Thursday, September 30, 2010

Hypomania -- A Day In The Life Of Bipolar II

Everybody knows about bipolar I.  Or they think they do -- the crazy shopping sprees, the missions to save the world.  So when I tell them I have bipolar II, I always hurry to explain, not that kind of bipolar.

So what is bipolar II, they ask.

Okay, it's like this.

Bipolar II Goes To A Party

President Sally Mason of the University of Iowa invited my wife, a University employee, to her house for a reception.  Spouses were invited, too.  Helen likes to show me off, because I am good at parties, can talk with anybody, good social skills.  And I am cute.

So I checked my mood chart.  It was time, past time for the suicidal stage to check out and the better part of the cycle to makes its return.  The better part usually means mild depression, with a few flights into actually feeling good.  The signs were favorable.

I got cuted up and skipped the afternoon dose of valium, anticipating there would be wine.  All my meds make me dizzy, and I wanted to remain on my feet.  Like I said, good social skills.

President Mason is a wonderful hostess.  Not only did she greet us at the door with more than a handshake, but she went around the house later and engaged her guests in more meaningful conversations.  She caught up to us standing next to her bookshelf.  A perfect spot for a meaningful conversation.

First the preliminary chitchat.  There are more books upstairs.  These are the ones they unpacked first.  Translation: they already owned these before they moved to Iowa, their own choices, their own tastes.  Not for show.

But some were written by Iowa Writer's Workshop authors.  We were standing next to books that lots of people have read.  That should have been a conversational advantage, because I have read them, too.


The University of Iowa is insanely and rightly proud of the Iowa Writer's Workshop.  Over the course of seventy years, it has produced seventeen Pulitzer Prize winners, including Robert Penn Warren, Jane Smiley and Marilynne Robinson.  Its faculty have included ZZ Packer, Kurt Vonnegut and Robert Lowell.

Helen commented we could tell their books had been read.  You know, the bent spines.  The President smiled and agreed.

That is when the evil twin version of my hypomania made her appearance.

Pointing to one of those Pulitzer Prize winning books, Gilead by Marilynne Robinson, the evil twin said, and I quote, Boring.  Boring, boring, boring.  Good hostess that she is, Mason responded softly, It's a difficult book to read.  Robinson, besides being a graduate of the program, has also been a recent faculty member.  She probably visited the President's residence and inscribed it.

I could have redeemed myself by saying that it was difficult for me, too, because I know so many depressed clergy in small towns across Iowa (the first person narrator of the book), have been one myself, and also have worked with the demoralized congregations these depressed clergy leave behind.  The clergy in our diocese all read Gilead, and discussed the difficult issues it raises at one of our continuing education conferences.

Now, there is nothing wrong with a strong opinion.  But it was a missed opportunity.  The three of us could have talked about the economic, social and cultural forces that these small towns experience, and the ambivalence with which they send the brightest and best of their children off to the University of Iowa, knowing they will not return.  You know, a stimulating conversation that includes Mason's sphere.  Those good social skills of mine.

But no.  The evil twin moved on to the next book, At Home In Mitford by Jan Karon, another Iowa Writer's Workshop grad.  If only we hadn't been standing in the Iowa Writer's Workshop section of this bookshelf.

This time I said, I hate this book.  So do all my fellow clergy.  Our congregations love it.  It's like, So this is what they want us to be.

This time she said, I really like mysteries.  The Mitford series are mysteries.

Awareness was beinning to dawn.  A glimmer on the horizon.

I did see P.D. James, and could have gone there, my literary love affair with Lord Peter Wimsey.  Or the mystery authors I am following lately.  But no, the bright social hypomanic animal was desperate and jumped at the closest at hand, Fried Green Tomatoes, by Fannie Flagg.  Fannie Flagg is not a graduate of the Iowa Writer's Workshop.  Fried Green Tomatoes is not a mystery.

President Mason said, for the second time, that she really needed to move on to her other guests.

Actually, that was the good twin all along, albeit with some recently acquired cognitive deficits.  The evil twin is just as vocal, only irritable and likely to enter Facebook arguments.

Bipolar Meds

If I tell this story to my psychiatrist at next week's appointment, she will say this part of my disease could be addressed by the meds I keep refusing.  But those meds would give me a flat affect, facial tics and forty pounds.  Helen would have no reason to let me out of the house at all.  I would no longer even be cute.

Psychiatrists say that bipolars go off our meds because we miss our highs.  An hour of feeling good at a party, in exchange for a day of regret.  I don't think so.

That is hypomania.

Bipolar means always having to say you're sorry.

photo by Bill Whittaker and in the public domain
Writer's Workshop logo from the University of Iowa
Goofy from Facebook flair

Friday, September 24, 2010

Weighing the Costs and Benefits Part III -- How to Measure Costs

The doctor said, You have to weigh your costs and benefits.  Today we continue to figure out how to do that, based on more than gut feeling and desperation.  We are building an algorithm, logical rules applied to objective data to solve a specific problem -- in this case, do you want to put these chemicals inside your body?

On August 19 I listed the factors to consideration, benefits, costs, and other issues that affect how these are calculated.  On September 2 I listed the immediate benefits of medication, and gave you a Down and Dirty way to calculate them.  I call it Down and Dirty, because it leaves out long term benefits.  Your psychiatrist will consider this a serious omission.  But we have to start somewhere.  And desperate people have to start with a time frame they can imagine surviving.  Think about the long term benefits once you feel better, and are thinking about quitting.

Today we turn to down and dirty costs.  This is more difficult to calculate, because the research on costs is filtered through the lens of noncompliance.

When you weigh your costs and benefits, if you should happen to decide the costs outweigh the benefits, it would seem logical to give the medication a pass.  On the other hand, if the doctor recommended the medication, it was because he/she has prejudged the matter and considers the benefits to outweigh the costs.

Yesterday the pharmacy attached a piece of paper to my refill.  Every single prescribing information sheet attached to any prescription I have ever received has said the exact same words.  They come in the section on side effects.  Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects.

Evidently the you in you have to weigh the cost and benefits refers to the doctor, not to you.  If your opinion differs from your doctor's, then you are noncompliant.

The Filter of Noncompliance Distorts Research

The information available about costs is filtered through this concept of noncompliance, the assumption that the doctor knows better than you.  So when they do research about costs, they are asking, Why do patients fail to comply with the doctor's more educated judgment?  The purpose of the research is to find strategies to get you to comply.

Our algorithm, on the other hand, asks a different question -- I believe a more neutral question.  How do the reasons to take the medication stack up against the reasons not to?  I do not presume an outcome, do not make any judgment, and certainly do not presume your decision.  While I am critical of the oversell, remember, I am currently conducting my own thirteenth trial!  But I have to get my information from people who have already made up their minds.

And they call themselves scientists.

Nancy Andreasen, a National Medal of Science Award winner and one of the world's leading experts on schizophrenia is studying creativity and mental illness.  Her first book on the subject is The Creating Brain: The Neuroscience of Genius.  Her initial hypothesis was that writers generally would not have mental illnesses, but that some family member would.

Andreasen's research proved her hypothesis wrong, at least the part about the writers themselves.  80% of writers have a mental illness, mood disorders being the most common.  This is called a robust finding, which means way more than might occur by coincidence.  And it goes some distance to explain the blogosphere, dontcha think?!  The way she puts it, when the data proves your hypothesis wrong, then you know you are on to something.  In other words, your presupposed ideas have not distorted the interpretation of your data.  This disproved hypothesis put her on a track that led to unexpected, new findings.

Nancy Andreasen is a real scientist.

If scientists started out asking Why don't patients take our good advice? and discovered, Because sometimes patients make better decisions, then they would be on to something.  They might even find a new track that would lead to new findings.

Why Use Noncompliance Rates Instead Of Research Results As A Measure of Costs?

Once you put the pill in your mouth, you are no longer playing the odds.  You are getting results.  Other people have preceded you in this chemistry experiment, first in small numbers in the clinical trials, and then in large numbers in the real world.

The clinical trials yield some information.  What happens in the first 6-8 weeks?  How many people experience fewer symptoms of depression?  How many people go into remission?  How many people get what sort of side effects?  How many people quit before the end of the trial, because the side effects are unbearable?  How do all of these results measure up against placebo?

The clinical trials also take place under circumstances that influence the results.  Three lead to a difference between their results and the results that people in the real world experience.

First, the trial subjects (the word for people who put the chemicals inside their bodies) may be cherry-picked.  This means they are people most inclined to get good results.  Researchers try to recruit subjects who have not tried more than one antidepressant already.  Remember, half of those who are experiencing depression for the first time recover and never get it again.  People who do not recover quickly take more medications, and get worse results with each one.

In the STAR*D study, one of the selection criteria was that the subjects had not already tried any of the meds to be tested.  Those for whom the medication had already been shown ineffective were eliminated.  Which kind of stacked the deck, dontcha think?  Other scientists do.

Second, subjects receive extensive support throughout the trial.  Monitoring itself inevitably influences the results.  When depressed people get to talk about their symptoms, it reduces their isolation and eases the pain that is part of depression.  Even if those administering the medication are trained to be neutral, subjects get better, just because somebody cares enough to ask.

Third, and most significant for our purposes, is that trial subjects receive encouragement, intense encouragement, to endure side effects and finish the trial. 

Your Results May Vary

First, in the real world, even if two antidepressants do not work, consumers are urged to keep trying.  And each subsequent trial reduces the odds that the next one will be effective.

Second, in the real world, consumers are not so carefully monitored.  They are handed a prescription and sent out the door.  Subsequent appointments get briefer and briefer.

Third, in the real world, consumers are less willing to consume chemicals that make them feel worse.  We have jobs, families, lives to live, as best we can.  Nausea, dizziness, blurred vision, anxiety, insomnia... these things make living our lives difficult.

Noncompliance rates over the course of a year measure results the real world.  My guess is that is where you live.

So, how many people have weighed the costs and benefits they experience inside their own test tubes, results, not odds, and run screaming from the door?  Or more likely, tiptoe out to exercise not overt, but covert noncompliance.

What Are Those Noncompliance Numbers Again? 

10% of those prescribed antidepressants never show up at the pharmacy at all.

28% quit within the first month.

50% quit within 60 days.

72% are outta there at six months, 78% within the year.

There are problems with these numbers for our purposes.  All the different reasons for discontinuation are lumped together.  As well, different meds have different rates of discontinuation.  For example, again with the STAR*D study, 16.3% quit Celexa in the first 60 day trial, while 45.5% quit a Lithium/Zoloft combo in the third trial.

Somebody needs to be collecting this data.  Some consumer group, looking at real world data, not the guys seeking permission to sell pills. 

And Why Don't Consumers Consume?

Regarding those first 10%, we just don't know.  We can have some fun guessing.  Top ten list, that sort of thing.  But these guesses do not add to our knowledge.  This is missing data, and we will have to work around it. 

Another 44% say they quit because the medication wasn't effective.

Here we run into a problem.  It takes a while for most of these meds to work.  We don't know how many who quit in the first four weeks could tolerate the medication, but did not give it an adequate trial.

Both providers and consumers have an interest in figuring out this number.  From the provider perspective, these early quitters might respond to a better sales job.  For our purposes, the early quitters fail to give us the information we seek to figure our own odds.

Our algorithm will have to assume that further research will provide the numbers.  Once somebody funds that consumer group.

44% consumers who discontinue medication before their providers would like (the research calls it prematurely) say they did so because it made them sick.  According to the clinical trials, the most common reasons are nausea, headache, drowsiness, and increased anxiety.  These side effects are more common in the 6-8 week time frame.  Eventually, consumers cite weight gain and sexual side effects as the most significant side effects.

These are the types of numbers we will crunch to create our algorithm.  Sketchy as they are, they will be used for illustration purposes, not actual calculations.

But I need another recess -- something fun next week.

Flair from Facebook
Cartoon from Microsoft images
Counseling photo in public domain
Andreasen photo used by permission
Book cover from Amazon.com

Thursday, September 16, 2010

The Chemistry Experiment: Muppets Version

When your doctor, pen poised over prescription pad, tells you to weigh your costs and benefits, you will have next to no information with which to do so.  Over the last several and coming weeks, we are constructing an algorithm to help you comply with your doctor's instruction to make this calculation.  But remember, the best this algorithm can do is give you the odds.

After you calculate your odds, you may decide to proceed with this chemistry experiment and put the chemicals at issue inside your body, your own personal test tube.   At that point, you no longer have odds.  You have results.  Your doctor may not expect this, but once you have results, you will weigh your costs and benefits again.  You will make a new decision, this time with new information.

This is a good thing.  This is what people who conduct experiments do.  They use the information they have gained from one experiment to move on to the next.

This week's post is brought to you from the laboratory of Dr. Bunsen Honeydew, with the aid of his assistant Beaker. My thanks to Beaker in particular, for his contribution to science.



photo by Linda Bartlett, in public domain

Sunday, September 12, 2010

OMGThat'sWhatTheySaid -- Noncompliance

Before I move to the costs side of Weighing the Costs and Benefits, I pause to consider the concept of noncompliance.

Noncompliance is not one of the best candidates for the OMG! Award, because I cannot point to specific usage -- it is ubiquitous.  On the other hand, it is precisely what this award is about, going to the heart of how language frames thought.  In this case, the word simultaneously names and creates a relationship between consumer and provider.

I don't particularly care for the terms consumer and provider when it comes to health care.  But I use them here, where they distinguish those who consume, literally put pills inside our mouths, from those who fill out those little slips of paper that provide the pills.  Providers replaces pushers, a term I used in a fit of pique last week.  This week, I have resolved to be more polite.

Consumers are told to weigh our costs and benefits.  When we comply with these instructions and, having done so, decide that the costs exceed the benefits, and therefore decide not to consume, then providers call us noncompliant.  What exactly is communicated here?

What is noncompliance, anyway?

I went to the dictionaries.


According to Webster's New World College Dictionary, noncompliant means failure to comply; refusal to yield, agree, etc.

MedicalNet.com puts it this way: Noncompliance: The failure or refusal to comply: the failure or refusal to conform and adapt one's actions to a rule or to necessity.

Don't you hate it when one word is defined by another word that still needs to be defined?  I went back to Webster's, and got these alternatives. 

COMPLIANCE
1: a -- the act or process of complying to a desire, demand, proposal or regimen, or to coercion; b -- conformity in fulfilling official requirements;
2 : a disposition to yield to others;
3 : the ability of an object to yield elastically when a force is applied.

So.  One has a desire, demand, proposal, regimen or official requirements, and may have access to force or coercion.  The other fails, refuses, or does not yield.  I wonder which is which? 

Scientists Study Noncompliance

Providers are disconcerted when consumers fail to consume, and spend a lot of time trying to figure out why.  By the way, this link goes to a review of literature by Alex J. Mitchell, a consultant and senior lecturer in liaison psychiatry at the Leicester Royal Infirmary in the United Kingdom, who receives no compensation from pharmaceutical companies.  I often link to reviews of literature.  Their authors read a jillion studies, including ones to which I do not have access.  Then they summarize the highlights of whatever consensus may have come from these studies.  Reviews of literature put a lot of information in one place.  Mitchell has 59 footnotes (okay, not a jillion -- I exaggerated), in case you want to look up the research behind a particular point.

So scientists speculate, do research, write articles, hold conferences and  train residents, all in efforts to increase compliance.  Their hypotheses about the causes of this behavior include inaccurate beliefs about medication, lack of insight into ones illness, lack of education in general, cognitive impairment, weight gain, sexual dysfunction, and poor patient/doctor relationship.

Mitchell even developed a flow chart to categorize the behaviors of patients: full, partial and excess adherence, intentional and unintentional non-adherence, for external or internal reasons, and various combinations of these.  Not telling your doctor that you have stopped taking your medication is called covert discontinuation, and in other places, covert noncompliance -- that word again, this time with the naughtiness of covert.

A friend noticed that Mitchell missed a category on his flow chart, the consumer who is compliant with other medications, but consistently, though inadvertently, forgets one particular medication that she thinks is the source of uncomfortable side effects.  That could be covert internal unintentional partial non-adherence.  Or would it be covert internal intentional partial non-adherence, covert here meaning that her intention is undisclosed to herself?  The flow chart matters, because having divided noncompliant consumers into subgroups, then they test different strategies to bring different subgroups back into compliance.

Some notice the non-PC nature of the word noncompliance.  While most articles I found use the term, occasionally, as in Mitchell, I come across non-adherenceNon-adherence is supposed to imply a mutual agreement between two parties about what the treatment regimen will be.  Other articles use the terms interchangeably, recognizing a fig leaf for a fig leaf.  After all, presumably the consumer and the provider have agreed together about the regimen to which the consumer will adhere.  Only notice, if the consumer does not adhere, then he/she has violated an agreement, or broken a promise.  Still naughty.

Matthew Keene, who serves as an adviser or consultant to GlaxoSmithKline, Cephalon and Pfizer, might have merited the OMG Award on his own, for Confusion and Complaints: The True Cost of Noncompliance in Antidepressant Therapy.  But why pick on just him, because, like I said, this language and weltangshauung (as they say in philosophy -- it means world view) permeates the literature?

Why Don't Consumers Consume Their Antidepressants? -- What the Providers Say

Mitchell cites a study indicating that 10% of those prescribed antidepressants never show up at the pharmacy at all.  Keene's figures are that 28% quit within the first month, 50% within 60 days, and only 28% are still in compliance at six months.  Keene asks, Why do patients prematurely discontinue antidepressants, medications that may improve and perhaps even save their lives?  His answer -- one of the 3 C's of noncompliance: confusion, costs, and complaints. 

Confusion, costs and complaints.  Notice that each of these is patient-centered.  He didn't say incoherent, financially foolish and picky.  But they are implied in the rest of the article.  Notice also that he did not describe the phenomenon from the patients' perspective.  He could have said inadequate communication, ineffective or intolerable medications and inaccessible health care and still preserved his clever alliteration.

Why Don't Consumers Consume Their Antidepressants? -- What the Consumers Say

What if patients wrote these articles, or were even consulted?  Actually, they have been consulted.

44% consumers who discontinue medication before their providers would like (the research calls it prematurely) say they did so because it made them sick, most commonly nausea, headache, drowsiness, and increased anxiety.  Well, duh.

I don't know.  Has it occurred to anybody besides me that we could solve this puzzle and put all that research time and money to better use if we gave the scientists a turn as the lab rats?

Another 44% consumers report that they discontinue because the medication is not effective.

That leaves 16% unexplained.  I will get back to them when I discuss costs more thoroughly.

I sorted through lots of these studies before it finally occurred to me to compare rates and reasons.  Noncompliance at six months is 72%.  Back to NIMH's STAR*D study, when trial subjects received compensation, free medical care, extensive information and regular support, antidepressants were ineffective for 50% of those who took them and intolerable for 16%, a total of 66%. -- That was the first trial.  By the third trial, medications were ineffective for 83% and intolerable for 26%, more even than the total.

What I want to know is just how many people take antidepressants when they make them sick and/or don't work anyway?  I personally know three.  Consistent with research findings, that better educated consumers are more compliant, these three have among them a BA, a Masters and a PhD.

Is there something going on here that is not about good medicine?

Rethinking Consumer Noncompliance

Psychiatrist Allan Showalter, Rethinking Patient Noncompliance, challenges the premises behind repeated and repeated research on noncompliance, a behavior which found across other diagnoses, not to mention life issues ranging from flossing to portfolio diversification, as well.  Here is the video of an Iowa Hawkeye football player on a motorcycle, one week before the game with our biggest rival.  A football player.  No helmet.  Despite repeated pleas of Kirk Ferentz, the Hawkeye coach.

I do recommend that you follow Showater's link for the novelty of his thinking.  One example: Nothing in [the definition of noncompliance] implies a moral obligation on the part of the patient to follow those recommendations or to the clinician who makes those recommendations to enforce them.

Countertransference

Yuval Melamed and Henri Szor, The Therapist and the Patient: Coping With Noncompliance, focus on the relationship between the patient and therapist as the source of noncompliance, rather than taking patients at their word.  On the other hand, they use a word that I did not find in any other article.

Countertransference.  Okay, ignoring the definition that includes the word transference, [again -- so irritating when dictionaries do that], Webster's defines countertransference as the complex feelings of the psychotherapist toward the patient.

Melamed and Szor think that noncompliance arouses reactions in therapists who feel that this behavior exemplifies a lack of trust in them and in the corpus of knowledge they represent.  I think that takes us part way there.

It is the therapist's job to manage the dynamics of countertransference in what is an unequal power relationship. That management would include not allowing the therapist's feelings toward the patient to misinterpret the patient's experience as hostility and thus misdirect the intervention.

I have not found evidence that providers of medication ever explore the impact of their own feelings on their treatment of consumers, at least in the arena of noncompliance.  Countertransference is a regular part of psychotherapists' training.  If it is ever mentioned in medical school, none of the literature gives evidence that the lesson sticks.

Weighing the Costs and Benefits -- Progress Report

Sorry about all the numbers in this post.  I have not found in the research any effort to measure the costs side of you have to weigh the costs and benefits that is not filtered through the concept of noncompliance.  So the algorithm will suffer from research that is compromised by its initial assumptions.  Thta is why we had to start with the OMG Award.

Next week, the Muppets will give us a break, while my brain does a bunch of number crunching.

drawing of dictionary in public domain
Adam and Eve by Albrecht Durer, in public domain
photo of Warren G. Harding in public domain
photo of woman pointing taken by David Shankbone,
used by permission under the Creative Commons 
remainder flair from facebook

Thursday, September 2, 2010

Weighing Costs and Benefits Part II: Benefits

Today the Free Range Lab Rat, yours truly, continues my extended series on the Chemistry Experiment, that effort to find the chemicals that will make a dent in the suffering of those with mood disorders.

I asked, Will it work for me?

And the doctor answered, We won't know until you try it. 

THAT is the Chemistry Experiment. 

So three weeks ago I published my

Manifesto

If I am a lab rat, I will be a free-range lab rat.

Because I am a free-range rat, I decide which experiments I am willing to try.

Of course I do.  The doctor expects me to decide.  Why else did she say,

You have to weigh the costs and benefits. 

Only -- there is no scale.  Which led me, two weeks ago to continue my manifesto.



I now insist that I contribute more to this enterprise than my body.

So I have decided to create the scale.  I call it an AlgorithmAlgorithm is science-speak for a set of logical rules applied to objective data to solve a problem.  The problem to be solved is 

Do I Want To Put These Chemicals Inside My Body?

It turns out there are lots and lots of these costs and benefits to weigh.  The numbers you get in your fifteen minute med check are abbreviated and oversimplified to the point of useless.  So this is going to take a few weeks.  I am breaking it down, one step at a time.  Like I said, a set of logical rules applied to objective data to solve a problem.  I promise as few numbers and as many pictures as possible.  Plus another musical interlude.

Two weeks ago, I made a list of factors, all the things that go into the scale.  Today we look at the good side, what the doctor calls BENEFITS.

Here goes. 

Effectiveness Rate

Does it work?  That would be the place to start, don't you think?  Let's work through an example with major depression.  The way we put it in the lab, if 100 people with this condition take these chemicals, how many will get reasonably better?  Better, not cure.

A research psychiatrist at the University of Iowa once told me that cure is a 50/50 proposition, the first time you get major depression.  Half the people who take antidepressants for clinical depression, the first time, never get it again.  Other psychiatrists say that, too.  Nobody really follows the experiment long enough to find the cure rate, like, does it really mean for the rest of your life.

Anyway, cure doesn't apply to us lab rats who have been through a few trials.  By the third episode, the Grim has the key to our door, 90% of us, and can enter and exit at whim.  Most of us would settle for better, even if our psychiatrist is a take no prisoners type who wants to keep trying new chemicals to get to best.

A few years back, the National Institute of Mental Health did a major study on antidepressants called STAR*D.  Breathtaking, really, the amount of money spent on this six year study that neglected to include a placebo.  But never mind.  And contained some enormous methodological flaws.  But never mind.  Having stacked the deck in favor of the chemicals, the one thing it clearly demonstrated was that the more meds you try and that don't work, the lower the odds are that the next one will work either.

The first trial (the first time these people put the chemicals in their bodies, 49 out of 100 got at least a little better.  They call that the response rate, when you feel better.  The second trial, 29 of 100 got better.  17 for the third, 16 for the fourth.

The numbers were lower for those who actually recovered, i.e., stopped being depressed for a while.  That is called the remission rate.  Those results were 37, 31, 14 and 13 for each successive trial.  They call remission the "Gold Standard." Response vs. remission makes a difference for another benefit, delaying the time before you get sick again.  I will get to that next month, the Grim willing.

By the way, STAR*D tried a handful of different treatments at each stage beyond the first.  These numbers reflect the aggregate.  The response rates for individual medications vary somewhat, but are in the same ballpark.  The intolerance rates are a different story.  More on that in a later post.

BAIT AND SWITCH ALERT!!!

Yes, 65% of those who try antidepressants find relief in one or two tries.  But those are the odds at your first trial.  If that one fails, the first odds are now irrelevant.  It is a new roll of the dice.  The odds of your next trial are 30%.  A doctor who gives you that 65% figure at your second trial is not lying.  Let's just call it misdirection.

Clearly, what you need to know is the effectiveness rate of the medication you are taking for the trial you are now conducting.  The first time out, your odds are 50/50.  The third time, 17 for/83 against.  That doesn't mean you don't place your bet.  It just means the odds are different.

Effectiveness compared to placebo

Not all of your benefit comes from the chemicals themselves.  Some of it comes from the trust you have in the doctor who told you it would help.  This is called the placebo effect.  The placebo effect is your friend, because it makes your meds work better.

Companies that want to market a medication have to prove to the FDA that it works better than a placebo, not a lot better, just better enough that the difference wasn't by chance.

So, back to our example, in addition to the 100 who take the medication, there would be another 100 who take a placebo, sometimes called a sugar pill, because it has the filler, but no chemicals in it.

The people who give you the pills are not supposed to know which one you are getting.  Otherwise, the rest of the scientific community will howl.  But it turns out the human lab rats often figure it out for themselves, because they don't get the side effects they were warned about when they signed on.  Or they get them, but not so bad.

You see, human lab rats are smarter than the other kind.  Our ability to figure out what is actually going on means we might guess when we are not getting the real thing.  We don't expect the sugar pill to make any difference.  That lowers the effect of the placebo, and makes the chemicals test better than maybe they really are.  But never mind.

The placebo effect is a matter of huge debate nowadays.  Irving Kirsch tabulated the stats of lots of these experiments done before 1998.  He found out that if 30 out of 100 got better on the med, 22 of them would have gotten better anyway on a sugar pill.  With fewer side effects.

But nowadays, placebos are working even better.  The chemicals aren't working better, just the placebos.  You can bet the pharmaceutical companies are trying to figure this out, because it's like changing the curve on the grading system, so that it is harder for the chemicals to pass.  This is not good.  For them.  [The link at the top of the paragraph is to an article published at wired.com on August 24, 2009.  My own version was published three days later.  Dang, he scooped me.]

I am now going to make my first controversial move in the creation of this algorithm.  I am going to ignore the placebo effect.  Yup.  Totally ignore it.

First, the thing about the placebo effect, it is your friend.  It helps your medication work.  But you don't get the benefit unless you take the med.  What's the difference between them?  Side effects.  We will get to side effects when we calculate costs.  Just stay with me here.

Second, while you get fewer side effects on the placebo, which would be a good thing, lowering the cost side of the scale, you can't get the placebo.  It is not an option.  I know this, because I am very sensitive to side effects.  So I asked my doctor for a placebo.  She wouldn't give it to me.

But not to fret, those of you who are howling over this decision.  I will now consider a factor that might not have occurred to you, and may give the placebo effect its proper weight. 

The Natural Course Of Mental Illness

What if you had no treatment at all -- meaning no chemicals, and no placebo either?  We won't deal with Cognitive Behavioral Therapy, exercise, mindfulness, ECT, any of the jillion other approaches right now.  Acupuncture.  Once we have the algorithm, we can run it on these approaches, too, and then compare the results for each and for different combinations of them.  Boy, this algorithm is going to get a workout!

For now our approach is Hey, Doc!  Open up this hood of mine, find the problem, and fix it!  [Thanks to John McManamy for that quote.]

Some people get better without treatment.  Did you know that?  Researchers have the numbers on this.  It is called spontaneous remission.

Go back to that experiment with 100 on the med and 100 on placebo.  What if there are another 100 who want into the clinical trial, but have to wait for room?  Over the course of twelve weeks, up to 20% of them will get as much better as those 30 for whom the med was effective.  In the case of Major Depressive Disorder, it goes away.

Of course, it comes back.  And it does brain damage every time it does, which is no small matter, believe me.  That is another set of numbers.  We will factor them in when we get to long term costs and benefits.  I am not recommending no treatment.  Right now I am determining how effective any particular treatment is.

And remember, other people do not get better, at least not over the 12 week period.  The odds you will not get better over the course of the same twelve weeks we are giving an antidepressant to work is 80 out of 100.  I will call that the NONREMITTER RATE. 

Remember, these numbers are for illustration purposes only.  They vary widely, depending on how many medications you have tried, and what the condition is for which you are being treated, and how long you take it, too.
 
CAUTION CAUTION CAUTION CAUTION

Do I have your attention?

I CANNOT recommend placing a bet on spontaneous remission for schizophrenia (not a mood disorder) or bipolar I.  Those odds are 0, nada, nil, zip.  There is some evidence that after decades of lost, lost, lost years, schizophrenia may partially remit.  And the manias of bipolar I are typically short-lived.  But the bankruptcies, divorces, sexually transmitted diseases, homelessness and criminal records that may be the consequences of no treatment are not short-lived.  If you dodge one of these bullets for one episode, you are still playing Russian roulette with a machine gun.  It is not easy, it really sucks to admit that you have a serious problem.  But if you want any shot at all for a decent life, suck it up and join the Chemistry Experiment.  You can still choose which one.

So where are we?

PROGRESS REPORT:

The essential short term benefit of the Chemistry Experiment is that you might feel better.  We have examined different factors to calculate the odds of this benefit.  Now let's give these factors some abbreviations, because abbreviations, being obscure, always make equations look more scientific, not to mention elegant.

E#PT = The Efficacy rate for the medication at the Number of Present Trial we are now undergoing.  (What are my chances now that I have already tried 1, 3, 8 different medications and/or combinations thereof?)

NSR = Non-Spontaneous Recovery Rate  (In the clinical trials, what percent of the recovery was genuinely caused by putting something in their mouths, not simply by the passage of time?)

NSR is a fixed number that depends on the time frame: 80% for Major Depressive Disorder over twelve weeks, 100% for schizophrenia, bipolar, and chronic depression, too.

When you are sitting there in the doctor's office, feeling like shit, and the doctor tells you you have to give this medication a shot for at least twelve weeks to know if it really does help you, but it's really important that you treat this disease or it will get worse, and you can hardly imagine feeling like shit for another twelve weeks, but what can you do, and then the doctor tells you to weigh your costs and benefits, then my guess is you are not looking any further down the road than those twelve weeks, if that far.  What you want is the Down and Dirty.

So here is the Down and Dirty way to calculate Benefits:

E#PT X NSR = Short Term Benefit.

That's Efficacy for Number of Present Trial times Non-Spontaneous Recovery Rate.

These numbers are very, very difficult to find.  The lab rats who are expected to put these chemicals in our mouths are told that the chemicals work better than placebo, which they bloody well better, because otherwise the FDA shouldn't have given the pharmaceutical company its license to print money.  The prescribing doc, otherwise known as the pusher, (okay, that was harsh) probably doesn't have any better numbers than you have.

But it is my contention that the FDA should require the true odds to be printed on the Prescribing Information sheets, the ones the pharmacy gives to the patients and the ones the sales reps give to the doctors.  And these numbers should be updated as laboratories other than the ones who make the medications try to duplicate the results.

Whew!  Next two weeks on costs, beginning with this month's coveted OMG Award.
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