Is the 'Awake Pill' the Real Deal?

In our fast-paced, 24/7 world, with round-the-clock jobs and nonstop interruptions, the average American gets less than seven hours of sleep a night, and millions get less than six.

That's why all sleep experts agree that, as Dr. Charles Czeisler of Boston's Brigham and Women's Hospital puts it, "we are an incredibly sleepy nation."

So it's not surprising that the sales of Provigil -- the first prescription drug to treat excessive sleepiness -- are exploding.

The drug brought in $800 million last year. Financial analyst Eric Schmidt of Cowen and Co. says, at least for Wall Street, this so-called "awake pill" is a dream, because the market of sleepy people is enormous.

"You're talking a Starbucks type of opportunity," he said. "The growth on this franchise is substantial. It's growing at about 30 [percent] to 40 percent annually, so this is a big drug already and it's getting bigger."

Watch the story on "20/20: Promises, Promises" Friday at 10 p.m. ET

"20/20" and ABC's chief medical correspondent Dr. Tim Johnson set out to discover whether the "awake pill" was really the wonder drug for sleepy America, or whether it was an empty promise, where profits, not patients, were the bottom line.

Off-Label Use

The Food and Drug Administration approved Provigil to treat sleepiness in only three sleep disorders: shift-work syndrome, narcolepsy and sleep apnea.

At least half -- and some say as much as 90 percent -- of Provigil's sales are for off-label use, though, or conditions not approved by the FDA.

"From a financial standpoint, we're really not that concerned with off-label use," Schmidt said. "To us, it's all about sales, and whether they come from an on-label or off-label indication, it's a dollar to [the maker of Provigil] Cephalon's top, and hopefully, bottom line."

But Dr. Jerome Kassirer, author of "On the Take: How Medicine's Complicity With Big Business Can Endanger Your Health," says it's time for drug companies to stop treating health care like it's just another business.

"This is medicine. This is not refrigerators. This is not cars," he said. "This is a profession in which we're taking care of sick people who trust us."

It's illegal for Cephalon to directly advertise off-label use of Provigil, but Kassirer says Cephalon indirectly creates off-label markets for its drug by funding continuing medical education, where doctors get paid to describe Provigil for possible off-label uses.

He showed "20/20" a journal from 2003 sponsored by Cephalon. The journal, called the Primary Care Companion, is a supplement to a well-known journal, The Journal of Clinical Psychiatry.

"It turns out that the people who write those articles have a relationship with Cephalon," Kassirer said.

'Not Real Science'?

Cephalon declined "20/20's" request for an interview about off-label use, but in fact, all seven lead authors of the journal got money from Cephalon as consultants, speakers or researchers. And these articles do not go through rigorous outside review as in a peer-reviewed journal.

Kassirer, who was editor in chief of the New England Journal of Medicine, says this is an important distinction.

"[These articles] would never make it into a really respected medical journal because it's not real science," he said. "I would say that it's a shabby marketing device for the drug by the company."

The marketing seems to be working.

"20/20" obtained a copy of a Provigil sales report. Allergists, internists, pediatricians and even dentists are prescribing the "awake pill." It's being used to treat excessive sleepiness in depression, multiple sclerosis, hyperactivity and cancer. It might lead you to think that Provigil is an amazing breakthrough, but a closer look raises questions.

Public Disclosure

Dr. Charles Czeisler, chief of sleep medicine at Brigham and Women's Hospital, was the lead investigator of the Provigil shift-work study, where one group got a placebo, and one got Provigil.

Czeisler makes it clear that he has served as a paid consultant to Cephalon. He says modafinil -- the generic name for Provigil -- "was shown to significantly improve the alertness and performance of those people."

The study shows that the "awake pill" kept participants awake 1.7 minutes longer than the placebo. A modest finding, at best. But in 2003, Czeisler appeared before the FDA on behalf of Cephalon to lobby for the approval of the drug.

Eight months later, Cephalon gave Harvard nearly $3 million to establish a chair in sleep medicine, with Czeisler as the first recipient.

"I think the public should worry about any issue of conflict of interest," Czeisler said. "And I think the first step toward resolving those issues is to make them public. That's why anytime I publish a paper there is a long list of any company with which I am interacting, including Cephalon."

It's called public disclosure, and it's in the small print at the end of Czeisler's study. But Kassirer says disclosure is a weak safeguard for the public: a watchdog with no teeth.

"Disclosure is not an ideal solution," he said. "The problem with disclosure is you just don't know what to do about it. A better solution is to have plenty of people evaluating clinical information who are not conflicted."

The Caffeine Comparison

"20/20" set out to discover how well Provigil worked when the studies were not funded by Cephalon.

That led us to the sleep labs of the U.S. Army. Brain scientist Nancy Wesensten studies drugs to help sleep-deprived soldiers stay awake and alert. She didn't just compare Provigil to a placebo, she compared it to America's No. 1 selling "awake drug": caffeine.

"We knew that caffeine was an effective means for sustaining performance during sleep loss," she said. "But we are always looking for other compounds that might be an improvement on caffeine, so when modafinil came along we wanted to compare modafinil to caffeine."

Wesensten compared Provigil to caffeine in terms of how well the soldiers performed on tests and how alert they were, and she also looked at side effects. The result?

"In our hands, at the dosages we tested, modafinil did not work any better than caffeine," she said.

In fact, the Army found that Provigil worked no better than the amount of caffeine you received in a big cup of Starbucks coffee. But soldiers on the battlefield don't get their caffeine in a cup of coffee, they use caffeine gum for low doses across many hours.

Whether you're getting your kick from a pill or a cup of coffee, at the end of the day, all the experts say the best answer for sleepiness is the oldest one. As Wesensten puts it:

"The ultimate cure is sleep. Nothing replaces sleep."

Cephalon issued a response to ABC's coverage of this story:

Although caffeine may well provide a needed boost for tired soldiers working overtime, PROVIGIL is not a replacement for sleep and is not intended to treat mere sleep deprivation.

Cephalon has studied PROVIGIL in sleep disorders and other serious medical conditions. Caffeine is not the treatment of choice for any of these more serious disorders.

There is tremendous interest from the medical community to explore the potential of PROVIGIL to help patients. We believe it is important that doctors have a complete understanding of all relevant scientific and medical information so that they can make independent and well-informed decisions on behalf of their patients.

Cephalon supports independent, accredited, continuing medical education programs that make this independent scientific exchange possible, but we do not control their content. In fact, these kinds of programs are not promotional and are permitted by the FDA regulations.