As the economy sinks, insomnia increases and America searches for a good night’s sleep

Chris Dalto is an affable fellow, a happily married father of two and a lawyer-turned-financial planner. Normally, he sleeps like a baby.

But last fall, when Lehman Brothers tanked and the stock market fell apart, Dalto began waking up at 3 a.m. “You take on the clients’ stress, which made it impossible to get back to sleep,” he says. He would spend the wee hours fretting and checking on the already-open Asian markets. Then, come 6 a.m., it was off to work again.

Even in normal times, an estimated 40 million Americans have trouble sleeping, according to the National Institutes of Health. Sleep troubles are more prevalent now because of the economy, some psychologists and psychiatrists say. A third of all Americans are losing sleep worrying about money, according to a poll done last fall and released last week by the National Sleep Foundation, a nonprofit research organization.

Uncertainty – and especially the fear of job loss – are precisely the kind of worries that makes for sleepless nights, says Carol Kauffman a McLean Hospital psychologist. “A hypothetical emergency is often harder to deal with, and can cause more insomnia, than an actual one,” she says; the worst place to be is “in limbo, waiting for the other shoe to drop, and there’s a millipede up there raining shoes.”

So what are the stressed out masses supposed to do to get some sleep? Sleeping pills, once frowned upon by doctors, are now increasingly prescribed if non-drug treatments don’t help.

Stress management, meditation, exercise, nighttime habits more conducive to sleep, and, of course, talk therapy, should be tried first, says psychologist Cynthia Dorsey, director of behavioral sleep medicine at the Sleep Health Centers, a for-profit network of sleep disorder clinics

But for those who need more – and many do; doctors wrote more than 56 million prescriptions in 2008, according to IMS Health, a healthcare information company – sleeping pills are an acceptable alternative.

What changed? For one thing, it’s clearer that extended use of some sleeping pills can be safe. Until relatively recently, doctors advised patients to take sleeping pills for no more than two weeks, partly out of the “concern that nightly use of sleeping pills would lead to ‘tolerance’ – the need to increase doses to get the desired effect,” says Dr. John Winkelman, medical director of the Sleep Health Center affiliated with Brigham and Women’s Hospital.

But then a study, funded by the makers of Lunesta, showed that the sleeping pill was just as effective at six months as at day one, suggesting that people did not become tolerant, and thus would not be inclined to boost their dosage. The US Food and Drug Administration approved Lunesta in 2004 for long-term use. Ambien CR and Rozerem are also now approved for long-term use, although there is less data on whether patients develop tolerance to these drugs.

The other change was in attitude. There is now “more acceptance of the fact that sleep disorders are very disturbing to the individual who has them,” says Winkelman. Thus, the medical community sees more value in correcting the problem, which can harm both mental and physical health, says Winkelman, a consultant to several companies that make sleeping pills.

A new study from Carnegie Mellon University illustrates the health risk of insomnia. It links poor sleep “efficiency” (the percentage of time in bed actually asleep) and shorter duration of sleep to a higher risk of coming down with a cold. People who slept fewer than 7 hours were 3 times more likely to get sick than people, equally exposed to the cold virus, who slept 8 hours or more.

Still, many people view sleeping pills with suspicion. A common worry is that stopping sleeping pills use will cause withdrawal symptoms, including worse sleep. This can happen, but is often preventable if a person tapers off a drug gradually, rather than stopping abruptly.

People also worry that sleeping pills will make them do strange things in the middle of the night. Bizarre side effects are rare, but people on Ambien have reported cooking, eating, talking on the phone, even having sex – with no memory of such things the next day.

Still others fear that sleeping pills will make them groggy the next day, which can occur if the dose is too high or taken too late into the night.

On the plus side, having a sleeping pill handy may help – even if you don’t take it, says Kauffman, the McLean Hospital psychologist. Much of the problem in insomnia is not worrying about a real fear – such as losing a job – but is the “secondary anxiety” about losing sleep. Just knowing you can take a sleeping pill if you really need it can allay this secondary fear.

As for Chris Dalto – the sleep-deprived accountant worried about his clients, me among them – he never turned to sleeping pills. Nor did he seek therapy or change his sleep habits.

What he did do was to figure out what he could, and what he could not, control. The larger economy, clearly, was out of his hands. So he focused intently on managing his clients’ portfolios – more bonds, fewer stocks – to reduce the inevitable losses of a bad market. It worked.

“Gradually,” he says, “I started to string together two, three, four normal nights’ sleep. Now, I’m sleeping like a baby.”

In July, researchers led by Robert Stickgold, an assistant professor of psychiatry at Harvard Medical School, reported that a full eight hours’ sleep after learning a motor task boosts performance by 20 percent the next day.

Even a one-hour nap can improve scores on a simple visual task, others reported in May.

Perhaps even more compelling, Belgian researchers, using a brain imaging technique called PET scanning, reported two years ago that when people perform reaction time tests, certain areas of the brain become activated. These same areas “light up” again when the people experience REM (rapid eye movement, or dreaming) sleep, as if their brains were actively rehearsing what had been learned.

Over the years, researchers have found tantalizing evidence that sleep may enhance learning and memory. Some have showed that infants who learn a head-turning response have more REM sleep than those who failed to learn the response. Others, that people given 90 minutes of training in Morse code showed an increase in REM sleep. Still others, that people who did well learning French increased their REM sleep, while poorer learners did not – and that the sooner the good learners started dreaming in French, the higher their scores on French tests. (The poor learners never did dream in French.)

Case clinched, right? Sleep, particularly REM sleep, seems to boost memory, just as many scientists – and mothers – have been saying for years.

Would that it were that simple.

“Everybody knows sleep has something to do with memory – except people who study sleep and memory,” says Stickgold.

Brain researchers would like nothing better than to come up with a neat paradigm of how sleep affects memory.

It would go something like this: Learning creates chemical changes in specific cells in specific parts of the brain. When a person sleeps shortly after learning, and perhaps especially when she dreams that night, the brain takes these fragile, new memories, shuffles them around into a more permanent home, or at least a more permanent set of neural circuits. And  – Presto! – the memories would be firmly “consolidated” by morning.

There are two main reasons why confidence in such a nice, simple scenario is impossible, as least for now: At the electrical and biochemical level, sleep itself is devilishly complicated. Memory, arguably, is even more so.

A night’s sleep typically goes from light (Stages 1 and 2 sleep to deeper stages 3 and 4, known as slow wave sleep). All of these are called non-REM sleep. Non-REM sleep alternates with REM, or dreaming sleep, with REM periods getting longer and non-REM periods getting shorter as the night progresses.

One reason for thinking that REM sleep may be involved in memory consolidation is that the brain behaves differently during slow wave and REM sleep. During deep sleep, the brain is relatively inactive, and electrical patterns are slow and synchronized; during REM, it is extremely active, and desynchronized..

Brain chemistry changes, too. During REM, some neurotransmitters, or chemical  messengers, especially norepinephrine and serotonin  are virtually shut off while others, notably acetylcholine, believed to be a memory booster, go up.

Memory is even trickier. Scientists divide memory into two basic categories, declarative and procedural. That’s the difference between “knowing that” and “knowing how,” notes psychologist Carlyle Smith of Trent University in Peterborough, Ontario.

Declarative memory involves learning facts – knowing that the French Revolution began in 1789. Knowing how is knowing, often without knowing that you know, how to turn the key in the ignition to start the car. Declarative memory is “explicit,” and usually consciously acquired; procedural memory is “implicit,” often unconsciously acquired.

The trouble is, although declarative memory is what most of us mean when we talk about memory, most of what researchers study is procedural memory – the less juicy stuff like learning finger-tapping exercises.

For declarative memory, there is little evidence that sleep, even REM sleep, has any effect, says Smith of Trent University.

“No matter what I have done – I have deprived people of sleep, I have deprived people of REM sleep, I have deprived them of non-REM sleep –  and I have never seen any difference [in declarative memory] between people who got a good night’s sleep and those who didn’t,” says Smith of Trent University.

Dr. Jerome Siegel, professor of psychiatry at the David Geffen School of Medicine at UCLA and chief of neurobiology research at the VA Greater Los Angeles Healthcare System Sepulveda, agrees, noting in a paper in Science in 2001 that the evidence for such a link is “weak and contradictory.”

And a link between sleep and procedural memory? That’s stronger.

In 1991, researchers studied people learning trampolining, which required  new, complex motor skills. The best learners showed increases in REM sleep (and no differences in non-REM sleep); those in control groups who expended the same number of calories but didn’t learn new motor skills showed no difference in either REM or non-REM sleep.

REM and some non-REM sleep may help with a different type of procedural task – visual learning. In a paper published in 2000, Stickgold and his team found that improvement on a visual task increased with stage 3 and 4 slow wave sleep in the first part of the night, and with REM later in the night. The real payoff, he finds, is with REM sleep in the final two hours of an 8-hour sleep.

In a sequel to Stickgold’s studies, doctoral student Sara Mednick wanted “to see if napping had the same effect as a night’s sleep.” To find out, she used the same visual memory task and tested volunteers on it at four points in the same day. They all got worse as the day went on.

So she let some volunteers take a half-hour nap between the second and third session and others, an hour nap. The half-hour nappers were able to stop the decline in performance. The hour-nappers not only stopped the decline but performed as well as they had first thing in the morning. The long nappers, by the way, exhibited both slow wave sleep and some REM sleep as well.

The bottom line in all this? There is still much that remains a mystery. Someday, maybe they’ll figure it all out. For now, “the simple answer is that we don’t know,” says Stickgold of  Harvard. “You  push this system just a bit and you stumble onto complete ignorance.

Mary Rourke, a 55-year old teacher from Salem, N.H., used to nod off all the time as a child, but people just shrugged and said, “Oh, she must be very tired,” she recalls.

Then, as an adult, she began having attacks in which her muscles would lose tone and she’d fall- every time she laughed or felt any strong emotion. “I was constantly falling,” she says. “If you told me a joke, I’d flip. I couldn’t be around people.”

In Massachusetts, a 49-year old nurse from Norwood who asked that her name not be published also used to crash helplessly to the floor whenever she laughed or got angry, a fact her children quickly learned to exploit. “I couldn’t yell at my kids when they were younger because if I got too mad, I couldn’t stand up,” she says.

Things were even worse for Bob Cloud, a 58-year old lawyer from Cincinnati, Ohio. It was bad enough falling asleep talking to judges, he says, but one day he went limp while swimming and had to be rescued.

At least, he says, that provided a “great educational opportunity” to tell stunned onlookers what was really wrong: A brain disorder called narcolepsy, characterized by extreme daytime sleepiness and caused by low levels of a brain chemical called hypocretin. In many cases, low hypocretin levels also cause cataplexy, sudden loss of muscle tone due to the intrusion of dreaming (REM) sleep in the waking state.

Though the true numbers are probably higher because many people go undiagnosed for years, narcolepsy is believed to affect at least 140,000 Americans and 3 million people worldwide – more than are affected by some better-known diseases like cystic fibrosis and muscular dystrophy.

Yet stunning brain research in the last three years, along with the hoped-for approval this spring of a controversial new cataplexy drug called Xyrem – known on the street as the date-rape drug, GHB – are catapulting this once-hidden condition into the limelight.

With luck, the research on narcolepsy and cataplexy – essentially, disruptions in the body’s normal sleep-wake cycles – may lead to novel treatments for insomnia and depression as well.

And there’s another reason for the limelight: A remarkable degree of cooperation on the Xyrem/GHB issue by Congress, the US Food and Drug Administration and law enforcement officials that shows that it is possible to treat the same substance as both legitimately needed by desperate patients and subject to criminal penalties when abused.  

In the illicit street form, GHB (gamma hydroxybutyrate), has been blamed for dozens of deaths and countless sexual assaults. The colorless, odorless liquid can be slipped into someone’s drink. It is so simple to concoct at home that “a 9-year old can make it,” says Bob Gagne, a public affairs consultant for Orphan Medical. “I stumbled upon a crockpot recipe” for one form of the drug on the Internet, he notes. Some people also drink industrial chemicals such as GBL (gamma butyrolactone) for their GHB-like effects.

Because GHB is also believed to promote the body’s production of growth hormone, some body builders take illicit forms of the drug to increase muscle bulk.

All in all, a dicey substance for a pharmaceutical company to pursue. But in the early 1990s, Congress, concerned that big, profit-minded pharmaceutical companies were showing little interest in making drugs for so-called “orphan diseases” passed legislation encouraging companies to make such drugs. (Orphan diseases are those that affect 200,000 or fewer people – a small market.)

So Orphan Medical, Inc. of Minnetonka, Minn. began researching Xyrem. It’s still not quite clear how it works, though it may act through a brain chemical called dopamine. It is clear that Xyrem seems to reduce cataplexy attacks, and restore restful sleep for narcoleptics, who, despite overpowering sleepiness during the day, wake up frequently at night. Indeed, Mary Rourke, Bob Cloud and the Massachusetts nurse have all taken Xyrem under research protocols – and all say it has significantly improved their lives.

Though GHB was classified in March, 2000 as a Schedule I (most restricted) controlled substance, its potential as the prescription drug Xyrem for cataplexy (but not narcolepsy) meant that it was recommended as “approvable” last summer by an advisory committee to the FDA. The agency usually follows the recommendations of such committees. To make sure it does not get into the wrong hands, Orphan Medical is setting up a special distribution system so that all prescriptions will be filled by one central pharmacy.

To be sure, there are skeptics. Dr. John Winkelman, medical director of the sleep health center at Boston’s Brigham and Women’s Hospital, says, “I think the jury is still out on Xyrem because of concerns about potential abuse.”

But other doctors are as positive as patients. “Many people are transformed by it,” says Dr. Emmanuel Mignot, a professor of psychiatry and behavioral science at Stanford University Medical School.

Some people with cataplexy have as many as 15 to 20 falls a day, says Dr. Michael Biber, medical director of Neurocare, Inc. in Newton. “People are unbelievably disabled.” Yet on Xyrem, which he has tried on three patients so far,  people can become “almost completely free of symptoms.”

But just as important as the advent of Xyrem is the remarkable confluence of brain research on the triggers for narcolepsy, notes Dr. Jerome Siegel, professor of psychiatry and behavioral sciences at UCLA and chief of neurobiology research at the Sepulveda VA Medical Center in Los Angeles.

“What is extraordinary is that everything has been done in the last three years,” adds Mignot, the Stanford narcolepsy researcher.

In 1998, while looking for brain chemicals believed to control appetite,  two independent teams – one in San Diego, one in Dallas – discovered a neurotransmitter in a part of the brain called the hypothalamus. It quickly acquired two names – hypocretin and orexin – and it is made by only by a few cells in the hypothalamus. Significantly, hypocretin-producing cells in the hypothalamus connect to other parts of the brain and brainstem that control arousal and muscle tone.

Curious, the Texas team went on to see what would happen if they deleted, or “knocked out,” the gene for hypocretin in mice. To their surprise, mice with the missing hypocretin gene seemed to wander around normally, then suddenly drop in their tracks, just like narcoleptics with cataplexy. Also like narcoleptics, the knock-out mice began their night’s sleep abnormally – with REM, instead of non-REM sleep.

Meanwhile, unaware of this work, Mignot’s team at Stanford University was trying to figure out the genetic causes of narcolepsy in dogs.

Within weeks of each other in 1999, the Stanford and Texas teams reported work that dovetailed perfectly. The Stanford team found that dogs with narcolepsy have a mutation in the gene for the hypocretin receptor. The Texas team found that mice missing the gene for hypocretin itself showed behavior remarkably similar to narcolepsy.

“It was quite amazing and convincing,” says Siegel of UCLA. The cause of narcolepsy suddenly seemed obvious: lack of hypocretin, or its receptor.

In early January, 2000, Mignot’s team reported that human narcolepsy patients had low levels of hypocretin in the fluid that bathes the brain and spinal cord. Another key clue.

But an important step remained. So both Mignot’s group at Stanford and Siegel’s at UCLA obtained brain tissue from narcoleptics who had died and they, too, published their findings in the fall of 2000 within weeks of each other. Both teams found that almost all of the hypocretin-producing cells in the hypothalamus of people with narcolepsy were missing.

Moreover, Siegel’s group found that there was scar tissue where hypocretin-producing cells should have been, a clue that (unlike dogs, in whom narcolepsy is often hereditary) people who develop narcolepsy are born normal and subsequently suffer damage to these cells, most likely because of a misguided attack on these cells by the immune system.

It’s still not clear why many people with narcolepsy also have cataplexy while others don’t. But a number of companies are now scrambling to make narcolepsy drugs that mimic hypocretin to restore normal levels.

In the meantime, prescription stimulants such as Provigil, Ritalin and Dexedrine often help people with narcolepsy stay awake during the day. And anti-depressants such as Tofranil and Prozac can partially control cataplexy. If Xyrem is approved, it may prove a valuable addition to the medical arsenal.

Longterm sufferers like Mary Rourke are crossing their fingers. Because she participated in a research study on Xyrem, Rouke has been allowed to take the drug, even though her participation in the study is over. She says it has changed her life.

Recently, she was standing in her classroom when a student snuck up behind her and said, “Boo!”

“If I hadn’t been taking this drug,” she says, “I would have gone right down.”