Coffee Shop Neuroscience

I went into my favorite coffee shop the other day for my usual mocha.  They typically post a trivia question of the day that gives you a 10 cent discount on the coffee.  After a conference with a recent focus on neuroscience it was interesting to see a question about the number of thoughts per day.  My wife ventured a guess.  I asked the barista for the source and all that she could tell me was: "We get it off the Internet like most of our questions."  No footnote or reference available.  The source was not difficult to find.  It was a typical Internet site that has never impressed me as a knowledge source, but it did have a link to the original paper.  It turns out to be a neuroscience site - The Laboratory of Neuroimaging (LONI) at UCLA.  Read the fine print at the bottom of this page for qualifiers on what counts as a thought.  I looked for any papers on this estimate on the web site as well as Medline and did not come up with anything.

Irrespective of the methodology the question poses interesting questions for clinical psychiatrists if they are comfortable outside the confines of the DSM.  How much attention is being paid the the baseline conscious state of the patient and why might that be important?  What is their stream of consciousness every day?  Is it disrupted by mental illness or addiction?  To what extent is that stream of consciousness broken up into daydreams, memories, and fantasies?  To what extent is it impacted by a process that is not even suggested by the DSM?  The best example that I can think of is boredom.  Being easily bored can be a diagnostic criterion, but it seems to be an uneasy mental state on its own.  People who are bored get driven to do things to alleviate boredom and sometimes those activities are very risky.  Are the thoughts mentioned in the coffee shop question memories, fantasies, or daydreams? Why the large number?  I am not aware of brief frequent thoughts.  My stream of conscious thought is comprised of more coherent stories or images.

I did a Grand Rounds on fantasy and daydreaming about 15 years ago.  There has never been much quantitative work on fantasy.  There were some new research approaches to daydreaming being used at the time and I incorporated some of those references into the presentation.  I don't recall the exact number of daydreams per day but they were considerably less than 100.  The only research approximating the numbers of thoughts per day may be the research on the exact number of spoken words per day.  This research has generally been a comparison between men and women and a test of which sex speaks the most words.  Those numbers across different cultures and sampling periods range from 12,867 to 24,051 words per day (5).  Standard deviation were large and the authors conclude that on the average both sexes spoke about 16,000 words per day.  To me speech and language is unconsciously processed thought, but even counting all of those words does not get us to the level of the coffee shop question.  Do the authors believe that they have a way to capture tens of thousands of unconsciously processed thoughts?  I am very interested in hearing how they arrive at these figures.

The research in this area has since moved into the area of the wandering mind.  Wandering mind is defined as a cognitive focus on information unrelated to the immediate sensory input or task on hand.   It would include daydreams, fantasies, and the typical stream of consciousness that every person experiences at times throughout the day.  The critical research questions include when is mindwandering adaptive as is the case of generative fantasies and when it is maladaptive?  Smallwood, et al (7) have written an excellent brief review of how mindwandering can negatively impact medical decision making and the cognitive performance of physicians.  They point out that fatigue, depression, and circadian rhythm disturbances can lead to increased mindwadering with negative consequences by decoupling attention to the external environment from the necessary memories, patterns and access to decision-making that are the physician's cognitive set.      
    
The question also involves neuroscience.  Is there a physical representation of this process in the brain and what is it?  Neuroscience tells us that the brain has a Default Mode Network (DMN).  It was initially noted to be a network of brain regions that remain active during functional brain imaging studies in the absence of an external task.  These studies typically involve an active task for the research subject and the resulting brain image is analyzed as a response to that stimulus.  It was determined that this DMN comprises the system that allows for internal dialogue and stimulus-independent thought.  The physical representation includes a primary system comprised of the anterior medial prefrontal cortex (aMPFC) and the medial posterior cingulate cortex (PCC) communicating with two subsystems.  The medial temporal lobe subsystem is comprised by the retrosplenial cortex (RSP), parahippocampal cortex (PHC), hippocampal formation (HF), the ventral medial prefrontal cortex (vmPFC), and the posterior inferior parietal lobule (pIPL).  The dorsal medical prefrontal cortex subsystem is comprised of the temporal pole (TempP), the lateral temporal cortex (LTC), the temporoparietal junction (TPJ), and the dorsal medial prefrontal cortex) (1).  Some groups differ on the physical representation of this system and some groups use Brodmann area designations.  I drew a slightly different model based on Sporn's text (6) with some obvious distortion due to the lack of a three dimensional representation (the rTC should be folded over to the right temporal area away for the medial view):

Subsequent research has shown that the DMN may be implicated in several psychiatric disorders (2). Several functions for the DMN have been proposed that cut across a number of disorders including mind-wandering when no specific external stimulus is present, memory consolidation, to possibly maintain a baseline level of arousal, to divide attention across tasks and for continuity across time (3).  Disruptions and functional disconnects to the DMN have been studied for a number of psychiatric disorders.  If the conceptualization is correct it is useful to think about the implications of functional or anatomic disconnects or hyperconnects to other systems.

How is all of this relevant to psychiatry?  Consider the case of two patients with severe depression.  They both have insomnia, anhedonia and decreased appetite.  They both have typical depressogenic thought patterns including abundant self criticism, hopelessness, and suicidal thoughts without intent to harm themselves.  The only difference is that one of these patients has intense rumination about a job loss.  This patient was downsized along with 50 other people.  The job loss was a straight business decision rather than any performance deficiency.  The patient without rumination is treated with standard methods and recovers.  The patient with intense rumination does not.  The depression and rumination persists despite multiple antidepressant trials.  The degree of disability persists.  There is not much guidance about how to treat this person from a biological standpoint.  It comes down to empirical drug trials and additional treatment for what has been considered anxiety, psychosis, or possible obsessive compulsive disorder.  I have seen these patients recover with detoxification from drugs or alcohol, treatment with antipsychotics, treatment with electroconvulsive therapy, but not treatment with benzodiazepines.  Will the cognitive neuroscience that incorporates models of the wandering mind and default mode network offer fast and more effective treatments?  I think that we may already be seeing that.  Mayberg's classic 2005 article (8) explicitly testing the network hypotheses about treatment resistant depression with deep brain stimulation was a start.  That literature has greatly expanded since that point.

There has been an explosion of network based theories of both psychopathology and normal conscious thought in the past decade.  These models are increasingly relevant as psychiatry is dragged out of a receptor and reuptake protein based discipline, where the practitioners may have a vague idea of where those receptors are located and what they really might be doing.  It was a necessary second step, but only neuroscience will get us to better models and models that we can apply to the treatment of unique individuals.  Psychiatrists have a critical decision to make at this point.  Are we going to remain stuck in a diagnostic and treatment paradigm that clearly applies to a minority of the people with mental illness or are we going to embrace the science that will both allow us to treat everyone better and give us a more complete understanding of human consciousness?

Learning about the Default Mode Network is a good starting point.  


George Dawson, MD, DFAPA



References:

1;  Barron, DS, Yarnell S.  Default Mode Network: the basics for psychiatrists.  Fundamentals of neuroscience in psychiatry.  National Neuroscience Curriculum Initiative.

2:  Mohan A, Roberto AJ, Mohan A, Lorenzo A, Jones K, Carney MJ, Liogier-Weyback L, Hwang S, Lapidus KA. The Significance of the Default Mode Network (DMN) in Neurological and Neuropsychiatric Disorders: A Review. Yale J Biol Med. 2016 Mar 24;89(1):49-57. eCollection 2016 Mar. Review. PubMed PMID: 27505016; PubMed Central PMCID: PMC4797836

3: Mason MF, Norton MI, Van Horn JD, Wegner DM, Grafton ST, Macrae CN. Wandering minds: the default network and stimulus-independent thought. Science. 2007 Jan 19;315(5810):393-5. PubMed PMID: 17234951; PubMed Central PMCID: PMC1821121.

4: Stafford JM, Jarrett BR, Miranda-Dominguez O, Mills BD, Cain N, Mihalas S,Lahvis GP, Lattal KM, Mitchell SH, David SV, Fryer JD, Nigg JT, Fair DA. Large-scale topology and the default mode network in the mouse connectome. Proc Natl Acad Sci U S A. 2014 Dec 30;111(52):18745-50. doi: 10.1073/pnas.1404346111. Epub 2014 Dec 15. PubMed PMID: 25512496

5: Mehl MR, Vazire S, Ramírez-Esparza N, Slatcher RB, Pennebaker JW. Are women really more talkative than men? Science. 2007 Jul 6;317(5834):82. PubMed PMID:17615349.

6: Olaf Sporns.  Networks of the Brain.  MIT Press.  Cambridge, Massachusetts, 2011.

7: Smallwood J, Mrazek MD, Schooler JW. Medicine for the wandering mind: mindwandering in medical practice. Med Educ. 2011 Nov;45(11):1072-80. doi: 10.1111/j.1365-2923.2011.04074.x. PubMed PMID: 21988623. (link to free full text).

8: Mayberg HS, Lozano AM, Voon V, McNeely HE, Seminowicz D, Hamani C, Schwalb JM,Kennedy SH. Deep brain stimulation for treatment-resistant depression. Neuron. 2005 Mar 3;45(5):651-60. PubMed PMID: 15748841.

9: Christoff K, Irving ZC, Fox KC, Spreng RN, Andrews-Hanna JR. Mind-wandering asspontaneous thought: a dynamic framework. Nat Rev Neurosci. 2016 Nov;17(11):718-731. doi: 10.1038/nrn.2016.113. PubMed PMID: 27654862


Supplementary 1:

Olaf Sporn's book Networks of the Brain is an excellent resource to study this topic and to try to catch up on a decade of research:

Supplementary 2:

Default Mode Network links that are relevant for psychiatrists (unedited):

"default mode network" dementia

"default mode network" addiction

"default mode network" "bipolar disorder"

"default mode network" schizophrenia"

"default mode network" ADHD 

"default mode network" depression

"default mode network" anxiety

"default mode network" mind-wandering

"default mode network" day dreaming


Supplementary 3:

The answer to the coffee shop question is a.

The Balanced Rhetoric Against Neuroscience

The New York Times editorial pages continue to be a place where anti-neuroscience rhetoric can be expressed primarily as decreased funding or more accurately portion of the available NIMH funding.  Maybe there has been some pro-neuroscience opinion expressed there and if there was I have missed it.  I recently posted an exciting development in neuroscience teaching for psychiatrists and psychiatric residents.  In that post I reference an opinion piece by Richard Friedman, MD a psychiatrist (1).  Dr. Friedman makes several arguments for psychotherapy as if it is unrelated to neuroscience and based on that premise concludes that there is no substitute for psychotherapy, that people are more than a brain in a jar, and that anyone benefiting from psychotherapy seems to prove  that.  I found that to be an incredible statement considering that (according to Koch in above graphic):  "The brain is the single most complex object in the universe." There is also the fact that with 7.4 billion people on earth - there are 7.4 billion unique conscious states - the vast majority of which are not accurately described by any DSM or psychodynamic diagnosis/formulation.  All the time that Dr. Friedman is mounting this critique he also discusses the importance of clinical research and suggests shifting the funding balance away from neuroscience.

In the recent case John C. Markowitz a professor of clinical psychiatry at Columbia has a more subtle form of the argument.  In this case and the previous opinion piece the authors both endorse the importance of neuroscience to a point.  In this case the argument is - yes neuroscience is important but let's reestablish balance between neuroscience and clinical studies such as looking at the efficacy of psychotherapies.  Breaking it down, Dr. Markowitz makes the following points:

 1.  Under the directorship of Thomas Insel, the NIMH clinical research budget was "strangled" and the resources were diverted to neuroscience research.  The author acknowledges both the need for neuroscience research and the primitive stage of psychiatric diagnostics based on clusters of signs and symptoms.  This was really the basis for Insel's RDoC initiative looking at more reliable markers of psychiatric syndromes.  Any practicing psychiatrist who has seen all of the iterations of the DSM realizes that we are as far as we can go with this manual.  That includes from the standpoint of validity but also in terms of the clinical examination by psychiatrists.  As long as we are all contained by this manual, the clinical method of psychiatry will remain stuck somewhere in the 1940s.  That should be extremely disconcerting to the profession and future psychiatrists.

DSM technology is extremely limiting in terms of the usual clinical trials.  The NIMH sponsored Star*D study is a decade and a half old at this point.  It has defined the response rates for both antidepressant therapies and provided a discussion point for psychotherapy trials of depression.  Clinical trials of antidepressants provide an equally varied result.  Any practicing clinician knows that these studies are all seriously flawed out of the gate by using DSM diagnoses and also an intent-to-treat analysis that does not resemble clinical practice.  The variation in diagnoses from depression to anxiety to depression plus anxiety as seen in clinical practice should point to the fact, that patient selection into clinical trials currently results in very heterogenous patient populations in terms of both therapeutic effects and medication tolerability.  We can continue to spend large sums of money on these trials of mixtures of patient populations and post modest positive results or we can attempt to identify patients who will respond specifically and not experience side effects from a particular therapy.  That is the real promise of neuroscience based research.

2.  The patients who need help are poorly served by current neuroscience research.  The helpful psychotherapies listed by the author like interpersonal psychotherapy (IPT), cognitive behavioral therapy (CBT), and other psychotherapies have been around for decades.  I happen to have copies of Interpersonal Psychotherapy by Klerman, Weissman, Rounsaville, and Chevron and Cognitive Therapy of Depression by Beck, Rush, Shaw, and Emery.  The publication date of the former is 1984 and the latter is 1979.  Both therapies have been out there for over 30 years.  At this point both have been studied hundreds of times.   Looking at clinical trials on Medline yields 1711 for CBT and 261 for IPT.  Not only that but some of the clinical trials that were successful (like IPT for cocaine use) have never made  it into clinical practice.  In fact, in most places getting a therapist who actually practices any of the specific research proven psychotherapies is impossible.  The problem does not seem to be a lack of psychotherapy research but a lack of access to practitioners who use research proven psychotherapies.  Mental health treatment is the most highly rationed treatment resource and additional studies that continue to prove that existing psychotherapies work seems superfluous at this point.  Any current studies are often compared to existing therapies and with the DSM problem contributing to diagnostic heterogeneity.  Any new trials should only be funded for serious conditions where the therapy might be useful.  There is no reason to expect that a new therapy applied using the current diagnostic system or clinical trials technology will lead to any enhanced treatment effects.

3.  Existing treatments are not "good enough".  The author attributes this "good enough" statement to Insel himself.  I understand the point he is trying to make.  The author points to continued suffering, treatment failures and suicides as evidence that more is needed now.  The problem is that there is no assurance that clinical research will add any more at this time.  Certainly a focus on suicide as a stand alone problem (not suggested at all by DSM) and on serious disorders with no treatment like adult anorexia nervosa is warranted.  But even then we are left with a clinical trials technology that consistently produces modest results at best.  More multimillion dollar trials of psychotherapy that we already know is somewhat effective when patients have no chance of ever receiving it against a backdrop of "is this really depression or anxiety" seems like a waste of time and money to me.  It seems like a much better idea to develop a neuroscience method to determine who needs psychotherapy and who might benefit from medications.  But even then, the only treatments that will be readily available will be the medications and even then less than half of the affected patients will get access to treatment.  Good luck trying to find a psychotherapist and an insurance company willing to cover the cost of the number of sessions used in the psychotherapy research. Research proven therapies are only as good as the number of practitioners using them and access to those practitioners.

4.  The placing all of your eggs in one basket argument.  This is basically saying that if the ratio of clinical to neuroscience funding is 10% to 90% the risk is missing something big in the clinical research and not getting any useful results from neuroscience.  Given the history that I have provided, there needs to be a clear advance on the clinical side in order to fund large trials.  It does not make any sense to continue to  fund more of the same  or slight modifications of treatment for common disorders.  Our eggs have been all in one basket and I would call that treatment as usual.  In the 30 years that I have been in practice, there is nothing that I would call a major breakthrough.  Clinical research results come and go.  Effective psychiatrists are effective psychiatrists not based on breakthroughs but how they approach clinical practice.  Even that mode of treatment is threatened by widespread support for "collaborative care" that is being justified using the same kind of research that justified managed care in the first place.  In the end there has been nothing more destructive in terms of access to care for mental disorders than managed care.

In many ways these ongoing arguments resemble the arguments of the biological psychiatrists and psychotherapy psychiatrists that I trained under in the 1980s.  Many programs were split under this artificial division with the residents left to identify with biological or psychotherapy faculty.  It is interesting to note that this division occurred at a time when Kandel wrote a paper on how psychotherapy is neuroscience in action (3).  That may have been missed because the biologically based psychiatrists at the time were really focused on pharmacology and neuroendocrinology rather than a comprehensive neuroscience.  Neuroscience and the old diagnostic technology and clinical methods seem to be the current points of division.

A lot of the criticism is directed at Insel.  I have heard him talk about the initiatives and the rationale sounded clear to me.  I think that rationale is very similar to what I have discussed so far, but for clinical psychiatrists it is also the realization that as long as we live in an approximate world - we will get approximate results.  The inertia to stay in that place is always puzzling to me.

But - it is time to move out of the 1950s.

Clinical psychiatry the way it is currently researched and practiced holds no promise for understanding the most complex known object in the universe.  Neuroscience is one of the big ways out of that predicament.



George Dawson, MD, DFAPA      



References:

1:  Friedman RA. Psychiatry's Identity Crisis. New York Times July 17, 2015. p SR5.

2:  Markowitz JC.  There’s Such a Thing as Too Much Neuroscience.  New York Times October 14, 2016. p A21.

3:  Kandel ER. Psychotherapy and the single synapse. The impact of psychiatric thought on neurobiologic research. N Engl J Med. 1979 Nov 8;301(19):1028-37. PubMed PMID: 40128.

              

National Neuroscience Curriculum Initiative - a brighter future for psychiatry

As any reader of this blog probably knows, I am a big proponent of neuroscience education for psychiatrists and always have been.  I have suggested in the past that it would take broad collaboration.  I posted some examples of an NIMH initiative on neuroscience  education.  I teach neuroscience (also known as neurobiology) myself and that has led me to be acutely aware of the lack of educational resources on the field.  That background is what has made this the happiest day at a CME conference that I have ever spent.  I am currently at the University of Wisconsin 4th Annual Update and Advances In Psychiatry - a conference that has really been in place for the past 41 years.  After watching a comprehensive update on eating disorders I settled in to listen to Melissa Arbuckle, MD, PhD; Professor of Clinical Psychiatry, Director of Residency Training; Department of Psychiatry, Columbia University Medical Center.  The title of her presentation was Discussing the Neuroscience of Mental Illness with Your Patients.  I turned to the section in the syllabus and there was one page with a case report on the front and a crude drawing of the brain (two views) on the back.  Being a traditional conference guy who likes a ton of technical information, no audience participation, and no role playing - I was prepared to be disappointed.

I was not prepared for what would transpire in the next 90 minutes.  I have posted here many times why I thought that every psychiatrist should know neuroscience and ways to do it, specifically the need for widespread collaboration due to a lack pf neuroscience manpower in most departments.  Dr.  Arbuckle started out explaining what the National Neuroscience Curriculum Initiative was.  It was started by a collaboration of like minded residency directors  to come up with a program to teach neuroscience to psychiatry residents.  She showed the explosion in neuroscience papers in psychiatry just over the past decade.  She referred to an article in JAMA Psychiatry (1) with her collaborators on why neuroscience needs to be integrated into psychiatry right now.  She discussed the New York Times editorial that showed up three weeks later with the criticism of their viewpoint (2).  Although she did not mention it, like a lot of articles it as written from the perspective of a psychiatric identity crisis.  Whenever I see that term it seems like the authors are firmly behind the curve and don't seem to understand what neuroscience encompasses.  Dr. Arbuckle said that the article was critical of the criticism that the brain was the basis of human behavior.  Quoting the article:

"Indeed an article in May in one of the most respected journals in our field JAMA Psychiatry echoed this view: "The diseases we treat are diseases of the brain."........ Even if this premise were true - and many would consider it reductionist and simplistic - an undertaking as ambitious as unraveling the function of the brain would likely take many years."  The author is a psychiatrist and goes on to say that he is all for neuroscience and even talks about some recent research techniques he (implicitly) just doesn't think psychiatrists should study it?  He also seems to conflate psychotherapy as being independent of neuroscience when in fact we have known just the opposite since since Kandel's 1979 seminal lecture Psychotherapy And The Single Synapse.  

I am equally incredulous when people seem to argue about the importance of neuroscience in psychiatry.  I find reductionism and reductionist approaches to be perfectly understandable and acceptable.  It is an interesting form of rhetoric to use these terms pejoratively.  Most people go into medicine because they want to know how things work.  If they did not enter with that goal, it soon becomes apparent that knowing mechanisms whether they are theoretical or not is an important aspect of studying medicine.  Some of the first mechanisms I studied in medical school involved cholera and diphtheria toxin. How is it possible to determine these mechanisms and recent significant epigenetic mechanisms without taking a reductionist approach?

The exercise that Dr. Arbuckle introduced to the audience was the diagnosis and treatment of complex cases.  The case vignette involved a young woman with borderline personality disorder.  The task for the audience was to pair up and role play discussing the relevant neuroscience concepts of treatment with the patient using the brain diagram as an aid.  Eliciting responses from 300 people in a room slows things down.  After the audience was done, she showed a film of an expert presenting this information to a patient and what presentation materials might be available.  It went very well and it presented the rationale for dialectical behavior therapy and not a medication.  It was a clear example of a neuroscience based discussion that provides a rationale for psychotherapy.  There are numerous materials on the web site (9 modules, 56 sessions, 40 authors) and wide scale participation is encouraged.

The information up to that point was quite exciting.  Dr Arbuckle had plenty of enthusiasm in her closing remarks.  In those remarks she pointed out the goal of "getting the entire field up to speed" in neuroscience.  She pointed out that everything on the site is free but at some point they may ask physicians to pay for CME.  She said that she realizes that this is literally "changing the world and that is what we are going to do."        

This was the most exciting commentary from a psychiatrist about teaching the entire field and the future of psychiatry that I have ever heard.  I have never been this impressed by any development in the field during my career.  And I am a psychiatrist who is as pro-neuroscience as anybody.  How is it that I am just hearing about this initiative right now and only because I am attending a conference?  That is why I am posting my experience here and a link to the NNCI web site and materials.

Dr. Arbuckle and her collaborators are one of the few bright spots for the future of psychiatry.

But they are very bright.


George Dawson, MD, DFAPA


References:


1:  Ross DA, Travis MJ, Arbuckle MR. The future of psychiatry as clinical neuroscience: why not now? JAMA Psychiatry. 2015 May;72(5):413-4. doi: 10.1001/jamapsychiatry.2014.3199. PubMed PMID: 25760896.

2: Friedman RA.  Psychiatry's Identity Crisis.  New York Times July 17, 2015. p SR5.


Attribution: 

The graphics at the top are two slides from one of my lectures.  I like to present data on the unique aspects of every individual brain and why that can happen.  The slides are not from the NNCI program and I am not affiliated with that program.  Click on each slide to enlarge.

Public Service Announcement - Moderation Policy

This is just a reminder and to establish an anchor point about moderation on this blog.  If you attempted to post a response on the blog and it did not show up it is most likely due to one of these reasons.  It is always possible that I made a mistake or that your response ended up in my spam file.  In fact, several posters clued me in about that happening and I did find and post their responses.  It should be pretty clear that you do not have to agree with me but there are some limits that are fairly basic to a small barely read blog like this one.  These limits follow:

1.  No trolls - I am not fascinated by trolls or the troll culture.  One of the reasons that I started this blog was that I used to post in what I thought was a professional forum that was dominated by a troll.  There was no moderation and eventually all of the interesting posters left and went elsewhere.  So spare me the First Amendment arguments - that kind of rhetoric just doesn't fly here.  My reasonable test is what would happen to a troll in any medical staff meeting?  Consider this a similar atmosphere.

2.  No advertising - This is a strictly non-commercial enterprise.  I type it up on my own and there is no sponsor or source of revenue.  As I have pointed out to people who want to advertise here, I have many copyright permissions at this point that are all contingent upon the non-commercial status of this blog so at no point is it possible for me to accept advertising.  The Creative Commons license allows anyone to repost the contents of this blog with the proper attribution.  If you like the content - just repost it or link to it.  No advertising also includes posts with hyperlinks to product advertising and that kind of link results in a rejected post.  It also includes posts with no content and apparent compliments that are hyperlinked to advertising through the name of the poster.

3.  No anti-psychiatry rhetoric - There can be discussions of anti-psychiatry from a philosophical standpoint, but if the main point of the post is to bash psychiatry or psychiatrists this is not the place and you probably already know that.  There are many anti-psychiatry blogs that you can flock to.  Some of them are even contain active posts by psychiatrists.  Psychiatry attracts a lot of haters and my original analyses of the problem in 2012 still stands as well as a clear anti-psychiatry bias in the media.  At least part of that media bias is that they are just being provocative to draw a crowd and of course they have no responsibility to people with clear problems.

4.  No personal attacks - ad hominem is the poorest form of criticism.  If the argument cannot be addressed, attacking the person is not a substitute - at least here.  There are many other blogs and media sites where that is acceptable.  The standard I use for physicians is the expected behavior in professional settings with colleagues.  If a post does not meet that standard it is on shaky ground.

5.  No medical advice - this blog is not the place to seek personal medical advice.  Nothing here should be construed as medical advice or a discussion of an actual patient.  My opinion stated here in many places is that only your personal physician or physicians knows enough about you to make suitable recommendations.

6.  No interminable arguments - I don't have to have the last word on anything and frequently just stop posting.  I will not post repeated posts making the same argument or with very slight modifications.  One of the most interminable arguments has to do with the link between psychiatrists and pharmaceutical companies.  I have debunked that argument on this blog many times.  I would refer you to blogs where they have interminable arguments about how bad psychiatric medications are and how corrupt psychiatrists are for their connections to Big Pharma.  Neither argument is accurate but this is the place to read about how medications are actually used.

7.  Stay on topic - It is a reasonable requirement to address the topic.  Newspaper web sites are good examples of what can happen when this simple rule is not followed.  A corollary is to address the topic in a timely manner.  I have had people notice posts from 3 years ago and write a response.  Blogger does not allow me to terminate discussions like some web sites.  My only option is to not post untimely responses.  Six months is a reasonable time frame.

That is what I have so far.  I reserve the right to add more as they come to me.  The goal is to maintain coherence and rational discussion.  Any inspection of the blog posts shows that there is not a lot of discussion and stimulating discussion is not one of my primary objectives. I appreciate the people who have taken the time to read this blog and post their comments - many of which make excellent points and do stimulate further discussion.

My goal all along has been to produce opinion and analysis consistent with the way that real psychiatrists train, work, and practice.  I do not see myself as unique in any way.  I routinely have contact with excellent psychiatrists who I have trained with and who are colleagues.  They approach problems in psychiatry and think about those problems in very similar if not identical ways that I do.    I see this blog as a creative outlet as well as one of the few places on the Internet where this kind of content is available.


George Dawson, MD, DFAPA




Attribution:


The photo:  John Schneider.  RCA 40A Ribbon Microphone. August 19, 2007.
Attribution-NonCommercial 2.0 Generic (CC BY-NC 2.0)

Big Data - What Is It Good For?

Big Data and Data Science have been buzzwords in science and industry for over a decade.  A Medline search shows over a thousand current references to Big Data in healthcare.  A good starting point is consider what is meant by Big Data and then discuss the implications.  A quick scan of the references shows that they vary greatly in technical complexity.  A standard definition from Google is: "extremely large data sets that may be analyzed computationally to reveal patterns, trends, and associations, especially relating to human behavior and interactions."  These techniques developed because of the widespread availability of digitized data and the ease with which sets of behavioral choices (in the form of mouse clicks) can be collected on web sites.  In many cases specific data collection paradigms can be used to elicit the information, but there is also a wealth of static data out there as well.  In health care, any electronic health record is a massive source of static data. Financial, real estate, educational records and records of all of these transactions are also a significant source.

Most  Americans logging in to set up a Social Security account online (ssa.gov)  in the past couple of years would be surprised at what it takes to complete the job.  After the preliminary information there is a set of 5 security questions.  Four of those questions are about your detailed personal credit history - home mortgage information and credit card history.  When Social Security was initially set up in 1936 there was widespread concern that Social Security Numbers would become national identifiers.  At one point Congress had to assure the electorate that the number would not be used for that purpose.  Since then the SSN has been used for multiple identification purposes including credit reporting.  At this point it seems that we have come full circle.  Congress invented the SSN and told people it would not be an identifier.  They mandated its use as an identifier. Congress authorized and basically invented the credit reporting system in the United States.  The federal government currently uses the credit reporting system to quiz taxpayers wanting to set up a Social Security account online.  In the meantime, large amounts of financial, legal, and health care data are being collected about you under your SSN in data systems everywhere.  At this point the full amount of that data and the reasons why it is being collected for any person in the US is unknown because it is all collected without your knowledge or your consent.  It is impossible to "opt out" from this data collection.  The federal government does have an initiative to remove SSNs from health records, but there are so many other identifiers out there right now, this effort is too little and too late.

Additional sources of data include your online foot print including sites that you may have visited and what you seem to be interested in.  A visit to Amazon for example and a quick look at an expensive digital camera may result in that same camera with a link to Amazon in the margin of very other web page you see for the next two weeks.  Expensive digital cameras of a different brand than the one you originally looked at may start showing up.  You may notice product ads showing up in your Facebook feed that you mentioned casually to your friends during a conversation there.  The conversation could be as generic as bicycle seats and suddenly you are seeing a flurry of ads for bicycle seats.  Any number of web sites encourage to sign in with other accounts and then share your account information with them.  All of this data provides companies with what they need to fuel their predictive algorithms to sell you a product.  It provides the major advertisers in this space like Google and Facebook with a huge revenue source because based on the scale and personalization of these ads - they are effective.  Big Data seems to be very good for business.  But is there a downside?        

That brings me to a current resource on the nefarious uses of Big Data written by an expert in the field.  Cathy O'Neil is a PhD in mathematics.  Her PhD work was in algebraic number theory.  She started work as an academician but subsequently worked for a hedge fund, work as a data scientist for several firms and currently heads the Lede Program in Data Journalism at Columbia University.  I am familiar with her work through her blog MathBabe.  Her newly released book Weapons of Math Destruction takes a look at the dark side of Big Data specifically how data collection and biased algorithms can be good for administrators, politicians and business but bad for anyone who falls under the influence of those agencies and their work.  In the introduction she leads of with the example of teacher assessments.  I was familiar with a scattergram that she had posted on her web site showing that year to year teacher assessment scores were essentially uncorrelated or random.  In the book she describes the human toll in this case a teacher fired because of this defective algorithm.  In another example later in the book, an experienced teacher scored a 6 out of 100 on a "value-added" teacher evaluation.  Only tenure kept him from getting fired.  The scoring algorithm was opaque and nobody could tell him what had happened.  The next year he scored the 96 out of 100.  But the algorithm was so flawed he knew that score was no more legitimate than the last one.  With the politicized environment surrounding teaching the proponents of teacher "accountability" like this variation since it fits their ideas about the system retaining incompetent teachers that need to be weeded out.  In fact, the algorithm is defective and like many is based on erroneous assumptions.

I personally know that physicians are subjected to the same processes as teachers, but so far it is less technologically advanced.  O'Neill points out that there is nothing magical about algorithms.  That they frequently incorporate the biases of the people who design and contract for them.  Opacity and a lack of correction by feedback is another feature.  I worked for the same employer for a number of years when physician "accountability" measures were put in place.  The "algorithm" for salary went something like this RVU Productivity + Outside Billing + Citizenship = Pay.  RVUs were the total number of patients seen according the the biased government and managed care billing schemes.  Outside billing was any consulting work done outside of the clinical work that was billed through the department.  Citizenship included teaching and administrative duties as well as any Grand Rounds or CME lectures that were done.  In other words apart from the subjectively based billing scheme all of the inputs are almost totally subjective and influenced by all kinds of pseudoaccountability measures along the way.  For example, in parallel with the teacher ranked on the algorithm, I was told one year that I had achieved the top rank in terms of documentation in a group of about 25 physicians.  The next year - making no changes at all in terms of that documentation - I was dead last.  My conclusion, like the teacher in the example was that the rating scheme was completely bogus and with that kind of a scheme who cares about the results?

The number of based algorithms applied to physicians has eerie parallels to those mentioned in WMD.  Here are a few that I picked out on the first read:

1.  The algorithm is based on faulty data - the teacher evaluation algorithms were based on a faulty interpretation of data in the Nation at Risk report.  The report concluded that teachers were responsible for declining SAT scores between 1963 and 1980.  When Sandia Labs reanalyzed the data 7 years later they found that an great expansion in the number of people taking the test was responsible for decreased average score but subgroup analysis by income group showed improved scores for each group (p. 136).  The only reason that teachers are still being blamed is political convention.  I posted here several years ago that the top ranked students in the world in Finland are taught by teachers who are assumed to be professionals and who are not critiqued on test results.

The parallel in medicine was the entire reason that medicine is currently managed by the government and the healthcare industry.  It was based on criticism in the 1980s that doctors were lining their pockets by performing unnecessary procedures and that work quality was poor.  That should sound familiar because that criticism has been carried forward despite a major study that showed it was completely wrong.  The massive Peer Review Standards Organizations (PRSO) in each state in the 1990s conducted rigorous reviews of all Medicare hospitalizations and concluded that there was so little overutilization and so few quality problems that it would not pay to continue the program.  The only reason that managed care companies exist today is by political convention.

2.  An effective teacher like an effective doctor is too complex to model - When that happens only indirect measures or "crude proxies" (p. 208) can be used to estimate effectiveness.  In medicine like teaching - the proxy measures are incredibly crude.  They generally depend on diagnosis, poorly account for comorbid illness, and the outcome measures are heavily influenced by business rather than medical decision making.  The best examples are length of stay parameter and readmission parameters.  Every physician knows that there are set payment schedules based on the supposed ideal length of stay for a particular illness.  The business influence in the discharge decision is so malignant these days that non-physician case managers are present to pressure physicians into discharging patients.  If the discharge beats the length of stay parameter - the hospital makes money.  I sat in a meeting at one point and asked the obvious question: "OK - we have completed the discharge checklist - do we know the outcomes?  How do the patients do when they are discharged by this process?  How many of them die?"  Dead silence followed.  Most people would be shocked to hear that what passes for evidence based medicine is often a checklist that has no meaning in the real world.  Making the points on the checklist is good for advertising though.

3.  There is a lack of transparency in the overall process - The teachers in WMD who were blindsided by the algorithm were never told how that conclusion was reached.  I encountered the same problem in a managed care organization when it was clear to me that administrators with no knowledge of psychiatry were telling us what to do.  In some cases, "consultants" were brought in to write reports to confirm the most recent administrative edicts.  When I asked my boss if I could talk with the people sending out the edicts I was informed that there was a "firewall" between clinicians and upper management.  This lack of feedback is another critical dimension of algorithms gone astray.  If you are writing an algorithm biased toward a business goal - why would you want feedback from clinicians?  Why would you want any humanity or clinical judgment added especially in the case of psychiatric care?  Let's just have a dangerousness algorithm and leave it at that.  Those are the only people who get acute treatment, even though it is patently unfair relative to how the rest of medicine works.             

Big Data is good for science.  We can't do elementary particle physics or genomic analysis very well without it.  Big Data is also good for business is much different ways.  There are clearly people out there who cannot resist buying items online if the Amazon algorithm shows it to them enough times across a number of web pages.  Big data in business can also come up with billing algorithms that have less to do with reality than making a profit.  Similar programs can be found for employee scheduling, performance analysis, and downsizing.  The problems happens when the business biases of Big Data are introduced to science and medicine.  Those techniques are responsible for an array of pseudoquality and pseudoaccountability measures for physicians, hospitals, and clinics.

Unfortunately physicians seem to have given up to the political conventions that have been put upon us.  Some administrator somewhere suggests that quality care now depends on a patient portal into an electronic health record and a certain number of emails sent by patient to their physician every month.  Across the country that will result in hundreds of millions of emails to physicians who are already burned out creating highly stylized documentation that is used only for billing purposes.  Terabytes of useless information that nobody will ever read again - the product of a totally subjective billing and coding process that started over two decades ago.  Is there any data that email communication is tied to the effectiveness or technical expertise of the physician?  I doubt it.  I worked with great physicians long before email existed.

It is about time that somebody pointed out these manipulations provide plenty of leverage for the management class in this country at the expense of everyone else.  It is well past the time that doctors should be confronting this charade.  


George Dawson, MD, DFAPA




References:

1.  Cathy O'Neill.  Weapons of Math Destruction - How Big Data Increases Inequality And Threatens Democracy.  Crown Publishing Group.  New York, NY, 2016.  I highly recommend this book for a look at the other side of Big Data.  It is written in non-technical language and is very readable.

Attribution:

The photo at the top is a Server Room in CERN By Florian Hirzinger - www.fh-ap.com (Own work (Florian Hirzinger)) [CC BY-SA 3.0 (http://creativecommons.org/licenses/by-sa/3.0) or GFDL (http://www.gnu.org/copyleft/fdl.html)], via Wikimedia Commons"   href="https://commons.wikimedia.org/wiki/File%3ACERN_Server_03.jpg"><img width="512" alt="CERN Server 03" src="https://upload.wikimedia.org/wikipedia/commons/thumb/d/d7/CERN_Server_03.jpg/512px-CERN_Server_03.jpg"/></a>

  

Psychosis Idealized

I thought I would provide a counterpoint to the New York Times editorial entitled "Medicating A Prophet" written by Psychiatrist Irene Hurford (1).  The opinion piece is available free online and I encourage anyone interested in the topic to read the article rather than accepting my summary here as adequate.  I will say from the outset that I am not a stranger to any of the issues that Dr. Hurford discusses either clinically or personally.  The bulk of my career was spent treating people with severe mental illnesses and addictions.  Once you have worked in that setting, it is clear that many people who are severely ill need involuntary treatment and that is one of the decision points that she addresses.

In her essay, Dr. Hurford describes an early call experience during her residency.  She was asked to assess a man in the emergency department (ED) who had been delusional for 30 years.  The delusions were religious and grandiose in nature.  He was a college graduate but was homeless living on the street in Philadelphia.  He also had AIDS and the complication Kaposi sarcoma.  His reason for being in the ED was "to preach".  Dr. Hurford encourages him to come in for voluntary treatment but he refuses.  At that point she ponders involuntary treatment but in the essay decides to discuss the patient's right to psychosis. Later we learn that she made the decision but has decided to analyze that decision in retrospect based on factors that she has encountered since.

One of those factors was the influence of a professional colleague who based on her own experience with psychosis and that colleague's mother's experience suggested that thoughts about living "in psychosis" and outside of psychosis need to be challenged.  She basically states that the problem may be within the beholder rather than the identified patient. Following that logic, it makes sense to show up in an ED to preach while ignoring serious health problems.  It also makes sense to make decisions about the person's "in psychosis" experience knowing so little about them.  In my experience, nobody in the ED calls the parents or family of a 50 year old street person, to get a clear picture of how the psychosis has truly affected him.  When I have treated these people on an inpatient unit and made those calls, I have never heard that the patient was well served by the psychosis.  Not a single time.  In many cases, family members were surprised to hear that person was still alive.

Dr. Hurford advances a number of other arguments that I call into question.  She uses a very loose definition of insight as a "failure to accept an alternative view of reality".  She turns this around to suggest that anyone who does not accept this premise (implicitly the treating physician) also lacks insight.  I don't think that you can practice psychiatry and not be comfortable with alternative realities.  I would suggest a more appropriate definition of insight as a decision-making process.  Can I accurately assess how I am doing in the world?  Am I making decisions in my best interest?  Are those decisions consistent with my ability to survive?  If I realize that I am not doing well can I get help?  Pretty basic decisions.  Not a question of lifestyle choices.  To have a lifestyle you have to live.  That is the kind of insight that I am used to dealing with.

Dr. Hurford discusses a case of a young patient with a psychotic disorder who stopped taking his medications and started using cannabis on  daily basis.  He dropped out of college and became progressively incoherent and then mute.  She is concerned about traumatizing the patient by "enforcing" treatment even though he cannot "eat, sleep, and talk."  I don't follow the logic that some treatment intervention - even basic detoxification from cannabis is somehow more traumatic than not eating, sleeping, or being able to communicate.  How is that a preferred alternative existence?

At that point she digresses to a very brief overview of the usual comments about mental illness being only peripherally associated with violence and the lack of evidence that forced treatment led to fewer hospitalizations, arrests, or a better quality of life.  She cites a meta-analysis of three randomized-controlled studies of more than 700 people.  There are a lot of reasons why meta-analyses are not superior to the actual trial data.  There are also a lot of reasons why truly clinical samples with these problems cannot be ethically randomized or included in the studies.  There are also reasons why I would expect the entry points into these studies to be highly variable as well as the treatment resources that are involved.  In Minnesota, we have 87 counties and the rule is that there are 87 interpretations of the commitment act for involuntary treatment.  There are two corollaries operating here.  The first is that the courts will be very liberal in terms of dropping commitments until something bad happens.  At that point the pendulum swings back in the direction of more frequent commitment.  The second is that only the wealthiest counties in the state can afford to provide adequate resources to treat the severely mentally ill.  Even then there is no assurance that the counties that can afford it will actually provide the care.  Some currently function like managed care companies and ration the care.  They can end up rationing care and commitments in order to save the county money.  The lack of evidence that forced care does anything may be more of an indictment of the lack of quality or consistency in delivering care and interpreting the law  and rationing care more than anything.  I have personally treated many times the number of people with forced treatment than in the meta-analysis and there is no doubt that the outcomes were better than with no treatment.

The outcome variables cited by Dr. Hurford are also dreadfully lacking compared with what can be seen routinely in clinical settings.  They include very adverse outcomes in encounters with the police including getting shot, dying from a treatable illness, suicide, loss of relationships with spouses and children, loss of a job and income, and acute loss of life due to poor insight and judgment.  In Minnesota, all that takes is going outside in the winter time without adequate protective clothing and you are dead or in the Burn Unit with frostbite.
     
Right now we are in the midst of a sweeping cultural change that idealizes psychosis and suggests that hallucinogens and cannabis are therapeutic drugs.  That will put the next generation or two of people with psychoses, mood disorders, and substance use disorders at risk for chronicity and every possible negative outcome.  A point that should not be lost on anyone is how no care for psychosis is "cost-effective" care when the total impact on the patient is ignored.  My point in writing this rebuttal is really advice for the people in these generations.  Ask any psychiatrist treating you or your family member where they stand on this issue.  

Especially if you value psychotic symptoms a lot less than your psychiatrist does.



George Dawson, MD, DFAPA





References:

1.  Irene Hurford.  Medicating A Prophet.  New York Times.  October 1, 2016.

Cancer Care In Psychiatry - Yes It Happens

Great Case Records of the Massachusetts General Hospital in the New England Journal of Medicine this week.  A psychiatrist is presenting a case of complicated disorder and coordinating care with oncologists after a cancer diagnosis is made.  It must have taken an editorial change in the Journal to get psychiatry more front and center in this prominent medical journal.  This article has a lot of meaning for me, because the bulk of my career was spent on these issues.  When you are the inpatient doc or the psychiatrist staffing the case management teams - either Assertive Community Treatment (ACT) or some other case management model a lot of this important work falls to you because there is nobody else out there.  Contrary to the popular hype about collaborative care - people with severe mental illnesses generally avoid medical clinics and non-psychiatric physicians.  There are always some exceptions, but as I have said many times there are reasons that people do not go into psychiatry.  Talking to people with communication problems, irrational thought processes, and atypical social behavior are high on the list.  Some of the best primary care physicians recognize this and like the oncology clinic described in this paper give people with severe mental illnesses wide latitude in terms of appointments and treatment schedules,  but they can only do so much.

What is needed on the front end is a psychiatrist with strong medical skills to figure out the problem and get other medical staff involved.  I don't mean looking at PHQ-9 scores and suggesting medication adjustments.  I mean actually talking with the patients.  Very frequently a person with impaired judgment due to a psychiatric disorder will be fully cooperative in one setting but not another.  Consider a patient who is acutely admitted with very high blood pressure (260/140).  He has a history of schizophrenia and hypertension requiring moderate to high doses of two different antihypertensives.  In this case the patient has gone off of both medications and maintenance antipsychotic medication.  He is agitated and paranoid.  It is impossible to determine if he is also delirious due to the presence of cognitive disorganization from acute psychosis.  He will not allow testing or physical examination beyond the blood pressure determinations and eventually stop cooperating with that.  The inpatient psychiatrist makes an assessment and swings into action.  He tries to establish rapport with the patient to convince him that this is a medical emergency.  At the same time he has contacted the hospitalist service and there is agreement that he needs to go to an acute care bed as soon as possible.  The hospitalist reminds the psychiatrist that they cannot touch the patient unless he consents "or it is assault".  His advice is to call when he is ready to cooperate or call when he gets obtunded by encephalopathy or a stroke and they will treat him acutely.  In this case the psychiatrist eventually convinces the patient to check out the ICU and walks him over there.  Once he is in the bed - he is fully cooperative with all recommended measures including a complete physical exam.

In addition to the lack of a logical progression to the care of severe medical problems there can also be obstacles at the level of presenting the diagnosis to the patient.  I have presented diagnoses of cancer and diabetes mellitus to patients with psychiatric disorders only to be told that the diagnosis is impossible.  "I could not possibly have diabetes doctor, because I don't have a pancreas." comes to mind.  In terms of evidence, holding up an image of a lung or brain tumor may get the response: "I don't think that is my x-ray doctor.  That is somebody else's x-ray."  Those responses and the lack of ability to cooperate can be very frustrating for primary care physicians and specialists.  These patients are always very easy to get rid of.  All it takes is a comment like: "If you want me to treat you - you are going to have to stop smoking.  If you can't stop smoking - I can't treat you."  At the other end of the spectrum I have had Internists coach me over the phone on what to do for a patient, because they knew the patient would never come into their office or pick up a prescription.

The most frustrating cases are the ones that I saw too late.  The mistakes of informed consent as in:  "Mr. Smith you have colon cancer and need to have surgery to have the tumor removed.  At this stage you have an excellent chance for recovery but we have to operate in the next few months."  Mr Smith has schizophrenia.  He smiles and seems to understand everything.  He just wants to get out of the clinic and away from doctors back to his home where he will be much less anxious.  He never returns until two years later when concerned relatives call the police because of their concern about him.  The police find him alone at home.  The house is in disarray.  There is blood everywhere.  Mr. Smith is emaciated and has lost 35 lbs.  He is brought to the hospital and admitted to inpatient psychiatry.  He is seen by the oncologist who originally consulted on his case.  He now has widely metastatic colon cancer and no chance for survival.  That whole sequence of events can be prevented by a psychiatrist willing to discuss these potential outcomes long before the clinical picture worsens.

An infrastructure that allows for continued outreach and rapport building is also useful.  I had many patients with terminal cancer diagnoses admitted to my inpatient unit, not only because they were mentally ill and medical services would not admit them, but because there was no place else for a mentally ill person with terminal cancer to go.  Pulling all of the necessary resources and teams together with an initial acute admission potentially saves lives.  This paper is a good example of that, but acute care psychiatrists may still be held to the "acute dangerousness" standard for care and these admissions are actively discouraged.    

In the case of the NEJM article, the patient is a 63 year old woman with a history of lung cancer, chronic obstructive pulmonary disease (COPD), hypertension, hypercholesterolemia, asthma, insomnia, and restless leg syndrome.  She has also had two previous cancer diagnoses.  A previous diagnosis of lung cancer had been treated surgically with lobectomy and adjuvant chemotherapy six years earlier.    She had a past history of stage IIa estrogen-receptor positive and progesterone-receptor positive, HER2/neu negative invasive ductal carcinoma of the left breast.   The breast cancer was treated with lumpectomy, whole breast irradiation, and chemotherapy.  The patient had a previous psychiatric diagnosis of Attention Deficit-Hyperactivity Disorder treated at times with various stimulants and modafinil.  She was a admitted to the inpatient psychiatry unit for treatment of depression with electroconvulsive therapy.

In the process her psychiatrist comes up with a list of 13 factors that affect cancer care in patients with severe mental illness and cancer and strategies to approach them.  The factors follow initially what is known about cognitive and social behavioral deficits in the population with severe mental illness.  That would include an inability to understand the diagnosis or treatment.  In many cases, the patient is unable to provide informed consent due to cognitive deficits.  System wide deficits are identified at the level of the provider, the health care system, and society and culture.  Any physician who tries to provide medical or psychiatric care to these populations has seen most of these deficits.

In addition to the factors affecting cancer care there is a separate table of Differential Diagnosis of Depression in a Cancer Patient that every psychiatrist working in these settings needs to be aware of.
      
The psychiatrist in this case provides psychotherapy focused on the patient's understanding of the illness and their decisions to cooperate with care.  That included but was not limited to biological interventions for depression.  ECT and lurasidone were the main identified treatment modalities.  An enhancing mass was noted in the right breast on chest CT scan to follow up on previous cancer treatment.  That was subsequently diagnosed as ductal carcinoma of the  right breast.  In this case, the radiation oncologist modified the radiation treatment to maximize the flexibility of treatment for the patient.  She was able to complete all 5 treatments without difficulty.  

From a psychiatric standpoint she was discharged as improved after 19 days taking lamotrigine, gabapentin, quetiapine, and modafinil.  She had received 6 ECT treatments.  But as importantly, she had follow up oncology care, identification of a new cancer diagnosis, and coordination of that care also occurred in that setting.  This is a very compelling study at that level and a clear departure from the rationed inpatient care that people have come to expect when psychiatric units are run by business people.


George Dawson, MD, DFAPA


References:

1:  Irwin KE, Freudenreich O, Peppercorn J, Taghian AG, Freer PE, Gudewicz TM. Case 30-2016. N Engl J Med. 2016 Sep 29;375(13):1270-81. doi: 10.1056/NEJMcpc1609309. PubMed PMID: 27682037.

2: Shtasel DL, Freudenreich O, Baggett TP. CASE RECORDS of the MASSACHUSETTS GENERAL HOSPITAL. Case 40-2015. A 40-Year-Old Homeless Woman with Headache, Hypertension, and Psychosis. N Engl J Med. 2015 Dec 24;373(26):2563-70. doi: 10.1056/NEJMcpc1405204. PubMed PMID: 26699172.

Supplementary:

From the New England Journal of Medicine earlier this year:

New England Journal of Medicine Discovers Assertive Community Treatment. link

The Reality Of Burprenorphine Therapy

It is increasingly popular for politicians and healthcare businesses to discuss their ideas about how to end the opioid epidemic that they started.  One of the common themes is widespread availability of both buprenorphine maintenance therapy and naloxone opioid antagonist therapy for acute overdoses.  I am certainly not opposed to either and in fact work in an addiction treatment environment where these are two of several medication assisted therapies used to treat addictive disorders.  I am skeptical of the idea that broad prescribing of these therapies in either primary care clinics or some treatment settings will ever occur.  Naloxone will be more readily available because there is a movement to create easy access without a prescription.  That will never happen with buprenorphine.  Last week - an article in JAMA backs up my skepticism (1).

The JAMA article looks at 3234 buprenorphine prescribers in the 7 states with the most buprenorphine prescribers.  In their introduction the authors talk about the policy initiatives to increase the maximum patients per prescriber from 30 to 100 patients after a year.  The average monthly patient census per month varied from 7 - 22 patients and a median monthly patient census of 13 patients.  The duration of treatment episode was 53 days.  This illustrates that the monthly census was well below the allowed limits and the duration of treatment was well below the recommended maintenance guideline of 12 months.  They cite evidence that novice prescribers wanted more access to substance use counselors or other prescribers with more experience as potential limiting factors.

The authors of this article do not offer other explanations for the low rate of buprenorphine prescribing.  I have a few.  I really do not like stigma arguments.  To me stigma seems like an excuse for not being able to overcome societal biases toward a particular problem.  I don't see how you can train to be a physician and not have most of these biases wrung out of you.  With addictions and mental illnesses there may be a stronger bias based on personal experience.  Some physicians may have come from a family where the the father was an alcoholic or a heroin addict living homeless on the street and everybody was used to that idea.  Some physicians may have come from families where the father was still drinking and dying of cirrhosis and the familiy opinion was that he "has a right to drink himself to death" rather than get treatment that he did not want in order to stop drinking.  Other physicians may have come from families where father and his father both had severe alcoholism.  Grandfather drank himself to death by the time he was 50.  Father got treatment for his alcohol problem and was in stable recovery for years.  All of these personal experiences and the reactions to them will affect how a physician approaches alcoholism and addiction.

Those biases are all part the the inevitable decision-making process that leads physicians down specific career paths.  I have lost count of the number of times that another specialist told me that they really liked psychiatry and were considering the residency except for certain features of the field.  A couple of examples include needing to try to predict suicide and aggression and live with the consequences or dealing with a certain diagnostic group like patients with severe personality disorders.  People are less specific about addictions, probably because as medical students and interns we all see the severe effects.  Most of the acute care hospitals where physicians train have 30-50% of their admissions based on the acute effects of alcohol or drug use.  That includes many admissions for acute hepatitis, hepatic encephalopathy from cirrhosis, acute alcohol poisoning, acute overdoses on addictive drugs, and various psychiatric morbidities like delirium and psychosis from the acute effects of addictive drugs.  It is less obvious but addictive drugs and alcohol are also overrepresented as reasons for admission to surgical trauma units and burn units.  Most interns and residents see these effects first hand and develop both short term and long term perspectives on these problems.

This seems like another case of managers and politicians not appreciating the intense interpersonal aspects of medicine.  Physicians are all not foot soldiers just waiting for the next assignment from a policy maker.  Physicians have probably carefully selected the type of practice they want to be in and there are more than the technical aspects of the speciality that were considered.  It takes a unique skill set to treat people with addictions.  Treating and maintaining an opioid addict in treatment long enough with buprenorphine maintenance for them to realize any benefit is a very unique skill.  Being affiliated with other buprenorphine prescribers is also a necessity to provide cross coverage for patients.  Speciality care centers for addiction seem like an idea to me that does not get a lot of consideration.  Trying to run a buprenorphine maintenance program in a practice environment that is rationed to the degree it currently is does not seem feasible to me.  Adding buprenorphine maintenance as just another task for a busy primary care physician practicing primary care medicine is not likely to work.  It should be obvious that these physicians have  more than enough to do right now.

There is a lot more to it than increasing the maximum numbers of opioid addicted patients on buprenorphine maintenance and trying to treat as many people as possible.  The data from this paper illustrates that.  There is also the issue of the preventing the pool of opioid users from increasing while trying to treat those who are currently dependent on these drugs.  That seems like the best long term option to me.

Addressing this complicated problem takes more than a licensed buprenorphine prescribing physician sitting behind a desk who is willing to prescribe it.  It takes better infrastructure including managers who are enlightened enough to get that physician the kind of resources they need to do the work.  I never hear politicians or policymakers talking about that.


George Dawson, MD, DFAPA


Reference:

1: Stein BD, Sorbero M, Dick AW, Pacula RL, Burns RM, Gordon AJ. Physician Capacity to Treat Opioid Use Disorder With Buprenorphine-Assisted Treatment. JAMA. 2016 Sep 20;316(11):1211-1212. doi: 10.1001/jama.2016.10542. PubMed PMID: 27654608.


        

An Excursion into the Psychiatric News - Blurred Lines Between Business and Professional Organizations

Psychiatry Eclipsed

Before anyone says that this is me going off the rails again - consider one small factor.  For over 30 years I have been paying the American Psychiatric Association (APA) significant amounts of money in annual dues.  Last year it was about $935.  During some of those years, I thought it might be useful to also donate to their political action committee and I gave them significantly more money.  All the time, I was expecting something to reverse the inexorable deterioration in the practice environment  and the rationing of mental health services.  During that time, I witnessed first hand the deterioration of psychiatric services in the state of Minnesota to the point that there is now a mandate that county sheriffs have priority in admitting their mentally ill prisoners to state psychiatric hospitals.  The psychiatrists in the state have no say in who gets admitted to these facilities or the severely rationed number of inpatient beds in the state.  The reason for professional organizations as I understand them is to speak for and advance the profession, support its members and advocate policies that benefit the people that interact with the profession.  In the case of psychiatry that is the patients that we treat, their families, and the larger society.  All I have to do is pick up a copy of the Psychiatric News to doubt that these mandates are very relevant anymore.

I will say in advance that in my assessment the APA does a fair job in terms of education and professionalism.  I have criticized them in this area in the past for not keeping the treatment guidelines up to date and relevant.  Subsequent to that there was a new guideline published.  Access to the educational materials is not contained in the membership dues.  A subscription to Psychiatry Online or the CME Journal Focus are additional charges as are CME credits for reading articles in the American Journal of Psychiatry.  There is also a CD version of courses and presentations at the APA Annual Meeting that is available for a significant cost.  The educational and professional materials are definitely available and some of them are first rate - but they do come at a price.

My biggest problem with the APA has been the total lack of rigor in countering the deterioration of the practice environment and in many cases seeming to directly participate in initiatives that are counter to the interests of psychiatrists and their patients.  Thumbing through the September 16, 2016 edition of the Psychiatric News provides some ready examples.

On page 1, there is a story Everett Appointed head of New SAMHSA Office.  The story is all about APA President Elect Anita Everett, MD assuming a new position as chief medical officer at SAMHSA - the lead federal agency for mental health and substance use treatment.  A direct quote from Dr. Everett: "Having a psychiatrist as a member of the leadership team at SAMHSA will enable psychiatrists to join other mental health and public health professionals in guiding the federal component of the nation's behavioral health systems."  My emphasis on behavioral health.  As far as I am concerned SAMHSA is a pro-managed care government bureaucracy - like most of them.  Secondly, there are plenty of psychiatrists out there who have been chief medical officers for managed care companies and I would challenge anyone to tell me why they are necessary and what they have accomplished.  Managed care companies tell psychiatrists what to do.  They are not interested in a reasonable practice environment, reasonable inpatient settings of even professional standards.  They are interested in cheap, rationed care by overworked clinicians.  I don't doubt Dr. Everett's qualifications or good intentions.  I don't think I am going out on a limb too far to say that she is going to be severely restricted by the current bureaucracy with a strong managed care bias.  That is not good for psychiatrists and it certainly is not good for patients.

The other story on page 1 seems worse - Are Psychiatrists prepared for Health Care Reform?  Yes and No.   I really can't think of a more nauseating term in the medical literature than health care reform.  I have been hearing those hot little words for the entire length of my career.  I heard them from the Clintons back in the days when Hillary Clinton headed up the health care reform efforts during the first Clinton presidency.  Some students of the topic like to recall that for one reason or another the initiative worked on by Hillary Clinton was not successful.  I think that depends on the standard.  There certainly was no expected global program, but it did make managed care a household word and set managed care as the predominant bias in all further discussions of health care reform.  Like most history - people seem to have forgotten this and the Clinton administration (and all that followed) as having a strong managed care bias.  The article suggests that psychiatrists need to get on board with the collaborative care model - another managed care rationing technique.  In the span of 3 decades psychiatry has gone from protesting managed care rationing (especially because it affects us and our patients the most) to suggesting you really have to get on board with this.  The usual buzzwords like further workforce development and merit-based payment reforms are evident.  When professional standards are abandoned what is merit-based payment reform? In all likelihood it has to do with rationing techniques rather than quality medical care.  Paragraph after paragraph in this article read like a managed care playbook.  Maybe the only way to see through all of this pro management rhetoric is to have actually worked in one of these systems of care.  Try working in one with a manager who is reimbursed to extract the maximum amount of productivity while not providing resources to physicians in the system.  In that case I believe the management buzz word is creativity.  In a rationed environment there is often an audacious statement about creativity as a solution rather than additional personnel.  Most reasonable people would be shocked at what constitutes merit-based payment or the hold back procedures before you can get to that level.  Just another in a long line of meaningless cliches flowing from health care reform.

As you might imagine I was a little tense and clammy as I went on to page 2.  There I was an editorial piece by APA President Maria A. Oquendo, MD.  It was title Why 'Physician Heal Thyself' Does Not Work.  I was mildly optimistic that she might come to the same conclusion that I have about physician burnout - it is not a disease it is just bad management.  Dr. Oquendo began  with a description of the recent suicides of a psychiatric resident and a medical student.  She presents the epidemiology of physician suicide and suicidal ideation.  She points out for example that suicide is the second leading cause of death for physicians between the ages of 24 and 35.  She discusses the stigma of a psychiatric diagnosis and the gap between problems and who gets treated.  Her solution is self identification of depression and excessive alcohol use.  There seem to be other factors that are operative.  She quotes a six fold jump in PHQ-9 scores during internship - using that as a metric for depression.  I can't help but think how physicians and trainees are more isolated now than ever.  No matter what the setting we had great teams when I was an intern and resident.  We took care of one another and we had attending physicians who cared.  I addressed some of that in my previous burnout article.  Nobody discusses what it is like to train in a managed care and rationed environment today compared with medical care as usual in the past.  During my last stint in a hospital I did not see well developed teams anywhere.  Most of the senior physicians who did a lot of the teaching and tended to view themselves as affiliated with residents had been replaced by hospitalists.  Entire teaching services had been replaced.  Non-medical management has left many medical institutions very arid places with few personnel and limited collegiality.  That is exactly the wrong environment for depressed and stressed physicians.   Training programs everywhere can help residents by making sure they build collegiality and that team factor in all of their rotations.  They need to provide highly motivated faculty who have the interests of trainees in mind as a priority.  The teams I am referring to here are teams of physicians, not teams that contain administrative staff telling physicians what to do.

The article most directly related to managed care hegemony was "Medical Necessity in Psychiatry: Whose Definition Is It Anyway? by Daniel Knoepflmacher, MD.  The title is of course purely rhetorical.  Like many things in medicine today medical necessity has nothing to do with medicine.  It is a pure business definition designed to give the appearance of legitimacy to what is a pure business driven decision.  The decisions are made by people with no appreciation of human biology or its complexity.  They are people who seem to think that a lot of meaningless business metrics somehow apply to the practice of medicine.  At the worst (and most probable) they are simply rationing to make a profit.  I would call them nerds but I really don't think that they are that smart.

In the article, Dr. Knoepflmacher makes that point.  There is not even a standard business definition of medical necessity.  Companies can basically say and do whatever they want.  He traces the history of the term and how various groups define it today.  Interestingly one of the largest managed care companies states that it is for payment purposes only.  He points out the overemphasis on acute or crisis care rather than professional guidelines or standards.  I would argue that in psychiatry, managed care companies do a very poor job of addressing acute care by using only a dangerousness metric.  The term cost effectiveness is incorporated into some of the definitions in the 1960s.  The acclaimed Mental Health Parity and Addiction Equity Act of 2008 lacks any definition of medical necessity or a more useful definition of medical appropriateness.  That may explain why this legislation has had negligible impact.  Dr. Knoepflmacher's thesis can be best summarized in the sentence:

"Without universal medical necessity criteria for mental health care, clinicians and their patients are saddled with a concept highly susceptible to abuse by insurers."

I would take it a step further.  The abuse has been institutionalized at this point.  Clinicians find themselves abused at every fork in the road.  Any time a psychiatrist refills a medication for a colleague or because the treatment setting has changed they are subjected to abusive prior authorization processes that are in place purely to harass physicians into giving up and patients to the point that they are paying out of pocket instead of using the insurance they have paid for.   In that case Congress is directly responsible for erecting two multibillion dollar industries and inserting them between the physician and their patient.  I would also propose a much better limit than arbitrary medical necessity criteria.  It should be apparent that any managed care company can get around legislation and rules that they lobbied to pass.  I propose that physicians recommend a course of treatment to patients and that they are totally removed from the payment process.  No more wasting time with insurance company employee-reviewers.  No more conflict of interest in favor of big business.  The physician recommends treatment.  The insurance company tells the patient if they will pay for it.  Other than civil action by the patient, the only oversight should be a panel of physicians carefully screened for conflict of interest at the state level to mediate disputes (sorry no insurance industry insiders).

Highlighting these four articles creates a portrait of what is wrong with the APA.  Like other professional organizations it has clearly bought into the pro-management zeitgeist that is generally sold by American businesses and government.  The general idea is that there are business managers that know more about what you do and can tell you what to do - irrespective of your professional training and experience.  That idea is a mile wide and an inch deep.  Anyone with middle school analytic skills should have come to the same conclusion as Dr. Knoepflmacher - about 20 years ago.  His article is there now as a necessary reminder that there is a much better way to do things.  Instead of affiliating with these outrageous business practices - they should be actively resisted at every level.  That should include the practice and training environments.  There is nothing worse for physicians and patients than wringing the humanity out of medical practice.

And there is nobody better at doing that than current healthcare business managers.


George Dawson, MD, DFAPA



Attributions:  The graphic is all me.  It is supposed to represent a progressive overlap by government and business interests with the profession.  There are psychiatrists that work in the overlap areas and some who work just in the black and gray zones.  The field is still plodding along as though it is an autonomous profession.  

Is Melatonin A Benign Supplement?

Before I get too carried away the answer to the question is most likely yes - it is a benign supplement.  That is based on all of the studies and reviews I have about melatonin used to treat insomnia and other sleep disorders.  Nobody seems to report any major side effect from even very high doses taken for periods of time.  Those same reviews have a lot of qualifiers.  As an example some will say that doses in the 4-6 mg per night range are unlikely to cause major side effects.  Others will suggest that even though melatonin use is widespread, there have not been any large clinical trials to assess long term safety.  There probably never will be.  When people ask me about the safety of melatonin that is exactly what I tell them.  Individual use of over-the-counter melatonin varies greatly.  The average self-administered dose that I encounter these days is 10 milligrams.  The range of outliers is to the high side.  Nobody uses the 1 mg or 3 mg tablets but there are people using 10-20 mg.

My concerns come from a number of perspectives.  First there is the issue of normal excretion of melatonin and pharmacokinetics.  Second there is the role of melatonin in other systems in the body. And third there is the question of the toxicology of melatonin.  In the case of supplements, the presumed toxicology is often based on the exposure of large numbers of people to the supplement and no alarming or immediate side effects.  Melatonin is ubiquitous in some tissues in the body and this gives the impression that it may be a benign compound.  On the other hand it is a metabolite of 5-HT (serotonin) and this has additional implications.  5-HT is a highly politicised molecule with unquestionable roles in human physiology and pharmacology.

When I start to think about the general approach to this problem - the first thing I look at is what the physiological levels of melatonin might be in both blood and CSF.  The published medical literature is scant. Normal levels are often determined as part of an experimental intervention like peripheral sympathectomy.  In one study (1), the normal diurnal fluctuations were noted with a peak ranges of peak plasma levels varied from 122-660 pmol/L, and the peak CSF levels from 94-355 pmol/L.   In this study the authors demonstrated that bilateral T1-T2 ganglionectomy abolished both the diurnal rhythms and resulted in lower levels of melatonin suggesting that the peripheral sympathetic nervous system has input into melatonin secretion.

Other studies have looked at the effects of melatonin supplementation on plasma and CSF levels.  This is always important because average natural melatonin secretion in humans is about 0.15 mg per day.  As I previously indicated supplementation is many times that.   An early study (2) showed that oral melatonin supplementation led to rapid increases in blood and CSF melatonin.  The authors also compared the ratio of CFS/blood melatonin and noted it was constant before and after supplementation suggesting that blood is the source of CSF melatonin.  Recent studies (4-6) suggest that melatonin is secreted directly into the third ventricle from the pineal recess or that there may be central or peripheral compartments of melatonin for different effects.

There was a recent comprehensive review of the pharmacokinetics of melatonin.  The authors reviewed 22 high quality studies looking at oral or IV  dose ranges of 0.1 mg  to 100 mg.   Cmax (maximum plasma concentration following the dose) ranged from 72.1 (10 ml/h; 0.02 mg, IV) to 101,163 pg/ml (100 mg, oral).  Tmax (time to peak plasma concentration) ranged between 15 (2 mg) and 210 min (10 mg).  T1/2 (half-life) ranged from 28 (0.005 mg, IV) to 126 min (4 mg, oral).  The response to melatonin for insomnia is unpredictable and no dose response curve has been determined. Of course there are a wide range of available melatonin preparations from pharmacies and health food stores.  Even in the research, it is often difficult to say what preparation was used, but the bioavailability is quoted as 15%.

The sleep research on melatonin shows that (as most clinician know) it has weak sleep effects but variability does exist.  Most people will notice very little effect.  Some will claim that they were "knocked out" and strongly sedated even the next day - an effect that is hard to reconcile with the short half-life.  The lack of a dose-response curve makes it difficult to determine dosing but a review in an authoritative sleep text (8) says that most studies use a dose of 4-6 mg and that the timing of the dose (1-3 hours before sleep) may be an important factor.  I have been advised myself by a sleep expert that a 1 mg dose of melatonin 3 hours before sleep may be optimal because it entrains the circadian rhythm of that individual and have seen that work in many cases.  The weak effects on sleep EEG to me suggest a strong placebo component.

 Getting back to the side effect issue - I was surprised to find a few pages on melatonin in last week's New England Journal of Medicine in their Clinical Implications of Basic Science Research section (9).   These authors discuss the implications of the MTNR1B variant as a risk factor for Type 2 diabetes mellitus.  This variant leads to an overexpression of MT2 melatonin receptors on pancreatic beta cells.  Melatonin in this case leads to a G-protein-coupled receptor (GPCR) initiated cascade that inhibits insulin secretion.  They reviewed the epidemiology of diabetes and the facts that Type 2 diabetes is typically a combination of insulin resistance in muscle and fat cells, increased hepatic glucose output and no compensatory insulin release.  They reference an experiment where the daily melatonin (4 mg dose) for 3 months reduced first phase glucose induced insulin secretion in an oral glucose tolerance test compared with baseline before melatonin secretion.  They point out that there has been some epidemiological work that associates shift work with susceptibility to diabetes mellitus.  They conclude that typical doses of melatonin of 4 mg/day or less are not likely to be associated with decreased insulin release and talk about the application of melatonin in jet lag with dosing for a few days.  They also point out in the 3-month long study that overall glucose tolerance was hardly affected and baseline glucose levels returned after 2 hours of dosing.  That may not be as assuring to psychiatrists who are seeing their patients take 5-10 mg indefinitely along with other medications that may cause metabolic syndrome.

To me this is also further evidence of just how crude many of our clinical trials are that look at the issue of metabolic syndrome and diabetes in clinical populations.  Whenever I discuss consent for atypical antipsychotics and the metabolic issues, I always tell people that weight gain and increased appetite is common.  I also tell them that I have seen people develop diabetes from these medications who were rail thin and never gained an ounce.  The 150 risk alleles for Type 2 diabetes mellitus, the thousands of associated intracellular signalling proteins, and the 300 GPCRs expressed in pancreatic beta cells probably has something to do with that.

Biological complexity rarely leads to simple answers.

I will probably encourage a lot of insomniacs from taking melatonin when there has been no clear benefit.  I will probably also discourage the practice of taking high dose (> 5 mg) of melatonin for the same reason.                


George Dawson, MD, DFAPA




References:

1:  Bruce J, Tamarkin L, Riedel C, Markey S, Oldfield E. Sequential cerebrospinal fluid and plasma sampling in humans: 24-hour melatonin measurements in normal subjects and after peripheral sympathectomy. J Clin Endocrinol Metab. 1991 Apr;72(4):819-23. PubMed PMID: 2005207.

2: Young SN, Gauthier S, Kiely ME, Lal S, Brown GM. Effect of oral melatonin administration on melatonin, 5-hydroxyindoleacetic acid, indoleacetic acid, and cyclic nucleotides in human cerebrospinal fluid. Neuroendocrinology. 1984 Jul;39(1):87-92. PubMed PMID: 6205317.

4: Leston J, Harthé C, Mottolese C, Mertens P, Sindou M, Claustrat B. Is pineal melatonin released in the third ventricle in humans? A study in movement disorders. Neurochirurgie. 2015 Apr-Jun;61(2-3):85-9. doi: 10.1016/j.neuchi.2013.04.004. Epub 2014 Jun 26. PubMed PMID: 24975205.

5: Leston J, Harthé C, Brun J, Mottolese C, Mertens P, Sindou M, Claustrat B. Melatonin is released in the third ventricle in humans. A study in movement disorders. Neurosci Lett. 2010 Jan 29;469(3):294-7. doi: 10.1016/j.neulet.2009.12.008. Epub 2009 Dec 11. PubMed PMID: 20004701. 

6: Skinner DC, Malpaux B. High melatonin concentrations in third ventricular cerebrospinal fluid are not due to Galen vein blood recirculating through the choroid plexus. Endocrinology. 1999 Oct;140(10):4399-405. PubMed PMID: 10499491.

7: Harpsøe NG, Andersen LP, Gögenur I, Rosenberg J. Clinical pharmacokinetics of
melatonin: a systematic review. Eur J Clin Pharmacol. 2015 Aug;71(8):901-9. doi: 10.1007/s00228-015-1873-4. Epub 2015 May 27. Review. PubMed PMID: 26008214.

8:  Krystal AD.  Pharmacological Treatment: Other Medications.  in Kryger MH, Roth T, Dement WH.  Principles and Practice of Sleep Medicine, 5th Edition.  Elsevier Saunders, St. Louis, 2011. p. 916-930.

9: Persaud SJ, Jones PM. A Wake-up Call for Type 2 Diabetes? N Engl J Med. 2016 Sep 15;375(11):1090-2. doi: 10.1056/NEJMcibr1607950. PubMed PMID: 27626524. (to full text link).


Attribution:

Serotonin metabolism graphic is from VisiScience.