University of Pennsylvania researchers conducted a clinical trial to test whether giving lisdexamfetamine (LDX), a psychostimulant currently approved to treat attention deficit hyperactivity disorder and binge-eating disorder, would improve the cognitive performance of menopausal women who complained of cognitive difficulties. The study showed an improvement in executive functions among the women after taking the drug, although the importance of that improvement is unclear.
This news release draws a flag for disease-mongering. The assumption of the release is that there is a large population of menopausal women who require treatment for menopause-related cognitive dysfunction. However, such a need is never established by the release and hasn’t, to our knowledge, been established in the medical literature.
Should it really be “a major public health goal” to promote “healthy cognitive aging” among menopausal women? That’s the contention of one of the researchers who’s quoted in this news release, and it’s obviously a key part of the rationale for testing this drug in menopausal women. But while many women experience transient cognitive issues during menopause, it’s not clear that there are, in fact, a large number of women who experience symptoms significant enough to interfere with their functioning or relationships (the threshold that would warrant treatment). And if such women don’t exist in large numbers, it’s questionable whether the primary goal here is improving the public’s health or the financial health of LDX manufacturer Shire. Let’s recall that within the past few months, Shire has successfully petitioned to have this drug, originally used for attention deficit hyperactivity disorder, approved for treatment of binge-eating disorder — a condition that some feel was created with significant help from the drug industry and which Shire has been aggressively marketing to the public with an “awareness” campaign. So its attempts to expand the use of this drug to a new population deserve careful scrutiny. Is this based on a real public health need? Or is this is drug in search of a new market — one that Shire will create for itself if necessary?
There is no mention in the release as to the cost of LDX although, since it is routinely prescribed for ADHD, the cost for users should be easy to provide. A cursory search of the internet suggests that a 30-day supply could cost between $100 and $300, depending on the provider and insurance coverage. Nor is it clear from the release how long women would need to take the drug to ward off any cognitive decline, since the trial the release reports on only continued for several weeks. Providing that information would allow readers to accurately gauge the value of the treatment.
The release describes benefits like this: “The researchers found a 41 percent overall improvement in executive functions for women receiving LDX, compared to a 17 percent improvement when taking placebo medication.” And it points out that in four of the five areas of cognitive loss, those taking the drug experienced “significant improvements,” although it fails to provide specific details on those areas.
We’d add that on the objective measures of cognitive function (the neuropsychological tests where performance is externally graded), only 2 of 12 tests showed a statistically significant improvement, and these would not have been significant if the study authors had made the appropriate statistical adjustments for multiple comparisons. This is perhaps more of a problem with the study itself and the journal that published it rather than the release per se, but it’s a problem that deserves comment. And while the subjects’ self-rated improvements in function were greater, as would be expected, than the objective measures, it’s hard to know whether these statistically significant changes are clinically meaningful. In other words, are they large enough and durable enough to make a real difference in people’s lives? The release doesn’t say or give us any context for judging the importance of the benefit.
The release fails to mention any harms in this release, although the paper mentions that this drug can raise both heart rate and blood pressure, although not precipitously.
This release does identify the nature of this trial, pointing to the randomization of the participants and that they served as their own control group as crossovers in the study. It also comments on the short duration of the study, noting that “long-term studies of menopausal women receiving LDX are needed.” However, the study only involved 32 women, and the original study paper recommends testing the hypothesis with a much larger cohort. Moreover, in the paper itself, the researchers state: “While these findings are compelling, there are several aspects of the study design that limit our ability to generalize these data to all women with cognitive complaints during the menopause transition.” (For example, women with mood problems were excluded from the study.) Both the lede of the story and its headline could have better represented this caveat by referring to “some menopausal women.” We’ll give the benefit of the doubt here with suggestions for improvement for next time.
As noted in above in this review, we’re concerned that this release engages in disease mongering. Fresh off of an approval of this drug for binge-eating disorder, study co-funder Shire appears to be looking to menopausal women as a new market and possibly pathologizing such women inappropriately. Are these women truly impaired enough to require drug treatment? The release says that reports of cognitive impairment are “widespread” in menopausal women. But to truly establish such a need, the release should have provided more context as to the degree of impairment and the number of women with severe impairment, and how long this lasts. The idea that this research is addressing “a major public health goal” needs more high-quality evidence to be accepted. In the study itself, the authors acknowledge that “the true prevalence and severity of mid-life onset of executive function difficulties among women experiencing a natural menopause are not known.”
While the release does identify the four funding entities underwriting the research, it fails to point out what the research paper actually does: That two authors receive grant support from Shire, the drug’s manufacturer, and that that the lead author has stock holdings with five different pharmaceutical firms (although not with the manufacturer of the drug used in the study). Readers need this information to be able to interpret the evidence.
The release offers no mention or discussion of alternative treatments for menopause-related symptoms or cognitive dysfunction.
The release establishes that the drug used in the study is now frequently prescribed for ADHD patients, suggesting that it is available and also could also be used for menopause-related symptoms..
Both the headline on the release and the lead paragraph both mention that this is the first study to show these results when using a psychostimulant to reduce losses in executive function among menopausal women.
As noted above, we don’t think it’s well documented how “commonly experienced” these cognitive complaints really are, to the point they interfere with life or functioning. However, since we’ve already dinged the story for that problem and there aren’t any egregious overstatements, we’ll award a Satisfactory grade.