Lexapro, Hot Flashes, and Doing What Works

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.

26 Responses to Lexapro, Hot Flashes, and Doing What Works

  1. medskep says:

    Hmm, I wonder if the Irwin Kirsch concept of the superplacebo is relevant here.(a drug works slightly better than placebo because it has side effects not because it actual treats the condition)

    Or how about Joanna Moncrieff concept that SSRIs have a better than placebo effect because the have a “drug” effect (Let’s go get stoned)and so the altered state reframes things a bit. See her book Myth of the Chemical Cure

    Here’s a quickly googled anecdote about how marijuana helped:

    …”So for half a year I endured my hot flashes, thinking there was no cure.

    Till one day my husband’s friend came by with a little bean of hashish and we made a joint. And lo and behold, after one or two drags I stopped sweating in the middle of a hot flash. It went so quickly that I started to freeze. And for the rest of the evening and the following night I did not have as much as one hot flash. It was absolutely amazing.”…

    Just food for thought. My sense if that there are many ways to help women with hot flashes that do not have quite so many side effects.

    The following is from the Lexapro site:

    “In clinical trials, the most common side effects associated with Lexapro treatment in adults were nausea, insomnia (difficulty sleeping), ejaculation disorder (primarily ejaculation delay), fatigue and drowsiness, increased sweating, decreased libido, and anorgasmia (difficulty achieving orgasm). Side effects in pediatric patients were generally similar to those seen in adults; however, the following additional side effects were commonly reported in pediatric patients: back pain, urinary tract infection, vomiting, and nasal congestion.”

    Good luck, it is a tough dilemma for a practitioner.

    PS I find it interesting that Japanese women rarely experience hot flashes.

    • Rob Lindeman says:

      I tend to agree that if a medication helps a patient, and does so without counterbalancing harms (including high cost). I’m for it.

      One caveat (at least). Let’s not be seduced into making a logical error about SSRIs that we make with depression. It goes like this: Depressed people feel better when they take SSRIs (observation); Therefore, depression is a disease characterized by an imbalance of serotonin in the brain (illogical inference). Similarly: Menopausal women with hot flashes feel better when they take SSRIs (observation); Therefore, hot flashes in menopause is characterized by an imbalance in serotonin, probably also in the brain (illogcial inference) Why not? what the heck?

  2. Tom says:

    Great article. And it illustrates why we should be able to prescribe placebos. If it works, go for it. Whatever gets you through the night and all of that…

    • Jackie says:

      I agree with you, Tom.

      Apparently you still get the placebo effect when you (the patient) know that it’s a placebo. So, a practitioner wouldn’t have to resort to any subterfuge — if it were legal, s/he could just openly say, “Ms. Hotflash, I’m going to write you a prescription for these new Placebo pills for the treatment of your condition. Clinical trials have shown that in some cases they act as well for the alleviation of menopausal symptoms as medications with active ingredients.”

      And then, the Placebo should have a price at the Pharmacy that is high enough to denote “quality and effectiveness” to the patient. Ah, the mind — we don’t want our placebos to be too cheap as otherwise “they can’t possibly work!”

      The doctor should also tell Ms. Hotflash of the commonly reported side-effects of the Placebo — which are probably the same (including increased sweating) as those listed by medskep above for Lexapro.

  3. Widespread clinical experience IS data. It is not a synonym for “clinical anecdote.” The women who find the SSRI helpful are often not helped by other drugs.

    I mean, it could be the “allegiance effect” – the placebo effect on the patient of having an enthusiastic physician. But I don’t think so. However, it’s almost impossible to prove because, as was pointed out, we are dealing with subjective experience in psychiatry.

    How exactly can we be completely objective about subjectivity?

    We still really don’t knowexactly how aspirin works, but few would argue that it does not help headaches.

  4. Jackie says:

    I only read the abstract, but the “elegant” study in the journal Menopause concludes that there is no benefit of Lexapro based, in part, on body temperature readings taken while the study subjects were asleep.

    But wouldn’t an overlooked benefit here be that the women WERE asleep? An oft-reported — perhaps the biggest — problem associated with hot flashes is the tossing and turning at night. Does Lexapro allow the woman — and any sleep partner — to get a restful night’s sleep and be functional the next day? Do women and/or their sleep partners care about hot flashes they sleep through?

    On the Edwards’ piece: this old bat found his “they’re all hormonal and gaga — give ’em all hormones” position offensive and potentially dangerous.

  5. Iatrogenia says:

    An honest risk-benefit analysis is the problem here.

    First, is an invasive treatment such as antidepressants necessary for hot flashes? Yes, the symptoms can be very troublesome. Hot flashes tend to resolve in intensity over time. How long should a woman be maintained on antidepressants just to treat hot flashes? Chronic treatment causes serotonergic downregulation, leading to emotional blunting and withdrawal problems that can be much, much worse than hot flashes.

    Acupuncture can be quite effective for treatment of temperature dysregulation (personally, I’ve had great success with this) and has no side effects.

    Sedentary women can reduce hot flashes with a little regular exercise, such as walking — which is available to everyone.

    Then, of course, there are the sexual side effects, which sometimes do not resolve after discontinuation. Should a woman sacrifice her sexuality for antidepressant treatment of hot flashes?

    How about the misdiagnosis of withdrawal for depression when she tries to quit — is an older woman buying into a lifetime on drugs that contribute to risk of osteoporosis and diabetes?

    Yes, the studies are contaminated by drug company interests. They’ve long targeted women for their products. It’s no coincidence that 2/3 of those taking antidepressants are female. Antidepressants are recommended for every stage of womanhood: menstruation, post-partum, menopause.

    Such a disgrace that psychiatry does not recognize that medicalizing normal female hormonal conditions is anti-woman, and cooperates enthusiastically in this destructive nonsense. The pretense of selectively medicating only very severe hot flashes is a sham — prescriptions for these drugs are thrown at older women as though they were vitamins.

    • Jackie says:

      I think a woman who wanted to try Lexapro for hot flashes would most likely get them from her OB/GYN or PCP — a reason that these studies were published in OB/GYN – General Medicine journals.

      I don’t see that “psychiatry” is involved in these two studies at all.

      • Iatrogenia says:

        Proposed DSM-5 http://www.dsm5.org/: diagnoses regarding women in particular:
        Unspecified Somatic Symptom Disorder (Pseudocyesis — false pregnancy)
        Major Depressive Disorder, Recurrent With Postpartum Onset
        Bipolar I Disorder – Current or Most Recent Episode Depressed With Postpartum Onset
        Female Orgasmic Disorder
        Sexual Interest/Arousal Disorder in Women
        Genito-Pelvic Pain/Penetration Disorder

        Why are any of these psychiatric diagnoses? Why does psychiatry presume to treat any of these possibly endocrine-related disorders (as are hot flashes)? How is psychiatry going to treat them — hint: it won’t be through sex therapy. It’ll be an avalanche of prescriptions, get the women hooked, and then you have customer for life — right?

        (By the way, studies have shown frequently the lack of female arousal is often due to ignorance about the clitoris — the ignorance being in the male partner. Why isn’t that a psychiatric disorder?)

        Tell me, Jackie, what percentage of your patients are women? Have you ever presumed to prescribe an antidepressant for a “female complaint”?

        How often do you see men as the target of antidepressant advertising? Why don’t psychiatrists complain about how the drug companies are driving women to them for prescriptions?

        Is it possible psychiatry hasn’t outgrown the misogynism of Charcot and Freud?

      • Jackie says:

        Hi Iatrogenia, I almost didn’t see your post — glad I did.

        I’m not a psychiatrist, so I have no personal stake in whether drugs are prescribed, what kind of doctor a person chooses to see, whether somebody goes to a sex therapist, etc. I’m also not the person to whom you should be posing your questions about the DSM 5.

        And I don’t bear any animosity towards psychiatrists, either — as I said to Duane below, why aren’t the other medical specialties stepping up to the plate and taking care of people with depression, where the cause falls within their domain? For example, if it’s an HPT/HPA disturbance (for want of a better term) causing the problem, where are the endocrinologists?

        As to your man/woman thing: not going there!

  6. duanesherry says:


    At the risk of sounding less than objective (again)…
    The patent on Lexapro is due to expire early next year.

    Call me a skeptic, but it’s likely that Forest Labs will try to milk the use for the product dry… before it goes generic.

    With an application here, and another one there..

    Who knows what they’ll come up with… an application for ingrown toenails, impacted wisdom teeth…. who knows?

    If so many people weren’t being hurt, it would be hilarious.

    Duane Sherry, M.S.

    • duanesherry says:


      Menopause produces powerful changes in a woman’s body.
      The cessation of ovary production can create strong hormonal imbalances.
      Not only hot-flashes, but lots of other symptoms.

      Heaven-forbid we look at these things.
      Or work with the real science that might offer some help.. Counseling someone through a mid-life change (crisis).


      A simple drug will do the trick.


      What has this got to do with psychiatry?
      Young women were some of the first to visit the wards, and Freud, et al experimented on them…. big-time.

      Look up the word ‘hysterical’, or better yet, ‘hysterical personality disorder’.
      A term that was used until 1980 by the APA.

      Once you begin to understand the history of psychiatry, you will have a better understanding of the ‘science’ behind it (lack of science), and the dismissal of people who suffer from ‘unexplanined’ strong, passionate emotions.

      Psychiatry continues to ignore the body.

      In fact, the long-term use of psychotropics often entails telling patients to “ignore the side-effects”… “It’s like insulin… a diabetic needs insulin”… while ignoring not only the hormones, but other key players related to mood, overall mental functioning.

      Psychiatry continues to ignore the mind (while focusing on the “disordered brain”)… Rather than helping people through personal crisis, or in this case, a mid-life one…. rather than providing emotional support, while empowering… a person is dismissed as “mentally ill”….
      The “hysterical” of old.

      Duane Sherry, M.S.

      • duanesherry says:

        “Whenever a doctor cannot do good, he must be kept from doing harm.” –

      • Jackie says:

        Duane, my comments were about the two studies mentioned in the above post only which, in my view, have nothing to do with psychiatry.

        In all likelihood, women will not be calling psychiatrists (and waiting 3-6 months for an initial appointment) about hot flashes . And psychiatrists, in all likelihood, would refer a woman making such a call to her OB/GYN or PCP — the person who would see the woman through all aspects of menopause and beyond.

        Nothing to do with “mental illness.” IMHO

      • Duane Sherry says:


        Behind “mental illness” of any kind there is something else going on… sometimes, something as simple as a thyroid disorder, or hormonal imbalance.

        That’s my point.

        It used to be that a person was referred to a psychiatrist when there appeared to be nothing physically wrong. Psychiatrists would work on emotional issues, at least during the Moral Era.

        Since that time, psychiatry has worked at finding a niche, and using psychoactive drugs to treat “brain disorders”… These disorders often have little to do with the brain, and much more to do with intestinal absorption, food allergies, and a host of other causes.

        The answers lie in finding the root cause(s)… Not labeling a person with a lifelong brain disorder.

        Psychiatry has been lazy.
        Plenty lazy.


  7. Jackie says:

    Duane, why don’t you try to get the other medical specialties — endocrinology, gastro-enterology, allergy, etc. to give a rat’s you-know-what?
    Because right now they don’t, at least that I can see.

    • AA says:

      Hi Jackie,

      You said in response to Duane:

      “In all likelihood, women will not be calling psychiatrists (and waiting 3-6 months for an initial appointment) about hot flashes . And psychiatrists, in all likelihood, would refer a woman making such a call to her OB/GYN or PCP — the person who would see the woman through all aspects of menopause and beyond.”

      I don’t disagree that if that is your initial problem, you won’t be consulting a psychiatrist.

      But if you’re seeing him/her for any other reason and have female issues, the chances are you will be offered a drug for your issues and not be referred to your OB/GYN or PCP. Once you have that “MI” label, there is a drug for any problem you have.

      As far as asking Duane to get other medical specialties to give a rat’s a–, you make some good points. Like psychiatrists in general, they go into denial mode when patients complain about med side effects.

      I definitely experienced that with an allergist who denied the allegra could cause insomnia.

      I just think people are vocal about issues that have affected them personally.

      For example, if people suffered drug side effects from ones other than psychotropics, they are ardent activists and are targeting the appropriate medical specialists. You won’t find them on boards like this.

      • Jackie says:

        Do you think that a person who was seeing a psychiatrist already would have that psychiatrist treat allergies, too? Do you think many psychiatrists would want to take on the role of allergist?

        Because, to me, that’s a similar situation to the “hot flash” scenario. Many psychotropic drugs are anti-histamines, at certain dosages. So, for all intents and purposes they are just like Allegra — and Allegra is just like, say, Seroquel.

        My own view is that most people who were already seeing a psychiatrist would go to the allergist, for allergies. And I think most psychiatrists would suggest they go to the allergist, for allergies. Then, of course, such a person should tell each doctor what the other has prescribed so the care is co-ordinated.

        That’s the thing: many of the drugs that we associate with psychiatry have other indications, and are prescribed by other kinds of doctors. Or, sometimes, you can skip the doctor and just pick them off the shelf at Walgreens.

      • Iatrogenia says:

        AA — “But if you’re seeing him/her for any other reason and have female issues, the chances are you will be offered a drug for your issues and not be referred to your OB/GYN or PCP. Once you have that “MI” label, there is a drug for any problem you have.”

        I could not agree more. If you’re a middle-aged woman (or any age female, really), and you walk into a psychiatrist’s office, it’s a foregone conclusion you’re going to walk out with a psychiatric diagnosis and a prescription or two or three.

        In fact, “walked into a psychiatrist’s office” should be added to the DSM-5 as a diagnosis, it would save the good doctor all that leafing through the manual.

  8. Jackie says:

    Quick questions: Why are these middle-or-any-aged women walking into a psychiatrist’s office in the first place? What made them pick up the phone, initiate contact, and wait 3-6 months for that first appointment?

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