In 2013, the Food and Drug Administration cut the dosage for the sleep aid Ambien in half for women because it left them drowsy in the morning and more at risk for accidents.
That was 21 years after the drug was approved for sale.
“Here we see a troubling but thankfully well-publicized example of what happens when women are not fully considered in medical research,” said Dr. Carolyn M. Mazure, Director of Women’s Health Research at Yale. “We should not have to wait for women to begin reporting drug-induced car accidents before they are prescribed medication in the proper doses.”
According to the Centers for Disease Control, about 4 percent of adults in the United States surveyed between 2005 and 2010 used prescription sleep aids sometime in the previous month, including 5 percent of adult women.
The FDA has reported the results of driving simulation and laboratory studies showing that after eight hours of taking the pre-2013 recommended dosage for immediate-release Ambien (zolpidem) and equivalent drugs, 15 percent of women and 3 percent of men had concentrations in their blood that could impair driving. For the previous dosage recommendation of extended-release Ambien, 33 percent of women and 25 percent of men had potentially dangerous blood concentrations.
Even at half of the extended-release dosage (the current recommendation), 15 percent of adult women and 5 percent of adult men had blood levels high enough to endanger their driving. For men, the agency only recommended that health care providers “consider” prescribing the lower doses recommended for women.
Subsequent research has shown that even after controlling for weight, quantitative measures of reduced perceptual processing and reaction time were worse for women than men.
“Researchers consider many variables when designing experiments and analyzing their results,” Mazure said. “What happened with Ambien demonstrates the necessity to include sex and gender as one of those variables.”
And it’s not just Ambien.
From 1997-2000, eight of the 10 drugs taken off the market posed a more serious risk to women than men.
In a study to determine the serious fainting risk of drinking alcohol while taking the newly approved female libido pill, Addyi, 23 out of the 25 people tested were men. That’s just two women studied for a drug intended only for women.
Last year, the FDA announced an action plan to improve the inclusion of women and the reporting of subgroup data in clinical studies.
Last month, the National Institutes of Health began implementing a new policy calling for grant recipients to use and report results for both male and female animals in preclinical studies unless they provide strong justification for studying only one sex. In addition, because every human and animal cell has a sex, the NIH will encourage researchers to consider and report on the sex of cells as a biological variable.
But the NIH policy does not require that researchers include adequate numbers of subjects of both sexes to ensure that they can draw statistically significant conclusions about the possible effect of sex on their experimental observations.
Mazure praised these steps as important, if incomplete.
“If health researchers know anything, it’s that they will never know what they don’t investigate,” Mazure said. “We need researchers to study and analyze their data by gender. To protect everybody.”