Scientists Try to Unravel the Riddle of Too Much Sleep

Getting too little sleep is bad for your health. But getting too much—as wonderful as it may sound to some—can be problematic too.

Getting too little sleep is bad for your health, but getting too much can be problematic. WSJ's Melinda Beck and Emory University sleep researcher Dr. David Rye have details on Lunch Break. Photo: Courtesy of Anna Sumner.

The powerful need to nap during the day can be a warning sign of many health issues, from diabetes to depression, low thyroid or obstructive sleep apnea. When doctors rule out such explanations, it is called "primary hypersomnia," an umbrella term for several conditions that make sufferers crave sleep, despite getting 70 hours or more per week. One of the best known is narcolepsy, a neurological disorder that causes sudden, irresistible bouts of daytime dozing. Other forms aren't well understood.

Recently, researchers at Emory University in Atlanta have begun to unravel the mystery of this often-debilitating condition. They've found that some sufferers have a substance in their cerebrospinal fluid that acts like a natural sleeping pill. They think as many as 1 in 800 Americans may have the substance and that it may be a factor in other conditions that involve excessive drowsiness.

Many people with hypersomnia go undiagnosed, experts say. The excessive sleep urges often begin in late adolescence, and are easy to confuse with typical teenage sleep issues.

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Raymond McCrea Jones for The Wall Street Journal

After Anna Sumner, an Atlanta attorney, suffered sleeping binges of more than 50 hours at a stretch, doctors discovered the culprit: a substance in her spinal fluid.

"It tends to hit people in their young, formative years when they are trying to get started in a profession or having a family," says Dr. David Rye, a professor of neurology at Emory and lead author of a paper on the discovery, published last month in the journal Science Translational Medicine. "A lot of them get dismissed as lazy, or as drug seekers."

Researchers now know that this condition "is something real," says Andrew Jenkins, an associate professor of neuroscience, molecular and system pharmacology at Emory. "We know why you're sleepy—your brain is sedating itself," he says.

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The Emory team discovered the mysterious sleep agent, or "somnogen," when Anna Sumner, a young Atlanta attorney, sought help at the sleep clinic in 2005. After napping prodigiously through college and law school (she says roommates at Princeton made up stories to cover for her), her sleep cravings began intensifying in her 20s. At one point, she says, "I'd go to bed one night and wake up two days later."

When the spells' frequency increased from once every two months to once a week, she says, "I had to take a leave from work."

After standard treatment with stimulants stopped working, the Emory doctors discovered that a substance in Ms. Sumner's spinal fluid was supercharging GABA, a natural sleep-inducing brain chemical. The effect was like being under constant twilight sedation. "I don't know how she was able to function," says Dr. Jenkins, whose team decided to try treating her with a drug called flumazenil, used in emergency rooms to counteract overdoses of sedatives. After several days in the hospital on an IV drip, she suddenly opened her eyes and said, "I feel alive!"

She has been taking it in a specially made lozenge form since then, and is feeling happily alert—and just learned she will be made a partner next year.

The Emory researchers think this same sleep-inducing substance in spinal fluid may play a role in other conditions that involve excessive drowsiness. They still haven't identified the exact chemical. But they can test for it in other patients by watching how their spinal fluid acts on GABA in a laboratory setting.

So far, they have found the somnogen in the spinal fluid of 32 sleep-clinic patients. They tested flumazenil on seven of them and found that it restored alertness in all of them to differing degrees. "I think what we've discovered is the biology. And the question is, what syndromes is it relevant to?" says Dr. Rye.

One may be narcolepsy, those irresistible sleep attacks that can hit multiple times a day. Sufferers go into REM sleep immediately when they nap, and tend to wake up refreshed—at least temporarily. Some also have cataplexy, which involves sudden loss of muscle control.

A rarer form of hypersomnia, called Kleine-Levin syndrome, occurs almost exclusively in teenage boys. Sufferers sleep for several days at a time, and when they wake up, they are irritable, ravenously hungry and sometimes hypersexual.

Dr. Rye and his colleagues have found the sleep-inducing spinal fluid in patients previously diagnosed with both conditions. They are also working with the Centers for Disease Control and Prevention and hope to test for it in blood samples from people with chronic fatigue syndrome. They are also tracking how it travels in families. One-third of the 32 patients in the study have relatives with excessive sleepiness to varying degrees.

Since the study appeared, they have been fielding calls from other patients and sleep clinics—95 last week alone. "There is a huge unmet need of people who identify with Anna," says Dr. Rye, referring to Ms. Sumner.

Traditional treatments for hypersomnia, including stimulants such as Provigil, have proven to be effective sometimes with conditions like narcolepsy. But side effects can include a feeling of being "revved up."

Flumazenil, the drug used to treat Ms. Sumner, is proving hard to come by. Since it went off patent in 2008, the amount of the generic version produced annually for all of North America—enough to counteract 10,000 sedative overdoses—would supply only a handful of patients like Ms. Sumner, Emory researchers say.

But they are investigating other drugs that may have the same effect. Past research shows that one class of antibiotics may have a similar action at GABA receptors.

Of course, the vast majority of people with excessive daytime sleepiness don't have hypersomnia—most just don't get enough sleep at night. Shelby Harris, director of the Behavioral Sleep Medicine Program at Montefiore Medical Center in Bronx, N.Y., recommends that patients get at least eight hours of sleep nightly for two weeks before exploring other causes. "Make sleep a priority, and if that fixes it, great," she says. "If not, mention it to your primary-care doctor."

Indeed, many underlying health issues can also make people drowsy, including thyroid conditions, hormonal changes, vitamin deficiencies and infections; some can be ruled in or out with blood tests. Sleepiness is also a side effect of many medications, alcohol use or psychiatric conditions.

So many factors can affect alertness and energy levels, and they vary so much over the life span, that many people with sleep disorders never realize they have one. They often mask it with coffee or view drowsiness as just a fact of life.

Dr. Harris also recommends that people who think they are excessively sleepy keep track of when the drowsiness occurs. Nodding off after dinner or wanting to sleep till noon could indicate circadian rhythm disorders. "Afternoon slump"—the urge to nap at your desk after lunch—is a normal dip in the body's 24-hour clock.

"I tell patients to go out and take a walk when that happens," says Dr. Harris. "Being exposed to light can be more alerting than a cup of coffee."

Write to Melinda Beck at melinda.beck@wsj.com