Drug keeps pilots awake

By Peter Mucha, Inquirer Staff Writer

A much-ballyhooed anti-drowsiness drug made by West Chester-based Cephalon Inc. is taking off as the Air Force's new "go-pill."

Provigil, also known by its generic name, modafinil, has been used more than 150 times this year by bomber crews to ward off sleepiness on missions of more than 12 hours.

The Air Force's main go-pill has long been the amphetamine Dexedrine, whose use has been questioned since a deadly friendly-fire incident in Afghanistan two years ago.

Because Provigil seems to bolster alertness for days with few side effects, it not only has caught on for its government-sanctioned uses with several sleep disorders, but it also has fired media imaginations as a lifestyle drug for cheating sleep and defeating jet lag.

The use of Provigil by the Air Force marks the first federal sanctioning of the drug for healthy people to stave off normal sleepiness.

The Air Force approved Provigil's use in December, limiting it to crews of dual-piloted bombers - B-1s, B-52s and stealthy B-2s - and to weapons specialists on F-15E fighters.

In the first half of the year, 159.5 doses of Provigil were taken during 56 B-1 and B-52 sorties, or flights, according to Betty Anne Mauger, spokeswoman for the Office of the Air Force Surgeon General.

The bombers are permanently based in the continental United States, said an Air Force spokesman, Lt. Col. Frank Smolinsky. Pilots can make endurance-challenging flights ferrying the planes to overseas bases, such as Anderson in Guam. From there, bombers can head to Iraq or Afghanistan and back.

"Pilots have the option of whether to use it or not. Nobody is required to," said John A. Caldwell, who leads the Air Force's fatigue countermeasures research at Brooks City-Base in Texas.

It is offered only to pilots who have passed ground testing for negative reactions, Caldwell said.

So far, Mauger said, no in-flight adverse effects have been reported.

Tests for the Air Force were conducted at the University of Pennsylvania, where researchers recently found that sleep-deprived subjects using a typical dose showed benefits in alertness and reaction time for 88 hours - more than 31/2 days.

"It stopped a lot of the uncontrolled lapses of attention and micro-sleeps or sleep attacks," said David Dinges, sleep-deprivation researcher and professor at the University of Pennsylvania School of Medicine.

Earlier Penn research showed that caffeine was of benefit for only about 24 hours, he said.

Unlike caffeine and amphetamines, Provigil does not quicken the pulse or produce jitters, apparently because it only mildly affects several brain chemicals called neurotransmitters. "It's not like having a Starbucks Super Grande," said Caldwell. "You feel more awake, but you don't necessarily feel stimulated."

The Food and Drug Administration has approved Provigil only for excessive daytime sleepiness caused by three sleep disorders. People with narcolepsy are prone to unexpectedly nod off, while those with obstructive sleep apnea or shift-work sleep disorder often feel exhausted and inattentive because of inadequate sleep.

Those patients, however, are not the only ones who have spiked Provigil sales, projected to reach $400 million this year, up 38 percent over last year's receipts.

Physicians have discretion to write prescriptions for unauthorized, or "off-label," medical purposes. According to Cephalon, about 14 percent of the prescriptions are for fatigue from multiple sclerosis, with an additional 10 percent for attention-deficit hyperactivity disorder, the next condition the company hopes the FDA will green-light.

Cephalon's breakdown also cites other fatigue-related conditions, including Parkinson's disease and depression. Psychiatrists write the greatest number of prescriptions, according to Cephalon spokeswoman Sheryl Williams.

The Army, Navy and Marine Corps say they are not dispensing Provigil for fatigue. The French Foreign Legion, however, reportedly used the drug, developed in France more than a decade ago, during the Gulf War.

The advantages of modafinil over amphetamines are not clear yet, said Caldwell. While he acknowledged that modafinil "doesn't produce the cardiovascular stimulation" - increased heart rate - "that amphetamines produce," he said Dexedrine was safe and effective in the well-monitored low doses the Air Force uses.

In April 2002, however, during a mission in Afghanistan, two F16 pilots mistook a military exercise for hostile fire. One launched a 500-pound laser-guided bomb, killing four Canadians. The pilots' attorneys blamed amphetamines for impairing the clients' judgment.

Neither pilot was court-martialed. Both were reprimanded; one retired and the other forfeited his pilot status and $5,600 in pay.

Dinges said one advantage to modafinil was that it preserved a person's ability to sleep. The drug seems to let sleep-deprived users nap while on it, then rest normally afterward, with almost no "rebound sleepiness."

Amphetamine users often cannot help sleeping deeply after the drug wears off. They also have trouble sleeping before it wears off, one reason the Air Force allows the use of "no-go pills" - sleep aids such as Ambien and Restoril.

It is too early to say if Provigil will become the Air Force's go-pill of choice for all pilots, but Caldwell plans to test the drug head-to-head with Dexedrine in simulated flight conditions beginning early next year.

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