February 7, 2006
Record Sales of Sleeping Pills Are Causing Worries
By STEPHANIE SAUL
Americans are taking sleeping pills like never before, fueled by frenetic
workdays that do not go gently into a great night's sleep, and lulled by a
surge of consumer advertising that promises safe slumber with minimal side
About 42 million sleeping pill prescriptions were filled last year,
according to the research company IMS Health, up nearly 60 percent since
But some experts worry that the drugs are being oversubscribed without
enough regard to known, if rare, side effects or the implications of
long-term use. And they fear doctors may be ignoring other conditions, like
depression, that might be the cause of sleeplessness.
Although the newer drugs are not believed to carry the same risk of
dependence as older ones like barbiturates, some researchers have reported
what is called the "next day" effect, a continued sleepiness hours after
awakening from a drug-induced slumber.
Ten percent of Americans report that they regularly struggle to fall asleep
or to stay asleep throughout the night. And more and more are turning to a
new generation of sleep aids like Ambien, the best seller, and its
competitor, Lunesta. Experts acknowledge that insomnia has become a cultural
benchmark — a side effect of an overworked, overwrought society.
"Clearly, there's a significant increase in people who report insomnia and,
from my perspective, that is the result of our modern-day lifestyle," said
Dr. Gregg D. Jacobs, a psychologist and assistant professor of psychiatry at
Harvard. Or at least that is an impression that drug makers are clearly
trying to capitalize on, he said.
And that concerns him and some other researchers who warn that despite their
advertised safety, the new generation of sleep aids can sometimes cause
strange side effects.
The reported problems include sleepwalking and short-term amnesia. Steven
Wells, a lawyer in Buffalo, said he started using Ambien last year because
his racing mind kept him awake at night. But he quit after only one month,
concerned about several episodes in which he woke up to find he had messily
raided the refrigerator and, finally, an incident in which he tore a towel
rack out of a wall.
"The weird thing was that I had no recollection of it the next day," said
Mr. Wells, who added that he found the episodes frightening.
Ambien's maker, Sanofi-Aventis, said the drug had been used for 12 billion
nights of patient therapy. "When Ambien is taken as prescribed, it's a safe
and effective treatment," said Emmy Tsui, a company spokeswoman.
A Food and Drug Administration spokeswoman, Susan Cruzan, said she was not
aware of an unusual number of complaints with the drugs.
Drug makers spent $298 million in the first 11 months of 2005 to convince
consumers that the sleep aids are safe and effective. That was more than
four times such ad spending in all of 2004.
In the last year, much of the advertising surge has been a result of
competition from Lunesta, which the drug maker Sepracor introduced last
April to compete with Ambien. Through November, Sepracor led the sleeping
pill advertising field, spending more than $185 million, according to
figures from TNS Media Intelligence, which did not have final figures for
In response, Sanofi-Aventis, marketing both Ambien and its
controlled-release version, Ambien CR, spent $107 million from last January
through November, according to TNS. That was nearly double its ad spending
on Ambien in 2004.
Even the most infrequent television viewers would have trouble missing the
Lunesta ads, which feature a luna moth fluttering around the bed of a
peaceful sleeper. Dr. Jacobs said that in one hour of prime-time television
recently, he saw three ads for sleeping pills: two for Lunesta and another
"You've got the patient population being bombarded with advertising on TV,"
Dr. Jacobs said. "You've got increased advertising to physicians. You've got
a formula for sales going up dramatically."
One financial analyst, Jon LeCroy of Natexis Bleichroeder, said Lunesta's ad
campaign last fall was tied to the new season of "Desperate Housewives,"
whose audience is about 55 percent female. Studies have shown that women
have insomnia more frequently than men.
Last week, Sepracor's stock jumped $8.53 in one day, after Sepracor reported
a profit and remarkably strong use of Lunesta in its first year on the
market, with sales of $329 million. More than 213,000 doctors wrote 3.3
million prescriptions for it last year, the company says.
Sepracor announced the addition of 450 people to its current sales force of
1,500 to increase marketing of the drug to physicians.
Sanofi-Aventis, with a sales force of 3,000, is working to shift patients
from Ambien, which loses its patent protection in October, to the newer
version, Ambien CR. The newer pill has a quickly dissolving outer layer
meant to immediately induce sleep, with a slower-dissolving inner layer to
Another drug in the class is Sonata, marketed by King Pharmaceuticals.
Because it is short acting, Sonata is recommended for people who have
trouble falling asleep but no trouble staying asleep.
Drugs in the class are frequently referred to as "Z" drugs, a play on both
their effect and the Z's in their generic names, like zolpidem (Ambien) and
eszopiclone (Lunesta). All aim at a brain neurotransmitter that is believed
to reduce neural activity.
Another new entrant to the market, Rozerem, by the Japanese company Takeda
Pharmaceuticals, has been available in drugstores since September but has
not yet been heavily advertised. The drug works by a different mechanism
from the others, acting on the brain's melatonin receptors, which are
believed to play a role in sleep-wake cycles.
Mr. LeCroy, the analyst, who is also a medical doctor, predicts the
advertising will intensify if Neurocrine Biosciences and its partner Pfizer
are permitted to introduce their new sleeping pill, Indiplon; an F.D.A.
decision on that is expected in May.
"That's going to make the competition get more cutthroat," Mr. LeCroy said,
predicting that the market for branded sleeping pills, currently about $2
billion a year, could grow to $3.8 billion, even with Ambien set to go
generic. "This is only going to get crazier."
The Carlat Psychiatry Report, a newsletter by Dr. Daniel J. Carlat, a
psychiatrist in Newburyport, Mass., reviewed the Z drugs recently and
concluded that their differences were merely subtle. But Dr. Carlat warned
that Lunesta, because it was longer acting, was more likely to cause
next-day sleepiness problems "in comparison with some of its cousins."
Dr. Carlat cited a 1998 study in Britain, published in The Lancet, which
found that taking zopiclone, the compound known as the "mother" of Lunesta
and marketed in Europe, was linked to an increased risk of automobile
But Sepracor's chief financial officer, David P. Southwell, said that
Lunesta, while a chemical variant of zopiclone, was a totally different
drug. He referred a reporter to the F.D.A.-approved label, which lists
clinical studies of next-day effects showing there was no consistent pattern
of impaired mental functioning the day after Lunesta use.
The possible role of Ambien was investigated in connection with
well-chronicled transportation disasters in 2003 — the crash of the Staten
Island Ferry, which killed 11 passengers, and an accident involving a Texas
church bus in Tallulah, La., which killed 8 passengers. The assistant
captain who was piloting the ferry, like the bus driver, had a prescription
for Ambien, but there was no evidence either had taken it before the
Dr. David G. Fassler, a clinical professor of psychiatry at the University
of Vermont College of Medicine, said he was concerned that the heavy
marketing and prescribing of the sleep medications would lead to use in
patients who have underlying conditions that are left untreated.
"I'm concerned that difficulty sleeping can be a sign of multiple disorders,
including problems with anxiety and depression," he said, expressing worry
that patients who are not thoroughly evaluated might be treated for their
insomnia while other problems, like anxiety or decreased appetite, are not
In clinical trials, the most common side effect of the drugs, however, is
that people wake up feeling sleepy the next day.
Dr. Daniel J. Buysse, a University of Pittsburgh psychiatrist who has
consulted for the industry on sleeping pills, said they were a rare example
of drugs in which the desired effect and the major side effect were the same
thing. "One occurs when you want it, and the other occurs when you don't,"
Another problem associated with using sleeping pills is a condition commonly
called traveler's amnesia, in reference to the frequent use by people who
travel across time zones. Such amnesia can occur when people return to
daytime activities too quickly after taking the drugs.
The labels carry warnings that the drugs should be used only when people can
devote a full night to sleeping. In some cases, however, users have reported
that they awakened during the middle of the night in sleepwalking states,
but — like Mr. Wells, the lawyer in Buffalo — had no recollection of their
The amnesiac effects of Ambien were a factor in the acquittal last week of a
United States Air Force linguist who had been charged with raping a
colleague while the two were stationed in Qatar. The woman who said she was
the victim, also a linguist, testified that she was not sure whether the
incident was a dream because she had taken Ambien, according to the Stars
and Stripes report on the military trial, which occurred in Britain.
Dr. Buysse said such bouts of nocturnal uncertainty occur occasionally with
various Z drugs.
"There have been some case reports of people who have been sleepwalking only
when taking the drug," Dr. Buysse said. "I think it's rare, and it's the
kind of thing that no one is going to have a very good estimate of. But if
it happens to you, who cares if you're the only person of many?"