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.

Crisis Chat Observations: “You’re Very Aware”

One of the frustrating things about depression (and other mental illnesses, but I spend the most time talking to depressives) is that… well, actually there’s a lot of frustrating things.  One is that finding good medical professionals is hard, finding good mental health professionals is harder because personality fit is more important, and depression takes out exactly the systems you would use to seek and evaluate treatment.   Even if you have no other obstacles (financial, social, transportation…), it is still really hard to find a medic taking new patients, make an appointment, keep an appointment, and follow up on what the provider tells you to do.

But the frustrating thing about depression I was thinking of when I started this post is that even when you do all of those things, treatment can take a while to work.  Typical protocol is to give an anti-depressant six weeks to work, and the first one may do nothing, or have intolerable side effects.  The STAR*D protocol study, which tested an algorithm for finding anti-depressants that worked for individual patients, found a 70% success rate over four months- excluding the 42% who dropped out.  Therapy can take years, and there’s often a painful period before it starts to help.*  Some people I talk to at crisis chat need help getting into treatment.  Others are doing everything I could possibly recommend to them- psychiatrist, therapy, social support, a list of self-care activities of which crisis chat is neither the first or last on the list- and are still miserable.

At least for the teenagers**, the most helpful thing I have found to say in this situation is the truth: you are doing everything right, and it is deeply unfair that it takes so much time to bear fruit.  Crisis chat is deliberately not an affirmation on demand service because generic cheerleading is emotionally draining for volunteers and even if they specifically request it, visitors tend to reject it as insincere- but if I see something someone is doing that will be long term helpful to them, or that they are especially good at, I will tell them.  I don’t give the same ones every time and I don’t make up things to make people feel better, I only say something if I see a genuine skill. This isn’t cheerleading or attempting to logic them out of depression so much as it is giving an objective, informed eye to people who know their brain is unreliable reporters but don’t know what specifically it is lying about.

I thought of this while reading Brute Reason’s Case for Strength Based Diagnosis.  Mental health treatment right now is all about the things you are bad at.  The strongest counter force is the pop culture romanticization of depression and bipolar disorder, which is not helping. But I could see it as very helpful to hear “the same gene that contributes to your depression also contributes to your high intelligence, and you can use that intelligence to fight depression”.  This seems like another problem caused by trying to use the same system for “accurately describe patient state to patient”, “accurately describe patient state to another practitioner” and “tell insurance why they should give you money.”

*When I’m detailing treatment options to crisis chat visitors I often make a point of mentioning CBT as something that isn’t a drug, works fairly quickly and doesn’t involve dwelling on pain.

**Adults tend to be more pessimistic, and I have no way of knowing if it’s because they’ve actually been depressed for 20 years straight or because their liar brain is telling them so.

Screen Bedtime Follow Up

A month ago I decided to start turning off all my screens (TV, computer, phone) at midnight.  It was a smashing success.  Within a week I’d moved to 11 PM, and I’m toying with 10.  Some if it is undoubtedly the red/yellow light effect and cutting down on stimulation before bed.  Coincidentally finding books that were interesting enough to read but not upsetting enough to disrupt bed time was also helpful.  But the single biggest effect I’m consciously aware of is giving me something to succeed at late at night.

Setting a real bed time never worked for me because if I wasn’t asleep by then I was failing.  Failing is no fun, and a sense of it inhibits sleep.  But not using screens is an action I choose.  And then I am succeeding at my goals, which is an excellent feeling to get to sleep with.  Plus apparently what I do when I can’t use screens but am not tired enough to get into bed is clean, and I am slowly undoing the damage done by six months of post-surgical fatigue.  Now when I wake up my apartment is slightly cleaner than I remember it.  This is an excellent way to wake up.

Downer Superbowl Post

The Seahawks made the Superbowl again, which means half the windows in town have a green and blue 12 in them.*  I have two instinctive reactions to this: reflexive nerd disgust feeding an urge to signal how little I care about sportsbowl, and happiness that people that live near me are winning a thing.  The reflexive nerd disgust is not coming from a healthy place and happiness is nice, so I start to go with that.  And then I remember the actual problem with football.

Football is hell on the body and the brain.  Watching people hurt themselves for our entertainment isn’t great, but they are at least adults that made the choice that this was worth the compensation.  What really bothers me is the tens of thousands of children (many poor or otherwise underprivileged) who are destroying themselves in the hope of financial reward.  Even very young children can damage each other.  I think anything that encourages this is immoral.  At the same time, I know people who enjoy football and I’m extremely uncomfortable calling them immoral.  They’re not watching with an eye towards torturing 8 year olds, they just don’t know.  And my feelings on the matter are so strong there’s no polite way for me to tell them.

2000 years ago people fed slaves to lions for entertainment.  100 years ago they watched men punch each other in the face.  Football needs to go the same way.

*It also means green and blue cupcakes in the crisis chat break room.