Tomas Thorne
WASHINGTON, Aug. 5 (UPI) — Working at night and sleeping during the day is not natural for any human body, but some people have trouble adapting to such arrangements to the point where their distress qualifies as a medical disorder. Now, this underdiagnosed and difficult-to-treat condition is the subject of the first-ever clinical trial of the promising medication modafinil.
Shift-work sleep disorder is marked by sleepiness during night-time working hours, insomnia while trying to sleep during the day and instances of fatigue-induced accidents and errors on the job in people whose work shifts include more than six hours between 10 p.m. and 8 a.m. Effects include higher rates of accidents, absenteeism, depression, ulcers and frequently missing family and social activities.
Charles Czeisler, lead author of the study — which appears in the Aug. 4 issue of the New England Journal of Medicine — told United Press International the condition affects 5 percent to 10 percent of night-shift workers. It also is often underdiagnosed because it is mistaken for ordinary fatigue.
Czeisler compared the difference between normal tiredness and the disorder to the scene at tourist destinations, where some travelers walk around examining landmarks and others slump on benches due to the effects of jet lag.
“Some people are more affected than others,” he said.
David Dinges, chief of the Division of Sleep and Chronobiology at the University of Pennsylvania in Philadelphia and a co-author of the paper, told UPI he has been conducting another study. This one, sponsored by the National Institutes of Health, is examining healthy people not on shift-work schedules who have spent non-consecutive nights without sleep.
He said he found that participants who have experienced great difficulty during their first night without sleep also had difficulty on subsequent nights without sleep — regardless of how much they slept in the interim. At the same time, participants who remained relatively functional after their first sleepless night retained that ability on other nights when they stayed up.
“This is a trait-like characteristic of people,” Dinges said.
Czeisler, who is chief of sleep medicine at Brigham and Women’s Hospital in Boston and a professor of medicine at Harvard Medical School, said that in addition to revealing a possible treatment, another notable aspect of the study was its findings on the effects of shift-work sleep disorder.
“It revealed how sleepy this group of patients is,” Czeisler said. “They’re just as sleepy as patients with narcolepsy or sleep apnea.”
In the study, researchers assigned 209 shift-work sleep-disorder patients to receive 200 milligrams of either modafinil or a placebo before the start of each work shift. Modafinil is sold under the trade name Provigil and is manufactured by Cephalon Inc., which provided research funds to Czeisler. The drug also is used for narcolepsy and sleep apnea.
The study measured sleep latency and lapses of attention. Sleep latency is the amount of time it takes a person to fall asleep given the opportunity.
Czeisler said that in the daytime, falling asleep in less than five minutes signifies excessive sleepiness. No standards have been developed for healthy sleep latency at night, so the sleep-latency figures collected in his study simply served as a measure of change. The average decrease in sleep latency for patients receiving modafinil was 1.7 minutes, compared to 0.3 minutes for the placebo group. The difference in sleep latency was most pronounced early in the night, around 2 a.m., and decreased toward 6 a.m.
The Psychomotor Vigilance Test was used to monitor lapses of attention. Patients in the modafinil group experienced a median rate of 2.63 fewer lapses of attention per 20-minute test, while patients in the placebo group experienced 3.75 more lapses of attention than they had before receiving the placebo.
Patients in Czeisler’s study worked a wide variety of occupations, including manufacturing, investment banking, police work and hospital nursing.
“Something that was common to all of them was actual or near-miss motor-vehicle accidents driving home from work,” Czeisler said.
Among the study’s placebo group, 54 percent reported accidents or near accidents during their commute home, while only 29 percent of patients receiving modafinil reported such incidents.
Czeisler acknowledged that although modafinil is helpful, it does not enable perfect functioning.
“It brings (patients) about a third of the way to what’s normal during the daytime, but we don’t know what’s normal during the night,” he said. Also, patients in the modafinil group experienced daytime insomnia at a 6-percent higher rate than the placebo group.
Czeisler said the brain sends out a strong drive for sleep at night, and that it is contrary to the body’s circadian rhythms to work at night and sleep in the daytime, but modern life sometimes demands the suppression of biological directives.
“There are many essential services provided by people who do work at night, and we live in a society that requires many round-the-clock operations,” Czeisler said.
Dinges said that with the number of U.S. shift workers at 6 million and growing, it would be economically unfeasible to bar even people with innate difficulties from night-shift work, even though numerous government and scientific studies point to dangerous consequences from such activities, such as industrial accidents and highway collisions.
“I don’t know how realistic it is to suggest that people who are vulnerable shouldn’t work night shift,” he said.
Other doctors suggest that more possibilities may be found for managing the disorder.
Robert Basner, associate professor of clinical medicine at Columbia University, wrote in the NEJM article that other researchers’ findings show 600 mg doses of caffeine can produce similar effects to modafinil in improved performance for people who have been awake more than 40 hours, and according to Czeisler’s study, modafinil does not affect the underlying circadian rhythm.
“Neither these data nor any other published studies provide evidence to indicate that modafinil is uniquely suited to be used as an enhancer of wakefulness and vigilance in humans subjected to nighttime shift work,” Basner wrote.
Czeisler said he did not test — nor would he personally advocate — the drug’s potential to keep people awake for indefinite periods of time, such as all-night studying.
Dinges said caffeine and bright lights have been used to treat shift-work sleep disorder for years, but they have not been tried in many experiments.
“In the experiments where they have been tried, they have limited utility,” he said. He agreed that more research needs to be done on the disorder and in establishing standards for normal levels of nighttime alertness.