Showing posts with label Prozac. Show all posts
Showing posts with label Prozac. Show all posts

Warning Signs and Suicide Hot Lines Won't Fix This

A psychiatrist remembered his first days on his ER rotation. He dealt with a woman who had tried to kill herself. She was homeless, had been taking meth so she wouldn't sleep ever since she had been raped on the street. The supervisor asked what the young doc intended to do. "Prescribe antidepressants?"

They both knew how stupid that sounded.

In the 80s and 90s, they thought they had this suicide thing figured out. As the number of prescriptions for Prozac rose, the suicide rate was falling. It was widely claimed by people who flunked logic that this was epidemiological evidence that Prozac prevented suicide. Just get more people into treatment. This kind of error is common enough to have its own name: post hoc ergo propter hoc. Or maybe there was some economic incentive behind that sloppy thinking...

Antidepressants and Suicide: Defending Prozac

It amazes me how many research scientists seem to have flunked statistics.  Or ought to have.  Me, I majored in the liberal arts.  But at Reed, even those who took Science for Poets would be required to rewrite some of the scientific papers I have read on the subject of antidepressants.

So the vocabulary terms for the week are observer bias and confounding variables.  No worries -- lots of pictures.

Clinical Experience in Defense of Prozac

Let's say you are a doctor treating 100 patients with severe depression.  You give them all antidepressants.  It seems irresponsible not to, doesn't it.  Thirty of them get better.  Fifteen do not make a follow-up appointment.  You switch the fifty-five who are still trying to another antidepressant.  Another fifteen get better.  And another fifteen do not make a follow-up appointment.

Over the course of a year, you get up to fifty whose depression is remission and ten who are still struggling.  You don't know what happened with the forty who are no longer seeing you. They couldn't afford treatment; they didn't like your face; they couldn't find parking; they got worse on your medication. You have no idea.  But you have fifty patients who think you saved their lives.  You feel pretty good about yourself, don't you.

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.

Grief/Depression II - Rise in Rates of Mental Illness

Are we really getting sicker?

A New York Times article, When does a broken heart become a diagnosis? sells papers with its usual technique - latch onto a fringe element and substitute good writing skills for substantive analysis.

I am all for good writing skills, and perhaps stumble in the same direction at times. But depression is my beat. So God willing and the brain permitting, I am going to beat this bit to the ground. Two weeks ago I discussed three contexts for the discussion, the cost of health care, the scientific value of the DSM and the hobby horse of the author featured in the Times article. I promised more contexts to come.

Are We Getting Sicker? - Context IV

James Wakefield's thesis is that we are turning natural human emotions, (the ones we want to get rid of, because they are unpleasant), into a diagnoses. His beat is depression, as well, but the Times is on this bandwagon with autism and no doubt other diagnoses to come.

Well, I grant some validity to the concern in general. Is it shyness or Social Anxiety Disorder? Is it artistic nonconformity or Attention Deficit Hyperactivity Disorder? Is it the sleep disruptions of normal aging or Overactive Bladder Disorder? Was it all those wings, doritos and beer you guzzled Superbowl Sunday (and most Sundays), or Gastroesophageal Reflux Disease?

Prozac Monologues - How It Began

First conceived as a stand up comedy routine, birthed as a book, morphed into a blog, on August 29, 2011 Prozac Monologues came full circle at Happy Hour at the Pato Loco, Playas del Coco, Costa Rica.  This was the very spot where in January 2005, the book was originally written over the course of eight heavenly (my wife wouldn't use that word), hypomanic days.  Micah pulled out his laptop.  Patricia set it up on top of a bar stool.  And I held forth.


You can hear a bit of our little beach town's rush hour in the background.  So here is the text:

Prozac Monologues - How It Began

2004 was not a good year for me.  My doctor tried to make it better by prescribing Prozac for major depression.  Only Prozac didn't make it better.  So she prescribed more Prozac.  And that made it so much more not better that I concluded the only way I could describe how much more not better would be a stand-up comedy routine.  And thus was planted the seed for what has become Prozac Monologues.

So I went off Prozac, and on January 25, 2005, I boarded an airplane for Costa Rica, armed with a yellow legal pad and a ball point pen. 

Hypomania In Action

For eight days in beautiful, tropical Costa Rica, my wife went to the beach, explored neighborhoods, visited with family, tried new foods, while I wrote.  And wrote.  And wrote.  When I filled up one side of the yellow legal pad, I wrote on the back.  When I filled up the back, I wrote in the margins.  When I filled up the margins, I wrote between the lines.

I came home with seven chapters.  Two weeks later, the book was done.

I told my doctor about my book and maniacally writing it.  That word maniacally raised a red flag.  So she screened for bipolar.  She said, Are you manic?

I said what anybody who thought she was Jesus Christ come back as Jessica Christ might have said, I'm not manic.  I'm excited!

Oh.  Okay.  So she prescribed the second antidepressant, and began what will have to become a new book, but I haven't recovered enough to write it yet.

Was I manic?  No, I was hypomanic.  But I didn't know that word.  And maybe you don't know it either.  So I submit for definition and for evidence the first four pages of

Prozac Monologues

by
Willa Goodfellow

Chapter One
Bizarre: In which I decide to write a book

Okay, let's start with the basic Prozac dilemma.  Just who is the crazy one around here?  If, after you read the morning paper, you are happy, content, secure, at peace, able to get up, go out and carry on your activities of daily living, full of confidence and a sense of purpose, then tell me -- are you pathologically delusional?

Or are you on Prozac?

Citizens of the United States of America (called Americans and thereby hijacking the identities of thirty-eight other nations in the Western Hemisphere -- Remember Canada?  Every heard of Paraguay?) make up 5% of the population of the planet and consume 24% of its energy resources.  We spend more on trash bags than the gross national product of 90 of the world's 130 nations.

What was that?


We spend more on trash bags than the whole gross national product of 90 nations.

So who is the crazy one around here? 


The Crazy Delusion 

We get such a sliver of time to enjoy this wildly extravagant planet, and we spend precious moments of it, watching couples on TV compete for cash prizes on the basis of how many maggots they can eat. 

Until the maggot-eating is interrupted by somebody who wants to sell you an air freshener that uses an electronically operated fan to circulate chemical compounds around your living room to make you think you are out of doors. 

The fan is the latest advance in civilization which will enable you to stop feeding your Shiatsu little treats, which you previously had to do to get it to wag its tail to disperse the chemical compounds around your living room. 

So now you have to take Prozac, so you can get yourself up off the sofa where you have been sitting in a semi-catatonic state, watching the maggot-eating and dog-treating, out of your pajamas and into your four-wheel drive SUV, which you were compelled to purchase after viewing those commercials of SUV’s climbing over mountainous terrain beside raging rivers,

But which you happen to use to commute an hour and forty-five minutes on some freeway to work in a cubicle with a picture of mountainous terrain and raging rivers and some motivational caption underneath, so you can buy the air freshener with its self-contained and electrically-operated fan that disperses the chemicals that make you think you are out of doors, because you wouldn’t want actually to go out of doors – the air is so nasty from the fumes of your SUV.  Who is the crazy one around here? 

And don’t even get me started on the taxes you will pay from your job in your cubicle to fund somebody’s research into that missile that can shoot another missile out of the sky, to protect us from the bad guys who can bring down two 100-story buildings armed with the equivalent of a Swiss Army knife.  If it’s your job to figure out how to shoot that missile out of the sky, stop taking Prozac and go do something else to do with your life.  Or just go back to your sofa.  Please. 

Okay, now I sound like Michael Moore.  Let’s just call this the Crazy Delusion, a concept not original to me, and of which you can think of your own examples, so I don’t need to continue this rant which is not really the point of this book, but only the context of our consideration of the title of its first chapter.

In short –

It’s hard to know whether depression is a problem of distorted thinking or the result of clarity. 

In either case, sitting on the sofa in your pajamas does not turn the economic engine of this great nation, no matter what you’re watching.

Except for the pharmaceutical industry’s economic engine.  They keep making money, as long as they are able to sell you images of people who are happy and confident, popping their Prozac, (nowadays it’s Abilify), which you really start to believe when you’re still sitting on that sofa, watching those images over and over and over again. 

Ads For Antidepressants

Have you noticed how all the ads for antidepressants run during the afternoon soaps?  (If you are not depressed, you haven’t noticed, because you’re off at work, turning that economic engine.)  No, those pharmaceutical guys know where to find their audience, and when, on the sofa, in our pajamas, in the middle of the afternoon. 

Now I’m talking to you, the one in the pajamas.  You thought you might get up and go for a walk, like you promised your sweetie (who has gone to work) that you would.  But here it is, two o’clock in the afternoon.  The recap of yesterday’s episode comes on, and before you can find the remote to turn it off after the last soap, that theme song begins.  It sounds inspirational, but for some reason, you start to cry. 

After the theme song, and before the start of today’s episode, it’s time for that gentle, compassionate voice, who lists all your symptoms, including another one you have, now that the voice mentions it, but up until now you didn’t realize that it also is on the list, so you must be even sicker than you thought.  Who is that voice that understands you so well, better than your doctor, it seems, and so must know exactly what you need to ask your doctor to prescribe.

Symptoms Of Depression

Here is that list, by the way: sadness (no duh!), sleep disturbance (too much, too little ) weight gain (or loss), lack of energy, loss of interest in the things you used to like to do, loss of motivation (hence, all that time on the sofa), slowed pace, poor memory, poor concentration (they don’t want you at work anyway – you might break something), loss of self-confidence (like, they really don’t want you at work – you might break something), guilt, feelings of worthlessness, suicidal thoughts or attempts.

If you have been sad or lost interest in things for at least two weeks, plus four of the others, I’m talking about you.  You and 12% of the population who will experience an episode of depression sometime in their life (that’s major depression), plus another 6% who just feel lousy all the time (that’s dysthemia), and another 6.4 who sometimes are way up and sometimes way down (that’s bipolar), or …

One in twenty people in any given month.

When you have so much company, how is it you feel so alone?

You are not alone. 

Prozac Monologues 

photo of Playas del Coco by Helen Keefe, used by permission
photo of trash bags by Yuyudevil, in public domain
photo of Cubicle Land by Larsinio, in public domain
photo of prozac by Tom Varco, used by permission
photo "Loneliness" by graur razvan ionut

Why Antidepressants Don't Work

Diagnosing Depression

You go to the doctor complaining that you don't feel like yourself.  You aren't having fun, you are tired, you don't sleep well, you have no appetite and feel pretty worthless about your inability to exercise control over anything in your life.  Sometimes you feel like just ending it all.

Your doc asks whether you have a plan (sometimes you think about how you might do it), if anyone in your family has bipolar (not that you know of) and checks your thyroid and glucose levels.

DSM On Depression -- The Chinese Menu

But before the blood tests come back, your doc has already checked the magic list from the Diagnostic and Statistical Manual of Mental Disorders:

Column A:
1. Depressed mood most of the day, nearly every day, as indicated by either subjective report (e.g., feels sad or empty) or observation made by others (e.g., appears tearful).
2. Markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day (as indicated by either subjective account or observation made by others)
Column B:
3. Significant weight loss when not dieting or weight gain (e.g., a change of more than 5% of body weight in a month), or decrease or increase in appetite nearly every day.
4. Insomnia or hypersomnia nearly every day
5. Psychomotor agitation or retardation nearly every day (observable by others, not merely subjective feelings of restlessness or being slowed down)
6. Fatigue or loss of energy nearly every day
7. Feelings of worthlessness or excessive or inappropriate guilt (which may be delusional) nearly every day (not merely self-reproach or guilt about being sick)
8. Diminished ability to think or concentrate, or indecisiveness, nearly every day (either by subjective account or as observed by others)
9. Recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide

Ding, ding, ding.  One from Column A, four from Column B. (Your weight loss has been too gradual to count.)  That is all the doc needs to write out a prescription for an antidepressant.  Zoloft is the latest favorite, being the newest.  But if your drug coverage is lousy, you get fluoxetine -- Prozac in its non-generic incarnation.

Depression As A Chemical Imbalance?


You are not sure you want to take an antidepressant.  But your well-educated neighbor assures you that there is no shame in it.  It's not your fault.  Depression is a chemical imbalance in the brain, and antidepressants fix the imbalance.
 


I call this the chemical stew theory.  Your brain is too bland.  Add some salt and you will be good to go.

What a great marketing technique.  It's simple.  It's morally neutral.  It's even kinda manly, if that's an issue for you -- chemistry, you know.  And your next door neighbor, whose education comes from TV ads, is part of a sales force which has been so effective that one out of every ten people in the United States of America is taking an antidepressant right now.

Too bad it hasn't worked out.

No -- Antidepressants Do Not Fix A Chemical Imbalance

There are a couple reasons (at least) why adding a chemical to the stew does not solve the chemical imbalance.

The first reason is that your brain is not a stew.  If you like the food metaphors (and as you can see, I like the food photos), adding a chemical to your brain is more like adding it to a souffle.  The chemical balance in your brain is finely tuned to a variety of interacting factors.  Changing one of the factors has multiple effects, not all of them intended, and not all of them so good for you.

For example, a souffle has fat in it.  Maybe the problem with your souffle is not enough fat.  But when you mix fat into the egg whites, the whole thing falls flat.

The second reason antidepressants fail to do their intended job is that they do not address the problem at the right location. The theory suggests you can fix the imbalance by increasing the serotonin in your synapses.  But scientists have figured out the problem occurs farther upstream.

Or at least that is what the scientists say who fund their labs with money from the pharmaceutical companies who still want to add a chemical to your brain, just maybe a different chemical than the ones whose patent protections have expired.

The Brain As Machine

The new meds are not going to work either, because they are working with, not a food, but a mechanical metaphor.  So second millennium!

Like this:



If only they can find the right place to change the course of the inevitable falling blade?  I don't think so.  Your brain is not a machine.

The Brain As A Living System

Here we go:


Your brain is a whole world.  Those who would tinker with it need to understand its ecology.

Put the internal combustion machine onto this planet, and the whole rest of it experiences the consequences.

Block serotonin from reentering your neurons, and your tear ducts and intestines dry up.  And your sex life.  Put enough of us on antidepressants and we could become an endangered species.

So if you want to do something about depression, if you have it or love anybody who has it, then you have to pay attention to the ecology.  Your interventions will have complex consequences.

And -- this would be a third reason and most intractable reason why antidepressants don't work -- the planet/body/brain/ecosystem is always working to restore balance to the system.  Up the serotonin in your synapses and eventually another part of the brain adjusts to overcome your interference.  In ecology this phenomenon is called homeostasis.  Psychiatry calls it Prozac Poop-out.

I kept complaining about insomnia, one of my Chinese menu choices that did not go away.  A psychiatrist told me my symptoms were caused by my depression.  Address the underlying depression and eventually the symptoms would be relieved.  Never mind about the symptoms that replace them.  Those symptoms are not on the depression menu, and have nothing to do with the psychiatrist.

A Twenty-First Century Approach To Depression?

But systems theorists tell us that any intervention will move the whole rest of the system.  This works in the environment, the economy, the workplace, the family dinner table.  And in the brain.

So what if we go back to that menu and devise some interventions that are not the equivalent of a chemical sledge hammer?

That brings me back round to last week's post about insomnia, when I promised that the next installment of my sleep series would be:

The Good News About Sleep Deprivation and Suicidality 

The good new is coming next -- implications for treatment of mood disorders and other causes of suicidal thoughts and behavior.

It just took me an extra week to get there.  So what else is new.  It's a Prozac Monologues series.

photo "Loneliness" by  Graur Razvan Ionut, from FreeDigitalPhotos.net 
photo of Chinese menu by Hoicelatina, permission to copy under the terms of the GNU Free Documentation License 
photo of bell by Salvatore Vuono from FreeDigitalPhotos.net 
representation of serotonin in public domain 
 photo of pote asturiano by jlastras and used under the Creative CommonsAttribution 2.0 Generic license 
photo of chocolate souffle by Akovacs.hu at the wikipedia project, who has released it to the public domain
representation of lactic acid in public domain
NASA photo of the Earth in public domain
photo of Anthia goldfish in public domain

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

Mood Disorders -- Tolerable, Bad and Downright Ugly, Part I

A friend recently asked me for a short description of the difference between Major Depressive Disorder and Bipolar II. I didn't keep it short.  This will not surprise my regular readers, and warn my newer ones.

But here is the short answer.  Normal mood cycles within a normal range, sad/okay/glad.  Major depression has bigger distances, between normal and really sad.  Bipolar has the biggest distances.  Bipolar I ranges from really sad to really really up, with more time spend down than up.  Bipolar II moves the base line down from bipolar I.  It goes up, though not so far, and way, way down, lower than the others.

There are other aspects to mood disorders, affecting thought, desire, motivation, energy, sleep, digestion, appetite and even physical pain.  But this astonishingly short answer says way more than your common perception that depression means you are sad; bipolar means you are crazy.

Since I regularly write about these and the other mood disorders in Prozac Monologues, it may be helpful to give the longer answer here.  So today begins another three-part series.  I do seem to like these three-part series.  Things stretch out when I want to make Prozac Monologues both clear and entertaining -- though I suspect that it's mostly people with diagnoses who get the entertaining part.

DSM 5 and Mood Disorders, Part III -- The Way Forward

 
Lost Creek Wilderness 

I have been writing about the newly released draft of the Diagnostic and Statistical Manual -- DSM V for the last few weeks.  Let's recap:

The DSM V -- What's at Stake: The pharmaceutical and health insurance industries have a huge financial stake in who gets diagnosed with what in the mood disorder section of the Diagnostic and Statistical Manual.  This stake has skewed the new draft version of the DSM to support the status quo/current market conditions.

The DSM V made almost no changes in the Mood Disorders section.  (Well, a few, not so minor for children and the bereaved.)  This despite the evidence that the current criteria for bipolar II exclude people who are instead diagnosed with recurrent unipolar depression, but who get much worse when treated as though they had recurrent unipolar depression, and who eventually are diagnosed with bipolar II anyway, if they are still alive.  Women spend eleven years on average before being diagnosed correctly.  That's eleven years of a lot of suffering on a lot of antidepressants.  One helpful modification in the bipolar II area will become important below.

The Draft DSM V -- How Did We Get Here?: Advances in the treatment of  depression have come about by serendipitous discoveries, followed by pharaceutical companies' desires to improve their own market share.  These have been genuine advances.  However, their manipulation of research to support their products is a national disgrace.  The AMA is finally embarrassed by it.

That is where last week's post left us, at Mile Marker #3 in "Up a Creek Wilderness" -- the sorry state of research on this map that is owned by the pharmaceutical companies.

So now we have arrived at:

Goose Creek Trailhead

Mile Marker #4 -- Their goose is cooked.  They have run out of product.  There are lots of ideas out there besides the tired old "chemical imbalance/neurotransmitter" fixation on one aspect of depression.  And research is being done on other neurological mechanisms of depression.  But Big Pharma got lazy and has been slow to develop these ideas into useful medications.

Patents have expired on almost all the antidepressants on the market today.  The sleight of hand trick is to repackage the same medication by altering its formulation a little bit (Celexa/Lexapro, Effexor/Pristiq) or by doing a time-release version to add a few years to the patent (Paxil CR, Wellbutrin XL).  But that strategy has a time limit, and lack of development has caught up with these companies.

I think Eli Lilly's new product Symbyax is the ultimate in failed strategies, combining the patent-expired Prozac/fluoxetine (originally used for major depression) with the newer and controversial Zyprexa (originally used for psychosis and lately the subject of successful lawsuits).  If it really were a good idea, you could get the same results with two prescriptions, the antidepressant that worked best and an antipsychotic less dangerous than Zyprexa, instead of the two products owned by Eli Lilly.  With the combination package, you get the side effects of both: sexual dysfunction, agitation, akathisia, insomnia, etc. for Prozac and ballooning weight gain, high blood sugar, risk of diabetes, high cholesterol, tardive dyskinesia, etc. for Zyprexa.

Nevertheless Symbyox will make Eli Lilly a bit of money for a while, because it has widened the market for Zyprexa.  They need another market since that successful lawsuit reduced its use among older people with psychosis (who experience a rather nasty side effect of death from Zyprexa's off-label use for dementia.)  Symbyax now is also indicated for people with treatment-resistant depression, whose doctors need to keep coming up with something new to give them. God forbid they should reexamine the diagnosis, or that the DSM V should encourage them to do so.  People with treatment-resistant depression account for half of the depression market, the half that stays on the market, because they "keep trying," like everybody tells them they should.  So good luck, Lilly.  I hope you are in court again soon.

That's Mile Marker #4.  And it makes me as depressed as Mile Marker #3 makes me mad.

Mile Marker #5 -- It turns out that we have been traveling in a circle, and now looped back to the beginning.  This is where I find the good news.

We have another serendipitous discovery!  Lamictal was first used as an anti-convulsant.  Following the pattern of other advances in the treatment of depression, Lamictal's mood-related effects first became apparent in people with epilepsy.  Happy seizures. -- Though unlike previous medications, Lamictal works just fine for its original purpose, as well.

Lamictal (generic name lamotrigine) is now approved for use in managing seizures and bipolar I.  Its off-label uses include bipolar II and treatment-resistant unipolar depression.  (When a doctor prescribes a medication for something that it hasn't been approved for, that's called "off-label" use.)

This "off-label" use issue is critical here to advance the treatment of depression, especially for those who are misdiagnosed (using DSM V guidelines) with unipolar depression.

The rules regarding marketing of off-label use are in flux.  Currently, sales representatives may not recommend their products for off-label use, but they may direct doctors to research about such use. They may not, however, pay doctors to tell other doctors about their experiences with off-label use, at continuing education conferences and the like.  That's what got Pfizer busted, for their marketing of Geodon, another anti-psychotic like Zyprexa, while searching for their market share of dementia and depression.  The money in these cases generally goes to Medicaid and Medicare, who paid for the prescriptions.

See, there's a swamp out there between Mile Marker #5, the next serendipitous discovery and:

Mile Marker #6: Ca-ching! Ca-ching! -- that huge new money-making machine.

Doctors prescribe medications for off-label use all the time.  Drugs that have been tested and approved only for adults are tried on children.  Otherwise, there wouldn't be anything they could give to kids, because who wants to risk clinical trials on kids?  Drugs approved for one type of cancer are tried for another, because who wants to say "no" to somebody whose cancer has metastasized?

Off-label use gets turned into approved use if it works out in new clinical trials.  If it doesn't work out, it goes away.  That's the way it's supposed to work.  But if the trials don't work out, and the drug companies fudge the data and market the medication anyway, then they get sued.

My doctor told me that Lamictal is the "go-to drug" for bipolar II, evidently very common off-label use.  I don't know how she knows, whether she read the research, whether the medical journals have been flooded with articles commissioned (or maybe not) by GlaxoSmithKline, whether she heard about it from other doctors who are on (or maybe not on) GlaxcoSmithKline's payroll, or whatever.  It is also on the top of her list for treatment-resistant unipolar depression.  I am not expressing doubt about Lamictal's effectiveness.  I am simply explaining how off-label use works in clinical practice.

So we are currently at Mile Marker #5.  Now we start climbing that hill to #6.  Just like they did with tricyclics and SSRIs, everybody is asking, "How does Lamictal work?"  They think it has something to do with calcium, but I won't go into that here.

The answer to the "how" question is particularly important to the other pharmaceutical companies, because they will use the answer for a grab at their market share, by trying to improve on the side effect profile.

Lamictal's side effect profile isn't so bad, as far as mood stabilizers go.  It is light years better than Lithium, which is beyond nasty, but desperate people take it, because it has been their only relief.  Lamictal also is not so bad compared to antidepressants.  It causes fatigue, headaches, muscle pain, but not in as many people.  Its big drawback is this pesky rare (but potentially fatal) skin rash.

Potentially fatal.  Wow.  Now, one in 500 people get this rash, and all you have to do to get rid of it is stop taking the drug.  I am not sure why this rash is the major concern about the medication.  Except there is no denying the cause.  Antidepressants cause suicidal ideation and behavior at a much higher rate than Lamictal causes rash.  But try to prove it in your case.  You already have a disease that carries a risk of suicide.  And even on the antidepressant in question, it might be that your disease is simply progressing.  You are as likely to get your dose increased as discontinued.  And you will not get your day in court.  Lamictal causes some kind of rash in 1 of 10.  But even if your rash is caused by the new soap you are using, looks nothing like the bad rash, and even if you are free from suicidal thoughts for the first time in a decade, you get yanked off Lamictal.

So here is an excellent opening for other companies, to come up with something with no rash, or even a rash that only one in 1000 get.  We can expect other mood-stabilizers to reach clinical trial stage in the near future.  Ca-ching!  Ca-ching!

Mile Marker #7:  At that point, interests will align, of the pharmaceutical companies and those who have been misdiagnosed because of the not-yet-published but already dated DSM V.  The pharmaceutical companies are looking for Ca-Ching! Ca-Ching.  And depressed people are looking for better medications.  We finally reach the operation of the free market system.  This is the United States of America.  Fortunately for depressed people, there are enough of us to make it profitable to treat us.

The fly in the ointment is the DSM V.  It does loosen restrictions on the diagnosis of bipolar II a bit.  The DSM IV said that a hypomanic episode brought on by antidepressant use does not count as a real hypomanic episode, and the person has unipolar depression -- suggesting to more conservative doctors that they keep looking for a better antidepressant.  The DSM V says that an episode brought on by antidepressant use is a real hypomanic episode, with a diagnosis of bipolar II -- pointing doctors toward mood-stabilizers.

So the task of the drug reps will be to direct doctors to the research demonstrating:
  • more than half of those with severe depression eventually are diagnosed on the bipolar spectrum;
  • incredible harm is done to these patients when given antidepressants;
  • therefore these depressed patients might benefit from receiving a mood-stabilizer from the very beginning of treatment, particularly the mood-stabilizer of which the drug rep happens to have samples.  
The true conservative treatment course might be to treat all depressive people with mood stabilizers, unless the doctor has time to sort between those with genuine unipolar depression (presenting their first episode and no history of anything that looks even slightly like hypomania) and those who have recurrent depression (or "cycling" depression), especially when Lamictal and future mood-stabilizers have better side effect profiles.  First do no harm.

Never mind what the DSM V says.

If the meds work, if they increase their makers' market share, then the pharmaceutical companies will continue to find ways to do their own education of doctors, including education in how out of touch the DSM V is with clinical practice.  These same market forces will make irrelevant the DSM's refusal to define a diagnosis for pediatric bipolar.  If the meds work, children may receive a nonsensical diagnosis, but they will also receive the appropriate medication.

Mile Marker #8:  Now all hell breaks loose with health insurance and HMOs.  They depend on the DSM for billing.  But the gap between the DSM and clinical practice in mood disorders will be so wide that case reviews and billing procedures will fall apart.  Doctors will either code according to the DSM and treat according to reality, or code according to reality and ignore DSM criteria.

But our health care delivery system is already broken, and will collapse anyway, long before we reach Mile Marker #8.

 
sign at Goose Creek Trailhead photographed by Steven Bernard
in public domain
photo of Lamictal by Parhamr and in the public domain
money bag from Microsoft clipart
"Book Burning" is licensed under the  Creative Commons Attribution 2.0 Generic license.

DSM 5 and Mood Disorders, Part I -- What's at Stake

Earlier this month, the American Psychiatric Association released the long awaited proposed revision of their Diagnostic and Statistical Manual of Mental Disorders (DSM-5).  It is available now for public comment, with an anticipated publication date for the final version in May 2013.  To call this the Bible of Mental Illness is to overestimate the significance of the Bible.


The DSM was first written to give clinicians and researchers a common vocabulary and a common understanding of the various diagnoses of mental illness.  John McManamy has related this history on his blog Knowledge is Necessity.  I refer you to his thorough account, found in the links at the bottom of his post. -- [Hey, John -- I recognized your image for "Few Surprises."  It was one that I considered for this post!]

The way the DSM works always reminds me of a Chinese menu.  For example, if you have one symptom from Column A and at least five from columns A and B, for over two weeks, you have Major Depressive Disorder.  You can upgrade your core diagnosis with specials offered alongside the basic menu.  These lists of symptoms provide a common vocabulary and simplify diagnosis, so that family practitioners commonly diagnose depression and prescribe antidepressants, without referral to psychiatrists.  This practice provides a boon to the pharmaceutical industry, which markets heavily to family practitioners.  If patients had to see a psychiatrist to get a prescription, fewer people would take antidepressants, since there is greater stigma attached to treatment by a psychiatrist, psychiatrists are in short supply in many parts of the country anyway, and health insurance plans provide inadequate coverage for psychiatric care. So family practitioners prescribing for depression sells more antidepressants.  Big Pharma wants to keep the DSM simple.

Over time, even as therapists have become more eclectic in their therapies, the sequence of DSMs has more narrowly defined the illnesses which therapists treat, adding more specificity.  The DSM gives a numerical identifier for each diagnosis, along with decimal points after the numbers to indicate variations and severity.  Health insurance companies rely on the DSM to determine coverage.  If you don't have a number, you don't get reimbursed.  But they have become concerned about the multiplication of diagnoses, raising the number of claims.  Health insurance companies want to limit the number of diagnoses and limit the number of people diagnosed.

Release the Kraken!!

Well, it's one of those weeks in a remitting/recurring disease. "Release the Kraken!" -- my favorite line from Clash of the Titans, a 1981 movie to be remade and released this summer.  Oh, you gotta check out that link to the trailer!

My apologies to regular readers who are looking for a new post.  It's an interesting one, Shadows.  Maybe I will be able to write it next week.  Come to think of it, the image on the right would fit that post, too. (Anonymous, in the public domain for copywrite expiration). For now, here is a reprint from last July:

What is Depression, Anyway?

When I thought the meds would work, I didn't ask this question (referring to the title, not the caption!) Depression is a disease of the brain and also of the mind. The best results are obtained by working on both fronts. Take your meds. Talk to your therapist. Simple.

Then I discovered that the meds made me worse. Whenever I say that, I rush to say that, my experience notwithstanding, for most people they work. They can save your life. And then I rush to say, but not for everybody. If you think they make you worse, you might be right.

The rhetoric keeps shifting on this point, depending on what the speaker is selling. I
think the current prevailing stats are that the meds help half of us, harm a quarter of us, and for another quarter, they just don't work. And for most of us in any of those groups, the disease does go away on its own anyway, though it leaves its wreckage behind. But that is what I am gleaning from the research. Nobody in the scientific community has summed it up so simply.

Prozac is Talking -- Anybody Listening?

Anybody know this story?  You get a new prescription.  Responsible consumer that you are, you read carefully the PI [prescribing information] sheet.  It says, "If xx happens, call your doctor immediately."  Sure enough, xx happens.  You call your doctor, who does not call back.  After persistent calling over several days, the doc says, "Really?  We'll keep an eye on it."

The other day, I had a nosebleed that wouldn't stop.  The PI sheet says my new med can interfere with platelets, admittedly not very high on the list of side effects.  But I contacted the doc.  "Really?"  she said, "Where did you hear that was a side effect?"  My answer, "On the PI sheet you gave me."  It turned out, my blood work was fine, and the humidifier took care of the nosebleeds.

No harm done.  Right?

On the other hand, five years ago my GP had me on Prozac.  After a couple months, I couldn't sleep, was irritated, agitated, couldn't concentrate, had thoughts of harming myself and others.  The PI sheet said I should tell my doctor.  My doctor increased the dose.

Thus began a series of antidepressants, and a downward spiral that has ended with disability.

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