··and sealing-wax…

Posted on Friday 1 July 2016

    “The time has come," the Walrus said,
    “To talk of many things:
    Of shoes··and ships··and sealing-wax··
    Of cabbages··and kings··
    And why the sea is boiling hot··
    And whether pigs have wings.”
    The Walrus and the Carpenter
    Lewis Carroll, 1832 – 1898

It seems like only yesterday, but it’s been three years since the DSM-5 was released [May 18, 2013]. Unlike Spitzer’s 1980 DSM-III, Kupfer and Regier’s DSM-5 was hardly cause for celebration. I was just glad to have it off of the front page. While the debates and harangues had gone on for years, the substantive questions about its basic structure were never even really addressed.

So when I saw the abstract below, I perked up. Dr Kendler was part of the DSM-5 Task Force and maybe he’s finally getting around to examining the flawed MDD category. However, in the days leading up to the DSM-5, Dr. Kendler wrote a report explaining the move to get rid of the Bereavement Exclusion in the DSM criteria for Major Depressive Disorder that I thought was an ill advised rationalization at best. My take is cataloged in depressing ergo-mania….
American Journal of Psychiatry
by Kenneth S. Kendler
Published online: May 3, 2016

How should DSM criteria relate to the disorders they are designed to assess? To address this question empirically, the author examines how well DSM-5 symptomatic criteria for major depression capture the descriptions of clinical depression in the post-Kraepelin Western psychiatric tradition as described in textbooks published between 1900 and 1960. Eighteen symptoms and signs of depression were described, 10 of which are covered by the DSM criteria for major depression or melancholia. For two symptoms [mood and cognitive content], DSM criteria are considerably narrower than those described in the textbooks. Five symptoms and signs [changes in volition/motivation, slowing of speech, anxiety, other physical symptoms, and depersonalization/derealization] are not present in the DSM criteria. Compared with the DSM criteria, these authors gave greater emphasis to cognitive, physical, and psychomotor changes, and less to neurovegetative symptoms. These results suggest that important features of major depression are not captured by DSM criteria. This is unproblematic as long as DSM criteria are understood to index rather than constitute psychiatric disorders. However, since DSM-III, our field has moved toward a reification of DSM that implicitly assumes that psychiatric disorders are actually just the DSM criteria. That is, we have taken an index of something for the thing itself. For example, good diagnostic criteria should be succinct and require minimal inference, but some critical clinical phenomena are subtle, difficult to assess, and experienced in widely varying ways. This conceptual error has contributed to the impoverishment of psychopathology and has affected our research, clinical work, and teaching in some undesirable ways.
I found this abstract confusing. I couldn’t quite land on what he was getting at. I thought the idea of surveying the textbooks historically for their take on the symptoms of depression was clever. At the end, I couldn’t agree more that people have reified the DSM Disorders, or that there’s a categorical error in the woodpile with MDD. But his main point eluded me, so I read the whole article. Alas, neither of those things is what Dr. Kendler seems to be getting at here.

What I think he’s saying is that the fully nuanced clinical picture of Major Depressive Disorder may have many of the features he found in his textbook review that are being overlooked, symptoms like depersonalization or derealization. He tells us that the DSM criteria are simply an index to the Disorder, not the Disorder itself – ergo, there’s nothing wrong with the DSMs per se. The problem is a conceptual problem in the users. I guess he thinks we’ve gotten sloppy. And he apparently buys that there is a unitary Disorder behind these various symptoms. That’s hardly the serious look at Major Depressive Disorder I had hoped to read.

The categorical error that I see is that Major Depressive Disorder [MDD] isn’t a category in the first place, and never has been. When I think back to the 1980 days when the DSM-III first arrived, that’s what I thought on first reading. Gone was the psychiatric disease Depression, AKA Melancholia AKA Endogenous Depression AKA Endogenomorphic Depression. This is the stuff of psychiatry proper that has been with us since the dawn of recorded history. And then there used to be something else – a heterogeneous collection of patients with widely varying severity who had the affective symptom, depression, but not the illness Depression. The DSM [-I] had used the term depressive reaction. The DSM-II gathered them together under the term depressive neurosis. In the DSM-III, they were all included under MDD [my mistake, there were other categories included but they never caught on because they felt too made-up].

It’s easy to see the problem. There are really no boundaries on the much larger second group. I personally thought at the time that this second group had problems in their relationships, or their lives, or carried over from the past, or in the basic structure of their personalities, and that depression was a symptom, a signal to them and to the world that something wasn’t right. Most of my internal medicine colleagues looked into the symptoms that brought them to a doctor’s office. Finding no underlying physical cause, they reassured them and sent them on their way. I did that too, and for many, that was enough. But for a sizable number, it wasn’t, and I got interested in working with those cases [I still am]. So in that group, the gamut runs from unhappy in a lousy marriage to structuralized lifelong personality disorder. No clear borders. And that drives actuaries and third party payers crazy. So I suppose that conflating the Depressions and the severe depressions looked like a solution to many. Major Depressive Disorder then became a way of certifying or validating illness. That’s the only explanation I could come up with at the time for the faux category.

We all know what happened. Instead of tightening a boundary, the DSM-III loosened it [maybe better said, destroyed it]. So the valuable research on Melancholia was stymied by dilution, and the huge number of symptomatically depressed people became fair game for the pharmaceutical industry and the [carpetbagger] KOLs who jumped at the chance to annex them as an eager market for the antidepressants. The scientifically sound ideas that were developing about Melancholic Depression [that it has a biologic basis, that it responds to medications or ECT, that it is a brain disease, that it has a genetic component] flowed into the whole population of people with depressive symptomatology who were told they had a chemical imbalance or a brain disease. And what flowed out was untold billions of dollars in sales of largely unnecessary and sometimes dangerous medications. And in the mix, millions of dollars of unnecessary and unproductive research depleted the funds available for continuing research pathways that might have clarified some more focused piece of the puzzle. In the process, progress in the psychological and social treatments also ground to a halt. We all went backwards.

Dr. Kendler’s offering seems to be an attempt to help us be more forgiving about the short-comings of the DSM and its Major Depressive Disorder category. What I’m able to follow about his idea seems trivial and off the mark – more "cabbages and kings". I found it particularly annoying that this is one of the few commentaries on the DSM-5 from an official and that it continues to skirt the real problems. In my opinion, as shepherds of the DSM, it would behoove he and his colleagues to take another tack. Fix the DSM rather than us, and restore the boundaries to more reasonable scientific domains so we can pick up where we left off 36 years ago and bring some kind of much needed clarity to the current sea of misinformation. And as a corollary, the place of medication in the symptomatic treatment of depression can only be clarified by clinical trials conducted without the epidemic corruption of our current era. The fact that the pharmaceutical industry, the clinical trial industry, and the third party carriers like things just the way they are right now is really not our concern.

So like Lewis Carroll’s Walrus, I think "the time has come … to think of many things." But right now, we’re sure not thinking about the right ones. We’re in the "whether pigs have wings" range. Somewhere on the other side of the morass of commercial interests, ideological differences, guild wars, and a sea of other bias, there’s some system that will deliver the best we’ve got with the resources available. And there’s some path that allows productive researchers to be in an environment that optimizes progress. Neither of those things are likely to happen without a sensible classification system that fits a lot better than the one we have now, without an insistence on honesty in the science we bring to bear on the problems, and without an oversight function that insures that we never again allow what’s happened here to repeat.
  1.  
    Bernard Carroll
    July 1, 2016 | 6:43 PM
     

    I recall warning Spitzer back in 1979 that he was leading us down a blind alley with the creation of MDD. He was not deterred. Now, 37 years later we can see that most of the research on depression since DSM-III is next to worthless on account of what you term the category error. You are right to observe that Kendler in this review article does not come to grips with the main problem. He doesn’t distinguish idiographic from nomothetic diagnoses. DSM criteria aren’t just an index – all they really can do is confirm that the idiographic diagnoses made by clinicians conform to a minimum nomothetic data set. They are not fit for purpose to make diagnoses, much less differential diagnoses.

    At the risk of repeating myself, here is another take on big D Depression: http://tinyurl.com/hvpqkff

  2.  
    July 1, 2016 | 7:58 PM
     

    Feel free to bring it up as often as it occurs to you. Little d depression is not a refined enough diagnosis to study with RCTs in my opinion. There are some cases that respond to environmental manipulation. Some that require some “archeologic” work. Some respond to meds. CBT helps others. But big D Depression is a good candidate for RCTs because of its homogeneity.

    I just read a comment by Peter Kramer, author of “Listening to Prozac” and now “Ordinarily Well: The Case for Antidepressants” who seems to deny this D d distinction [here] though the logic is elusive. He also seems to think it unnecessary to address the rampant corruption in the RCTs of the antidepressants.

  3.  
    Caroline
    July 1, 2016 | 9:55 PM
     

    Keyword: “cognitive”
    Vortioxetine’s proposed market differentiation has always been a supposed positive effect on cognition. That is why Lundbeck hoped to get away with calling it Brintellix. (Brilliant/intellect) Trouble is, cognitive complaints aren’t a component of the public’s conception of depression. So let’s us now write articles that suggest to prescribers that cognitive problems are a significant problem for their depressed patients. To newly discover a symptom of depression would be costly and might appear to be self-serving, on the off chance anyone thought a drug company would self-serve. Reviewing old conceptions of depression filled the bill.

    If he has exaggerated or over-emphasized cognition relative to its prevalence or importance in the materials he studied, I would take it as support for my cynical conjecture.

    If I am right in saying that cognitive problems are not a big part of the shared concept of depression, then I fear for the elderly even as I note my excellent progress toward joining their ranks. Lundbeck wouldn’t bother touting the drug’s purported ability to improve cognition if there were no market for drugs that do that. There sure is. It’s the top of what used to be called the age pyramid but which is more accurately termed the age planarian nowadays. See here: http://populationpyramid.net/united-states-of-america/2016/

    If my second cynical conjecture is correct, invest in antiemetic futures.

  4.  
    Sid
    July 2, 2016 | 10:32 AM
     

    Sad is sad,
    And that ain’t bad.

  5.  
    James OBrien, M.D.
    July 2, 2016 | 11:22 AM
     

    I guess Kramer can claim antidepressants work as well as other medical treatments if those include meniscus surgeries, statins and ACE inhibitors for mild hypertension. The problem is that these treatments are marginal in terms of NNT.

    Is he looking for a Venn Diagram with distinct nonintersecting circles? That doesn’t exist anywhere in DSM.

    Grief is certainly a distinct entity given that the phenomenology doesn’t include loss of self-esteem. The fact that DSM-5 can’t get that obvious one correct doesn’t speak well for the immediate future of nosology.

  6.  
    July 2, 2016 | 12:49 PM
     

    James,

    Amen! and Amen!

  7.  
    James OBrien, M.D.
    July 2, 2016 | 1:09 PM
     

    Thank you Mickey.

    Grief is a no-brainer and they blew it pretty much based on one questionable study out of San Diego, so to me there’s no hope they will distinguish big D and little d.

    For a real life example, if one has the requisite laundry list of symptoms of depression due to a loved one dying in the Orlando massacre, you now have MDD since two weeks have passed. I find that to not only be unscientific, but disgustingly inhumane and robotically unempathic.

    It’s still grief in my book, no matter what the best and brightest had to say in a secret committee.

  8.  
    Bernard Carroll
    July 2, 2016 | 1:27 PM
     

    Here is a good epidemiological study of the differences between grief and clinical depression. It may look like a duck when you count symptoms, but it doesn’t walk like a duck or quack like a duck in terms of clinical validators.

  9.  
    Catalyzt
    July 2, 2016 | 2:40 PM
     

    Just read Kramer’s comment:

    “Research that follows people over time finds that as neurotic depression worsens, it becomes indistinguishable from melancholic depression. The apparent difference in type is only a difference in severity.”

    I know I live and work in a different world than you guys, but I still find it astonishing to see someone actually put a statement like that in writing. I suppose it’s exactly the kind of crackpot conclusion one would reach using RCT results. It’s not quite “We all know pepper comes from ants,” but it’s edging into that territory.

    Sure, neurotic depression could escalate to melancholic depression– it’s possible, though I haven’t personally seen what Kramer is talking about… like, EVER. (In my very limited clinical experience.) Or heard my colleagues complain about this. Or had a clinical supervisor present a case that followed such a trajectory.

    If that DID happen, I would wonder, what kind of therapy are you doing with the client? What drugs were they on when you started seeing them?

    Neurotic depression, or situational depression, even grief… I mean, shoot me if I’m wrong, but they’re not that hard to treat. Sure, I haven’t had an opportunity to follow them for 30 years or whatever, but a lot of the time, you can knock that out in 26 sessions.

    Uncomplicated grief– sometimes the ghastly EAP six-or-eight session insurance model, it could work for that. Sometimes.

    Scary stuff.

  10.  
    James OBrien, M.D.
    July 2, 2016 | 3:23 PM
     

    If he’s not working in the jails and prisons how would he know anyway?

    This is a major point he is missing and a profound difference in the treatment setting for major mental illnesses.

  11.  
    Joseph Arpaia
    July 2, 2016 | 4:27 PM
     

    So many people who come to me meeting criteria for MDD, DSM-IV or 5, turn out to be struggling with chronic stress or addiction issues. Struggling to make ends meet at a demanding job with a special needs child, dealing with chronic pain, a miserable relationship but no economically viable way out, a hidden addiction or an eating disorder. The idea that someone will tell the interviewer for an RCT everything about their life that is relevant to their mood is absurd. People are simply not going to reveal very shameful things to someone just because they have signed up for a study, like being in a heterosexual marriage but identifying as homosexual, or being forced to have anal intercourse regularly by the husband, or the wife cheating on him and he doesn’t want to hurt the kids by leaving, or drinking a pint of liquor per day, or binging and purging several times per week, and on and on. The effects of these rarely show up in lab tests. The person can conceal them for months or even years with the only clue being the mood disorder is “treatment resistant”. Or the stress is obvious, for example, long-term socio-economic deprivation but ignored in the RTC,

    I have come to the conclusion that most mood disorders are an adjustment disorder with various mixtures of emotional distress and behavioral dysfunction that is an unsuccessful attempt to adapt to an intolerable situation. Localizing the pathology in the person is a convenient fiction. Treating an individual when the pathology is in the environment may give symptomatic relief but is not going to yield cures.

    In some ways our situation is analogous to that in the Middle Ages when physicians were diagnosing disease as caused by an imbalance of humors; blood, phlegm, black bile and yellow bile, if I remember correctly. People were given medications to restore their humoral balance. Of course, a lot of the diseases were caused by infectious agents in the environment and the real solution was to reduce the exposure.

    The book “Stress, the Brain, and Depression” by H.M. von Praag and E.R. de Kloet has some interesting ideas along these lines.

  12.  
    July 3, 2016 | 10:26 AM
     

    I’ve said this before, Kramer is selling a book that depends on people believing and expecting to be on medications. God, is the profit mongering at hand so insidious to some folks here?!

    Oh, and while I agree with Dr Arpaia to some degree, I think a driving force to much of what I have seen in private practice travels is anxiety that metastasizes into mood and thought disorder features.

    Have many of us forgotten that anxiety disorders were, and in my opinion still are, the largest group of mental health disorders out there? But, we all agree, I would hope, to not put folks on benzos, and while SSRIs have their place as well, the impetus of treatment for much of anxiety is psychotherapy, and there lies the injustice psychiatry has dumped on the public.

    Psychiatrists by in large can’t or won’t provide therapy, so, instead of referring out to legitimate resources to treat the problem, nah, let’s mislabel it, mistreat it, and mislead both colleagues and the public what is at hand.

    You know, shame and humility are great tools to redirect and ground those who want to be better and functional, but, don’t see that in the personality disordered, eh?

    Cue the Mexican guys in that line near the end of Blazing Saddles: “Shame, we don’t need no stinkin’ shame!” And humility, that requires insight and judgment, gone and forgotten with the antisocial and narcissist, true?!

    https://www.youtube.com/watch?v=TFwprS_L6tg

    Well, Happy 4th of July to all, 240 years later, and where are we today? I’ll let anyone interested to ponder go there…

  13.  
    Tom
    July 3, 2016 | 12:36 PM
     

    I suppose Kramer thinks that extreme shyness and introversion, left untreated, will morph into catatonia. He’s just pushing product.

  14.  
    James OBrien, M.D.
    July 3, 2016 | 1:27 PM
     

    Which was a parody of the bandit in Treasure of the Sierra Madre—“Axis four–we don’t need no steenking Axis four!” No money in that.

  15.  
    Cate Mullen
    July 4, 2016 | 10:36 AM
     

    FYITHE DAWN OF THE PHARMACEUTICAL-INDUSTRIAL COMPLEX OF THE MODERN AGE

    I’ll not argue that some or all of these things wouldn’t have occurred had Gore, not Bush, sat in the Oval Office, or that Democrats aren’t also responsible for many of our nation’s travails. But I can tell you with absolute certainty that the 2000 election brought forth a massive tidal wave of corporate influence that infected our government at all levels. Corporate titans, today’s equivalent of yesterday’s robber barons, were permitted to buy elections, purchase state legislatures, appoint judges, and write laws to benefit themselves. Nowhere is this more evident than with the pharmaceutical industry chieftains, whose lobbyists became key players in the Bush administration, and under whose influence the FDA became the “fast drug approval” agency.

    Lilly bldg credit turner 615×438.jpb

    Among the most powerful of those pharmaceutical corporations is Eli Lilly, whom Gary Farmer and I would take to court in the same state where we had earlier filed voter fraud charges, and which was the case that became the genesis of the litigation described in these pages. In retrospect, our choice to team-up and take on Lilly was providential—either that or a recipe for disaster. Not only were members of the Bush family major stockholders in Eli Lily and other pharmaceutical companies, but they were beholden to the industry in other ways as well.

    After leaving his post as CIA director, George H. W. Bush was appointed a director on the Lilly board, an honor bestowed upon him by the wealthy and influential father of future Vice-President Dan Quayle, the owner of a controlling interest in the company. Then, and later, George H.W. Bush would successfully lobby to permit drug companies to sell obsolete or domestically-banned pharmaceuticals to Third World countries. While Vice-President, he would continue to act on behalf of pharmaceutical company interests by personally requesting the IRS to give special tax breaks for Lilly and other drug companies.

    Also serving on Lilly’s board of directors was Bush 2000 campaign contributor Ken Lay, the former CEO of Enron, whom the President George W. Bush and the First Lady joined on an Enron corporate jet on their first trip to Washington after winning the election. All of us know, of course, what happened there: Enron would go on to become the poster-child of institutionalized, systematic and creatively planned accounting fraud, that which would set the stage for the Wall Street subprime mortgage crisis of 2008.

    Eli Lilly Board Members pharmaceutical-industry-financial-analysis-6-728 661x297As would soon become evident to Gary and me, the Bush connection to Eli Lilly and the Big Pharma “alumni club” ran much deeper than just this. Mitch Daniels, a former vice president of Lilly, became Bush’s director of management and budget. Sidney Taurel, another former Lilly CEO, would join Bush’s Homeland Security Advisory Council. Secretary of Defense Donald Rumsfeld served on the board of Eli Lilly partners Amylin Pharmaceuticals and Gilead Sciences. Similarly, administration veterans would transition easily back and forth to Lilly’s senior management. Among them was Alex Azar, who was Bush’s deputy secretary of the Department of Health and Human Services, during which he oversaw such agencies as the FDA, the National Institute of Health (NIH), the Center for Disease Control (CDC), and the Centers of Medicare and Medicaid Services. After leaving the Bush administration, Azar would become the senior vice president of corporate affairs and communication for Lilly.

    Then there was Big Pharma’s shill Dr. Andrew von Eschenback, whom President Bush appointed the head of the National Cancer Institute and who would later be tapped to head the FDA. As the Union of Concerned Scientists and the National Academies of Sciences, Engineering, and Medicine’s Institute of Medicine would report in 2006, under Eschenback’s tenure, the agency was “perverting science for political and financial benefactors.”

    Care to guess which drug company dominated the lobbying pack? In our new pharmaceutical litigation, Gary and I encountered so many conflicts of interest that our case should have been justifiably called Lillygate.

    THE ENTIRE BOOK “PHARMAGEDDON: A NATION BETRAYED” WILL BE RELEASED SUMMER 2016 AND AVAILABLE ON AMAZON.COM AND WH

  16.  
    Joseph Arpaia
    July 4, 2016 | 11:45 AM
     

    I agree with you Joel about anxiety morphing into mood disorders. That is why the chronic pressure or distress is so relevant. The anxiety is a symptom of the chronic neuroendocrine overactivation (and not everyone who is overactivated has the symptom of anxiety, low HRV is one physiologic symptom), which then depletes the person’s resources. As those get depleted mood symptoms start to arise as the neuroendocrine system is trying to conserve the depleted resources.

    In that phase anxiety and mood symptoms overlap. Depressive symptoms when the resources are depleted and anxiety when they recharge, and “hypomanic” when the resources are recharged and the person is trying to get as much as possible done while they have some energy.

    Eventually the resources are so depleted they can’t recharge and then depressive symptoms predominate.

    The paradigm I use for this is to reduce perceived demands relative to perceived resources, reduce the influence of desire and aversion on demands, reduce excessive activation to increase the ability to recharge. Then medications and therapy techniques can be used together to bring this about.

    Examples:
    Authorizing reduced time at work to reduce pressure (reduces demands).
    Medications or CBT to improve restful sleep (increases rate of recharge and resources).
    Bringing a spouse in to explain how depression is affecting the relationship and increase empathy (reduces demands from the spouse and increases resources as well as reducing emotional distress). I saw a study in which 5 sessions of couples therapy focused on this had a clinically significant effect on the depressed spouse.
    Changing unhelpful thoughts to reduce perceived demands and increase perceived resources.
    Meditation/Imagery/Self-hypnotic techniques to reduce excessive activation.
    etc etc etc

  17.  
    July 4, 2016 | 12:00 PM
     

    Dr A, appreciate the reply.

    Cate, Lilly is the Hillary Clinton of personification of the evils per lying, misdirection, projection, and denials that are Big Pharma, what they did with first Prozac, then Zyprexa, and even to a degree with Strattera and Cymbalta.

    And, to Dr N, you had a nice new banner at the top, liked that porch scene, was it for an honor or anniversary event as it is gone now?

    Happy 4th, read the Declaration of Independence, and watch this scene from National Treasure, it captures the moment, I think at least!

    https://youtu.be/he2jDZkzgiM

    People really don’t talk like that anymore, eh?

  18.  
    July 4, 2016 | 12:46 PM
     

    I teach these concepts in a seminar course for the LMFT grad students at the U of Oregon (nominally on “mindfulness” as we had to call it something).

    I wrote up a lot of notes for the course and the text for the course was the book Real Meditation in Minutes a Day, Arpaia and Rapgay, Wisdom 2008.

    I will try to tighten up the summary notes and put them up on my blog today as a pdf file. jparpaiamd.com

  19.  
    July 4, 2016 | 7:27 PM
     

    After looking at my notes its going to take more than an afternoon, or a week of afternoons to make them coherent enough to post. Sorry.

    And I am incredibly impressed at Dr. N’s ability to generate quality material for this blog at the rate he does. Much appreciated.

  20.  
    1boringyoungman
    July 4, 2016 | 8:43 PM
     

    Happy 4th 1bom
    ????

  21.  
    1boringyoungman
    July 4, 2016 | 8:44 PM
     

    Sorry for the ? marks. Tried to paste in firework/flag emojis.

  22.  
    Cate Mullen
    July 5, 2016 | 9:33 AM
     

    Another FYI
    Commonweal zine has a late last month article on Big
    Pharma outlying the negative and shall I say almost ghastly game plans
    Used outside of the U S
    This is global not just local with ripples like a nuclear blast being felt by so many
    Jonas Salk had it right
    How can you patent sunshine in reference to a truly good drug
    If others could have been so wise and compassionate and taken
    The Hippocratic oath to heart in every part of their mind and souls
    Maybe less human life could have occurred
    Remember
    Lady McBeth

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