Differences between men and women prompted the FDA last year to recommend that each take different dosages of this country's most popular sleep drug, Ambien. The FDA cut the suggested dose for women in half after new studies showed that women were more likely to be left the next morning with levels of the drug in their bodies that could impair driving an automobile. That's because women metabolize Ambien differently, reaching maximum blood levels 45 percent higher than those of men. Despite the fact that many other drugs are also metabolized differently by men and women, Ambien is the only drug on the market for which the FDA has different suggested doses based on sex. Lesley Stahl talks to scientists who believe Ambien is typical of a much larger problem and that further study of sex differences is needed. Her report will be broadcast on 60 Minutes Sunday, Feb. 9 at 7 p.m. ET/PT.
Larry Cahill, a neuroscientist at the University of California, Irvine, admits that like many fellow scientists, he used to think men and women were fundamentally the same outside the obvious areas of reproduction and sex hormones. But he and many others have changed their minds. He says Ambien, (known generically as zolpidem) which was approved back in 1992, is a case in point. "That is a textbook example of what is wrong. How did it happen that for 20 some years, women, millions of them, were essentially overdosing on Ambien?"
The FDA knew about the 45 percent difference between men and women 20 years ago when it approved Ambien, but tells 60 Minutes there was no evidence at the time that the difference mattered. Says Dr. Sandra Kweder of the FDA, "If I saw this today, in light of today's science, I think we would go back and try to tease this out a little bit further," she tells Stahl. "But I think at the time this was generally...business as usual for what you saw in clinical pharmacology studies."
Sex differences are being discovered in areas large and small. Low-dose aspirin lowers the risk of heart attacks in healthy men, but not in healthy women, though it does protect women against stroke. Women and men can display different symptoms when having a heart attack. There are differences in pain receptors, liver enzymes and the wiring of the brain. Dr. Doris Taylor at Texas Heart Institute has discovered differences between male and female stem cells.
Cahill thinks science needs to re-think the importance of sex differences and study them from the earliest stages of animal research, including reviewing existing drugs. Knowing there are many differences and still operating on the assumption the sexes are the same must change he says. "So the assumption we're making that it really doesn't matter, sex, is not a valid assumption," he says. "It may not matter. It may matter hugely...the way we're doing business has to change."
Kweder says reviewing every drug is an enormous undertaking that may not be necessary, since she says doctors already know to start out with low doses to find the right amount. "In medical practice, there is a general awareness that that there may be individual differences among patients...every patient needs to have the right dose," she tells Stahl. Pressed by Stahl that the FDA seems to be taking a more reactive than aggressive stance on sex differences, Kweder responds, "I think we're being very aggressive about bringing the most sophisticated science to new drugs and being aggressive about applying the science, where we have reason to believe there is a concern, to older drugs."