Sunday, March 28, 2010

PTSD and DSM: Science and Politics -- Again

With the ongoing war in Iraq, Post Traumatic Stress Disorder -- PTSD is much in the news nowadays.  We can expect that to continue.

Nancy Andreasen, author of The Broken Brain, traces the social history of this mental illness in a 2004 American Journal of Psychiatry article.  The features of what we call PTSD have long been noted in the annuls of warfare.  More recently, in World War I it was called shell shock, and those who had it were shot for cowardice in the face of the enemy.  In World War II it was recognized as a mental illness and called battle fatigue.  Afflicted soldiers were removed from the front and given counseling designed to return them to battle within the week -- though there is one infamous story about General Troglodyte Patton who, while touring a hospital, cursed and slapped one such soldier for his "cowardice."

The DSM I, from the post-WWII era, recognized battle fatigue as Gross Stress Disorder.  It was removed from the DSM II in the early 1960s , when U.S. society was not regularly confronted with this cost of war.

Andreasen had the task of addressing Gross Distress Disorder again in the 1980s for DSM III, when veterans' groups wanted its return as Post-Vietnam syndrome.  Given her experience with burn victims, Andreasen pressed for a more inclusive description of the illness.  Post Traumatic Stress Disorder entered the new edition, described as a stress reaction to a catastrophic stressor that is outside the range of usual human experience.

In both DSM III and IV, the first criterion for PTSD is not a symptom, but an event.  The DSM IV widened the application to include events that are not necessarily out of range of usual human experience:  The person experienced, witnessed, or was confronted with an event or events that involved actual or threatened death or serious injury, or a threat to the physical integrity of self or others. In addition, The person's response involved intense fear, helplessness, or horror.  This criterion has been applied to a wider assortment of events, the traumas of rape, child abuse, auto accidents, earthquakes and even witnessing events not experienced directly.  David Conroy argues that being suicidal fits the description, and that those who have been suicidal may exhibit the symptoms of PTSD, as well.  The literature on suicidality, depression and PTSD notes that these three sometimes co-concur, but I have found no one else who considers that the threat of death may come from ones own self.

The DSM V tightens the criteria, though some would say not enough.  The traumatizing event now is described this way: The person was exposed to the following event(s): death or threatened death, actual or threatened serious injury, or actual or threatened sexual violation.  It also identifies specific means of exposure to the event, and eliminates others.

Andreasen expresses a conservative approach, Giving the same diagnosis to death camp survivors and someone who has been in a motor vehicle accident diminishes the magnitude of the stressor and the significance of PTSD.  Sally Satel, also a psychiatrist and a Fellow at the American Enterprise Institute puts it more provocatively, "We've dumbed down PTSD."  There is a false assumption, she added, that ''if something bad happens, people are damaged unless they talk about it.''

Perhaps the confusion about what we now call PTSD arises from the focus on the traumatic event.  The world has long known that war messes with soldiers' minds.  Other traumas are more individual and not so easily observed by the general public.  So similarities are obscured.  Common sense says that a death camp and an auto accident are of a different magnitude of trauma.  However, the differences become less obvious when viewed from the perspective of symptoms.  Each edition of the DSM has struggled with the differences and similarities, and each lurched from one direction to another.

Focus on some precipitating event for PTSD runs counter to diagnostic criteria for other mental illnesses, where the symptoms are given priority.  In some illnesses, such as depression, it is widely accepted that experiences and environment play a role in causation.  Past attempts to diagnose depression by its source (reactive, meaning in response to an event, or endogenous, meaning arising from biological sources) have been abandoned as unhelpful, since biological processes are part of any depression.

People with similar circumstances do not necessarily develop the same illness.  And most people who experience even a significant trauma do not develop PTSD, or they have symptoms that are easily resolved.  So why do some experience intrusive memories, feel numb and avoid triggers for years after the original event?

As it happens, the same therapies, antidepressants, anti-anxiety medications and cognitive behavioral therapy are used to treat both depression and PTSD, suggesting that these illnesses may be similar in other ways.

In fact, the brain science supports the comparison.  Stress plays a significant role in both.  Neuroscientists are studying three biochemical changes in the brain that occur under severe stress and persevere past the stress.
  • The locus ceruleus (marked in pink to the right) becomes over-active and releases too much of hormones called catecholamines, used to respond to an emergency, even when there is no emergency.
  • Pathways that connect the hypothalamus, pituitary gland and amygdala (HPA axis) fail to regulate another hormone used in crisis, called corticotropin-releasing factor (CRF).  (The hippocampus is green in the graphic, the amygdala blue and the pituitary gland yellow. -- Yes, I did have fun with the airbrush in my paint program!)
  • The opioid system of the brain also becomes overactive, releasing more endorphins, which cause a higher tolerance for pain, accounting for the numbed feelings of PTSD, and which eventually become depleted, causing loss of interest, one of depression's core symptoms.
In addition, each of these systems feeds into the others.

These hormones are necessary to help the body deal with potential pain and danger.  Under smaller stress, feedback systems tell the brain to back off when the danger has passed.  However, an intense enough stressor changes these underlying brain functions.  It destroys the feedback systems and dis-regulates processes that otherwise right themselves and return the brain to a stable state when the stress has passed.

But what is intense enough?  It depends on the individual.  Those who perceive they have some control over the traumatic event are at less risk.  For example, a fire fighter has more resources and so more control than somebody else caught in a burning building.  The fire fighter would be at less risk for PTSD.

Adults who were abused, or who faced many extreme stresses in their early lives, are at greater risk for developing PTSD following later trauma than others who do not have the same history.  The brain science demonstrates that their brains have been primed, by damage to these critical areas of the brain.

Another finding reveals the original insight behind calling it shell shock.  Explosions send out waves of energy that can cause concussions, traumatic brain injuries or TBIs.  These physical injuries create the same neurological stresses as what are thought of as psychological stresses.  Even minor TBIs, in which there is only short or no loss of consciousness, set up the brain conditions for developing PTSD.  TBIs also result from blows to the head, as in an assault, flying debris or a motor vehicle accident.

These findings explain why individuals vary by the trauma threshold that can cause the brain changes and consequent symptoms, and why an event that most are able to shake off is devastating to a smaller portion of the population.  Just as "reactive depression" became an obsolete notion, perhaps it is time to stop defining the exact nature of the trauma behind PTSD and focus instead on the biology. 

In fact, a Walter Reed Army Institute study of 2,525 U.S. Army infantry soldiers discovered that minor TBIs are more likely to result in PTSD than severe TBIs with loss of consciousness for ten or more hours.  The theory is that PTSD comes from recording memories in a malfunctioning hippocampus.  Those who go in and out of consciousness, or remain conscious but are dazed, have more memories to be recorded, hence more memories to become intrusive at a later date.

At stake are billions of dollars, as diagnosis has increased exponentially, as the illness is asserted in personal injury lawsuits, as Viet Nam vets present themselves for treatment of "reactivated" PTSD, and as the war in Iraq produces more soldiers with more problems.

The scope of the problem from the Iraqi war is enormous.  From the Washington Post report of the Walter Reed study: Head and neck injuries have been reported in one quarter of troops evacuated from [Iraq and Afghanistan.]  The proportion of soldiers with concussion may be as high as 18 percent... Almost 44 percent of soldiers reporting an injury involving loss of consciousness met the criteria for PTSD versus only 27.3 percent of those reporting an injury involving altered mental status, 16.2 percent of those with other injuries and 9.1 percent of those with no injury.  A 2008 RAND Corporation study put the incidence of PTSD in soldiers who have served in Iraq at 13.8%.  Other studies claim much higher numbers.

Debate continues about how inclusive or restrictive the criteria for diagnosis should be, with the proposed DSM V drifting toward the more restrictive criteria, where the economics of PTSD converge with the politics.  Repeating Andreasen from above, Giving the same diagnosis to death camp survivors and someone who has been in a motor vehicle accident diminishes the magnitude of the stressor and the significance of PTSD.

There is, of course, another way to honor those whose mental illness is the result of war, in line with Andreasen's original insight.  Instead of their own diagnosis, we might give them a Purple Heart.

Next up: Treatment and Prevention.

U.S. Army Soldiers attached to 3rd Squadron,
2nd Cavalry Regiment patrol and search for weapons
or Improvised Explosive Devices (IED) during a clearing mission
photo in public domain

Thursday, March 25, 2010

Agoraphobia Day

It's taking a while to get the next post written -- PTSD and DSM: Science and Politics -- Again.  It has turned into a two-parter, i.e., I got long-winded.  Meanwhile, as long as we're on the topic of anxiety disorcers...  This one comes from one of the blogs I like -- a link is on the sidebar and also in the credit.

Saturday, March 13, 2010

OMGThat'sWhatTheySaid! -- They

"We are more alike than we are different."  That was the first thing they wrote on the whiteboard at my Peer to Peer class.  And that was the first thing I wrote in my new notebook.  I had a sense that a revolution was coming.  But I didn't know yet what it was.

The next week we introduced ourselves by how we are different, our differential diagnoses.  We were Mary Obsessive Compulsive Disorder, Frank Bipolar, Sarah Borderline Personality Disorder, Peter Bipolar Antisocial Schizoaffective Disorder ("But I'm not so sure the schizoaffective part is right"), James Schizophrenia, Anna Major Depressive Disorder, Henry Bipolar Alcoholic, Willa Major Depressive Disorder ("But I wonder about Bipolar II").  Of course, I have changed the names.

The power of naming -- the third week we sorted out our seating arrangements.  That wasn't part of the class.  It just happened, when we entered the room and chose our seats.  The OCDs sat with the OCDs.  The Mood Disorders sat with the Mood Disorders. Interestingly enough, those with Schizophrenia did not sit together.  They dispersed themselves among us Mood Disorders.

I have focused for the last three weeks on the Diagnostic and Statistical Manual.  You could call it The Book of Names. The series brought me back to the reshaping of my imagination that began at Peer to Peer. I need to go back there. 

The Book of Names gave us our differential diagnoses, in the language of psychiatrists and therapists and insurance companies, words to speak of difference.

The sixth week we introduced ourselves again, by telling our stories.  That was the first step in the revolution.  Our stories began to reshape our imaginations, as we found the language of narrative.  We discovered how we are alike.

They weren't the most pleasant of words -- the nightmare of high school, child abuse, hospitalizations, prison time, misdiagnoses, meds.  Each story was unique.  But all the way through, I could identify with bits of each.  And in the widest sense, we were all of us survivors, and all there as a commitment to survival, all continuing survival as our essential life's work.  None of us told everything.  But each was vulnerable that night, and each was brave, and each was held in the tender listening of the rest.  I came away that night profoundly moved and profoundly respectful of my classmates, each one.

The next week, some of us rearranged our seating.

Oppression locks us in segregated seats when we use the language of they. The revolution begins, we can move again when we create the language of we.  It is true of all revolutions, all struggles for human dignity.  For those of us who are mentally ill, our resistance to the stigma of mental illness has to include a transformation of language.  The they of the differential diagnosis must become the we of our essential humanity, created in the image of God.

A regular feature of Prozac Monologues is an award given for the use of language that diminishes us, the language of stigma.  I call it the "OMGThat'sWhatTheySaid! Award."  This month is what they all said, what we all said.  We say they.

I will make this personal.  I gulped that first night at Peer to Peer, to think I might be more alike than different from that young man over there with schizophrenia.  I gulp to think I am more alike than different from that person who has had several courses of ECT.

I go to a NAMI meeting and I try to figure out -- which ones have a diagnosis, which ones don't.  I want others to think that I don't.  That I am not them.

My diagnosis is so safe.  I can tell you, and expect that you won't be afraid of me and my nice safe Major Depressive Disorder.  But I need to change it on my chart and on my disability applications, so that I get the right treatment and get my disability benefits.  I still don't want to change my diagnosis on my blog.  I struggle to say we when writing of my own diagnosis.

I struggle whenever pronouns come up in this blog.  In January I wrote:

...most people with Bipolar II do survive the disease without self harm or suicide. And with proper treatment, including the correct meds, they can thrive.

That felt icky to write.  But that's what I did.  I wrote they.  And I wonder if... No, I know that the we decreases the credibility of my scholarship in some circles.  I want to be taken seriously by doctors, scientists, professors, by -- well, by those who are not they.  If I show my anger, if I take it personally -- Well, what did you expect?  She's not one of us.  She's a mental patient.  She's having a bad day.  It's transference.  It's hypomania.  It's the meds.

To say we is to invite even more loss into my life.

Sometimes I do manage it.  From last October:

Hello, my name is Willa and I have a mental illness.

Words have power.  When one of us says we, we create we.  Somebody else says we -- not out loud, but to the first.  But eventually out loud.  And then another, and then another.

Most of my classmates aren't there yet.  But we will get there.  10.9% of people in the United States are taking antidepressants right now.  Some more of us are taking mood stabilizers.  Some more are taking anti-psychotics.  Right now.  We are everywhere.

When you say psycho, when you say lunatic, when you circle your finger at your temple, when you take a step back, physically or in your mind, when you go on high alert around somebody who is mumbling to himself, we hear, we see, we know.  We are everywhere.  Sometimes you drive us underground, you create the solitary.  Sometimes we do it for you.  We say they too.  That is how oppression works.

Sometimes we speak up.  Because we are we.

We will get there.

Saturday, March 6, 2010

DSM V 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.