Showing posts with label chemistry experiment. Show all posts
Showing posts with label chemistry experiment. Show all posts

Giving thanks for Jerod Poore

Jerod Poore is the walking, talking, tweeting, posting wikipedia of all meds psychiatric and neurological. His manifesto: At Crazymeds [his original website] we make psychiatric and neurological conditions (AKA brain cooties) our bitches with evidence-based medicine and a healthy dose of gallows humor.

When I caught brain cooties fourteen years ago, Jerod was the first person I found who gave me genuine information. When the docs turned my brain into a chemistry experiment, Jerod told me what was happening to it.


That's the sketch I drew of my brain on drugs. Not the drugs they warn you about, but the drugs they scold you for refusing to take. Prozac, Celexa, Remeron, Cymbalta, Effexor.

Physician-Assisted Suicide for Mental Illness - It's Complicated, or Not

Two years ago, Mark Komrad attended and presented at a symposium in Belgium on physician-assisted suicide for people with mental illness. Komrad is a clinical psychiatrist, ethicist, and faculty member at Johns Hopkins. He just finished a 6-year tenure on the APA Ethics Committee and helped craft the current APA position on Medical Euthanasia for non-terminally ill patients. [That position joins the AMA to say, in a word, Don't.]

Komrad reported back on his experiences to PsychiatricTimes.com. You can read or listen to the his entire report here. This post quotes the parts that particularly struck me from a suicide prevention perspective.

In 2002 Belgium legalized euthanasia by physician (typically by injection) at the request of patients, and removed any distinctions between terminal vs. nonterminal illness, and physical vs. psychological suffering. As long as the condition is deemed "untreatable" and "insufferable," a psychiatric patient can be potentially eligible for euthanasia. There is a consultative process that basically needs a minimum of two doctors to agree about the patient's eligibility. Also, the patient gets to weigh-in on whether their condition is "treatable." Since the patient has the option to refuse treatments, this refusal may create an "untreatable" situation.

Bipolar, Not So Much - A Review

Recurrent depression, treatment-resistant depression, depression with mixed features, cyclothymic disorder -- if your file at the doctor's office is coded for any of these, my heart goes out to you. Chances are you have taken a number of turns around the antidepressant not-so-merry-go-round. I call it "The Chemistry Experiment," and you are the test tube.


Chris Aiken and James Phelps have written the book for you. Bipolar, Not So Much: Understanding Your Mood Swings and Depression introduces the reader to the Bipolar Spectrum. No, they are not talking about the movie version of bipolar, throwing furniture out the window, driving the car into the river... They mean the vast ground between that and your basic depression. They mean depression - with something more.

The authors use a conversational style, speaking directly to the reader and skipping the jargon. They begin by explaining the spectrum. They don't ask the question the way the DSM frames it, Does this person have bipolar? Rather, their question is, How much bipolar does this person have?

Like this:



You won't find the spectrum in the DSM, the manual of diagnoses. The DSM’s symptom silos are designed to put you in one slot or another. The silos came into existence in the 1960s. The spectrum approach is much preferred by the acknowledged experts in bipolar, starting with Goodwin and Jamison who also prefer the name manic depression. But in the recent revision,there was huge resistance to making the change back to the earlier understanding of the disorder. Symptom lists with their precise cut off points seem so tidy and are easier to code. So they remain in the DSM-5, and people like Aiken and Phelps write books to try to inform people who don't know anything more about bipolar than the damn lists. But I digress...

Aiken and Phelps take the approach that you will get the best recovery if you know what is actually going on. So first they thoroughly ground the reader in the spectrum concept, and include the diagnostic and predictive instruments that all the docs can access, but usually don't take the time to use. Damn, I am digressing again...

Next they spend a lot of time on lifestyle changes and other nonpharmocological treatment measures. The thing is, the meds were all developed and work best for the folk on the far ends of that spectrum. Which you already know if you are somewhere in the middle, because they don’t work so well for you, which is how you became a Chemistry Experiment. 

Actually, even if you are clearly unipolar or clearly bipolar 1, Aiken and Phelps have good advice for you regarding sleep, diet, exercise, supplements, and the rest. You’re just going to do better if you don’t ask the meds to do all the work. Mood disorders are more complicated than that mythological chemical imbalance. 

The book's third section is a thorough listing and discussion of all the meds. They have their favorites which may be different from your doctor’s, because they don’t talk to drug reps nor read the ads. They read (and do) the research. Are you getting the sense that I have an agenda here?

Bipolar, Not So Much is the essential resource for for anybody who has depression and maybe something more. It is backed up by Phelp's excellent website PsychEducation.org. It is a humane book by humane doctors who listen and learn from their patients. What a concept, huh? Their dedication page tells the tale:


To our patients. You showed us what life is like in the mood spectrum, and we hope we got it right, or at least close, in this book.

flair from Facebook.com
book cover from Amazon.com
bipolar spectrum graphic from PsychEducation.com.

Return to the Chemistry Experiment

What is it like, this chemistry experiment, you ask.  Somebody did ask, honest.

Prozac Monologues strives to be journalism, not journaling.  I write for education (mine first, then yours), not for therapy.  So when the story turns to the Chemistry Experiment, a topic I write about so often, it gets its own label, I have tried to season my prose only lightly with my personal story.

But the Chemistry Experiment has been excruciatingly personal these last several weeks.  And nowadays, the personal story is one way that journalists frame their reporting.  So here goes.

More on Mood Charts

This is my personalized mood chart.


You can find a larger and clearer image here. It was inspired by the one my mental health insurance provider sent me when I began taking mood stabilizers. Last week I described how their chart works and how people with mood disorders benefit from using any of the great variety out there.

Cigna's chart primarily tracks mood. Using theirs, I learned that lamotrigine made a difference to the course of my symptoms. After years of inappropriate prescriptions of antidepressants, I had moved to rapid cycling. No, rapid cycling means several cycles in a year. More like, I was spinning, from the depths of depression to raging agitation within each week, week after week. Lamotrigine did modify that pattern. It stretched the cycles, down from four to two a month. By recording the pattern, eventually I concluded, and I had the evidence to support it to my doctor, that the costs of the medication (dizziness, fourteen hours of sleep and grogginess a day, losing words) outweighed the benefits.

More Than Mood

But Cigna's chart was missing vital information. Mood dysregulation was only part of my experience. It was the agitation, sense of urgency, poor concentration, lack of sleep that put me on the disability roles. And, I began to suspect, these disturbances in energy levels were driving my suicidal thoughts as much as my depression was.

Mood Charts Revisited

Mood chart is one of the top search terms that bring people to Prozac Monologues. I wrote about mood charts in July, 2010, first as a recovery tool and later as a way to illustrate the differences between various mood disorders. Both posts promised sequels, promises that remained unfulfillable until now that I have spent several months doing cognitive remediation at Lumosity.com. Maybe cognitive remediation is worth another post -- later.

Following last week's tale of misdiagnosis and mistreatment, this week's long delayed return to mood charts seems timely.

What is a Mood Chart

Anniversary - Prozac Monologues

Do you take antidepressants for depression and you are not getting better?  Do they make you agitated, anxious, insomniac?  Have you heard it often takes a while to find the right med, so you keep trying, you brave little soldier, you?

My friend, today you tapped your ruby slippers together, and Google brought you here.  Maybe not to your home, but to mine.  What follows is the back story to Prozac Monologues.  But first things first:

Stop.  Stop trying.  Go no further until you have taken the MDQ, Mood Disorder Questionnaire, right here at this link, and have asked a friend or housemate who knows you really well and loves you enough to tell the truth to fill it out for you, as well.

Recovery Redefined

 The Medical Model Failed

We got sick.  Well, we were already sick.  We sat in the doctor's office, while the doctor quizzed us about our behavior, sorting out where we belonged in the DSM's symptom silo.

Next the doctor enrolled us in The Chemistry Experiment, prescribed the chemicals that were supposed to reduce those behaviors.  Not fix our brains, mind you.  Nobody has been testing whether these chemicals fix our brains, just whether they change our behaviors.

Recovery - The Medical Model Continued

Last week I began scavenging my upcoming Mental Illness Awareness Week presentation Recovery: Rewiring the Brain for a series of blog posts.  I left you in the middle of the Medical Model.  The graphic is on the left.  The narrative left off as the person with the broken brain was reading the patient information sheet, gulped at that list of side effects, remembered the doctor said she should weigh her costs and benefits, and then discovered that, according to the patient information sheet, the doctor had already done the weighing for her, and all she had to so was swallow the damn pill.

The Chemistry Experiment

The way it actually happened was this.  The sixth antidepressant my doctor wanted to try, she said, I get really good results with this medication.

So I wanted to know, remembering the results I got from her last brilliant idea, or rather, from the samples she had just received from the last sales rep, What kind of results will I get?

Grief? Depression? Both?

The New York Times reports this week on a proposed change to the definition of depression for the Diagnostic and Statistical Manual (DSM) V. Asking, When does a broken heart become a diagnosis? it raises the specter that normal grief at the death of a loved one could be classified as a psychiatric disorder.

An estimated 8 to 10 million people lose a loved one every year, and something like a third to a half of them suffer depressive symptoms for up to month afterward, said Dr. Jerome Wakefield, author of The Loss of Sadness. This would pathologize them for behavior previously thought to be normal.

Okay, before we get our knickers in a twist -- oops, too late. Knickers in a twist is the current US national pastime. Nevertheless, there is a larger context here. Several, in fact.

DSM Context I - Follow The Money

I Told Them I Was Sick - DSM Revisited

Have you heard about the man whose tombstone read, "I told them I was sick"?

A New Diagnosis Or Two

So, the docs earned their big fee and the Pension Fund got its money's worth out of this three-day psychiatric evaluation.  I have a couple new diagnoses.

That is really not so remarkable.  If you attend a Peer to Peer course, NAMI's signature ten-week self-help program for loonies, you know this.  One week, the participants go round the circle and tell their diagnoses, or rather, their history of diagnoses.  Most trace a whole tour through the DSM, the Diagnostic and Statistical Manual.

Where Diagnoses Come From

Dopamine and Dementors



Dementors are among the foulest creatures that walk this earth. They infest the darkest, filthiest places, they glory in decay and despair, they drain peace, hope, and happiness out of the air around them... Get too near a Dementor and every good feeling, every happy memory will be sucked out of you. If it can, the Dementor will feed on you long enough to reduce you to something like itself...soulless and evil. You will be left with nothing but the worst experiences of your life.
-- Remus Lupin to Harry Potter
Harry Potter and the Prisoner of Azkaban

Been there?

While we wait with bated breath for the final episode of the Harry Potter movie series, here is a post on the neuroscience of Harry's worst nightmare.

Dementors, you see, are dopamine depleters.  They are not to be messed with.

Neither is any other kind of dopamine depletion.  Here is one clinical case, an experiment conducted on one highly-functional, never-a-whiff-of-mental-disturbance 21-year-old who received a dopamine depleting drug over the course of 25 hours.

The Future is Bright -- For Whom?

The Future is Bright for Psychopharmocology Breakthroughs --

Okay, I'll bite.

I subscribe to an online journal Psychiatric Times.  Or at least, I have access to the articles for which there is no charge.  I don't get paid for this, you know.  Anyway, I get emails that link to the articles of the week.

So that was the subject line on the email dated 4/21/11, The Future is Bright for Psychopharmocology Breakthroughs.

This I'd like to know about.

Inside the email was a link to Novel Treatment Avenues for Bipolar Depression: Going Beyond Lithium, by Roger S. McIntyre and Danielle S. Cha.

This I'd really like to know about.

The article was not what I had been led to believe.  But I learned a lot, will share some of that with you, and explore the miscommunication at the end. 

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.




flair from Facebook
Photo "Tired Man" by graur codrin
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
the Creative Commons Attribution 3.0 Unported license.png
photo of Warren G. Harding in public domain
photo of woman pointing taken by David Shankbone,
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
photo of effexor by Parhamr who has placed it in the public domain
photo of John LeCompte of Evanescence by Samuel Lang,
permission to copy and modify granted under GNU Free Documentation License

Weighing Costs and Benefits Part IV: Costs

Some people quit taking meds that their doctors believe will relieve their symptoms of mental illness.  Why?

Because the meds don't work, because they can't afford them, because the meds make them sick.

Manifesto:

For any of these reasons, people who quit are making intelligent decisions in their own best interests.

On The Other Hand 

Sometimes the meds do work.  Sometimes people have decent health insurance with good drug coverage.  Sometimes the side effects are not as bad as the disease.  In that case, those who quit their meds are stupid.

Let's just get that right out front.

Moving On To The Costs

Today my series on weighing costs and benefits turns to the costs.  The costs do not tell you whether you should try a medication.  They simply give you the odds.  It is up to you to decide how you want to play the odds.  I calculate the odds based on the numbers of those who quit.  Those who consume have the best information about costs, what actually happens when they put these chemicals in their own particular test tubes.

How Many Of Us Are Noncompliant?

Out of 100 prescriptions that providers write, 10 consumers never consume.  They don't show up at the pharmacy at all.

28 consumers quit within the first month.  That includes those first 10.

50 quit within 60 days.

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

That leaves 22 compliant consumers.

How Do Noncompliant Consumers Explain Their Decision?

10 out of the 78 don't.  Providers failed to close the sale.  Providers would be interested to know why these 10 are pharmacy no shows, because it might help them improve their pitch.  Their assumptions are that it was because the consumers didn't understand, or the providers didn't establish trust, or that good old back up -- stigma.  But often, consumers don't report their decision.

We could invent reasons, which might be fun, top ten list, that sort of thing.  The drinking buddy said, Buck it up.  Real men don't get depressed.  The transmission fell out of the car on the way to the drug store.  My favorite -- the primary care physician said, Are you kidding?  With your blood glucose and lipid levels?  Does this so-called doctor even own a blood pressure cuff?  However, all this speculation is just that.  These 10 do not give us information about the costs of taking the medication, because they never take it.

So now we have 68 consumers who quit after they tried the meds.  AK Ashton et. al. actually asked them why.

30 (out of the 90 who actually filled the prescription) say they quit because they could not tolerate the side effects.

30 say the medication was not effective.

That already adds up to 70 nonconsumers, counting the nonstarters and leaving eight who quit for other reasons.  I will suggest some of these other reasons, and you will have to come up with the odds yourself that any of them might put you among these 8.  (They may have reasons similar to the 10 who never started.)

And by the way, these numbers vary by how many different medications the consumer has already consumed, which primarily affects the efficacy number.  They also vary by which medication is currently being considered, primarily effecting the side effect number.

We don't have all the numbers we need.  Somebody needs to be collecting this data.  A consumer group, looking at real world data over the course of a year, not the guys with 6-8 weeks of information, seeking FDA permission and doctors' cooperation to sell pills.  But the algorithm itself will work for whatever the numbers turn out to be. 

Let's Start With Side Effects

30 of the 68 who consumed and quit say they quit because of side effects.  The clinical trials, lasting eight weeks or so, report much lower numbers.  The numbers the providers give you are from the clinical trials.

The common belief among providers is that they could improve compliance by giving consumers more information up front about side effects.  Small isolated studies sometimes confirm this over the short haul.  But this belief does not stand up to more research and more time.

Up front discussion of side effects can give the consumer strategies for dealing with insomnia, reducing nausea, preventing falls when they get out of bed.  These are the side effects we notice immediately.  Maybe they are tolerable if you have social supports to get you through the roughest first weeks.  Sometimes your body does  acclimate, and the immediate side effects become less bothersome.

But sometimes these strategies don't work.  Social supports wear out.  Mom has to go home and stop helping you with the kids.  You run out of sick leave.  The body does not adjust.  And sometimes these side effects are indications that you are taking the wrong medication!

But the major side effects appear later.  Which are the most bothersome?  The results: weight gain (31%), erectile dysfunction (25%), failure to reach orgasm (24%) and fatigue (21%).

Weight gain -- a few pounds in the first few months are not a problem.  You hardly notice.  But over the months, when you are moving from overweight to obese, you get a reality check on what this medication really costs.  Morbid obesity takes 8-10 years off your life.

Tell that to your psychiatrist when you complain and he/she says you have to weigh your costs and benefits.  Your doctor may not even know about how serious the health risks of obesity are.  Obesity even increases the risk of dementia.  But psychiatrists treat psychological problems with pharmacology.  They do not treat your heart, pancreas or liver.

Then there are the sexual side effects.  When you started the medication, you weren't getting much anyway.  That was one of the symptoms -- loss of interest in formerly pleasurable activities.  But six months later when you're not getting any, you (and your partner) recalculate your costs and benefits.

Hence, these noncompliance numbers go up over time.

Side Effects In The Algorithm

The major competition between makers of psychotropic medications has always been on this side effect issue.  It turns out, we just won't keep taking stuff that makes us feel worse.  So sometimes you can find studies that pit one against the other and get real numbers about side effects.

STAR*D found that in just 8 weeks, a combo of lithium/sertraline (Zoloft) got an intolerable rate of 45%, 2-5 times any other treatment.  Effectiveness rate -- 9%.  I wonder how many of the 91% who didn't get better would have been better off if they had taken nothing at all.

Or to put a finer point on it, did lithium/sertraline make matters worse?  They didn't test against placebo, so we don't know.

If the odds of harm are five times the odds of help, I will give it a pass.  That is like rolling the dice, looking for one particular number.  Only it's not dice; it is my body.  That is my personal decision, made after my eighth trial.  It is up to you how you play the odds.

For the sake of the algorithm, SE means the odds that you will quit taking this medication within a year because of side effects.

Efficacy -- What If It Just Doesn't Work?

We already discussed effectiveness in detail on September 2, Weighing Costs and Benefits Part II: Benefits.  Go back there for the details.  It makes more sense if you know the back story.  In summary:

Efficacy for Number of Present Trial (E#PT) means how many people got better with this med after they tried a number of others that didn't work.  Non-Spontaneous Recovery Rate (NSR) means how many people would not have gotten better if they had simply waited for the depression to go away on its own.  Efficacy for Number of Present Trial times Non-Spontaneous Recovery Rate equals Short Term Benefit (STB).  Those are the odds that it will work.

Or, E#PT X NSR = STB.

The abbreviations are there to make me look smart.  Which, as a matter of fact, I am.  Some days, I can make the smart parts of my brain connect  again and actually work smart.

Another way of looking at it: STB is a number between 1 and 100.  That many times out of a 100 are the odds that you have come up a winner.

So then the odds that the medication will not work are 100 minus Short Term Benefit.  We will call that Not Effective (NE)100 - STB = NE.  You have wasted your time, and are more discouraged than ever.  Bummer.

Now you may have noticed, the algorithm calculates the Short Term Benefit for eight to twelve weeks.  And the Short Term Cost refers to one year.  Why the difference?  Because you will likely be one of the early quitters (50%) if you don't get relief by twelve weeks.  And if you do get relief by then, you are likely to keep taking the medication for a year.  It may quit working for you eventually.  But you are probably good to go for a year.  Hence, twelve weeks for STB and twelve months for STC are probably equivalent measures.

Efficacy -- What About Those Who Quit Before They Gave The Medication An Adequate Trial?

I did not consider how many reported that they discontinued because the medication was ineffective, the 30 out of 90 that Ashton, et al, discovered in their survey.  This number is not helpful, because some of these 30 quit before the full 60 days needed to determine efficacy.

Instead, I used the efficacy numbers reported from the clinical trials.  As a result, those 8% discussed below is a larger group.  It would include the early quitters, because some of them might have gotten better if they had been more patient.

But these numbers are for illustration purposes only.  The algorithm is designed to be general, so that you can insert whatever the numbers turn out to be.

If you quit simply because the medication does not work faster than it works, and for no other reason, then you go into the stupid category.  Just to get that right out front.

Other Costs

8% (plus) quit taking the medication primarily for other reasons.  I expect that money, stigma and trust are the the big ones, with stupid in there, too, as stated above.

Money

Let's face it.  These medications cost money.  There are two costs to consider.  The first is the pills themselves.  The provider may provide you with samples, if yours is the newest wonder drug being promoted this week.  The samples likely last for two or three weeks.  This is good, if it helps you determine early on that there is no way you can tolerate the medication, even long enough for some of the side effects to become less troublesome.

On the other hand, it does not help you determine whether the medication will be effective.  That takes more time and your own money, a lot of it, if yours is the newest wonder drug being promoted this week, which you can count on, if you have failed to prove your provider a genius by getting better with his/her first or second choice.

If you have a good drug benefit, cost of medication may not be a major issue.  I now get my generics for free.  I represent a very, very small portion of the U.S. population.

I used to have insurance with a high deductible and mediocre drug benefits.  After the samples ran out, I paid $120 for a two month supply from a company that required I buy from them by mail order.  By the time the pills arrived, I had already discovered I couldn't tolerate the med.  I never even opened their bottle.  Meanwhile, I had to pay through the nose at my local pharmacy for the two weeks it took me to taper off.

In addition to the medications, you will pay for medical management, trips to the provider who will monitor your condition and tweak the chemistry experiment.

Again, these costs will vary by insurance plans and whether you have insurance at all.  With my current insurance, I pay $5/visit.  In my previous plan, I paid $40.  If I had no insurance at all, the cost would be $135.  And I see my doc every six weeks on average.

I cannot assign a number to the odds that you will quit a medication because of how much money it will cost you.  That is your call. Out of 100, what are the odds that you will quit because you cannot afford it?  We will call that $$$ in the algorithm.

Stigma

Okay, if you have made it this far through the Costs and Benefits series, you ought to be motivated enough to resist those who shame you (including yourself) for relying on a pill, for being weak, for being sick... whatever garbage they throw at you and you throw at yourself.  Please let's get over it.  I hope your stigma number is low.  But again, that is your call.  Out of 100, what are the odds you will quit for reasons of stigma? -- STG.

Trust

Next, out of 100, what are the odds that you will quit because you cannot find a provider you trust with your body, or because you think the pharmaceutical industry is corrupt? -- TR.

Stupid

Stupid is a side note.  Providers prescribe the medication because they already believe that the benefits outweigh the costs.  So they expect the stupid category is a large proportion of the noncompliers.   Only they call it confused.

Stupid is irrelevant to the algorithm, which is designed to weigh costs and benefits.  So stupid (or confused) is not in there.  Like stigma, stupid can be fixed.  But it is not a cost.  It is a prior condition.

Down And Dirty Costs

So now we simply add the odds of each of these costs together:

Side Effects plus Not Effective plus Money plus Stigma plus Trust (lack thereof) equals Short Term Costs.

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

So How Do You Decide?

STC versus STB give you the odds.  Once more I repeat, they do not give you your decision.

We will look at a couple other issues and pull this all together in our next installment.  Whew.  My brain is about to explode.

Flair from Facebook
Clipart from Microsoft
Photo of die by Roland Scheichder, in the  public domain
Photo "Solution" by Salvatore Vuono
Photo "Angry Father" by Akapl616.  Permission is granted to copy
under the terms of the GNU Free Documentation License
Photo of "Tired Man" by graur codrin
Photo "Aces" by Felixco, Inc.
Photo "Loneliness" by graur razvan ionut 
Photo of Pristiq by Tom Varco.  Permission is granted to copy
under the terms of the GNU Free Documentation License
Mademoiselle Zizi Feints at Fainting, by John Sloan

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

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