One of the most common—and distressing—symptoms of menopause is the “hot flash.” As many as 85% of perimenopausal women complain of hot flashes, characterized by a sensation of intense heat, a flushed appearance, perspiration, and pressure in the head. An effective remedy for hot flashes over the years has been hormone replacement therapy, but many women shun this treatment because of the increased risk of breast cancer, heart disease, and stroke. In its place, antidepressants like SSRIs and SNRIs have become more commonly prescribed for hot flashes. Many women report great improvement in symptoms, both anecdotally and in some small open-label trials, with antidepressant therapy.
But do antidepressants actually do anything at all?
Jim Edwards covers this story in a post today on bnet’s “Placebo Effect” blog. Edwards describes a study published in the Journal of the American Medical Association (JAMA) in January 2011 (PDF here). The study showed the clear benefit of Lexapro (an SSRI made by Forest Labs) relative to placebo in a randomized clinical trial of more than 200 menopausal women with hot flashes. However, Edwards also reports that a brand new study (which he calls “elegant”) published in the journal Menopause found NO effect of Lexapro. This second study measured hot flashes not by patient report, but instead by a “battery-powered hot flash detector” worn by women participating in the research.
Does Edwards conclude that the first study was bogus? Well, not quite. Edwards argues that the integrity of the JAMA study was dubious from the start because its lead author, Ellen Freeman, received money (honoraria and research support) from Forest Labs, while the paper in Menopause was not tainted by drug company money. (Note: he neglected to point out that the author of the second study, Robert Freedman, holds a patent, US # 60,741,376, on the “hot flash detector” used in his study. Yeah, that’s “elegant.”)
Now, I understand that pharmaceutical company funding has a potential to bias research (sometimes a great deal), even when the researchers swear by their objectivity. But in this case, Edwards’ axe-grinding seems to have obscured some more relevant arguments. In his zeal to criticize Freeman for her nefarious Forest ties, he ignores the fact that patients often do report a benefit of Lexapro. A more relevant (and convincing) argument might have been: What makes Lexapro that much better than a generic SSRI—which would be significantly cheaper—in the treatment of hot flashes? But no, that question was overlooked.
It’s also important to consider the methods used in the Menopause study. Freedman and his colleagues used “objective” measures of hot flashes (using a device patented by the author, remember) instead of patients’ self-report. What did these ambulatory monitors measure? “Humidity on the chest”—that’s it. (Hmmm… maybe the Exmovere Corporation could build an “Exmobaby garment” for menopausal women??) Lexapro had no significant effect on this objective measurement.
But the problem is, hot flashes are subjective experiences. Just like depressed mood, fatigue, pain, gastrointestinal upset, and many other symptoms we treat in medicine. There’s probably a physiological explanation, but we don’t know what it is. I’m sorry, but it seems presumptuous (if not downright arrogant) to say that a biometric device is an “accurate” detector of hot flashes, regardless of what the woman reports. It’s like saying that a person is depressed because his ethanolamine phosphate level is high, or that another has OCD because she has a thicker right superior parietal gyrus in an MRI scan.
Anyway, back to Edwards’ blog post: His opening sentence, dripping with obvious sarcasm, is “Never mind the evidence; just treat patients’ complaints.” He then proceeds to completely downplay (if not ridicule) the fact that women frequently report a benefit of Lexapro and other SSRIs.
I wonder whether Edwards has paid any attention to what we’ve been doing in psychiatry for the last several decades. Trust me, I would love to understand the biological basis of my patients’ symptoms—whether depression, psychosis, anxiety, or hot flashes—in order to develop more “targeted” medical treatment. But the evidence is just not there (yet?). In the meantime, we have to use what we’ve got. If a woman reports improvement on Lexapro without any side effects (in other words, if the benefit exceeds the risk), I’ll prescribe it.
Let me be clear. I’m not defending Lexapro: if there’s a cheaper generic alternative available we should use it. Similarly, I’m not defending Ellen Freeman: pharmaceutical funding should be fully disclosed and, moreover, it does skew what gets published (or not). And I’m not criticizing Dr Freedman’s Hot Flash Detector (why does that sound like something out of a 1920’s Sears Catalog?): objective measures of subjective complaints help us to understand complicated pathophysiology more clearly.
But if patients benefit from a treatment (and aren’t harmed by it), we owe it to them to provide it. Arguments like “the research is biased,” “it’s not scientific enough,” or “doctors don’t know how it works anyway” are valid, and should not be ignored, but should also not keep us from prescribing treatments that alleviate our patients’ suffering.