F.D.A. Warns of Sleeping Pills’ Strange Effects
By STEPHANIE SAUL
Published: March 15, 2007
The most widely prescribed sleeping pills can cause strange behavior like
driving and eating while asleep, the Food and Drug Administration said
yesterday, announcing that strong new warnings will be placed on the labels
of 13 drugs.
The agency also ordered the makers of the well-known drugs Ambien and
Lunesta and the producers of 11 other commonly used sleeping pills to create
patient fliers explaining how to use them safely.
The fliers, which the agency says it requires when it sees a significant
public health concern, will be handed out at pharmacies when consumers fill
Although the agency says that problems with the drugs are rare, reports of
the unusual side effects have grown as use of sleeping pills have increased.
Sales in the United States of Ambien and Lunesta alone last year exceeded $3
billion. Use of those medications and other similar drugs has soared by more
than 60 percent since 2000, fueled by television, print and other
advertising. Last year, makers of sleeping pills spent more than $600
million on advertising aimed at consumers.
The review was prompted, in part, by queries to the agency from The New York
Times last year, after some users of the most widely prescribed drug, Ambien,
started complaining online and to their doctors about unusual reactions
ranging from fairly benign sleepwalking episodes to hallucinations, violent
outbursts, nocturnal binge eating and — most troubling of all — driving
Night eaters said they woke up to find Tostitos and Snickers wrappers in
their beds, missing food, kitchen counters overflowing with flour from
baking sprees, and even lighted stoves.
Sleep-drivers reported frightening episodes in which they recalled going to
bed, but woke up to find they had been arrested roadside in their underwear
or nightclothes. The agency said that it was not aware of any deaths caused
The reports gained credence from scientific studies. A forensic toxicologist
in Wisconsin, Laura J. Liddicoat, gave a presentation at a national meeting
on six instances of Ambien-impaired driving.
And Dr. Carlos H. Schenck and Dr. Mark W. Mahowald of the University of
Minnesota said that they had been studying cases of nearly 30 Ambien users
who developed unusual nighttime eating disorders.
Last May in Washington, Rep. Patrick Kennedy, Democrat of Rhode Island,
blamed Ambien when he crashed his car near the Capitol building.
The agency also received reports of people making phone calls, purchasing
items over the Internet, or having sex under the influence of sleep
In each case the consumers had no recollection of the events, which they
said had occurred after they took their pills and headed for bed.
An agency official said yesterday that the activities associated with the
drugs went beyond mere sleepwalking.
"We do believe that sleepwalking is different from these behaviors," said
Dr. Russell Katz, the F.D.A.'s director for neurology products.
"Sleepwalking is considered more of a reflex. These behaviors are complex
and they're different fundamentally because of the complexity. People get
up, they take their car keys and they go drive. As you might imagine, that
might be potentially dangerous to the patient and others as well."
Dr. Katz said that it was not entirely clear whether people reporting the
problems had been technically asleep or awake. Although Dr. Katz said the
side effects were rare, the agency said that the few dozen reports it had
received probably did not represent the full extent of the problem.
Drinking alcohol before or after taking the drugs appears to increase the
chances of having such a reaction, Dr. Katz said.
A defense lawyer in Atlanta who specializes in impaired-driving cases,
William C. Head, said he had received calls from people around the world who
had been charged after using such medications.
"Ninety percent of these cases involve alcohol as well," Mr. Head said.
Often, though, the people arrested had only a glass of wine or two, then
took a sleeping pill, he said.
"You can't even keep your car on the road," Mr. Head said. "I think any
warnings that they give, any advertisements should say not a drop of
The medication guides that the agency has called for will clearly explain
that risk, according to Dr. Katz, who said the drug makers must submit
drafts by May. He said the drug makers had been working with the F.D.A. on
the wording since the agency notified the companies three months ago that
the changes would occur.
Besides warning against alcohol use, the new labels and guides will tell
consumers that they should not take the pills with other drugs that suppress
the nervous system.
The warnings labels will include some general language required by the
agency, along with language that the companies will be required to draft
that describes the side effects of their specific drugs.
The drugs affected include newer products as well as older and widely used
ones that are sold under brand names and generic names.
Most of the drugs already carry statements warning against alcohol use and
of the risk of hallucinations. Advertising for the drugs has also included
such warnings. But the labels will make those statements more prominent, and
the medication inserts will emphasize the risks when the consumer gets the
The warnings also are to include information about an unrelated and rare
risk of life-threatening allergic reactions with sleep medications. Some
patients have recently reported such reactions, in which the air passages or
face swells up, after using one of the newest drugs in the group, Rozerem,
Dr. Katz said.
After reviewing reports, the agency determined that those reactions were
also a potential side effect with other drugs in the group, he said.
Although most of the reports of sleep-driving and sleep-eating have involved
Ambien, the agency concluded that the behavior can be caused by any of the
One sleep expert, Dr. Mahowald of Minnesota, said that Ambien had received
the most publicity because it was the most widely used. But "there's no
question that any of the sedative hypnotics can do this," he said.
Ambien and its extended-release formula, Ambien CR, made by Sanofi-Aventis,
dominated the market last year, accounting for 27.6 million of the 44
million sleep drug prescriptions in this country, according to data from
In second place, with about 7.3 million prescriptions, was the drug
temazepam, a generic that is also sold by Tyco Healthcare under the brand
Lunesta, by Sepracor, was next with 5.8 million prescriptions.
Dr. Mahowald directs the Minnesota Regional Sleep Disorders Center, where
doctors have been involved in a study of about 30 patients who developed
sleep-eating while using Ambien. Some of the patients gained weight before
discovering that they were getting up at night to cook and eat.
"Hopefully this will make doctors think twice before blindly giving patients
a prescription," said Dr. Mahowald, who advocates a combination of
medication and behavioral therapy to treat insomnia.
He also criticized marketing of the products. "I personally think the extent
of advertising has just been unconscionable," he said.
Data from the research firm TNS Media Intelligence shows that in 2005 and
2006, Sanofi-Aventis spent a total of nearly $350 million to advertise
Ambien and Ambien CR.
Sepracor spent more than $500 million on advertising for Lunesta during that
same two-year period. And Takeda, which makes Rozerem, spent about $100
After yesterday's F.D.A. announcement, Sanofi-Aventis immediately posted the
text of a "Dear Doctor" letter to its Web site, outlining the new warnings.
The agency has ordered all the companies to send such advisories to
In a statement last night, Sanofi-Aventis said that information about
sleepwalking had always been included on its label. In company clinical
studies, it occurred in fewer than 1 in 1,000 patients, the statement said.
The agency also said that it was recommending that the drug makers conduct
additional clinical studies involving sleep-driving and other reactions to
determine whether any of the sleeping pills do not cause those problems. But
those studies will not be required. And so far, none of the companies have
announced plans to conduct them, Dr. Katz said.
The agency's move follows a warning last month by authorities in Australia,
where Ambien is marketed as Stilnox.
The Australian drug agency said that it had received 16 reports of unusual
activities by consumers using the product, including sleep-driving and
sleep-eating. In one case, a woman woke up with a paintbrush in her hand,
discovering she had painted the front door of her home while asleep.