 healthy young-adult men who spent 29 consecutive days in laboratory apartments free of time cues at the Brigham and Women's Hospital in Boston. The men lived on 42.85-hour "days" consisting of 28.57-hour wake episodes and 14.28-hour sleep episodes.

The researchers crafted the 42.85-hour cycle to permit scheduling of wake and sleep episodes across a range of circadian phases. The long waking period, they noted, mirrors that of resident physicians on on-call shifts and of pilots on long-haul combat missions. The U.S. Air Force, which funded the study, specified that all study subjects be men.

To minimize the influence of the light/dark cycle on body rhythms, the researchers kept room lights dim throughout the men's waking hours. They required the men to remain in bed in near darkness during scheduled sleep times.FIG1

Every hour during the extended wake periods, eight men ingested one capsule of caffeine (0.3 mg per kg per hour), and eight took a placebo. For an average adult man, Wyatt said, one capsule provides the equivalent of about a quarter cup of coffee.

Wyatt and his colleagues monitored all sleep episodes polysomnographically and gave the men a battery of tests to assess mood, cognitive performance, and subjective sleepiness. They also measured levels of the hormone melatonin, which serves as a marker of time on the body clock.

The men who took caffeine performed almost as well on various tests after being awake 28 hours as they did after being awake for only two hours, Wyatt reported. They far outperformed the placebo users. They also dozed off far less often in waking hours than did the placebo users. The wake-promoting effects of caffeine, Wyatt cautioned, do not replace the restoration sleep provides. Nonetheless, consuming half a cup of coffee every two hours may help people who must stay awake much longer than usual and stay more alert than they otherwise would. A small amount of caffeine provides this benefit, Wyatt said, without causing the tremulousness or nervousness larger doses frequently induce.

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The study is believed to be the first to show that caffeine acts on the body's homeostatic system, not its circadian system, a previously unresolved debate, Wyatt said. While both systems contribute to the control of sleep and wakefulness, sleep drive from the homeostatic system builds with each successive hour of wakefulness. People normally are able to stay awake and reasonably alert for about 16 to 18 hours at a time.

Findings from the study, Wyatt said, hold implications for the design of work schedules that maximize performance and minimize times of vulnerability to errors.

Such schedules could benefit the 6 million Americans who work regular or rotating night shifts. Night-shift workers are 6 to 14 times more likely than day-shift workers to feel severely sleepy on the job, Milton Erman, M.D., president of Pacific Sleep Medicine Services in La Jolla, Calif., said at APA's annual meeting in May.

Night workers report more accidents and injuries at work and near misses while driving home after work than do day workers, Erman said. They sleep more restlessly and get less sleep than day workers, since they must sleep in the daytime, when the body's circadian clock is programmed for wakefulness.

Erman and colleagues conducted two 12-week, double-blind, placebo-controlled studies in healthy male and female night-shift workers; 265 took 200 mg or 300 mg of modafinil, and 190 took placebo. Subjects took their pills 30 to 60 minutes before starting each night shift.

Questionnaires showed modafinil improved vigilance, activity, productivity, and other aspects of workplace performance, as well as overall quality of life, Erman reported. Workers taking the medication reported fewer errors, near misses, or accidents at work and while commuting. A 200 mg dose of modafinil was better tolerated than 300 mg, he said. The drug did not affect workers' ability to sleep when desired; workers also reported that they slept better. About 1 in 5 patients developed headaches and nausea on the higher dosage, but otherwise had a low frequency of adverse events.

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Also speaking at the APA meeting, James Walsh, Ph.D., executive director and senior scientist in the sleep medicine and research center at St. John's/St. Luke's Hospitals in St. Louis, Mo., described another 12-week, double-blind, placebo-controlled study of modafinil in night workers.

In this study, 30 to 60 minutes before starting their night shifts 96 workers took 200 mg modafinil, and 108 workers took placebo. They also took their assigned medication before a simulated night shift in the sleep laboratory on the night after they finished three or more consecutive night shifts at their usual workplace.

Walsh and colleagues assessed sustained attention and objective and subjective sleepiness on the simulated night shifts at the study's start and at monthly intervals thereafter.

Over the study period, subjects who took modafinil proved consistently more alert on the night shift, as indicated by a standard laboratory measure of sleepiness. They responded faster on computerized tests and reported feeling less sleepy at night. Clinical global impression ratings affirmed their self-reports.

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Polysomnographic studies showed both modafinil and placebo users continued to sleep poorly in the daytime; both groups averaged about 6.6 hours of sleep per day. That was expected, Walsh said. Modafinil does not improve sleep, he noted, nor does it promote a circadian shift that would favor improved sleep in the daytime. As in the other study, headaches proved the prime adverse event associated with modafinil's use.

The FDA approved the marketing of modafinil in January to improve wakefulness in patients with shift work sleep disorder. The agent first received FDA approval in 1998 for use in improving wakefulness in patients with narcolepsy. Studies are in progress to assess the medication's utility in improving alertness in patients with other disorders in which fatigue is a prominent symptom, including depression, chronic fatigue syndrome, and multiple sclerosis. ▪

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