What Happened to My Bipolar Brain and How Do I Fix It?

The most troublesome statement in Goodwin and Jamison's Manic Depressive Illness may be this: "Complete symptomatic remission does not ensure functional recovery." This is no small problem. For some 30% to 60% of patients with bipolar disorder, simply treating their mood symptoms is not enough to help them return to a full life.

There’s a third pole that needs to be addressed for that to happen: cognitive symptoms. These often persist even when patients are euthymic, and they range from problems with memory and attention to more subtle deficits such as picking up on social cues and making wise decisions. 

Chris Aiken's article, Eight Ways to Improve Cognition in Bipolar Disorder, opens with these paragraphs. Ironically, what Aiken calls troublesome, I find immensely reassuring. My experiences are real!

Misconceptions about Antidepressants

What do you think are the most common misconceptions about antidepressants?

Prozac Monologues: A Voice from the Edge is at the press kit stage with Q&A in development. My publicist wants me to answer questions that interviewers might ask. My responses should be in the three to seven sentence range, she says.

Three to seven sentences are not my forte. I am doing my best and taking comfort that in an interview format, there might be a follow-up when I can say more.

They are good questions and worth a blog series, I think, where I can expand to three to seven paragraphs. Mostly seven. Maybe more. Plus, you know, pictures. So that's what you get for a few weeks.

No, antidepressants are not happy pills

Antidepressants and Suicide: A History

Do antidepressants prevent suicide, or do they cause it?

Yes.

Well, maybe.

It's a no-brainer, right?  People who commit suicide are depressed.  Take away the depression, and how better than with an anti-depressant, and you decrease the risk of suicide.

So what's with the question?  Here is the story:

History of Antidepressants

Looking Under the Hood - A Better Depression Diagnosis?

Corrected July 7, 2013

Maybe my writer's block is an Ecclesiastes issue.  There is nothing new under the sun.

But finally, there is.  No, not the DSM.  Keep reading.

The DSM. Sigh.

But regarding the DSM, and it makes no difference at all which edition, you have to wonder when somebody who is suicidal, losing weight, irritated at the drop of a hat and can't sleep gets the same diagnosis as somebody else who is immobile, gaining weight, couldn't be bothered about anything anymore and sleeps the night and day away.  It's all depression -- the DSM's junk drawer.

Finally, somebody thought to sort the junk drawer, by looking inside the brains of these two sorrowful souls, both taking the same meds for God's sake.

PET Scans - Looking Under the Hood

Helen Mayberg and her team at Emory University School of Medicine used PET scans to look under the hood (to use John McManamy's favorite metaphor).  PET scans use a radioactive tracer to determine where glucose is being used in the brain, i.e., what part of the brain is busy.

Schizophrenia -- Taming the Dragon

Imagine you have a dragon in the house.

It has been there a long time.  When it was little, you could hide it.  You knew your parents didn't like it when you talked about it.  So you guarded it as a secret for the longest time, even with its nasty habit of singeing your fingers.  But when the couch caught fire, they knew, and insisted you get help.

They want you to get rid of the dragon.  Some of them think you can.  Others think you can tranquilize it, and the couch will never catch fire again, and nobody need ever know you have a dragon in the house.

Iron Rule #1:  You cannot get rid of the dragon.  It is here to stay.

Recovery - From What?

Recovery is the individual lived experience of moving through and then beyond the limitations imposed by the disorder, by the world around us, and even by the treatment itself.

Huh?

Okay, the deal is, unless you know where you are going, it's tough to get there.

Recovery Defined as Escape from the Symptom Silo

The docs know where they want to go.  They want to get rid of your symptoms.  Your illness is defined by a list of symptoms, found in the DSM and measured by survey instruments, and when you score in the normal range, then you have recovered.

Which is sort of like saying that if you don't have chest pain or shortness of breath, then you have recovered from heart disease.  Cardiologists don't think that way.  They want to know the condition of your heart, not just your symptoms.

No New Year's Resolutions - Change Your Life

Weight Loss For Sale

It's all done with computers.  Automatically, 12:01 AM !2/25/2011, the Target ads disappear from television screens and Facebook sidebars, the Jennie Craig ads go up.  Next morning, the Lifestyle section of the newspaper switches from appetizer and eggnog recipes to yogurt and exercise programs.  After months of selling excess, now it is time to sell restraint.

How did it work for you last year?  It worked really well for the media.  How did it work for you?

You can't buy change.  And sure as one set of ads replaces another at 12:01 AM, you cannot lose weight by buying a weight loss program.  You yourself, not just your body but even your brain has to change.

Meanwhile, Excess Weight is Killing Us In The US 

How many times have you heard that the US has the best health care in the world?  I won't dwell on that nonsense.  But clearly we do not have the best health.  Out of 221 nations, the US ranks #50 in life span.  That puts us at the 77%, a low C at St. John's Parochial School where I went, maybe a B in public school, grading on the curve.  So to speak.  Meanwhile, compare Jordan at #29, South Korea at #41 and Bosnia/Herzegovina at #45.

Those numbers come from the CIA's World Factbook, where they say Life expectancy at birth is also a measure of overall quality of life in a country and summarizes the mortality at all ages. It can also be thought of as indicating the potential return on investment in human capital.  In other words, a low C, B if grading on the curve, is the quality of life you get healthwise if you were born in the US, the country with the best health care in the world.  Who came up with that claim, anyway?

In a different but related index, the World Health Organization charts BMI, Body/Mass Index, a measure of weight in relation to height.  The US ranks #54 out of the 60 nations for which it has data, for percentage of people with normal weight, neither too heavy nor too thin.  That puts us at the 10th percentile, an F-, whether grading on the curve or no curve.  Only 36% of US citizens have a healthy weight. 

And the cost?  Cardiovascular disorders (high cholesterol, high blood pressure, heart attacks, stroke), metabolic disorders (diabetes) cancer (breast, cervical, uterine, prostate, colon, kidney...), arthritis, sleep apnea... That is the short list of health complications and loss of life associated with excess weight.  I will let you come up with your own list for what you have less of on account of what you have more of...

Excess Weight Is Slaughtering Those With Mental Illness

Meanwhile, back in Prozac Monologues Land, people with severe mental illness beat out the rest of the population in the race to break the scale.  Clinical studies have reported rates of obesity in patients with schizophrenia or bipolar disorder of up to 60%.  That compares to 34% in the US population, a number that already staggers the imagination as it is.

The reasons for the difference are many:

• The most common medications for these disorders, lithium and antipsychotics, especially the new ones are notorious for weight gain.  It is surmised that the weight gain comes from disrupting both metabolism and the neurotransmitters that regulate appetite.

• But medication-naive patients also have a higher risk for overweight and obesity.  The negative symptoms of schizophrenia and the depression-part of bipolar (lack of interest, inability to feel pleasure) lead to more sedentary lifestyles and more weight gain. 

• From the Damned-If-You-Do-And-Damned-If-You-Don't Department, the medications for schizophrenia and bipolar mostly reduce the positive symptoms (delusions in the case of schizophrenia, high energy in bipolar - the symptoms that scare your families and your care providers who write the prescriptions).  They tend to increase the negative symptoms (thereby relieving the anxieties of your families and your care providers who write the prescriptions), providing that synergistic effect that nails you to the sofa.

• There may be pre-existing genetic connections between what is considered two different conditions, overweight and mental illness.  The DSM defines mental illnesses on the basis of certain symptoms.  It does not describe what is actually going on inside the body to produce the symptoms.  Metabolism, energy levels and regulation of appetite are all controlled by parts of the brain, often with genetic predispositions.  While these are included in the symptom lists for mental illness, they are not the defining symptoms targeted by treatment.

Add it all up, what do you get?

People with severe mental illness die 15-25 years before the US national average.  Rwanda beats us.  We have the life span of people born in Sudan.

What do we die of?  No, suicide is not a significant factor in this equation.  We die of cardiovascular disorders, metabolic disorders and cancer.  Just like everybody else who weighs what we weigh.

What Are Our Doctors Doing To Save Our Lives?

Our doctors are doing their best to prevent symptoms of our mental disorders, the scary symptoms, hallucinations, delusions, too much energy combined with poor judgment that get us into trouble with the law.

They are not doing anything about what is going to kill us.

Well, okay, they are psychiatrists; they treat psychiatric disorders.  They are not general practitioners nor weight-loss specialists.

So here are two more reasons embedded in the US health care system that contribute to our lethal obesity.

• Notwithstanding that excess weight is a symptom of our disease and also a side effect of treatment, our psychiatrists consider our weight issues to be none of their business.  Never mind how significant this unaddressed health issue is when it comes to whether we are even willing to take the meds they prescribe.

• People who have mental illness are less likely to have health insurance.  We are less likely ever to see any doctor other than the one at the community mental health center who is treating our mental illness.  Not to mention access to weight loss programs.  Not to mention money for fresh foods or exercise programs.

The upshot: what are our doctors doing to save our lives?  Precious little.

Okay, having said that, some doctors are doing more.  My doctor listened when I told her my family medical history, that everybody in my family dies of heart disease, that my younger brothers had heart attacks at age 55 and age 29.  When I said I would not take Seroquel unless I was psychotic, she paid attention.  She tried to find meds that are weight neutral that I could tolerate.

But from the things I have written lately about my current psychiatrist, my readers who have real life experience with psychiatrists know that she represents a minority in the profession.

We Have To Lose Weight Anyway

What most patients get from most doctors is the pro forma reminder that we won't gain weight if we don't eat more than we expend in energy.  So all we have to do is eat less and exercise more.

There.  Their responsibility has been discharged.

Here, as in almost every area of our recovery, we are on our own.  Recovery is up to us.

We have to lose weight anyway.  We have to.  It's our hearts, our blood vessels, our pancreases, our knees and hips, our brains, our lives, 15-25 years worth of our lives that are at stake.

 

We will be swimming upstream, up against the forces of whatever is going on in our genes, our dopamine channels, our pineal glands, our medications, our lack of health care, our poverty.  So?  Salmon swim upstream all the time.

Salmon are programmed to swim upstream.  We have to program ourselves.

A New Year's resolution will not change the program.  Did it last year?

So here comes a series on reprogramming our brains.  It is a series, because we have to take it step at a time.

Word of encouragement: If you made it to the bottom of this post, you are probably already past the first step.

Who knows, maybe this series will carry us past the New Year's/Jennie Craig/NutraSystem et al season and up to the Super Bowl/Bud/Doritos season!

Note added, 01/02/13 -- The following are links to the rest of this series:

The Stages of Change and Weight Loss January 3, 2012 -- How do you change a habit?

My Food Autobiography and the Stages of Change March 8, 2012 -- Pre-contemplation and contemplation.

Changing Food Habits -- Contemplation and Preparation March 15, 2012 -- Reviews The End of Overeating by David Kessler and introduces the brain science of the sugar/salt/fat trifecta.

Dopamine -- Can't Live Without It March 23, 2012 -- The brain science behind habit formation and an experiment to try.

Preparation/Action -- Reprogramming Your Brain for Healthy Eating April 26, 2012 -- How to change a habit.

Relapse/Maintenance -- Stages of Change May 24, 2012 -- Review and finishing up the series.

clipart and photo of school paper from Microsoft

photo "Angry Father" by Akapl616.  Permission is granted to copy under the terms of the GNU Free Documentation License

photo of salmon in Ketchikan Creek by Wknight94 and used under the terms of the GNU Free Documentation License

Sleep -- The Real Antidepressant

Your sink has backed up three times in as many weeks.  This time the plunger won't work, and it's beginning to stink.

The hardware salesman says you need a new garbage disposal -- $169.00.

Your plumber takes the pipes apart and clears the plug.  Depending on the plumber, she might show you how to do it yourself next time.  (My plumber is a woman.) -- $60.00 in my neighborhood.

Your brother says, stop putting banana peels in the garbage disposal.  (My brother owns rental property, and tells me what the plumbers almost always find in the plug.) -- $0.00.

The hardware salesman says a better garbage disposal could handle banana peels, and whatever else might also be causing that plug -- $249.00.

All of them are trying to help.  Each of them is working with the tools at his/her disposal.

Okay, now let's look at your depression.

Remember last week's list?

DSM On Depression -- The Chinese Menu

Weighing Costs and Benefits Part V -- Down and Dirty Algorithm

SE + NE + $$$ + STG + TR = STC.

E#PT X NSR = STB.

STB TO STC = ODDS OF SUCCESS

There it is, the Prozac Monologues Down And Dirty Algorithm, to weigh your costs and benefits for medication or any other treatment for any mental illness, or any other medical condition, for that matter.  Click on the first and second lines.  They will take you to the posts that develop the formula.

Can you believe we finally made it?

We started with the:

Manifesto of a Lab Rat. 

I am a Lab Rat.  Yes, I am.

The Manifesto begins there.


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

What I mean by free-range lab rat is this: 

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

Your doctor tells you to weigh your costs and benefits, but gives you no way to do so, other than insufficient information + gut + desperation = noncompliance, if you don't come up with the same answer as your doctor.

What we need is an algorithm: logical rules that we can apply to objective data to solve a problem.

This algorithm does not exist.

So as an interested party, a very interested party, given that my body is the test tube, I decided that my contribution to this chemistry experiment would be the algorithm.

The problem we want to solve is this:

Do I Want To Put These Chemicals Inside My Body?

This task has continued over several posts this fall, interspersed with a few sick leaves and vacation days.  Click on costs and benefits to follow the whole development.  (The first post is at the bottom, dated August 19, 2010).

What To Do With The Algorithm

The resulting algorithm can be applied not only to the chemicals you put in your body, but any other form of treatment as well, talk therapy, aerobic exercise, yoga, Chinese medicine, acupuncture, even aroma therapy, should you choose.

You can compare the results of the cost/benefit analysis of different treatments, and do the same with various combinations, when you can find the numbers.  Which admittedly, you cannot for any of these that do not get Blue Cross Blue Shield reimbursement.

There are numbers out there for talk therapy and aerobic exercise.  But doctors do not usually use the word therapy for anything other than chemicals or electro-convulsive therapy (ECT) or any of those new-fangled electrical interventions.  That is the context in which you are told to weigh your costs and benefits.

For the most part, I have used antidepressants as examples.  One out of every ten people in the United States is taking them right now.  So this would be the most common application, among psychotropic medications.

It was helpful to look at chemicals as I developed this algorithm, because they are the form of treatment with the greatest costs and greatest variety of costs:

dizziness and confusion,





insomnia and fatigue,

weight gain, irritability, sexual dysfunction,  irritability.




So this is what you do when you use the algorithm to weigh your costs and benefits -- you compare two numbers, STC (Short Term Costs) and STB (Short Term Benefits).

And how do we get those numbers?

Remember,

SE + NE + $$$ + STG + TR = STC.
E#PT X NSR = STB.

The abbreviations increase the confusion quotient, and thus make it look scientific.  Here is a translation:

Side Effects (SE) plus Not Effective (NE) plus Money ($$$) plus Stigma (STG) plus [lack of] Trust (TR) are your costs (STC).  These costs are based on the reasons people give for discontinuing their medication.

Efficacy Given The Number of Present Trial (E#PT) times How Many Would Not Experience Spontaneous Remission Unless They Took the Medication (NSR) are your benefits (STB).

Did you like my illustrated tour of the previous posts?

And Where Are We Supposed To Get Our Data?

They ought to be provided to you by your doctor, who has told you to weigh your costs and benefits.  Except for money, stigma and trust -- you have to come up with your own odds that you will quit taking your medication because you can't afford it, you are afraid for your reputation, or you do not trust your doctor.

They ought to be provided to your doctor by the drug reps.

But they are not.

So you have to do your own research.

I think the algorithm would make a fabulous app.  The numbers could be regularly updated, from the latest research by scientists not funded by the companies that sell these chemicals.

I claim copyright, by the way. 

Long Term Costs And Benefits Are Missing

Notice that I refer to short term costs and benefits.  Some will object that I left out good reasons to take meds: the difference that meds make to how quickly another episode occurs (relapse rate), how long various approaches take to work (time to remission), how medications affect things like brain mass, suicide risk.

Others will object that I left out good reasons not to take them: the possibility that medication might accelerate the natural progression of the disease, the possibility that the diagnosis is off and you will flip into mania or hypomania, liver damage, the consequences of weight gain, such as heart disease and diabetes, suicide risk.

Someday I will do a post or two on that suicide risk issue.  There is a lot to say about that.

Well, this algorithm is complicated enough and took five posts already.  This one has that i-Pod potential.  The one that includes all those other issues will take more gigabytes.

STC versus STB give you the odds.

Once more I repeat, they do not give you your decision.  There are additional personal factors that influence or even override logical rules, objective data, and problem solving.

Personal Factors:

You have used up your sick leave, your vacation time and your family leave for this year and next, and your boss will fire you if you don't start taking meds.

Your wife has issued a similar ultimatum.

You can't get out of the loony bin any other way.

You are desperate.

You have the knife to the wrist.

Like I said, it is your decision.  I am merely your humble servant.  Who does occasionally buy a Powerball ticket.

How Does The Algorithm Work?

Let me give you a personal example.

When I first took Prozac, Eli Lilly's website said that it had helped 70% of the 55,000,000 who had already taken it.  I didn't know anything about spontaneous remission or the effect of which trial this was.  So STB = 70.

Meanwhile, none of the side effects (SE) reported went above the 15% range; the odds that it would not be effective (NE) were 30 out of 100; it was already generic, and I could afford it ($$$); stigma (STG) was not an issue for me; and I had total trust (TR) in my doctor.  So STC was 15 + 30 + 0 + 0 + 0 = 45.

That meant (with the information I had) that the odds for Prozac were 70 to 45 in favor.  And I could put off therapy.  No brainer.

Next up -- actually, five keep trying's later, we had moved on to a psychiatrist who prescribed Effexor.  Crazy Meds says: for deep, despairing clinical depression that needs to respond to the standard tweaking of the three most popular neurotransmitters, Effexor XR (venlafaxine hydrochloride) often pulls people out of the abyss.  By then, the deep, despairing abyss -- that would be me.

My doc said I get good results from Effexor.  She didn't say how good results translated to a number,.  (That's case studies, by the way -- not research.)  But she did tell me to weigh my costs and benefits.  By then I knew that most antidepressants have about the same effectiveness level, which I took to be around 40%.  I didn't know it mattered that I was on my sixth go round.  Odds for benefit, STB = 40%

She also gave me the usual side effects, because I asked.  Since insomnia was a major issue for me, and we had run through a number of sleep aids, she said that the insomnia risk (SE) was 15%.  Not effective odds (NE) would come in at 60 out of 100.  Since she didn't ever answer phone calls, and I knew I couldn't stop this med without help tapering off, and I was wary of her by now, I grilled her on how to discontinue without her help.  Trust, lack thereof, (TR) was in the 40% range.  STC was 15 + 60 + 40 = 115.

With Effexor, my odds were 115 to 40 against.  Not so good this time.  However, desperation overcame gut instinct.  So I kept trying.

The rules of the algorithm work, but the results are only as good as the objective data.  What if I knew then what I know now?  Without going into the whole story, and by tweaking numbers actually available: 

Prozac -- 

STB = 40 (E#PT) X .8 (NSR) = 32.
STC = 30 (SE) + 60 (NE) + 0 ($$$) + 0 (STG) + 20 (TR) = 110. 

110 to 32 against.  I still had issues with therapy (nothing to do with any therapist I have ever known, by the way).  And being over-educated, I am on the compliant side.  So I would have given it a shot. 

Effexor --

STB = 10 (E#PT) X .8 = 8.
STC = 34 (SE) + 92 (NE) + 0 ($$$) + 0 (STG) + 95 (TR) = 221.

221 to 8 against.

The numbers for Effexor come from the STAR*D study, and were available at the time I started taking it.  But I didn't know that.  STAR*D's original conclusion was that after two antidepressants have been tried, subsequent results are dismal, and more research for better medications should be a priority.

Since then, a jillion articles have been written about how STAR*D was a lousy research design that cooked the books in way favor of the chemicals at every step, starting with the selection of subjects.  Click here for my posts that reference STAR*D.  But Google it for for what the scientists say.

Anyway, 221 to 8 against -- I would have given it a pass.  Even I could tell the books were cooked.  And I got so much better after I went off it.

And So The Manifesto Of A Lab Rat Concludes

Of course, your results may vary.  Just remember, it's your test tube.

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Photo "Angry Father" by Akapl616.  Permission is granted to copy
under the terms of the GNU Free Documentation License

i-Pod family photo by Matthieu Riegler, licensed under

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photo of Warren G. Harding in public domain
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used by permission under the Creative Commons 
Attribution-Share Alike 3.0 Unported licence and modified

photo of prozac by Tom Vasco and is licensed under

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permission to copy and modify granted under GNU Free Documentation License

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.

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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

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-adherence.  Non-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.

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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 Algorithm.  Algorithm 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