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
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
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
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
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.
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
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. ▪