Source: LA Times
Date: 30 March 2009

Sleeping pill use grows as economy keeps people up at night

More Americans are turning to such medications, but they're not without risks,
such as dependence, next-day drowsiness, memory loss and sleep-walking.

By Denise Gellene

Lost jobs and lost careers. Promising businesses in shambles. The college acceptance letter returned to its envelope. This is how President Obama recently described the effect of the tanking economy on ordinary Americans -- and the stresses keeping them up at night.

Sleeplessness is a problem even in good times. One in 10 U.S. adults routinely has trouble getting to sleep or staying asleep, and 3 in 10 experience occasional sleeplessness, federal statistics show.

But these are definitely not good times. More than 1 in 4 -- 27% of Americans -- say anxieties about personal finances, the economy or a job loss kept them awake in the previous month, according to a new poll by the National Sleep Foundation.

If that isn't enough evidence of our increasingly sleep-deprived state, consider this: Since September, audiences of such after-prime-time network shows as "Late Night With Conan O'Brien" have risen. No wonder the collective experience of "sleepless nights" found its way into a presidential address.

As Americans struggle for a good night's rest, they are looking for help from a pill. Prescriptions for sleeping medications topped 56 million in 2008 -- a record, according to the research firm IMS Health, up 54% from 2004.

Those numbers could grow. With an economic turnaround not expected before late 2009, some specialists are predicting another record year for sleeping pill use.

"The first stress symptom people experience is insomnia," said Dr. Gregg D. Jacobs, an insomnia specialist at the University of Massachusetts Medical Center in Worcester. "The size of the sleeping pill market can only go up because of the economy and stress."

But sleep medications are not without risk: next-day drowsiness is the most common among a list of adverse reactions that include dependence and memory loss. As more people take the drugs, the number of people experiencing problems is likely to rise.

For those reasons, some sleep disorder experts say, it may be time we learned to fall asleep on our own.

Effects on the brain

Sleep is a complex physiological process connected to such environmental factors as light and temperature. As night falls and temperatures drop, chemicals in the brain begin to slow the activity of neurons responsible for attention and wakefulness -- and drowsiness sets in.

The two largest classes of sleeping pills enhance the activity of one of these brain chemicals, a neurotransmitter called gamma-aminobutyric acid, or GABA. This neurotransmitter is an imperfect drug target because it performs multiple functions in the brain. Depending on the receptors involved, GABA may promote sleep, decrease anxiety or relax muscles.

Benzodiazepines, an older class of sleep medicines that includes Valium, enhance the broad range of the neurotransmitter's effects -- one reason why benzodiazepines are also used to treat panic attacks. But benzodiazepines lost their popularity as sleep medications in the 1990s after reports of side effects, including drug dependence. England removed the sleeping pill Halcion from the market in 1991 because the medication was associated with depression and memory loss. Although Halcion is still available by prescription in the U.S., it carries a strong warning.

The newer GABA-enhancing pills are known as the Z drugs, so-called because the drugs have the letter "z" in their generic names. Now the most popular prescription sleep medications, the class includes Ambien (zolpidem), Sonata (zaleplon) and Lunesta (eszopiclone). Ambien and Sonata act on the receptor connected to sleep more selectively than other GABA-enhancing drugs The Z drugs carry a smaller risk of dependence than benzodiazepines, a key reason for their popularity. However, the U.S. Drug Enforcement Administration classifies both the benzodiazepines and the Z drugs as scheduled drugs, meaning they all have some risk of dependence.

Another of the newer pills, Rozerem (ramelteon), does not target GABA. It acts on the melatonin receptors in the brain, which are thought to help regulate sleep-wake cycles. It is the only prescription sleeping pill that does not carry a risk of dependence. But doctors tend to think it is not as effective as competing pills.

The perceived safety advantages of the newer drugs over the benzodiazepines -- and aggressive consumer advertising -- have spurred prescription growth.

During 2007 and 2006, drug manufacturers Sanofi-Aventis (the maker of Ambien), Sepracor (maker of Lunesta) and Takada (maker of Rozerem) spent an average of $11.8 million a week to advertise sleep medications, according to the market research firm TNS Media Intelligence. Total prescriptions for sleep medications increased 10% and 15% respectively in those years, according to IMS Health.

Drug makers have since slashed ad spending in response to competition from lower-cost, generic versions of Ambien, 50% in 2008 alone, but the demand for sleep help continues to rise. Those cheaper pills are now driving most of the prescription growth.

The Z drugs reduce the average time it takes to fall asleep by 18 minutes and increase total sleep time by 28 minutes compared with a placebo, according to a National Institutes of Health-funded analysis published in 2005. Some sleep specialists believe the improvement is minimal, but other sleep experts contend the extra sleep makes a difference when accumulated over several nights.

Rozerem was approved in 2005 and not included in the analysis, which was performed by the Agency for Healthcare Research and Quality. The agency noted it used published studies to get its results, so the real-world performance of the drugs may be worse.

Researchers are continuing to search for better insomnia drugs. Swiss drug maker Actelion is conducting a late-stage clinical trial of almorexant, a drug that blocks the activity of a peptide called orexin, which is believed to have a role in wakefulness. In a previous study, 147 subjects taking almorexant fell asleep 18 minutes faster -- no better than what is seen with existing pills. But researchers found no association between almorexant and "next day" effects.

Side effects

Sleep specialists say the pills can be useful to help break a cycle of sleeplessness, or to overcome jet lag. But some doctors are concerned that the heavy prescribing contributes to a false impression that the medications are perfectly safe. In fact, many sleep medications can cause what doctors call a "next-day effect" - a pill-induced drowsiness that spills into the next day.

The Food and Drug Administration two years ago required strong warnings on 13 sleep medications, including Ambien and Lunesta, because rare but bizarre behaviors have been linked to the pills, including cases of sleep-walking, sleep-driving and sleep-eating. Some people have set small fires while trying to cook, their minds in a fog induced by sleeping pills. In the morning, they don't remember the incidents.

Researchers aren't sure why the pills cause odd reactions. One theory has it that the people reporting bizarre behaviors are neither fully asleep nor awake. They have no memory of their nocturnal forays because the pills can have a mild amnesiac effect, blocking the formation of memories.

In January, a 51-year-old Wisconsin electrician was found frozen to death after sleep-walking outdoors in subzero temperatures. Sawyer County coroner Dr. John Ryan said the man had been drinking and the sleep aid Ambien was detected in his bloodstream. Alcohol is known to increase the risk of side effects from sleeping pills, he noted.

"It's my strong suspicion that's what did it," Ryan said.

Drug makers say patient safety is a priority and the labels on their products display information about side effects, including advice to avoid alcohol when taking the pills.

Dr. Michael Thorpy, a sleep specialist at Montefiore Medical Center in New York and a consultant who commented at the request of Ambien maker Sanofi-Aventis, said strange sleep behaviors can occur naturally and it's wrong to blame the pills in all cases. Some complaints of memory loss might be due to sleep, which also has an amnesiac effect; it's one reason why people forget waking in the middle of the night, he said.

But the risk of side effects and dependence isn't the only potential downside to a prescription for sleep medications.

Dr. David Fassler, a clinical professor of psychiatry at the University of Vermont, said some doctors may be prescribing medications instead of treating the underlying cause of sleeplessness, such as depression or anxiety.

"Trouble sleeping can be a sign of multiple disorders," he said in an e-mail. "It can also be a response to stress or conflict at home, in school or at work. People need a careful assessment to figure out that's actually going on. Effective and appropriate treatment really depends on an accurate diagnosis."

Younger pill takers

Of particular concern to some sleep specialists is the age at which people are turning to sleeping pills.

Adults under age 45 are fast replacing the elderly as the prime market for sleeping pills, according to the research firm Thomson Reuters. The most dramatic growth was seen among college-age adults, whose use of prescription sleep aids nearly tripled to 1,524 users per 100,000 in 2006 from 599 users per 100,000 in 1998.

"If they start to depend on sleeping pills in their late teens and early 20s, they are setting themselves up for a pattern of sleeping pill use," said Jacobs of the University of Massachusetts Medical Center's sleep clinic. Like many sleep specialists, he recommends patients first try behavioral therapy to help them overcome the negative thoughts keeping them awake. Jacobs also has a company that markets a drug-free insomnia treatment program.

Many college students probably use the pills to manage sleep habits that are often out of sync with class schedules.

"Going to bed at 3 in the morning and sleeping until noon on weekends is not unreasonable at that age," said researcher James K. Walsh, a spokesman for the National Sleep Foundation, who manages the sleep clinic at St. Luke's Hospital in St. Louis. Students with an early-morning class might use medications to help them get to bed earlier the night before, he said.

But college students are not immune to the economic stresses that are taking a toll on older adults. Scripps College sophomore Jane Logenbaugh Sherwood said she takes a pill to lull her to sleep when worries about her career prospects keep her awake. "I'm in college so I can go out into the world and find a job," she said. "I'm stressed out about the rest of my life."

Go To Good Drug Guide
The Good Drug Guide
mental health in the third millennium

'Sleep driving'
Ambien drivers
Drug Companies
Just For Chemists
Sleeping Pill Hype
A Pill For Every Ill?
Relaxation Therapy?
Hardwired Happiness?
Health, Wealth and Happiness
The Futile Pusuit of Happiness?
Big Pharma and Madison Avenue
Happiness: the Recipe for Success?
Zaleplon (Sonata): prescribing information (PDF)