When doctors prescribe new medications for me, I always wonder whether they’re getting the dosage right. There’s a reason I’m wary, and it has nothing to do with distrusting my doctors personally.
I’m reminded of it whenever someone complains that too few women are included in clinical trials of drugs. Most of those trials have always been done on men, and that’s a problem because women and men sometimes react differently to medications. This is not exactly news—I researched the subject for a magazine article I wrote back in 1993.
Since then, there’s apparently been little progress in pinning down which medications affect the sexes differently and what the consequences might be. That worries me now on two levels: as a woman and as an older person. In later life, we—both sexes—react differently to medications than younger people do. And it seems scientists are paying even less attention to the age gap than to gender disparities.
Where the male/female difference is concerned, until a couple of decades ago most doctors and researchers assumed that the sexes were alike physiologically except for reproductive organs and hormones. Therefore, they thought it was perfectly all right to test medications entirely on men and extrapolate the results to women. Researchers preferred not to include women in drug trials for fear the effects of their menstrual cycles and hormones would throw off the results.
By 1993, it was becoming clear that the sexes are quite different physiologically, so the National Institutes of Health instructed scientists to include women when testing drugs and medical procedures. That was 23 years ago.
Yet a study of the popular sleep drug Ambien revealed that its effects wear off much more slowly for women than they do for men because women metabolize it differently. People have been using Ambien for more than 20 years. When it was approved, researchers knew it had a stronger impact on women but they failed to say so in recommending dosages. It wasn’t until 2013 that the Food and Drug Administration (FDA) recommended that women take half as much as the amount still suggested for men. Ambien is one of the few drugs that specifies different dosages for women and men.
Why hasn’t there been more progress? In 2006, when investigators analyzed research published in nine influential medical journals, they found that fewer than 25 percent of the subjects in drug trials were female, and the vast majority (87 percent) of studies actually failed to report on differences in the way men and women reacted.
The fact that so little has changed for women isn’t good news for older people because our problem is similar. As I mentioned earlier, older bodies tend to respond differently to drugs than younger ones. Yet when researchers are recruiting subjects to test new therapies, they often exclude anyone over 65.
We change with age—and pharmaceutical companies should be paying attention to that. For instance, older kidneys and livers don’t clear medications from the body as efficiently as they once did, so drugs can accumulate and their impact can last longer, increasing the likelihood of unpleasant side effects. Or dangerous ones: adverse drug reactions come fourth on the FDA’s list of the leading causes of death in the United States.
Experts warn that for many medications, the recommended dose may be too high for older people. According to the Merck Manual Home Health Handbook, “Starting in late middle age, the risk of side effects from drugs increases. Older people are more than twice as susceptible to the side effects of drugs as younger people. Side effects are also likely to be more severe…” The Handbook doesn’t define “late middle age,” but the Public Citizen’s Health Research Group notes that those who are 60 or older experience more adverse drug reactions.
Since 1998, the FDA has required researchers to take age into account when they analyze their results on the safety and effectiveness of the drugs they’re testing. Yet as two Stanford researchers noted in May (2014) in the New York Times, an analysis of studies important enough to have their results published in top medical journals found that almost 40 percent excluded anyone over 65. Why? Investigators say they don’t recruit older people because they have health problems that could affect results.
But that’s assuming everyone over 65 is unhealthy. The Stanford researchers suggested that if the investigators are worried that including subjects with certain health conditions in a study would make it more complicated to interpret the results, they should exclude those individuals—not everybody over a certain age.
Even if investigators begin to do that, and we someday reach the point when all trials of drugs include both women and men, old and young, that won’t tell us anything about many of the medications already on the market. And nobody is talking about retesting them.
Meanwhile, as a woman and an older person, how can I know how much of any medication is safe for me? How can my doctors know? The only advice scientists are giving right now—to both women and elders—is to start with low doses and increase gradually if necessary.
I’d love to know whether anyone has heard that advice from their doctors.