Weighing the Costs and Benefits Part I -- What Counts?

Manifesto

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

There.  I feel better already.

To recap from last week:

You Have to Weigh The Costs and Benefits

That is what the doctor says.

Last week I promised I would develop a way to do that.  So this week we play math games.  For the next few weeks, actually.

Now, don't freak out.  I am not going to ask you to do math.  I am going to make up some rules.  You are along for the ride.  Though do feel free to suggest better rules.  Plus, I promise lots of pictures.  And a musical interlude.

I am a rat.  I live in a laboratory, where I participate in the Chemistry Experiment.  Along with other scientists, I am trying to find the chemicals that will make a dent in my mood disorder.  Not theirs.  Mine.  Which is how I got the rat end of this job.  But because I am a free-range rat, I get to decide which experiments I am willing to try.

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

Manifesto of a Lab Rat -- Weighing the Costs and Benefits Part I

I Am A Lab Rat.  Yes, I am.

Here is the deal.  I was lucky enough, and you were lucky enough to be born after the discovery of penicillin (1928).  Well, I don't know when you were born.  But evidently penicillin was discovered before it became a life or death issue for either of us, or I wouldn't be writing and/or you wouldn't be reading Prozac Monologues.  This is good.

In another age, my ruptured appendix might have been treated with leeches.  That would not have been good.

As far as my more immediate health challenge goes, we are barely out of the leech stage.  Okay, that's a bummer, the timing of my life, that is.  But like I said, ruptured appendix, penicillin.  It could have been worse.

Research Into Mental Illness -- Rats

In the treatment of mental illness, they have figured out that leeches don't work.  They think chemicals might. They just haven't figured out which ones.  They are working on it.  They have lab rats, rattus norvegicus to be specific, who do the heavy lifting in this Chemistry Experiment.  Some people question the ethics of what gets done to these poor rattus norvegicuses who participate with not a single informed consent form in sight.  But that not only is another post, it is another blog.

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.

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.

OMGThat'sWhatTheySaid! -- Stigma

On November 26th, the New York Times published an article about the presidential policy not to write letters of condolence to the families of service men and women who commit suicide in a war zone.  These letters of condolence have gone out since Abraham Lincoln started writing them during the Civil War.  Given the upswing of suicides in the Armed Services lately and the attendant publicity, this policy of silence, which began in the Clinton era, is coming under scrutiny and challenge.

In response to this article, psychiatrist Dr. Paul Steinberg wrote an Op-Ed commentary titled "Obama's Condolence Problem," winning him this month's OMG Award for -- oh, it's hard to choose.  There are so many prize-worthy lines.  But let's call it for: Indeed, there is nothing wrong with stigmatizing suicide while doing everything possible to de-stigmatize the help soldiers need in dealing with post-traumatic stress and suicidal thoughts. I will deconstruct this sentence after putting it in context.

Dr. Steinberg is concerned that any recognition of suicide, even the reporting of it, glorifies it and makes the taking of one’s life a more viable option. If suicide appears to be a more reasonable way of handling life’s stresses than seeking help, then suicide rates increase.

Dr. Steinberg is clearly in the voluntarist camp, believing that people make a conscious, reasoned choice to kill themselves.  Suicide, in his view, is an option, a way of handling life's stresses.  He is in, if not good, then plentiful company, who believe that even while the thought processes of those who commit suicide are impaired, their will is not. They remain responsible for their choice.

Regular Prozac Monologues readers know that I am not in the same company.  Dr. David L. Conroy gave me the words.  From Out of the Nightmare: Recovery from Depression and Suicidal Pain, "Suicide is not chosen; it happens when pain exceeds resources for coping with pain."

Conroy describes the many ways that people who are suicidal attempt to reduce their pain and save their own lives.  Those who are suicidal sometimes use the language of choice and reason.  Conroy, who speaks from personal experience, says it is terrifying to have such little control over our own emotional state that it can shove us headlong over the abyss.  This lack of control is part of, and adds to suicidal pain.  To claim that we have considered the options and are making a reasoned decision is a grasping for the image of control; it is an effort to relieve pain.

Steinberg asserts that choosing suicide over treatment is deserving of shame.  Now that first-rate treatments for depression and post-traumatic stress have evolved and are readily available, and people with emotional problems do not have to suffer quietly, are we taking away the shame of suicide?  When he decribes depression treatments as first-rate, he parts company with the National Institute of Mental Health and many doing research in the field, who acknowledge the true state of treatment.  At least a third of those who seek treatment are not able to find a medication that is effective and tolerable.  Meanwhile, certain side effects of these first-rate treatments themselves increase the risk of suicide, doubling it in the case of insomnia, a frequent side effect of SSRI's and SNRI's.  Akathesia (called "inner restlessness" on prescribing information sheets) is one of the most under-reported side effects, due to euphemisms, and among the five top risk factors for suicide among hospitalized patients.  [Side note: when you read "inner restlessness" on your prescribing sheet, did you realize that "inner restlessness" could significantly raise your risk of suicide?]

Steinberg believes that letters of condolence to family members could be an inadvertent incentive to suicide.  In light of the condolence-letter controversy, the administration is appropriately reviewing the policy that has been in place for at least 17 years — and may indeed want to consider leaving it as it is. But as a country, let’s focus our energies on doing everything we can to diminish inadvertent incentives that might increase self-inflicted deaths.  And elsewhere: We need to find the right balance between concern for the spouses, children and parents left behind, and any efforts to prevent subsequent suicides in the military.

I feel downright silly answering this argument.  But here it is:

First, the shaming of suicide is indeed one of the resources that we possess against it.  But it is an even more significant reason why people do not acknowledge and seek help for thoughts of doing it.  Shame interferes with willingness to report symptoms.  And failure to report symptoms is a significant factor in failure to recover.  To think that we can shame suicide and prevent it at the same time is fanciful. There is no balance to be found here.

Second, it is well known that surviving family members are themselves at greater risk of suicide.  Shame increases their pain, including their suicidal pain.  It is a barrier that prevents them from seeking support and prevents friends from offering it.  A letter from the President could go some distance in reducing the shame of family members and providing comfort in the midst of their pain.  If prevention of suicide is the goal, here is the most direct intervention the President could make.

Now back to the beginning.  Indeed, there is nothing wrong with stigmatizing suicide while doing everything possible to de-stigmatize the help soldiers need in dealing with post-traumatic stress and suicidal thoughts.  Putting to one side the impossibility of de-stigmatizing the second while stigmatizing the first, let's take a closer look at what Dr. Steinberg wants to de-stigmatize -- the help soldiers need.  What help would that be?  Psychiatry, leading the mental health professionals.

Steinberg wants to stigmatize suicide and de-stigmatize himself.  That's natural enough.  Nobody likes to be the object of stigma.  People who experience suicidal pain can identify with him in his desire. But I took a fanciful direction upon reading this op-ed piece.  I imagined Dr. Steinberg as a chaplain taking a course in Clinical Pastoral Education.  Are my clergy readers following me here?  Think back to your CPE experience.  Imagine the conversation in group after Dr. Steinberg says Indeed, there is nothing wrong with stigmatizing suicide while doing everything possible to de-stigmatize the help soldiers need in dealing with post-traumatic stress and suicidal thoughts.  Somebody from my CPE group would surely have asked, "How does it feel to be the object of stigma?"  And if he returned the question with a quizzical look, "How do you feel to know that people would rather commit suicide than come to you for help?  What does that mean to you personally?"

To my psychiatrist readers (do I have any?), do you have any training like CPE, where you are asked to examine your personal feelings and consider how they affect your judgments and your treatment of patients?  Does it include your judgments about suicide?  How do you feel about yourself when one of your patients commits suicide?   How do you feel about that patient, and the next patient with suicidal ideation?  Can you acknowledge those feelings?  Is shame part of your own experience?  Where have you put your shame?  Your feelings are just that, feelings.  Can you use them to inform your understanding of your patients?

I posted a facebook status last week with a link to Dr. Steinberg's article, asking, "Do patients with any other disease face such disrespect from their doctors?"  I am going out on a limb here.  But I wonder if many psychiatrists have not yet dealt with their feelings about their patients' dying.  When oncologists did, the treatment of cancer patients changed.  Now, who even remembers that cancer once was shamed?

Weighing the Risks and Benefits - Will My Life Be Better?

"You have to weigh the risks and benefits."  That is what the doctor says.  It's your body, your decision, your responsibility.

But how do you weigh them?  There is that list of side effects.  They sound pretty scary, but the doctor assures you they are usually manageable.  Then there is the potential benefit of feeling better.  Well, that would be the gold ring, now wouldn't it?  Being able to get back to your family, your job, your life?

It's not a hard sell.  Reach out your hand and the pharmaceutical company will place in it that most precious of all commodities, hope.

Perverse little smarty pants that I am, after my hopes had been dashed six times, I started to read.  For four years I read journal articles about clinical studies.  The basic format begins with a measurement of depressive symptoms, usually the Hamilton Rating Scale for Depression, HAMD, depressed mood, suicidal ideation, sleeplessness, loss of appetite, etc.  You get points for severity.  Unlike your junior high math exam, the higher the score, the worse off you are.  In fact, if you ace this test, they will administer electric shocks to your brain (yes, I know, you will be unconscious at the time and won't feel a thing) until you forget how bad you feel and get a lower score.

So there are two groups, as alike as possible, Group A averages a HAMD score of 21.6, Group B's average is 22.1.  That's the mid range for moderately depressed, and the typical test subject score.  They don't include you in medical trials if you keep getting a high score, because now it's the medication that is being tested, and they want an audience that is easier to please.  Group A gets the medication being tried, Group B gets the placebo.  After 8 weeks, Group A's HAMD score is 8.2, Group B's score is 10.9, both in the mildly depressed range, but the difference is "statistically significant."  [That would depend on how big the sample is, and I am not doing the math.]  More people in Group A than Group B reached remission, a HAMD score of 6 or less.  A certain number dropped out because of side effects, so they don't count.  And there we have it.  The medication improves depressive symptoms by a statistically significant amount and is well tolerated, and you should get yours today.

But you know what?  That study with all its statistics did not answer your question.  Will you feel better?  Will you get your life back?  It told you what the odds are that your depressive symptoms would be reduced.  But that is not the same thing.  Not at all.

For example,the truck driver who is sad, not sleeping well, has no appetite, worries a lot and feels guilty is given Zoloft by his family practitioner.  Now he's eating better and is learning to put past sins behind him.  But he is too dizzy to drive, gets in fights with his friends and can no longer satisfy his wife, or even himself in bed.  So he decides to quit his meds.  The doctor is focused on his HAMD score and is very concerned, convinces him to try another med, then another.  But each time he gets the same side effects, and meanwhile has lost his job.

The truck driver has weighed the risks and benefits, asking is my life better? No, it isn't.  Let's hope his doctor knows that Cognitive Behavioral Therapy is often as effective as antidepressants for mild and moderately depressed people.  Ditto aerobic exercise, which could help his lose those extra pounds, improve how he feels about himself, and change the nature of what happens when they turn out the lights.

It turns out there are lots of psychological tests.  Many try to do what the HAMD does, and their inventors think that their tests do it better -- measure depressive symptoms.  But there is also a test that asks the real question: Are the lives of the people who take this medication better?  The Sheehan Disability Scale is a three question test, answered by the patient.  On a scale of 1-10, how much have the symptoms disrupted your work/school, your social life, your family/home responsibilities this past week?  It's simple.  It's easy.  It's what the people who are taking the meds want to know, will my life be better.  The people doing the research are focused on symptoms, not on the patient's life.  So that is how I read journal articles for four years and had never heard of the Sheehan Disability Scale (SDS).

For some reason, the clinical trials for Abilify decided to ask the patient's question, using the SDS.  Actually, they used seven different tests.  When the journal articles came out, they reported only one, the Montgomery-Asberg Depression Rating Scale (MADRS), a substitute for HAMD.  My September 4 post, OMG!! That's What They Said! Significant, reported its not particularly impressive, but FDA passable,  "statistically significant reduction in depressive symptoms."  The other test results disappeared.

But somebody noticed, and called them on it.  That is when I learned that the SDS even existed.  Why would they go to all the trouble of doing seven different tests, and then publish the results of only one?  Turns out that while Abilify.com says that "Clinical studies of adults with depression showed that adding ABILIFY to an antidepressant helped to significantly improve depressive symptoms compared to adults treated with an antidepressant alone," as far as the people who actually swallowed the stuff were concerned, it was a wash.  When you weigh symptoms and side effects, they reported that there was no improvement in their work/school life, a little improvement in family life.  But overall, it was a wash.

What was the author's response?  "Robert Berman from Bristol-Myers Squibb wrote... "this may be due to the lower sensitivity" of the measure."  I got that from "Abilify, Depression and the Memory Hole" at clinpsyc.blogspot.com.  Robert Berman, chief author of the research report, is not only an employee of Bristol-Myers Squibb, his compensation also includes stock options -- a little side note on how medical research is conducted in a for-profit health care system.

Okay, so the Sheehan Disability Scale is not sensitive enough to pick up what were pretty small decreases in depressive symptoms anyway.  That isn't its purpose.  What it will do is weigh your risks and benefits. Will Abilify improve my life, at work, at home, at play?  Nope.  Not if you are taking it for depression.  It won't.

What Prozac Monologues wants to know is what the Sheehan Disability Scale would tell me about Lamictal, the medication I have just added to my antidepressant instead of Abilify.  But as far as I know, nobody asked.

photo by Hans Anderson, This file is licensed under the Creative Commons Attribution ShareAlike 3.0

Costa Rica and Depression

This is my breakfast view on the left.  It is called patita, a vine on the edge of my porch.  I planted the seeds myself.  A stranger gave them to me when I admired it in his yard.

If I look to the right, I see "bird of paradise," outside my neighbor's door.

Some friends invited us for drinks and this view at sunset. 

 

Why the hell would anybody be depressed in Costa Rica?

I prepare my answer for friends back in Iowa.  Most of my friends already know the answer, or else are too discrete to ask.  I really just ask myself.  Why the hell am I depressed in Costa Rica.

Five years into studying this disease, it still baffles me.  I know the answer, too, and yet it baffles me.  There are psychiatrists in Costa Rica.  There are psych wards in Costa Rica.  I have seen the boxes of Effexor on the shelf of the pharmacy where I go to buy contact lens solution.  There is even Electro-Convulsive Therapy in Costa Rica.  I have read the brochure.

So there must be depression in Costa Rica.  I am simply one of the people who have it.  There is something about the way that my brain works, as there is something about the way that other people's brains work, that give us this condition that is found across the planet, in every culture, even in a place where plants grow that are called "bird of paradise."

If other people have trouble believing that it is real, why should I be surprised?  I still wake up mornings and think, "This is crazy!  Snap out of it!"

When I packed for my latest trip, I didn't pack enough medication.  Oh, I knew I couldn't get nortriptyline here in the formulation and dosage that I take -- a question I had asked in a previous trip.  So even though they aren't as effective as they used to be, I counted those particular pills carefully.  But the Valium that takes the edge off until my psychiatrist and I can find the next solution, or at least decide on the next chemistry experiment -- well, who would need Valium in Costa Rica?

So last week I found myself in the pharmacy again, asking about Valium.  It is one of the drugs for which you have to have a prescription.  (You don't for Prozac, nor for Viagra, if that might influence your travel plans.)  It turns out that the eighteen year old with the ponytail who was talking with the staff is the doctor.  No, he must be older than eighteen, not a blemish on that beautiful skin.  I went to his office yesterday, where he had his prescription pad, and he was very understanding.  Still not wanting to believe that I take Valium, I kept underestimating how many I would need before I got back to Iowa.  But he convinced me that if I truly had enough, then I wouldn't worry about it.  I had  said that at the pharmacy, that I was worried about it.  He heard me, and he remembered.  For an eighteen year old, he is really good at paying attention.

Then I asked about Lunesta.  I don't take it very often.  Insomnia is not a side effect of my current med.  I just need it when I get caught at night reliving a living nightmare.  I wondered if I could find a cheaper source.  No, they don't have that one in Costa Rica.  But that started a conversation about side effects, insomnia, SSRI's and all those things I think about.  He said they have a different attitude in Costa Rica.  These side effects are terrible, he said.  So they don't use these heavy duty meds like Zoloft, except as a last resort.  First they try psychotherapy, then very small doses of tricyclics.

I know that Prozac became so popular because it was supposed to work better and have less side effects than the older meds that they prefer in Costa Rica.  And I realize a lot of people swear by it.  But I don't get it.  Over time, SSRI's and SNRI's have turned out to be no more effective than the TCA's.  As far as side effects go, maybe fewer people have them with the newer meds -- I don't know.  That's what the drug reps say.  But if you have to choose between hard core insomnia (Prozac/SSRI) and dry mouth (Elavil/TCA), between suicidal impulses (Cymbalta/SNRI) and constipation (Pamelor/TCA), I have experienced them all, and I'm going for the Costa Rican approach.

Meanwhile, back in the world of publishing papers, there is a current buzz about an old idea, that depression serves a purpose for the species.  It may surprise you to know, but not every culture and every time has tried to extinguish the Grim when it rears its head.  The approach of the European Middle Ages was to classify it as one of the four humours, melancholia.  It may cause difficulties when the humours are out of balance.  But there is a place in this world for the melancholic.  We are good gardeners, night watchmen, writers.  Paul Andrews and J. Anderson Thompson argue for Depression's Evolutionary Roots, that it exists because it "is not a malfunction, but a mental adaptation that brings certain cognitive advantages," among them the ability to ruminate, to think carefully about complex issues and solve problems.  That is not the way my therapist talked about rumination.

I will keep reading and thinking about these ideas, because that is one of the things I do.  I ruminate.  So you will find out more about rumination in the coming months.  Meanwhile, I have a new determination to treat my depression, my body, my mind gently, to discover what I can do with what I have been given.  I am not quite ready to call it a gift.  But I am disinclined to poison myself in order to get rid of it.

Costa Rica is a gentle place.  

photos by Helen Keefe

The Chemistry Experiment -- Placebo

Wouldn't you know.  I take a few days off before my placebo post, and wired.com scoops me with Placebos are Getting More Effective.  Drug Makers are Desperate to Know Why, by Steve Silberman 08.24.09.  Well, Steve put a lot more into his article than I intended for mine.  It makes for a fascinating read, about the history and current study of the placebo effect, beginning with its discovery during World War II, when an Army nurse lied to a soldier in pain.  They were out of morphine.  So she told him the injection of saline solution was a potent new pain killer.  And the patient's pain was relieved.  

That story is the essence of the placebo effect.  "When referring to medicines, placebo is a preparation which is pharmacologically inert but which may have a therapeutical effect based solely on the power of suggestion." -- thefreedictionary.com.  

In 1962, the Food, Drug and Cosmetic Act began to require that medications prove their safety and effectiveness against placebos.  One group takes the medication.  Another group takes a placebo, or "sugar pill."  Their rates of improvement and side effects are then compared, to find out whether the medication itself causes the healing, or something else does, like the belief  in the medication, which marshals the body's own healing powers.  

Fast forward to the last decade, when more and more antidepressants have "failed trials," meaning that they perform no better, or not much better than the little sugar pills.  It seems that the new neurological medications are performing just as well as the old ones.  (I think this usually means that within 8-12 weeks, about 30% of people who take them improve their scores on various questionnaires that measure levels of depression.)  But oddly, over time, the placebos are performing better.  Which means the bar that the new meds have to cross to get approved is getting higher.

The Chemistry Experiment -- Augmentation

When I began The Chemistry Experiment, there were about twenty options out there for me to try.  I was a wuss and quit at six.  I said "no" to a fifth SSRI/SNRI, and rejected the whole class of MAOIs (Monoamine Oxidase Inhibitors) -- which were just too tempting to use as a backup plan.  Instead I headed east, and Chinese herbs got me through almost two years.  Later I returned to an antidepressant that hadn't been effective before, but at least it did no harm.  This time it helped.  Was this because I was taking Xiao Yao San as well?  Who knows.  But now it doesn't work any more anyway.

Meanwhile, there is a new strategy called augmentation.  If one med doesn't work, try combining two, an antidepressant with an anti-psychotic, anti-convulsant, mood stabilizer, atypical anti-psychotic.  Suddenly the number of possibilities is up to forty.  That doesn't actually give you 1600 potential combinations, because if you combine MAOIs with most of the others, it'll kill you.  Most days, that doesn't seem like a good thing. Anyway, the number of potential trials has increased exponentially, and I am nowhere near the end of the chemistry experiment.

The Chemistry Experiment -- The Cure

I saw a movie in 1995, The Cure. It was about two boys, eleven year old Dexter and Eric, a little older. When Eric learns that Dexter has AIDS, he decides to find a cure. People find cures all the time in unexpected places. Since Dexter is not allowed to eat candy, Eric thinks that might be why he has AIDS. Keeping track of Dexter's temperature in a notebook, the boys try a lot of candy. After the first trial results were in, finding low efficacy and an unwanted side effect of stomach ache, they switch to plants down by the river, making a series of infusions (tea). This time a stomach ache leads to a hospitalization. When Dexter's mother ends the experiment and Eric's mother tries to end the relationship, the boys head south on a raft to New Orleans, where there will be new plants.

The Chemistry Experiment was something like The Cure, only my doctors didn't monitor as closely as Eric, nor respond as quickly to my side effects. Part way through it, I drew this picture of The Chemistry Experiment. The bottles crossed off were of Prozac, Celexa, Remeron, and Nortriptyline. Cymbalta is the one being added to the test tube, which was my body. I was willing to try no more than three per series, insisting that I wash out the test tube between. I also changed psychiatrists after three, and quit entirely for a while after Effexor.

I saved all my unfinished scrips. The pills fascinated me. They were the evidence of the violence to my body with which I was collaborating. My therapist really wanted me to throw them away. Eventually I did. But now I wish I still had them. Not to take all at once, that's not my plan. Just for evidence.

Thank You For Being My Friends

Try this experiment on yourself.  Imagine that you are standing at the base of the hill.  What do you see, smell, hear?  Put yourself in this picture.  Are you with anybody?  If so, who is it?  What is your relationship like? 

Now, tell me. How steep is the hill?  Really steep?  Sort of steep?  Not so steep? 

Friends And The Perception Of Difficulty 

In The Beginning

In the beginning I went to my doctor for a med check. I had been on Prozac for three months. I was anxious and agitated, irritable, couldn't concentrate and couldn't sleep. I thought I needed a higher dose.

I was wrong. 

As I walked in the door, I had a thought. It was more intrusive than a fantasy, and less welcome. Never mind for now what it was, but it involved a nail file... I didn't tell my doctor about this thought. I just got my higher dose.

That is when things started to get really bizarre. 

The Birth Of Prozac Monologues 

A short while later, while coming off Prozac, I tried to imagine how I could tell people about what it was like to have to come off Prozac. The only medium that seemed appropriate was the stand-up comedy routine.

And that was the birth of Prozac Monologues, with its first chapter, Bizarre.

Someday, Prozac Monologues will be available to the purchasing public. For now, come here to find out about depression and its treatment, drugs and research, the brain and its wonders.

Welcome -- Willa

photo modified from original by Tom Varco

reformatted 11/26/10