http://www.boston.com/dailyglobe2/265/nation/Who_needs_sleep_New_pill_hits_sceneP.shtml Who needs sleep? New pill hits scene By Carey Goldberg, Globe Staff, 9/22/2002 Just to see what it was like, the Cambridge computer programmer stayed awake four straight days. He felt fine, he reported later, not jittery, nicely focused. ''Imagine,'' he wrote in an e-mail, ''having all the time you could want to goof off, knowing that you still have just as much time as usual to spend on things you have to do.'' On the other hand, he added, ''if you lack imagination and run out of things to do, you could end up bored real fast.'' The programmer, who asked that he not be identified, has not repeated his ''little experiment,'' partly because of its questionable legality. To stay awake, he borrowed a prescription drug, modafinil, that is meant for narcoleptics, whose affliction causes excessive sleepiness. But he appears to have plenty of company in his desire to cheat time by cheating sleep. In the three years since the drug was introduced under the brand name Provigil for narcolepsy, sales have skyrocketed to more than 250,000 prescriptions every three months, outstripping the needs of the nation's estimated 150,000 narcoleptics. Cephalon, the company that makes Provigil, says the seemingly excess prescriptions mainly go to patients with other diseases that cause fatigue. But the buzz about modafinil as a potential elixir for millions of ''sleep when I die'' Americans has been building for months. Some predict it may become the next Viagra or Prozac, the next ''lifestyle drug.'' Sleep specialists hate that idea. Though modafinil causes few side effects, they say, and though it shows little potential for addiction, using it lightly to deprive the body of sleep, especially long-term, is asking for trouble. Nonetheless, talk about modafinil has been spreading, including debates online and in print about whether such a pill could be a dream come true for the underslept or a nightmare for a society that is already running too fast. On the Web site Metafilter.com, a group weblog with thousands of chatty members, some loved the idea of Provigil. ''Heck, imagine making love all night, and still being alert at work the next day!'' one posting read. ''Ever since I was a kid, I imagined having a magical clock that stops time,'' read another. But other posters worried. ''Drugs like this become a bit of an arms race,'' wrote one. ''What do you do when all of your classmates are taking Provigil and are more prepared for exams than you are? What do you do when the job promotion goes to the keener putting in 16 hours a day?'' A Washington Post reporter who tried staying up for two days on Provigil gave it warm reviews in the paper, writing that ''Modafinil may have the power to change Washington, D.C., and other high-powered cities.'' But then, he wrote that story during a 40-hour period of modafinil-enhanced wakefulness, so his judgment may have been affected. Modafinil is believed to target areas of the brain responsible for maintaining wakefulness more precisely than caffeine or other stimulants, so it does not bring on a wired feeling or later crash, but experts say it does not completely do away with all the mental impairment that comes with sleep deprivation. The military, too, has added to the attention paid modafinil by reporting publicly that it has been testing the drug as ''performance enhancement'' for combatants who must stay awake for days. It turned out that they could function well for 40 hours, sleep eight hours, and then get up and go another 40 hours before needing rest. For all the talk, however, it remains unclear how much Provigil is already being used by otherwise healthy sleep-cheaters. Since the biotech firm Cephalon introduced Provigil in early 1999, the drug's sales have jumped to a rate of $200 million per year, if current sales keep up. Quarterly sales are up about 70 percent over last year, and prescriptions are now running at the rate of 250,000 in a three-month period, according to IMS Health, a health information company. Those numbers seem particularly high given that there are only an estimated 150,000 narcoleptics in the country. And company officials have acknowledged that perhaps only a quarter of the prescriptions are going to narcoleptics. But they also say they are not encouraging the use of Provigil by people who do not need it, and they have no indication that it is being widely abused. Rather, they believe it is being prescribed ''off-label'' by doctors to help patients with a variety of sleep disorders. And they are seeking approval from the Food and Drug Administration to broaden Provigil's label to include a wider variety of diseases that cause fatigue. However, there is anecdotal evidence of a nonmedical demand for Provigil. For example, Dr. Richard J. Castriotta, a sleep expert at the University of Texas, said a handful of people have asked him for a Provigil prescription just to perk them up, but he has refused them. Meanwhile, Web sites offer to sell Provigil without a prescription. Modafinil may be OK for pilots or emergency workers, Castriotta said, but it would be wrong ''to make that leap and say, `Well, gosh, why can't I just sleep three hours a night as a way of life?' We don't know enough about sleep deprivation to be able to determine what the long-range effects might be, and that's very, very dangerous.'' He and other researchers predicted that in any case, because Provigil is a controlled substance, and because it brings users no euphoria, it is unlikely to be very widely abused. But in a country where more than half the population is averaging more than three cups of coffee per day, it does seem to have broad potential appeal - particularly for the truckers and students and new parents and others whose lives sometimes require all-nighters. International Antiaging Systems, a company that has one of the offshore pharmacy Web sites that sells modafinil, says its modafinil sales have at least doubled in the last year, but it would not specify the numbers involved. A swath of studies, many sponsored by Cephalon, are underway to see if Provigil might help patients with the fatigue caused by diseases ranging from multiple sclerosis to attention deficit to sleep apnea to depression. Much of the initial research shows tentative promise. Another set of extensive studies is looking at whether modafinil will help shift workers who have to stay awake at times when their bodies beg to sleep. Their numbers are estimated at about 15 million. Provigil's side effects tend to be mild, Cephalon says, with headache and nausea the most common. It can also interact poorly with some other drugs; in particular, it can reduce the effects of birth control pills. The prospect of Provigil or even better ''wake-enhancing'' drugs gaining broad usage deeply concerns sleep specialists like Dr. Thomas Scammell of Beth Israel Deaconess Medical Center, a leading authority on modafinil. ''For society, it does bring up a really key question,'' he said. ''The simplest way to answer it is to say, `If I could give you a pill that would take away your hunger, does that mean you shouldn't eat?' Well, duh, you've got to eat and you know why, because you'll waste away.'' ''The problem,'' he added, ''is that the science of sleep research hasn't reached the point that we can say, `If you don't get enough sleep, X, Y, and Z will happen to you.'' However, a growing body of research does indicate that lack of sleep may be even more harmful than previously thought. It may be contributing to obesity by changing the metabolisms of the underslept and to heart disease by causing low-grade inflammation. But Americans are nonetheless sleeping less and working more, according to the National Sleep Foundation. Its polls have found that Americans sleep an average of about seven hours a night during the work week, an hour and a half less than in 1900, and that one third of adults are so sleepy in the daytime they could be dangerous. Federal highway officials say lack of sleep causes 100,000 crashes a year. To Dr. Daniel F. Kripke, a sleep expert at the University of California at San Diego, excitement over a new drug like modafinil is neither new nor very exciting - not to a veteran doctor who remembers when cocaine and amphetamines spurred similar reactions. ''I think it is a promising drug but it has only been tested a little,'' said Dr. Kripke, whose own research suggests that people who sleep somewhat less than average may live longer. ''I'm very much in favor of broader scientific testing,'' he said, ''but I'm not in favor of people jumping off the deep end.'' Carey Goldberg can be reached at firstname.lastname@example.org.