WASHINGTON – For two decades, millions of Americans have taken Ambien to help them sleep at night. But for years, the Food and Drug Administration has gotten complaints that people felt drowsy the morning after taking the medicine or its successors, and sometimes got into car accidents.
After laboratory studies and driving tests confirmed the risks of drowsiness, the agency said that women should be taking half as much.
The new recommendation applies to drugs containing the active ingredient zolpidem, by far the most widely used sleep aid. Using lower doses means less of the drug will remain in the blood in the morning hours, and will reduce the risk that people who use it will be impaired while driving.
Sleeping pills have boomed in popularity with the increasingly frantic pace of modern American life. According to IMS, a health care information and technology company, about 60 million prescriptions were dispensed in 2011, up about 20 percent since 2006. About 40 million were for products containing zolpidem.
The agency’s announcement was focused on women because they take longer to metabolize the drug than men. An estimated 10 percent to 15 percent of women will have a level of zolpidem in their blood that could impair driving eight hours after taking the pill, while only about 3 percent of men do, said Dr. Robert Temple, an official in the agency’s Center for Drug Evaluation and Research.
Reports of aftereffects from sleeping pills have circulated for years, and some doctors questioned why the drug agency took so long to act. Mishaps with sleepy driving – and even strange acts of texting, eating or having sex in the night without any memory of it in the morning – have long been familiar to the medical community.
“In this case, the FDA may be behind the eight-ball,” said Daniel Carlat, an associate clinical professor of psychiatry at Tufts University, referring to residual drowsiness. “This has been a known problem. Few doctors will be surprised hearing about this. They’ll say, ‘Oh yeah, we’ve already seen this in our patients.”’
He added that the recent announcement “will be good for public health because it will get patients to ask their doctors about the appropriate dosage.”
Agency officials acknowledged that they had received about 700 reports of driving mishaps with people on zolpidem over the years, with a spike in 2007 after a change in labeling caused more people to call in complaints. But they said it was not easy to draw a direct connection between the reports and the drug. Patients often did not remember what time they took the pill. Sometimes they had been drinking.
It was not until the drug agency reviewed driving simulation studies from controlled trials of the drug Intermezzo, which was approved in 2011 for middle-of-the-night waking, that a more complete picture of the risks emerged. The agency linked the driving simulation information with data from manufacturers on the amount of zolpidem in patients’ blood and determined that levels above about 50 nanograms per milliliter increased the risk of crashing while driving, said Dr. Ellis Unger, an official at the agency’s Center for Drug Evaluation and Research.
Unger said that all makers of new sleeping drugs would now be asked to conduct driving trials; a spokeswoman clarified that it would not be required.
“A lot of people are wondering about the elephant in the room,” Unger said. “Why did this take so long? This is
science, and our thinking evolves over time.”
The drug agency told manufacturers that the recommended dose for women should be lowered to 5 milligrams from 10 for immediate-release products like Ambien, Edluar and Zolpimist. Doses for extended-release products should be lowered to 6.25 milligrams from 12.5, the agency said. Most sleeping drugs containing zolpidem are now generic.
For men, the agency informed manufacturers that labels should recommend that health care providers should “consider” prescribing lower doses.
Patients taking the higher doses should continue them for the time being, officials said, but should consult with their doctors about lowering them. Doctors can still prescribe the higher dose if the lower one does not work. The lower doses are already commercially available, Unger said, as they are recommended for older patients.
Sanofi, the manufacturer of Ambien and Ambien CR, said in a statement that it agreed that people taking zolpidem “should always talk to their doctor about the most appropriate dose,” and that the label “provides important information” to determine what that is. The company added that it “stands behind the significant clinical data demonstrating the safety and efficacy of Ambien.”
The drug has also been known to cause sleepwalking incidents, and Unger said there was evidence that the lower dose might ease such events, though it is weaker than the evidence about next-morning-drowsiness. Carlat said one of his patients discovered that her weight gain while on the drug was from midnight trips to the kitchen she did not even remember taking.
Dr. Daniel Kripke, professor emeritus of psychiatry at the University of California, San Diego, and a leading critic of sleeping pills, welcomed the move but said the agency was still not doing enough to investigate other possible side effects.
“It’s a very small step in the right direction,” he said. He added that sleeping medications like zolpidem might increase total sleep time by 20 minutes a night, but that most studies suggest that the use of sleeping pills impairs a person’s performance the next day.
Critics of the drug agency said the label on Intermezzo, which very clearly denotes the risks for women, indicate that the agency was aware of these problems earlier.
But Thomas Roth, director of the sleep center at Henry Ford Hospital in Detroit who has been a consultant to sleeping pill makers, said that the drug agency had always been concerned about the potential risks with driving, “but they care about it more now.” He said he believed the lower dose would still be effective for many patients.
Agency officials say all patients are unique and doses will need to be tailored. They say the drugs should be prescribed at the lowest dose required.
Dr. Daniel J. Buysse, professor of psychiatry at the University of Pittsburgh School of Medicine, said he already prescribed the lower dose when he feels it is necessary, by telling patients to cut a tablet in half along the score.
“This just tells me, maybe be a little bit more cautious,” said Buysse, who has been a consultant for drug companies including the maker of Ambien. “But I do not think it will have a big effect on what I do.”