Review: Selling Sickness ( Ray Moynihan, Alan Cassels)

(Previously)

Selling Sickness‘s goal was to convince the reader that pharmaceutical companies manipulate perception to create an impression of disease where none exists.  I was going to say it failed, but no, it didn’t.  It actually has some pretty good examples of how pharma manipulates perceptions.  I just find it’s own view problematic as well.  E.g. Pharma is trying to make the diagnosis of Female Sexual Dysfunction equivalent to male impotence, when it clearly isn’t, and that’s bad.  But Selling Sickness’s  implication that the components of FSD (low libido, anorgasmia, pain during intercourse) should not be taken seriously by medics is ridiculous.  Sexual pleasure is important to many people in its own right, and any of those issues could be a symptom of a serious underlying problem.  Testosterone is a bad treatment for low libido because it’s a major hormone with far reaching effects, but it is an excellent treatment for low testosterone, a serious health problem for which low libido may be the most obvious symptom.

Selling Sickness talks about how pharma companies manipulate disease definitions (by sponsoring educational conferences and key decision makers), but it doesn’t explain anything else about how those decisions are made, or what would happen in the absence of pharma money.  Without that information it’s hard to draw conclusions.  Which I guess is how I feel about the book as a whole: its advocating a very specific point of view rather than informing you on the topic as a whole.  There’s nothing wrong with that, except that it (rightly) condemns pharmaceutical companies for doing the same thing.

*Obviously there’s a lot of variation and some doctors respond to those symptoms properly.  My sense from the literature and anecdata from my friends is that they’re going against the grain when they do so.

ETA: Slate Star Codex provides an example of pharma criticism done right, because he talks about the cracks in the system capitalism is filling.

Selling Sickness: Depression and Anxiety

Previous: Aceso Under Glass Valentine’s Day Special

Like many people, the authors of Selling Sickness believe that drugs for depression and anxiety are over-prescribed, that they are used to escape everyday emotions, and that this is terrible.  Again, I wish they’d defined their terms better.

For example, it sounds ridiculous to give someone Prozac because they’re sad their mom died.  That sadness is categorized as natural and healthy, in fact barring very unusual circumstances it would be viewed as sick not to feel sad at that point.  But you only get anti-depressants for “being sad” if it lasts more than two years.  Until then, anti-depressants are given only when negative emotions* start destroying a person’s ability to run their own life, and thus become self-reinforcing.  It’s completely natural and healthy to still be morning your mom’s death two months later, but if you’re unable to shower or eat for that length of time it doesn’t matter that the depression has an obvious external cause, it’s hurting you and there shouldn’t be any shame in accepting medical treatment for that.

A common fear I hear around anti-depressants is that they make people tolerate situations which should be depressing, and thus impede their exit.  That’s a real concern, and I think we should watch for it.  On the other hand, there are lots of people who want to leave but are unable to do so because they’re so depressed, and anti-depressants give them the activation energy and hope in the future that lets them leave.  And the same drug can have both effects in different people, or even the same drug at different times, because humans are weird and we don’t understand what we’re doing.

“We don’t understand what we’re doing” is not a great endorsement for something that’s screwing with the chemicals inside your brain.  I do think we need to use caution, that the risks are poorly understood, especially by GPs, and that nutrition and exercise are underutilized as treatments.  I also think that even when anti-depressants are the best individual decision, mass use of them can indicate a problem (I’ve heard 50% among PhD students, which cannot be okay).  And there will always be room for debate- should you be expected to work productively a month into grieving?  To work in a really difficult, dehumanizing office environment?  Would you need anti-depressants to take care of your kids if you had better community support?

But big pharma is not the one creating those societal conditions, and destigmatizing mental illness because it benefits them financially seems like a success story to me.  If we’re going to counter over prescribing let’s look closer to the problem (doctors) or further away (societal structure), not question the people receiving needed help.

*Not necessarily sadness.  In fact in men depression often manifests as anger, which leads to under-diagnosis.

Gender-based variation in grading and teacher attitudes.

Jezebel (via NYT): “Girls Outscore Boys on Math Tests, Unless Teachers See Their Names”
New York Times:  “How Elementary School Teachers’ Biases Can Discourage Girls From Math and Science”
Study Abstract:  “We’re going to skip explaining how we proved gender bias and just talk about its effects”
Actual Study (no public link): “Young Israeli girls outscore boys on anonymously graded national math exams but receive lower classroom grades, but eventually begin to underscore them in national exams as well.  The size of the discrepancy in scores is positively correlated with discrepancy in teacher attitude reported by boys and girls.  This pattern does not hold for English or Hebrew.”

I went in to reading this study pretty guns blazing, but it actually looks quite well done and robust.  You could argue that the teachers and tests are evaluating different things and the teachers’ goals are not necessarily worse, but

  1. Stereotypically, girls are better at pleasing teachers than boys.  And that is in fact the pattern we see in Hebrew and English.
  2. Low-biased teacher grades was correlated with a decrease in performance among girls in later grades (beyond that that would be predicted by low grades alone). The best case scenario is that the teachers are spotting some hidden weakness in the girls that the lower grade tests didn’t cover.  Except…
  3. Grade bias was positively correlated with negative student reports of the teachers attitude, and specifically discrepancies in the attitude reported by girls and boys.

So the actual study is pretty impressive, and astonishingly so for being in the field of education.    Touche, Lavy and Sand.  I also found it interesting that bias against girls was strongly correlated with the socioeconomic status of girls in the class as a whole, but not with any individual girl’s SES.  E.g. having a poor girl from a large family with uneducated parents lowered the grades of other girls in the same class, regardless of their own status, which suggests all kinds of unpleasant things.

The popular reporting on this paper is less impressive.  Jezebel flat out lies, implying that the same test was graded blindly and with the name (but no other data) available, which led to 100 comments asking how math grades could even vary that much, and 100 other comments saying “partial credit for showing work”.  The New York Times isn’t quite so egregious but does describe the input as “The students were given two exams, one graded by outsiders who did not know their identities and another by teachers who knew their names.”  That’s technically true, but implies that the two exams were much more similar than they actually were.   I expect this kind of crap from Jezebel, but the New York Times shouldn’t have to sensationalize results that are already this interseting.

Aceso Under Glass Valentine’s Day Special

My original plan was to finish Selling Sickness and write an overall book review, but I have reached that stage where I can’t continue reading it until I get some of my current thoughts out of my head, so we’ll be doing this in stages.

There exist many, many criticisms of the pharmacutical industry, all of which I dislike for framing it as the fault of the pharmaceutical companies and not the FDA.  If you want to learn more about this, Bad Pharma is a good source.  Selling Sickness‘s is more specifically about claim is that pharmaceutical companies deliberately manipulate both the public’s and the medical field’s view of illnesses, and “defines health people as sick” for their financial benefit.

I really, really wish Selling Sickness had defined its terms better.  Let’s use heart attacks as an example, because it is Valentine’s day.  No one questions that heart attacks are extremely bad, that they are associated with high blood pressure and high cholesterol, and that giving medications that lower blood and cholesterol to people who have already had a heart attack lowers the chance of a second one and increase life expectancy.  From this some people concluded that high blood pressure and cholesterol cause heart attacks, and we should lower them with drugs even in people who have never had a heart attack.  Selling Sickness describes that as turning healthy people into sick people.

Let me say out several different possibilities that would account for all available information:

  1. High blood pressure and/or high cholesterol damage your coronary system, causing heart attacks.
  2. Sufficiently high blood pressure and/or high cholesterol damage your coronary system, causing heart attacks, but we have drawn the cut off in the wrong place.
  3. High blood pressure and/or high cholesterol damage your coronary system, causing heart attacks, if and only if you have already had a heart attack.
  4. High blood pressure and/or high cholesterol and heart attacks share a root cause, the common treatments treat that cause, and the indicator numbers go down as a result.
  5. High blood pressure and/or high cholesterol and heart attacks share a root cause, the common treatments treat only the symptoms and leave the chance of a first heart attack unchanged, but coincidentally help after a heart attack.
  6. There are multiple causes of high blood pressure and high cholesterol have multiple causes, one of which also causes heart attacks.  Drugs happen to attack root cause if you have it, lower blood pressure and cholesterol to no effect if you do not.
  7. High blood pressure and/or high cholesterol damage your coronary system only in conjunction with an unidentified third factor, and so drugs reduce lifetime mortality if and only if you have that factor.  People who have a heart attack have that factor by definition and thus benefit from blood pressure/cholesterol medications.  They would benefit from them before their heart attack as well, but we have no way to identify them ahead of time.

Under which of these scenarios would you call someone with high blood pressure sick?  It’s a trick question because sick and healthy aren’t actually medical terms. The term for something given to an asymptomatic person that keeps them from developing symptoms in the future isn’t “making them sick”, it’s  “preventative medicine”, and it’s generally considered a good thing.

If high blood pressure and cholesterol don’t immediately cause symptoms but do damage your coronary system, taking drugs to combat them is a good call (dependent on side effects).   You could call them sick or not, it doesn’t matter.  If there was a pill that kept you at your physical and mental peak for 100 years you’d take it, even if your only health condition is being mortal.  Or maybe high blood pressure/cholesterol does indicate illness, but for one of the reasons outlined above, medication helps the numbers without improving symptoms or outcomes.  Then you’re sick but shouldn’t take medicine.  How useful medicine is has nothing to do with the English words “sick” and “healthy'”.

To be fair, researchers make the same mistake.  What we ultimately care about is if medication improves an individuals quality and quantity of life (with exact weightings dependent on the individual).  That takes a long time to do because people take forever to die.  You only get 20 years total from when you first register the molecule.  For a drug intended to prolong life given to people in their 50s, the drug could go off patent (destroying any ability to recoup the cost of the trials) before it got out of trials.   Even waiting for heart attacks takes a very long time and a very large sample size,because heart attacks aren’t actually that common.  So researchers use proxy measures like high blood pressure and cholesterol, on the assumption that anything that lowers those must prevent heart attacks.  Even researchers who aren’t trying to recoup financial costs do this, because they would like to produce results some time before they retire.  The problem is that even if high blood pressure and cholesterol are tightly coupled with heart attacks, this method will inevitably over-include things that somehow affect the proxy measures without affecting heart attacks, and miss things that decrease heart attacks or lifespan without affecting the proxy numbers.  And of course it’s entirely possible the FDA let pharma companies nudge the cut offs for treatment much lower than they should be, because that’s easy.

So yes, there are a lot or problems with aggressively treating proxy numbers, but “applying the sick label to healthy people” isn’t one of them.

Things I Say a Lot in Crisis Chat: You Are Worthy of Help Too

I talk to a lot of people in crisis chat who feel bad taking up my time, or are reluctant to seek treatment from a professional, or would pay for help but are reluctant to accept free help, because there are so many people out there with more serious problems.  How serious their problem is varies: sometimes it really is a mild problem, sometimes it is years of horrendous abuse that is still technically not the worst thing a human being has ever experienced in the history of time.

The most useful response I’ve found is: “We treat people with sprained ankles even though there are other people with broken bones.  Be honest about your situation and trust the doctor/therapist/charity to prioritize their resources appropriately.”  Nothing works all the time, but I can’t think of a time it didn’t at least help.

Anticholinergic agents and dementia

A new study came out this week suggesting use of a particular class of drug after age 65 was associated with dementia.  Here’s what you need to know.*

The study is retrospective, meaning it took people who developed the disease of interest and then looked backwards at their medications.  Retrospective studies are prone to a number of problems, the biggest one being that even young people with healthy memories are crap at giving you their drug history over the past 10 years, and this is a study of people with dementia.  The researchers dodged this by using an HMO database of the subjects complete medical history, which is a neat trick.  The second problem is that retrospective studies can easily end up being painting the bulls-eye after they’ve fired the arrow.  Mere chance dictates that if you track enough traits, any random subset of a population is likely to have something more in common with each other than with the rest of the population.  If you use the traditional bar of statistical significance (5% chance of results arising by chance), checking 20 traits gives you an expected value of 1 false positive.  To be fair, this study has a much higher significance level, and the effect was dose dependent, which is a very good sign that it’s legit.  The authors heavily imply they deliberately studied anticholinergics rather than shotguning it, but without preregistration there’s no way to be sure.

Anticholinergics come in two forms: antimuscarinics, and antinicotinic.  Short version: these work on different types of neuroreceptors, which live in different parts of the body and do different things . Every example drug they give is an antimuscarinic and of the classes of drugs they list, many have no antinicotinic members.  Even if they technically included antinicotinics in the analysis, they would be such a small portion of the sample that their effect could be overwhelmed.  So I don’t think you can apply this study to drugs like bupropion, which is an antinicotinic.

I don’t like the way they calculated total exposure at all.  Essentially they counted the normally recommended dose of any medication as One Standardized Daily Dose.  But those dosages vary wildly (even the examples they give span an order of magnitude), as do the particular drugs’ ability to cross the blood-brain barrier.  The drugs are prescribed for a huge variety of causes, and what’s sufficient to stop incontinence has nothing to do with what’s sufficient to slow Parkinson’s.  This oversight may cancel out with the fact that they created buckets of dosages rather than do a proper linear regression, in the sense that low-def pictures cancels out bad skin.

The obvious question is “but maybe the same thing that drove people to need anticholinergics increases the likelihood of dementia?”  This study has a much better retort for that than most, which is that anticholinergics were prescribed for a variety of causes, and it’s unlikely they all correlate with dementia.  I find that explanation extremely satisfying, except that they only evaluated the drugs as a single unit.  Antidepressants make of over 60% of the total SDDs taken.  The next most common is antihistamines at 17%.  But since more than 60% of the population took at least one SDD, it seems likely that those were taken intermittently, as opposed to the constant drip of antidepressants.  This leaves open the possibility that the entirety of the effect they attributed to anticholinergics was in fact caused by tricyclic antidepressants alone- and that the real culprit was depression.  The obvious controls were to evaluate the anticholinergics separately, and to compare rates of dementia among TCA treated patients with those treated with other antidepressants.

The subtler version of this question is “what if anticholinergics prolong life, giving you more time to develop dementia?”  I don’t see anything where they checked for that either way.  They did ask for people’s perception of their own health, and that was negative correlated with TSDD, but if TSDD is correlated with depression it’s hard to know how to interpret that.

For all those criticisms, this is an amazingly strong result for a medical study**.   No one study can prove anything (even if i think they had the data to do more than they did).  It definitely merits further investigation (ideally some with animal models, so we can do the causality experiments that would be super unethical in humans), and maybe even behavior change in the meantime, although a lot of the drugs studied are already obsolete or second line.  Plus it another piece of data that will help us figure out how to fight dementia, and that makes me really hopeful.

*Read: here’s what I learned.

**Yes, this should worry you.

Loratadine for Allergies?

The Decision Tree casually describes loratadine (brand name: Claritin) as barely better than placebo for treating allergies.  This is news to me because Claritin was absolutely critical to me graduating middle school.  If I forgot to take it in the morning my mom had to drop it off at school by lunch.  Without it I slept 16 hours a day,* woken up only by hives that itched so intensely they burned.  This isn’t actually relevant to me now because my allergies were taken care of my unprocessed honey and moving, but I couldn’t believe something once so important was essentially a sugar pill. So I investigated.

First stop, Wikipedia, which definitely backed my claim that Claritin treated sneezing, runny nose, itchy or burning eyes, hives, and other skin allergies.  But of 19 citations, 5 were unavailable to me (either they were books or in languages I don’t read), 13 were on topics other than clinical efficacy (e.g. side effects or mechanism), and 1 had a sample size of 192 and was a comparison against another anti-histamine, with no placebo or no-treatment group.

So I checked google scholar, where I found numerous minuscule studies (n = 14, 7 treatment groups) in which loratadine was better than placebo but worse than other drugs in the same class.**  If that’s true, why did loratadine get so much more attention?  I looked up the other drugs, and it turns out that some of them (cetirizine/Zyrtec) had similar efficacy but came out later, and went over the counter later as well.  Others (Terfenadine/Seldane) had much uglier side effect profiles (e.g. cardiac arrythmia if you eat a grapefruit).  So Claritin’s advantage seems to be being the first drug to market that treated the problem with minimal side effects.  I also wonder if Decision Tree‘s author (Thomas Goetz) was looking at a particular symptom set?  For example, loratadine appears to do well as a treatment for hives but there are better options for hay fever.

Some people suggest that having multiple drugs with similar response rates in the same class on the market is some sort of failure.  They are wrong and they should feel wrong.  First, these drugs were developed in parallel by different companies. While all the ones we heard of worked out, very few chemicals that pharma companies research become prescribable drugs, and they can’t predict which ones will do so ahead of time.  What if McNeil stopped researching Zyrtec because Bayer was researching Claritin, and Claritin made you grow arms out of your face?  We’d have lost years of allergy relief.  Second, the fact that they had similar average efficacy and side effects doesn’t mean they have the same effect in every person.  People are squishy and they don’t make sense, and differing reactions to drugs is one of the milder ways this manifests.

*No, fatigue is not a normal symptom of allergies, but I got it most springs and it went away with anti-histamines, which is good enough for a field diagnosis of allergies.

**I also found a lot of studies detailing the effects of loratadine in conjunction with another drug, mostly montelukast, and abstracts that reported loratadine’s efficacy relative to older antihistamines but without absolute numbers.