Thursday, September 2, 2010

Weighing Costs and Benefits Part II: Benefits

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

I asked, Will it work for me?

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

THAT is the Chemistry Experiment. 

So three weeks ago I published my


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

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

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

You have to weigh the costs and benefits. 

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

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

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

Do I Want To Put These Chemicals Inside My Body?

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

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

Here goes. 

Effectiveness Rate

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

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

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

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

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

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

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


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

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

Effectiveness compared to placebo

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

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

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

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

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

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

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

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

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

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

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

The Natural Course Of Mental Illness

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

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

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

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

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

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

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

Do I have your attention?

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

So where are we?


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

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

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

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

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

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

E#PT X NSR = Short Term Benefit.

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

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

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

Whew!  Next two weeks on costs, beginning with this month's coveted OMG Award.
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Sugar cube photo by Uwe Hermann, licensed under the Creative Commons Sharealike 3.0 License
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  1. Love your blog. Always makes me think, always makes me laugh.
    I just read my medical records from 2004 - 2006 when I was treated by a psychiatrist for Bipolar II, (having graduated from my first diagnosis of Major Depressive Disorder after taking an SSRI antidepressant). My medical files were very detailed and thorough. In my case it was clear that the medications made me worse. I ended "treatment" when the results were so bad that the psychiatrist insisted I undergo ECT. I refused to allow the ECT as I did not think the $20k hospital bill (which I had no health insurance to cover) would make my depression anything but worse. So I went home, stopped all medications and applied everything I knew about brain health and nutrition to my body. And I waited, and I slept, and I waited and I slept. I reduced my responsibilities down to the bare minimum, and I waited, and I slept, and I waited and I slept.
    I was very fortunate. I went into remission.

    I have never had any mania, only SSRI induced hypomania (hence the diagnosis of Bipolar II) from years of taking Prozac. While recovering I spent many hours online researching medical journals to really acquire a clear understanding of what the psychotropic medications actually do to the body, while they are "treating" the brain. My experience was the medications actually made me worse off mentally, plus caused health problems I had never had prior to taking such medications.

    For those with the more serious Bipolar I, or Schizophrenia, there is no spontaneous remission, so psychotropic medications must be used consistently, and the health issues dealt with as they arise.

    I may return to my former psychiatrist, and have him officially document my current state of remission so that it can be included in my medical record.