'Wake-Up Pills' Try to Replace Sleep

Medically Reviewed by Gary D. Vogin, MD
From the WebMD Archives

Jan. 16, 2002 -- We're a sleep-deprived nation, fighting stress and insomnia, and squeezing as many hours as possible out of every day.

But could a drug ever replace a good cup of coffee to keep us alert after a bad night's sleep? What's the buzz about the "wake-up" pills that have been in the news lately -- a compound called NADH (sold as ENADA and ENADAlert), and modafinil (a drug sold as Provigil)?

WebMD spoke with sleep experts to find out what you need to know about these pills. However, they caution that long-term pill popping isn't the answer to our chronic sleep problems.

"There is real hard evidence that sleep deprivation is not good for performance, health, or immunity," says Joyce A. Walsleben, MD, director of the Sleep Disorder Center at the New York University School of Medicine in Stony Brook. "A drug cannot replace sleep."

In fact, even cutting sleep for one week's time can affect the body. Studies at the University of Chicago show that when college-aged men were allowed to sleep for just four hours a night for one week, their insulin reactions were that of "old diabetics," she tells WebMD.

"To flog the brain to stay awake just doesn't make sense," says Richard Castriotta, MD, a sleep disorders expert and associate professor of internal medicine at the University of Texas Medical School at Houston. "We have a physiologic need for sleep. I liken it to the pain receptors that warn us to take our hand away from the flame. There are reasons why we evolved to need sleep."

But What About ENADA?

Sold as nutritional supplements in health food stores, ENADA and ENADAlert are pill forms of NADH, a co-enzyme that is present in all living cells and necessary for cell development and energy production. It stimulates dopamine, noradrenaline, and serotonin receptors, thereby improving mental clarity, alertness, and concentration, says the web site for Menuco Corp., the manufacturer.

NADH is not a hormone, not a steroid, "not a stimulant," says Margaret Moline, PhD, director of the sleep-wake disorders center of New York Presbyterian-Weill Medical College of Cornell University.

Small studies have shown that the compound helps people cope with chronic fatigue syndrome -- "it helps people feel more alert," she says. It could also help with jet lag.

Those all-nighters that people can't avoid -- that's what Moline looked at in her study. A group of 25 people, all between 40 and 59 years old, were kept up all night under supervision, then were randomly given either ENADAlert or placebo right before breakfast the next day. Researchers measured their sleepiness and gave them cognitive tests to perform.

Despite feeling sleepy, those taking ENADAlert still performed better than those who took the placebo. "They performed better in terms of performance efficiency -- they had higher numbers of correct answers per minute," Moline says. The effects of taking the supplement long term to compensate for chronic sleep deprivation have not yet been studied, she says.

Is it addictive? ENADA developer Georg D. Birkmayer, MD, PhD, reports that more than 1 million Americans have been taking the supplement on a daily basis for a number of years. "I have not heard of any effects related to addiction," he tells WebMD.

The Buzz on Modafinil


Available only by prescription, modafinil is only approved to treat narcolepsy, a disorder in which sleepiness is uncontrollable even during daytime.


"It's a good wake promoter," Walsleben tells WebMD. "It takes two hours to get going but has a half-life of 10 hours, so it works all day long. By evening, there are no after-effects that affect overnight sleep. It allows the sleep rhythm to be normal."


Extensive studies have shown that modafinil is not addictive because it works on different receptor systems than do amphetamines, she says. "There are very few side effects, if any, and there's little concern about abuse. People don't develop a tolerance to it. It's a really neat drug."


Military fighter pilots can stay alert for several days at a time on modafinil -- and perform mental tasks with "near normalcy," she says. The drug may also help people with depression and related psychiatric disorders, "people who get the doldrums and just can't get going."


Night-shift workers also might benefit from modafinil. At the University of Pennsylvania, a study involving 16 participants tested the theory. The group first had to stay awake for 28 hours. Then they began a four-day period of sleeping from 11 a.m. to 7 p.m. and being awake at night. Half were randomly given modafinil during their awake hours, half got a placebo.


Those taking the drug were able to stay alert and performed well on tests, while the placebo group had a significantly higher error rate, she reports.


Modafinil is also being tested as a complementary treatment for sleep apnea (a breathing disorder that causes chronically interrupted sleep) and as an option to treat syndromes like multiple sclerosis, where fatigue is a big problem, Walsleben tells WebMD.


The only caution: modafinil does seem to have problems interacting with other drugs such as anti-seizure and heart medications. "It also lessens the effectiveness of birth control pills," she says. "People need to discuss this with their doctors."


Words of Caution

"It's clear [modafinil] can make people more alert," says Thomas Scammel, MD, a sleep disorder specialist and assistant professor of neurology at Beth Israel Deaconess Hospital in Boston.

"The danger," Scammel tells WebMD: "It's easy to imagine people using it casually. One of our real concerns is that people will start taking it to make up for the fact that they're not getting enough sleep."

The average person needs eight hours of sleep, yet the average American gets about seven hours. "Many, many people get far less than that," says Scammel. "Sleep serves a very important purpose. Sleep deprivation causes serious changes in endocrine and immune systems. To patch up that sleep loss is to do our bodies a real injustice."

"If people are having sleep problems, they need to get to the underlying problem," says Walsleben. "The drug can only serve people well if their underlying condition is first treated."