Drug Fights Fatigue During Night Shift

Modafinil doesn't erase lack of alertness on the job, study notes

WEDNESDAY, Aug. 3, 2005 (HealthDay News) -- For those battling the fatigue of working the graveyard shift, a new study suggests that a prescription drug approved for narcolepsy may reduce sleepiness and improve alertness for nocturnal employees.

The medication, called modafinil (Provigil), does not appear, however, to erase excessive sleepiness, which strikes those suffering from "shift-work sleep disorder."

The disorder is typically characterized by insomnia during the resting daytime hours and extreme fatigue throughout the working night. Such uncontrollable sleepiness provokes attention and performance lapses which, in turn, make sufferers more liable to experience work-related accidents while on the job.

The syndrome affects an estimated 5 percent to 10 percent of the approximately 6 million Americans who work overnight on a permanent or semi-permanent basis.

"Modafinil did not make these patients into day people at night," said study author Dr. Charles A. Czeisler, chief of the Sleep Medicine Division at Brigham and Women's Hospital in Boston. "It reduced the frequency of lapses of attention and the duration of these lapses, and it increased the ability to stay awake and markedly improved their clinical condition. But it did not restore anyone to the same level of alertness that a person would have in the middle of the day."

Modafinil is currently approved by the U.S. Food and Drug Administration as a treatment for patients suffering from narcolepsy, as well as for those with obstructive sleep apnea.

Recent studies have indicated the drug may also prove helpful in easing the extreme fatigue that accompanies multiple sclerosis, as well as serving as a potential treatment for cocaine addiction.

The new research, reported in the Aug. 4 issue of the New England Journal of Medicine, is the first to explore the potential of any medication to specifically aid those dealing with "shift-work sleep disorder."

Between 2001 and 2002, Czeisler and his team assessed the drug's impact on sleep problems experienced by 193 male and female night-shift workers between the ages of 18 and 60.

All the patients had been diagnosed with chronic excessive sleepiness as a result of working at least five night shifts a month. At least three of those shifts were scheduled consecutively, primarily between the hours of 10 p.m. and 8 a.m.

The researchers administered 200 milligrams of modafinil to half the patients within an hour before each shift, for a period of between one to three months. The other half received a placebo.

All the men and women were evaluated in person after completing a round of at least three consecutive night shifts. During the shifts themselves, the patients were monitored for both alertness and sleepiness, and all kept a diary concerning any sleep issues during work and on the commute home. Caffeine use was also noted.

Czeilser and his colleagues found that 74 percent of those taking modafinil experienced at least some sleepiness reduction and alertness improvement during their night shifts. By contrast, only 36 percent of those who did not take modafinil experienced similar improvements.

By the study's conclusion, momentary lapses of attention due to extreme fatigue were cut in half among the modafinil patients -- occurring 10 times in a 20-minute period. By comparison, upwards of 24 such lapses occurred among the placebo patients in the same time frame.

Among the patients taking modafinil, there was a 25 percent drop in the number of men and women who reported having had an accident or near-accident on the commute home after work, although no such drop was observed during work hours themselves.

While no differences were observed between the two groups in terms of daytime sleep habits, the length of time it took for patients to fall asleep -- a measure known as "sleep latency" -- increased nearly two-fold among the modafinil patients, but not among the placebo group. Longer sleep latency times are considered the mark of a healthy sleep pattern, whereas falling asleep too quickly is a sign of extreme fatigue.

Nonetheless, while the researchers observed alertness increases among the modafinil patients, they noted that attention lapses and overall fatigue remained high among the group during the night shifts.

They strongly emphasized that, despite some benefits, the drug did not help the workers achieve normal sleep functioning or wakefulness -- and did not have any effect on an individual's internal clock, otherwise known as the circadian rhythm.

"There was a clinically significant improvement with modafinil, but the patients remained sleepy," said Czeisler. "So it's not that they shouldn't remain cautious at work. And more research is needed to find other compounds -- in place of, or in combination with, modafinil -- that can be even more beneficial."

Czeisler said the research was nevertheless important in that the problems plaguing some night-shift workers are poorly appreciated and rarely studied.

"Even though it's been on the books since the early 1980s, night-shift sleep disorder is a very under-recognized condition," he said. "We're all different, and some people have much more difficulty adapting to these sleep inversions than others. We don't understand why, but we do understand that there is a greater risk for other associated problems for those that can't adapt. People with this disorder have a much higher prevalence of ulcers, accidents and other long-term problems. So, it needs to be studied."

Dr. Robert Vorona, an associate professor in the division of sleep medicine at Eastern Virginia Medical School in Norfolk, agrees.

"There's no question this is an interesting and important study because not an insignificant number of Americans do shift work, and those who do are plagued by a reduction in the total hours of sleep they get, and a reduction in the quality of that sleep," Vorona said.

"Human beings are not geared to work at night, and so when we try and reverse that we're working against a very strong biological imperative," he added. "So, it doesn't surprise me that a drug would not completely reverse that effect -- that modafinil would not abolish all the effects of sleeping at day and working at night. But it sounds like they're being honest and direct in stating that this is just a first step. So, there's certainly going to have to be more research to come."

More information

For more on sleep disorders and insomnia, check out the American Insomnia Association.

SOURCES: Charles A. Czeisler, Ph.D., M.D., chief, Sleep Medicine Division, Brigham and Women's Hospital, Boston; Robert Vorona, M.D., associate professor, department of medicine, division of sleep medicine, Eastern Virginia Medical School, Norfolk; Aug. 4, 2005, New England Journal of Medicine
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