The NIMH Director and the RDoC - The Politics and The Science

from: Insel TR, Cuthbert BN. Medicine. Brain disorders? Precisely. 

Science. 2015 May1;348(6234):499-500.

I caught this article about the RDoC criteria for classifying mental illnesses based on various non descriptive parameters and neuroscience in the journal Science a couple of weeks ago.  As any reader of this blog can attest, there is no stronger advocate for the role of neuroscience in current psychiatric practice and the future of psychiatry than me.  There has been media controversy on this subject and it is always difficult to determine how much real controversy exists and how much of it is just made up for the sake of media self promotion like much of the DSM-5 controversy was.  Reading through the article by Thomas Insel and Bruce Cuthbert  there are statements that can be taken at face value.  I think these statements are consistent with the position that clinicians in general are not very scientific and are also outright clueless in some areas.  This is a bias that I have certainly heard from other scientists and it does not serve the cause of science very well, especially if the goal is to advance neuroscience and bring everyone up to speed on that discipline.  Dr. Insel has presented his view that all of the trainees in the clinical neurosciences of psychiatry, neurology, and neurosurgery should rotate through a year or two of a shared neuroscience.  When I first heard him present it five years ago I thought it was a great idea.  In the time since and especially after getting a response from him, I think it is less clear.  It would be great if every department of psychiatry had neuroscientists on staff to teach neuroscience.  But they don't and there is also the problem of neuroscientists being focused on research rather than teaching.  On the other hand, there are plenty of bright people in those departments who know a lot about the brain.  It is a question of reconciling these two points to come up with the necessary infrastructure yet in this article the authors make it seem as if large clinical problems are not addressed and that clinicians are fumbling around with very crude assessment methods.

They list three articles as examples of the RDoC.  The most interesting of these articles is one from the American Journal of Psychiatry that proposes that computer abstracted data from hospital notes that is converted to RDoC criteria are better predictors of hospital length of stay (LOS) than DSM criteria.  Just considering that method my first impression was that there was a lot wrong with that picture.  First of all,  LOS data is tremendously skewed based on non-clinical practices.  All it takes is hospital case managers with some success in intimidating physicians to skew the data in favor of business rather than actual medical or psychiatric discharge decisions.  Second, the quality of data from inpatient settings is incredibly bad due to the toxic combination of electronic health records and government billing and coding regulations.  As a reviewer, I have seen thousands of inpatient records, some of them hundreds of pages in length and I have found EHR records are notoriously poor in information content.  And finally, I thought the RDoC was a new system designed to be dependent more on neuroscience than the DSM-5?  How does methodology that looks at this DSM biased, sketchy clinical data result in a RDoC diagnosis?  Looking at the graphic from the Science article at the top of this post, it is pretty clear that 3 out 5 data dimensions under "Integrated Data" are basically clinical data.  There is a smugness displayed in the report similar to what might be seen in a rant by an antipsychiatrist: "For now clinicians might be best advised simply to be aware of the usefulness of dimensional models to capture psychopathology."  and "This result should provide some reassurance to clinicians that their notes do contain relevant detail for deriving dimensional measures of illness; like Molière’s Bourgeois Gentlemen speaking prose without knowing it, clinicians may already speak some RDoC."

Really?

The average person I see has chronic insomnia and has had possible sleep terrors and nightmares in childhood along with social phobia.  At some point they developed either severe anxiety or depression, but they can't recall the sequence of events and they currently have both.   They typically think that they have had "manic episodes" and may have been diagnosed with bipolar disorder even though they don't know what a manic episode is.  All they know is that their symptoms have persisted usually without remission for the past 10 to 15 years.  Of course that is complicated by the fact that they have been using marijuana, alcohol, and opioids in excessive amounts since then,  they may not have a significant family history of psychiatric and addiction problems, and they have the expected childhood adversity and adult markers of psychological trauma and abuse.  Further, I know from talking to the same people in repeated initial evaluations over the years that they don't give the same history twice and rarely remember much about their medications or psychotherapy treatment.  Should I use a "placeholder diagnosis" (pejorative term from reference 4) or should I assume that I am dealing with the social phobia that the patient may have had in childhood?  The idea that an RDoC diagnosis is going to give me an answer to that question any better than a DSM-5 diagnosis is pure folly if you ask me.  At least until we get the promised neuroscientific markers promised by the NIMH.  In fact, the description of the RDoC in these articles is reminiscent of another technology that was supposed to diagnose mental illness and that was quantitative EEG or QEEG.  I know quite a lot about QEEG, because I purchased a machine in the 1980s after a promising article on the technology came out in the journal Science.  I researched it using highly skilled EEG techs and an expert in neurophysiology to run the protocols, and concluded the diagnoses that came from the computerized analysis of the tracing were no better than chance in terms of what patients presented with.  Like RDoC diagnoses, the computerized analysis of QEEG data was highly dependent on the input of clinical data collected by the clinician.  It allowed the clinician to add and subtract clinical variables and look at how the diagnosis varied.  

The staff and researchers at the NIMH need to decide if a superior and critical attitude toward physicians who use current clinical approaches and are successful with them is the best one.  It should be obvious from the above analysis that many of us are not as naive or as ignorant about science as they expect. My proposed solution would be a more collaborative approach including the following:

1.  Recruit and train neuroscience teachers - most of them are already out there.  For example much of what I teach to trainees interested in addiction and addiction medicine is neuroscience.  It is also much more realistic than waiting for every department to have access to neuroscience researchers and then expecting those researchers to teach in addition to doing research.  My guess is that every Psychiatry department already has faculty that teach neuroanatomy, pharmacology, brain science and neuroscience already and that most of them are not officially scientists.

2.  Make the reading list available online - the article refers to over 1,000 published articles that focus on the RDoC criteria.  These should be available though the National Library of Medicine web site along with other neuroscience articles of interest to psychiatrists.  An added bonus would be CME activity available for self study.

3.  Post a list of neuroscience modules and build on that list -  In a previous post, I posted two links to neuroscience modules through the NIMH.  I would put up two lists, one containing a growing list of modules and the second with a list of the neuroscience concepts that need to be illustrated.  This would be useful for psychiatrists, psychiatrists in training, and medical school professors hoping to make their basic science lectures more relevant, since many clinicians still seem to have difficulty understanding how neuroscience is important in psychiatry.

4.  Better graphics - make high resolution graphs that illustrate detailed brain anatomy and basic science available online for teachers.  Pulling this material together is often the most difficult part of the teaching job and it requires an intensive effort to not run afoul of copyright laws.   It would be easier to recruit neuroscience teachers if there are high quality teaching materials available.

5.  A neuroscience teaching blog - In addition to the NIMH staff posting the references, concepts and modules, an open teaching blog should also be available.  I would encourage it to be a platform for discussing concepts and how to present them to trainees.  Ideally, it would be a place for active dialogue about the concepts and teaching them.

I think that all of these measures would be helpful in building an infrastructure of neuroscience teachers, neuroscience teaching, and a mechanism for the widespread dissemination of this material in residency programs and in educational programs for practicing psychiatrists.  If the RDoC is in fact worthwhile, there is plenty of brainpower outside of the NIMH to figure that out.

It is the brainpower that is currently focused on coming up with solutions and resolving problems of incredible clinical complexity.  And that happens every day.

I plan to send these recommendation to Director Insel and see what he thinks.



George Dawson, MD, DFAPA

1: Insel TR, Cuthbert BN. Medicine. Brain disorders? Precisely. Science. 2015 May 1;348(6234):499-500. doi: 10.1126/science.aab2358. PubMed PMID: 25931539.

2: Casey BJ, Craddock N, Cuthbert BN, Hyman SE, Lee FS, Ressler KJ. DSM-5 and RDoC: progress in psychiatry research? Nat Rev Neurosci. 2013 Nov;14(11):810-4. doi: 10.1038/nrn3621. Review. PubMed PMID: 24135697.

3:  NIMH.  Research Domain Criteria

4:  McCoy TH, Castro VM, Rosenfield HR, Cagan A, Kohane IS, Perlis RH. A clinical perspective on the relevance of research domain criteria in electronic health records. Am J Psychiatry. 2015 Apr;172(4):316-20. doi: 10.1176/appi.ajp.2014.14091177. PubMed PMID: 25827030.

Supplementary 1:

The above figure is licensed through the American Association for the Advancement of Science - license number 3637270124183.

Minnesota Finally Rejects Managed Care

In a rather stunning reversal of thirty years of public policy, the Minnesota Legislature voted last week to fund for a "network of small treatment centers" to compensate for all of those years of rationing.  The details are still vague  but it is described in the StarTribune article by Serres as a "network of small treatment centers, to be built across the state, anchoring a broad package of preventive services so children don't end up in emergency rooms or inpatient psychiatric wards where many of them are discharged prematurely for a lack of beds."  The funding is about $13 million for 2 years and $6.6 million "to create a network of 30-bed treatment centers for children with highly aggressive or self-injurious behaviors, who are often turned away from hospital inpatient units."  Political speak is evident in that sentence.  I can't imagine that $6.6 million or even $19.6 million gets you a lot of 30-bed treatment centers.  Later in the article a total new bed capacity is described as 150.

The author of the article is oblivious to how this all happened in the first place.  Was Minnesota an idyllic place with no mental illness in the first place?  Did the problem arise because an epidemic of mental illness?  Absolutely not.  Thirty years ago, the state had more bed capacity and more treatment options for both children and adults with mental illness.  Minnesota is a state with massive managed care presence and those managed care companies currently run all of the acute care psychiatric beds in the state - for both children and adults.  Once managed care companies learned that they could deny hospitalizations based on some fictional "dangerousness" criterion and otherwise ration psychiatric services at multiple levels there was - in effect - no rational psychiatric care.  As I have posted on this blog many times, people are discharged from hospitals in a few days essentially without treatment, treatment units are chaotic without a therapeutic environment, people who require medical detoxification form drugs and alcohol are generally out of luck, and it creates and ongoing demand on emergency departments and correctional facilities.  All it took was getting these practices embedded in the state statutes and setting up a cursory review of complaints against managed care companies at the state level to seal the deal.  The reporter in this case makes it seem like the Minnesota Legislature and a "bipartisan coalition of lawmakers" are solving a problem.  This is a problem they created in the first place and I will believe in a solution when I see it.

I have some first hand knowledge of the problem with children's services from my contact with child psychiatrists around the state.  Their experiences are echoed in the story in this article of what happens when your child is out of control and nobody is willing to help.  The family in this case describes a 17 year old boy with severe mood problems, aggressive thoughts and thoughts of self harm.   He was hospitalized 6 times and discharged in a heavily medicated state.  He was turned down by 30 residential facilities before being accepted by an out of state facility.   His parents describe themselves in a "perpetual state of anxiety" trying to manage all of these scenarios.  But the most incredible line in the article:

"For years, children who exhibit highly aggressive or violent behavior in Minnesota have been forced to drift from one short term hospital to the next, often returning to their families heavily medicated but with their illnesses largely untreated."

This is not surprising to any psychiatrist.  This is the end product of managed care rationing and it occurs whether the patient is a child or an adult.  It happens when businesses and governments collude in providing some bastardized version of psychiatric care.  It happens when psychiatrists in this case are ignored.  When state officials ignore psychiatrists. When psychiatrists who are trained to treat aggressive and violent behaviors are not allowed to do their jobs.  After all, why would anyone with aggressive behavior because of a mental illness be turned away from a psychiatric unit?  Aggressive and suicidal behavior are the main reasons that psychiatrists exist today.  It is what we do.  Let us do our jobs.

So far this is one small victory for children's mental health advocates and my cap is tipped to them.  But to reverse more of the problem we need to acknowledge what it is and it is managed care or more specifically their marketing word for mental illness - behavioral health.

Let's get rid of it entirely.

   
George Dawson, MD, DFAPA

Reference:

Chris Serres.  Facing chronic shortages, Minnesota's mental health system gets a boost.  Minneapolis Star Tribune, May 29.  


Supplementary 1:  The image used for this post is of Dexter Asylum attributed to Lawrence E. Tilley [Public domain], via Wikimedia Commons.  The original image was Photoshopped with a graphic pen filter.

Supplementary 2:  For a detailed post on some of what happened try this.

Physicians Replaced By Computers - Lessons From A Roomba

My Memorial Day project was purchasing a Roomba and getting it up and running.  I am a big believer that robots will make all of our lives easier at some point and decided now is the time to start walking the walk.  For those not familiar with the Roomba, it is designed as a robotic vacuum cleaner.  Once you have set up the rooms and programmed it, it is basically supposed to vacuum your floors automatically and then park itself in a docking station for charging.  The machine itself is about a 14 inch diameter disk that rises to a height of about 3 1/2 inches off the floor.  It is a light 8.4 pounds.  It is able to accommodate sharp angles with a secondary brush that spins on an arm that extends from under the main disk.  This combination of the main disk spinning and the extended spinning brush cleans the corners of a room.  I purchased the latest model, a Roomba 880 after consulting with friends and relatives who had earlier models.

One of the considerations in buying the Roomba was whether it would help turn my home into an even cleaner environment than it currently is.  That is a tough act.  One of my friends who is a physician gave his opinion that my home is "museum-like".  My office is probably the only problematic room with stacks of books and journals piled everywhere.  Disarray certainly but minimal dust.   My entire first level is hardwood flooring that is typically vacuumed with a built in system.  To its credit the Roomba contains all of the debris in the machine until it is emptied and all of the exhausted air is HEPA filtered to avoid exhausting any dust particles.  The main cleaning mechanism consists of two debris extractors that are rubberized bars that spin at a high rate of speed across the floor surface to capture dust, hair and larger particles.  But the most interesting aspect of the Roomba was going to be its observed behavior.  It has two modes when vacuuming.  It can start in a spot and spin increasing circles in an outward direction until gets to about a 3 foot diameter and then it spirals back in to the center spot.  In the more typical mode it heads to the room perimeter and then "automatically calculates the room size and cleaning time."  The most valuable tip in the manual was to take measures to restrict it to one room at a time and it comes with two Virtual Wall^®Lighthouse^TM devices that allow for easy demarcation of the work area.

The most fascinating aspect of getting started with the Roomba was going to be setting it up and watching how it went about the task of vacuuming.  I did some very minor room preparation, charged it up, and turned it loose.  As expected it headed straight for a wall and then attempted to establish the perimeter.  I remembered this as standard rodent behavior.  If you have ever confronted a mouse in an open area of your floor, their first move is to dash to the baseboards and run parallel to them to escape.  That strategy works well in the wild because the maneuver is associated with more cover and makes them less susceptible to predators.  It works much less well when confronted by a human who knows that it is their first move.  And yes, scientists have bred mice that do not exhibit this behavior.  My guess is that they would not fare well if they made it outside the lab.  The Roomba's behavior is less rigid than a typical mouse with some exceptions.  In the hour and 20 minutes it took to vacuum the adjacent kitchen and great room - it circled a kitchen island perfectly at least 10 times, but at the wall perimeters it was much less predictable.  At times the Roomba would peel off and take off across the room in a single pass or rarely return and continue along the original wall.  Sometimes it would head off the wall at a 45 degree angle and at other times 90 degrees.  There were never the usual adjacent passes that a human would make using a standard vacuum cleaner.

According to the literature,  the Roomba is supposed to "crisscross" the room in order to clean the floor.   I placed two small pieces of popcorn in the middle of a large section for flooring to use as markers of cleaning efficiency.  In the course of an hour, the Roomba passed these markers many times, sometimes very closely without vacuuming them up.  During that time it was very difficult to detect how much crisscrossing had occurred since mouse-like it spent the majority of the time in the periphery, bumping and spinning around walls and furniture.  It eventually did break free from the walls and set off on a 45 degree path picking up one popcorn fragment at about the one hour mark and the other at about one hour and ten minutes.  The old adage about pictures is true and I happened across this 30 minute time lapse photo of the Roomba working a room (with permission from the SIGNALTHEORIST web site).  It correlates well with my description of the actual paths.

As I surveyed the job afterwards, the floor was definitely clean and the warning light on the machine was saying that the dustbin was full.  When emptied, it contained an impressive amount of debris and dust relative to what seemed visible to the naked eye.  Another win for the robots?  Well, not really.  It is an interesting tool that I will continue to use and study, but in comparison with humans it is not efficient and at this point certainly not autonomous.  Despite all of the guidance in the manual the Roomba can still encounter unpredictable surfaces and get itself into trouble.  In my case it was the pedestal of a recliner.  The wood at the edge was about 3/4 of an inch high.  For some reason, the machine did not recognize it as an obstacle and continued to run up the base and get hung up.  A loud spoken error message would sound advising the human in the room to pick it up and start it in a new place.   The other concern is efficiency.  It spent far too much time in the perimeter and a low percentage of time covering the main floor areas.  That was tremendously inefficient.  It took at least 5 times longer to vacuum the main rooms than I would have if I was pushing a vacuum cleaner.  Even though it allows me to do other things, it says something about current state of available and affordable domestic robots.  They can't match the performance of humans on a fairly basic task.  This is an important concept.

Before any of the futurists out there jump on me for being a Luddite, let me disclose a few details.  I am a member of the IEEE and have been for the past 18 years.  I am currently a member of the IEEE Robotics and Automation Society.  I am not an electrical engineer and I have not designed or built any robots, but hope to start doing this when I retire from psychiatry.  I consider myself to be an expert in the human brain and the advantages it confers on humans over other animals and machines.  The Roomba is a basic case in point.  It cannot sense and adapt to novel conditions quickly enough to match a human doing the same task.  Even more striking is that although it is designed to vacuum homes and I have a fairly typical home with a better than average floor surface, it still encounters situations that exceed its response capacity.  In those situations it needs a human assist.  What is it about the human brain that leads to that kind of an advantage?  First and foremost, it is a rate of pattern matching and pattern completion capacity that allows us to recognize vacuuming problems, anticipate them and correct them by developing novel solutions even before the problem leads to a stop in action.  Some of this happens when a human goes around the room to set it up for the first time for the Roomba.  That human has made some assessment of the machines capacities and limitations and is problem solving for the machine before it is turned on.

Observing the limitation of the Roomba leads me to a point where I can address both the idea of computers replacing doctors and how that fits into the common anti-physician narrative in this country.  Is there a connection between the two?  My experience tells me that there is.  For nearly 30 years there has been a constant stream of antiphysician rhetoric.  The sources have been expected.  One of them is the key opinion leaders (KOLs) of the managed care industry.  I can recall reading one of the the first books written by one of them, a non-physician who was widely acclaimed as being an expert in managed care.  His early theory was that the high cost of health care was due to the decisions that physicians make.  But in the middle of the book he wrote what he thought of physician salaries and only grudgingly acknowledged that they should probably be paid a good wage due to their education.   I have posted here many times my experience at a managed care conference in the 1990s.  The speakers at that conference were very clear that the explicit agenda of their industry was to replace all of the specialists with primary care physicians.  The examples given were orthopedic surgeons and psychiatrists.  When a psychiatrist in the crowd pointed out the shortcomings of that philosophy - he was called a "whiner" by a Governor who was an anointed KOL in the industry.  Then the KOLs from the financial services industry started weighing in.  You could find glimpses of it while reading the investment literature.  People who were investors with no particular degree started saying that some day, physicians would get what they deserve - with the implication being that whatever that was - it was not good.  Any physician has experienced this prejudice.  The comments about how physicians are "expensive" as a rationalization for working them to death by not hiring any additional help.  Replacing physicians with computers seems like a logical extension of this rhetoric.  Googling this topic returns a number of provocative articles written from a point of view that is generally consistent with who the author is.

I know that some of those authors know the difference between a robot or a computer and a doctor, but it is also clear that some do not.  They certainly don't seem to understand that the real processing power of a human diagnostician's brain is in the area of pattern matching.  In order to duplicate that property with current technology, takes a massive computer and it is one of the reasons why my new $700 Roomba, although well designed - can easily be beaten by a human with a standard vacuum cleaner.  But the human advantage goes far beyond that.  Human diagnosticians do far more than match simple patterns.  They are able to complete fragments of patterns and anticipate what the whole pattern should be.  For example, is it likely that a depressed person is in this current state as the result of an inherited form of depression, their current state of detox from an opioid and/or benzodiazepine, current stressors or interpersonal conflicts, brain trauma, an undiagnosed medical condition, childhood adversity, psychological trauma as an adult, or defects in reasoning at either the emotional or cognitive levels.  Then there is the matter of acquiring all of the data to make the determinations.  Patterns upon patterns of data.  The Roomba-like approach would be to give the person a checklist of depressive symptoms and pretend that is all that needs to be known.  Checklists are already being administered by a computer and may be administered by robots someday.  

Yet it takes the pattern recognition, and several layers of it, as well as human experience dependent learning in order to make a real medical or psychiatric diagnosis.
        

George Dawson, MD, DFAPA






Supplementary 1:  The graphic at the top of this post is a photo that I shot of the inside of the box that my Roomba came in.

Supplementary 2:  I don't want to give the false impression that I do a lot of vacuuming.  My wife does practically all of it, but I am trying to do more especially if there is a high tech twist to it.  Some of the first robotics I hope to work on will be human controlled arms and hands designed to do yard work and move heavy objects around in the house.  I can't believe this is an area that has been ignored.

Moral Bias

Lisa Rosenbaum's final installment of her three-part conflict of interest series in the NEJM is out and full text is available online for free.  My associations and observations in response to the first two can be found here and here.  As a student of bias and rhetoric, reading Dr. Rosenbaum's series has been a breath of fresh air both on its own merit, but also relative to the grim anti-industry and anti-physician bias that permeates the popular press and medical settings these days.  The hypocritical nature of many of these comments was always obvious to me, but there was only very qualified support for anyone who did not see all physicians (especially psychiatrists) as tools of the pharmaceutical industry.  But the types of moral and ethical biases that Rosenbaum highlights goes far beyond the issue of free lunch from a pharmaceutical rep.  It shakes the very foundation of a system of evaluation based on weak empirical evidence or pure politics as I have pointed out many times on this blog.  At some level it is such a stunning expansion of many of the old NEJM editorials, it seems surrealistic that these articles have been published.  But on the other hand, the page below this last article invites readers to participate in a poll on the ".....suitability of three potential authors to review articles for the Journal."  Combined with the fact that these articles have a series editor that suggests to me that this may be all part of a social media-like initiative to attract interest to the NEJM.  On that basis, I expect a full gamut of future authors including the more typical opinions equating the appearance of conflict of interest with conflict of interest and suggesting zero tolerance for contact with industry.

This article starts out with commentary on the medical school "anti-pharma animus".  The organization of American medical students apparently grades medical schools on the basis of how free from pharmaceutical company influence their conflict of interest policies and environment are.  She gives a quote from a medical student to illustrate the mind-set involved in at least some members of this movement, namely the need for "pure" information to medical students.  Some early critics of Rosenbaum's article cite this as anecdotal data but that misses the point.  Her point is that this kind of mind-set exists and it is one of a number of mind-sets that makes the ethical climate around conflict of interest an unreasonable one.  She also points out that the rhetoric associated with this statement clearly indicates that this is a moral argument and at that point the psychology of moral arguments may apply.  From the perspective of medical education, is it better to take an insular approach and suggest that all research can be assessed by looking at the funding source or should medical students be taught to read and critique research independent of funding source?  A study quoted one of Rosenbaum's previous article suggests that internists are able to look at research abstracts and classify them according to research rigor, but that the introduction of funding source forces a re-evaluation with a bias against industry funded research.

The article progresses to talk about the psychology of moral argumentation at that point and a set of arguments that I have summarized in the table above.  I think it is also instructive to address one of the early arguments about the Rosenbaum essays and that has to do with evidence and the use of evidence in arguments.  In order to look at that, it requires a quick look at the type or argument, whether it is a scientific or non-scientific argument and whether the corresponding type of evidence exists.  I think there is no doubt that Rosenbaum's arguments are moral arguments rather than scientific ones.  As such they seek to address the ethical climate around conflict of interest.

There are two aspects of the concept of ethical climate that are missing from Rosenbaum's analysis.  The first is the ethical climate as a way to control physicians.  The best example during my career has been managed care and the research that supported it.  Like today's collaborative care research, the early managed care research was focused on the idea that it was more "cost-effective" than fee-for-service or treatment as usual.  In both cases (collaborative care and managed care), the research was generally done by advocates of the proposed methods.  Thirty years later, any objective analysis on the effect of managed care on psychiatric services will show that it has been devastatingly negative.  Bed capacity has been shut down, the criteria for inpatient care is "dangerousness" rather than any specific medical indication, people are clearly discharged from hospitals based on optimizing meager DRG based payments rather than medical indications, detoxification and addiction services have practically been eliminated from most hospitals,  only a small percentage of hospitals have psychiatric services, state hospital systems have also been shut down, and the only place where psychiatric care has increased has been county jails and prisons.  That entire system wide change for the worse was based on a moral argument of cost-effectiveness rather than scientific research.  Once that ethical landscape was established physicians could simply be shouted down with the slogan: "Times have changed - you are no longer in charge."  I doubt that any physician who heard that slogan was ever in charge of anything.  It was political rhetoric, designed to elicit an emotional reaction in the people taking over and the physicians they ultimately came to control.  Nobody thought that cost effectiveness was the same thing as cost shifting to correctional systems.

The second aspect is the explicit control of physicians by managed care companies and a conflict of interest that greatly exceeds that of any other industry.   Rosenbaum's three articles are all focused on the pharmaceutical or medical device industries.  There is no mention of the managed care industry or its spinoffs, despite the fact that it controls the medical care of over 80% of Americans.  As I have consistently pointed out, the theoretical concerns of the affiliations of authors on research papers about drugs or medical devices is nothing compared with a managed care company that tells your physician that you need to be discharged from a hospital or use a particular medicine that the physician is not recommending.  In the case of psychiatric care, that company is free to make even more life altering decisions such as denying a patient with a drug addiction any functional detox services, deciding that a patient with significant suicide risks can be treated on an outpatient basis, or maintaining a person in a disabled state with minimal treatment options for a complete recovery.  The regulatory environment that concentrates that much power in an industry that can generate profits by denying care is a complex story, but it all started with an ethical environment  that blamed physicians for the high cost of health care.  That physicianscold environment has too many elements in common with the pharmascold environment to ignore.  In both cases there is a predominate moral bias that greatly oversimplifies the problem and at least in the case of managed care leads to clear long term adverse consequences.              

The good news is that these articles have been published along with the evidence that moral reasoning can be seriously flawed and associated with biases.  Rosenbaum's focus has clearly been on the relationship between physicians and the pharmaceutical or medical device industry.  She has discussed her personal experience as a Cardiologist and how it has affected her largely in terms of interventions, statin therapy, and as a potential consultant to the industry.  Psychiatry has been an easier target for the same biases and rhetoric that she lists in her article.  I pointed it out in a Washington Post article where the narrative was clearly skewed to fit the idea that psychiatry was corrupted by Big Pharma and attempting to make it easier to diagnose depression in order to sell more antidepressants.  That article included selected information to make it seem like the American Psychiatric Association was the only professional organization to make advertising profits from Big Pharma.  The suggested quid pro quo for advertising revenue should be absurd to anyone familiar with advertising but it was not to this reporter.  But the real issue was that the DSM does not recommend treatment anyway and the majority (80%) prescribers who treat depression don't use a DSM-5 or even care about what it says.  Less formal approaches adopt a similar scolding moralistic tone toward psychiatry that is possible only by ignoring the deficiencies in other medical fields and idealizing them while devaluing psychiatry.

I think that Rosenbaum's articles are must reads, especially for psychiatrists who may be unfamiliar with rhetoric, moral reasoning, and politics.  That may be why physicians in general have been inept in mounting any kind of a counterattack against political strategies that work by changing the ethical climate.  These articles provide some points for discussion.   Watching the counterattacks will also be instructive.      


George Dawson, MD, DFAPA

1: Rosenbaum L. Beyond moral outrage--weighing the trade-offs of COI regulation. N Engl J Med. 2015 May 21;372(21):2064-8. doi: 10.1056/NEJMms1502498. PubMed PMID: 25992752.

Bias Cuts Both Ways

Lisa Rosenbaum's second article (1) in a series of three appeared in the New England Journal of Medicine this week.  It continues the theme that bias is more complicated than following the money (or pens or pizza slices).  It was interesting to note the response to the original article.  On at least one blog a poster apparently Googled Dr. Rosenbaum in order to point out all of her potential conflicts of interest.  It probably would have been more relevant to look at the standard International Committee of Medical Journal Editors disclosure form on file at the NEJM.  But it does provide a good example of one of the references in this week's piece - financial disclosure (or in this case suspicion) as an ad hominem approach to evaluating science.  In a similar vein, one of the authors of a previous NEJM editorial pointed out that the science has to stand on its own merit independent of disclosures or credentials.

The initial part of the article points out a fact that has always seemed pretty obvious to me.  Association is often used to suggest that there are significant meaningful conflicts of interest.  The oft quoted statistic is that 94% of physicians have "relationships with the industry".  This includes counting drug samples or donuts in the workplace as a significant relationship.  One of my previous employers decided that all hospital employees should participate in "donut rounds" and not just the physicians.  I viewed this as a pseudo-egalitarian managed care tactic, but by definition that means that 100% of the employees at that hospital had a "relationship with the industry".  The article also points out that physicians who request drugs be included in a formulary are also more likely to have industry relationships than not.  I have a history of being on two separate Pharmacy and Therapeutics (P&T) Committees of a major healthcare system and a major hospital where the overriding biases were drug cost and deals with pharmaceutical companies.  There were major changes on a year to year basis due to price differences in the cost of commonly prescribed drugs and they were often based on the flawed assumption that all drugs in the same class are equivalent.  On the other hand if an exclusive deal could be made, that company might also be able to combine that with a preferred deal for a more common drug.  It was a curious situation where decisions that were supposed to be science based were not.   The P&T Committee was biased by the managed care industry operating strictly on a cost basis.

I decided to part ways with the P&T Committee on the day we were presented with forms to fully disclose all of our finances to assure there were no conflicts of interest.  The usual hype about how we were all cherished guardians of the public trust was included.  I thought about it for a second and looked around the room.  There were approximately 15 MDs and 4 PharmDs on the committee.  Some of the brightest and most well read staff in the organization.  I ran the hypothetical through my mind: "What are the odds that if I owned stock in XYZ Pharmaceutical that I could convince my 20 colleagues that it was a good idea to put their most expensive drug on the formulary just based on my word?  What are the odds that I could overcome the predominate bias of the financial well being of the company that employed all of us?  What are the odds that if I accomplished those first two unattainable goals that I would actually see a profit in my XYZ Stock?"  I also thought about the drug approvals that we did based solely on public relations considerations.  Drugs that were practically worthless, but that were demanded by advocates for incurable diseases.  The explicit decision was that we did not want to run afoul of some of the very vocal advocates for those illnesses.  It would be bad public relations and press.  I looked back at the 5 page disclosure form and decided that I was not going to play that game.  I was not going to pretend for one second that I needed to be vetted by an organization that apparently saw itself as destined for sainthood.  I walked away at that time.  I had long been familiar with the other bias listed in the Rosenbaum article and how any disclosure at a CME presentation could result in mockery or discreditation.  It is difficult enough to present the pertinent information to an audience who may want to be entertained without being the butt of jokes as a sponsored presenter.  Any way you look at it my behavior was a reaction to a modern day witch hunt mentality and I was not about to be declared a witch.  Even beyond that, I was not the only "clean" person in the room.  Getting heavy handed about a conflict of interest disclosure as a public relations gimmick after many of us had already figured it out 20 years ago was more than a little insulting.

Rosenbaum also discusses a previous study from the NEJM (2) that as far as I can tell has not received press anywhere else.  In this study, the authors designed identical fake clinical trial report abstracts of studies with varying methodological rigor.  The studies had three possible funding disclosures - the pharmaceutical industry, the NIH or none.  In this experiment the internists involved in the study were less likely to read the entire report, less likely to prescribe the study medication, and less likely to see the experiments as rigorously conducted if they were sponsored by industry rather than the NIH.  They were half as likely to prescribe medications recommended in an industry sponsored trial than an NIH sponsored trial.   The authors were naturally concerned that physicians would be skeptical of even high quality but industry sponsored trials and that might slow the acceptance of that information in clinical practice.

In an interesting study done by the industry that same year,  a team (3) at the biotechnology firm Amgen  examined 53 studies that were considered to be 'landmark' preclinical studies in the field of oncology.  The goal was to see if they were reproducible.  The findings could be confirmed in only 6 or 11% of these papers.  The non-reproducible research led to hundreds of secondary articles and in some cases led to research that exposed patients to agents that resulted directly from the original research.  A team (4) at Bayer HealthCare did a similar review of preclinical studies to identify potential drug targets and concluded that only 25% of the work was reproducible.   That same article referenced the general industry rule that up to 50% of published results from academic settings cannot be reproduced in an industrial lab.  The Amgen and Bayer HealthCare studies suggest that is really an underestimate of what amounts to academic bias.  A common criticism leveled by Big Pharma critics is that they have benefited from all of the taxpayer funded basic science research at the NIH.  These studies suggest that there are plenty of problems with that research independent of funding stream and that they are less rather than more likely to lead to drug discovery.

In addition to unique information to examine the issues of bias (the author lists many more),  she also points out the origin of the word Pharmascolds (5) as those who "vilify the medical products industry and portray academics working with it as traitors and sellouts".  The authors here describe an inadequate public response from both the companies and the physicians who were criticized.  The full text of the reference is available online.

This is another highly informative article by Rosenbaum which demonstrates that analyzing conflict of interest is not as easy as some members of the press and some professional critics make it out to be.  She gives a great example of an 85 year old woman who needs an aortic valve replacement and what the considerations might be based on the characteristics and biases of two different Cardiologists assessing this situation.  It is even more complex in a setting where some would be quick to refer the woman to a hospice service.  In my experience outlining all of the potential biases in that situation is a significant task and one that few physicians would attempt.

Some day a more measured discussion of conflict of interest might provide a better approach.  Until then be skeptical of any critics who suggest that it is inappropriate for a physician to have a relationship with the pharmaceutical or medical devices industry just based on the face of it.  And for any physicians out there who want to take the most conservative path to avoid unwarranted criticism, stay out of the Sunshine Act database.

        


George Dawson, MD, DFAPA        
                   

1:  Rosenbaum L. Understanding bias--the case for careful study. N Engl J Med. 2015 May 14;372(20):1959-63. doi: 10.1056/NEJMms1502497. PubMed PMID: 25970055.

2:  Kesselheim AS, Robertson CT, Myers JA, Rose SL, Gillet V, Ross KM, Glynn RJ, Joffe S, Avorn J. A randomized study of how physicians interpret research funding disclosures. N Engl J Med. 2012 Sep 20;367(12):1119-27. PubMed PMID: 22992075.

3: Begley CG, Ellis LM. Drug development: Raise standards for preclinical cancer research. Nature. 2012 Mar 28;483(7391):531-3. doi: 10.1038/483531a. PubMed PMID:22460880.

4:  Prinz F, Schlange T, Asadullah K. Believe it or not: how much can we rely on published data on potential drug targets? Nat Rev Drug Discov. 2011 Aug 31;10(9):712. doi: 10.1038/nrd3439-c1. PubMed PMID: 21892149.

5:  Shaywitz DA, Stossel TP.  It's time to fight the 'pharmascolds'.   Wall Street Journal.  April 8, 2009.    http://www.wsj.com/articles/SB123914780537299005 accessed on May 17, 2015.

APA's Feelgood Move of the Year?

I noticed on another blog that there were expected praises and a few sarcastic comments for the American Psychiatric Association (APA) announcement that they had signed on with another 600 organizations to support the AllTrials initiative.  In case you are unaware of this initiative, Google the name and it will bring you to the web site.  The web site will give you more than enough information on why transparency and enforcement of pharmaceutical company behavior is important and why you should sign the petition.  It will even provide you with a section on "Myths and Objections"  to dispel any concerns that you might have about - well, myths and objections.  It really did not address my concerns about the fact that clinical trials technology as we know it is incredibly crude, they are practically all short term, and they have little to do with how the medication is used in clinical practice.  To me it seems like an exercise to try to keep the pharmaceutical companies honest.  If it also succeeded in keeping the useless meta-analyses of flawed studies out of the literature and prevented the same people who produce those studies from drawing even more flawed conclusions about psychiatry, I would be all for it.  But I doubt that is going to happen.  I also doubt that it will have any effect on the drugs marketed in the USA.  It should be fairly clear from observing FDA behavior that their decisions aren't based on good studies or even the reviews done by their own scientific committees.  You could list any study in the AllTrials database and it could lead to FDA approval whether it was positive, equivocal or negative.

My biggest objection to the APA using its vanishing street cred to sign on to this feelgood initiative is that doesn't do me any good as an APA member, it doesn't do my patients any good and it has no implications for the future of the field.  It is like signing on to any feelgood initiative, you seem to get credit along with all of the other do-gooders, and all you have to do for it is sign your name.  That would bother me a lot less if I did not pay the APA $935/year for professional membership and if they would return my calls once in a while.  It would also bother me a lot less if they actually addressed real problems that their membership was concerned about.  The kind of heavy lifting that might really cost something.  Ignoring these problems is also costing them something right now in terms of members who are walking away.  It doesn't take too many members walking away at $935 apiece to have an impact on the organization.   I have discussed the problems many times before on this blog but here are a few items that should be APA priorities:


1.  MOC/MOL -

The maintenance of certification issue is not fading away with benign neglect at this time.  Interestingly, the revolution in this area is being led by the generally more conservative internists and internal medicine specialists who have eloquently described how little sense it makes to oppress the most oppressed and most accountable professionals out there and pretend that "the public" is demanding more testing and arbitrary exercises to maintain board certification.  As if that is not enough, the idea that this MOC can be converted into a necessary step in licensure (Maintenance Of Licensure would really put a lock on that unnecessary industry.  Until very recently the APA has been completely deaf to member's efforts in the area.  I don't know some recent interest reflects members voting with their feet and just walking away or the message that some specialists are not going to cave in on this issue and will go so far as starting their own organization for MOC.

2.  Managed care - utilization review -

Managed care companies and pharmaceutical benefit managers harass psychiatrists to  greater degree than other physicians.  These companies have destroyed the infrastructure for inpatient care and any concept of quality in psychiatric care.  Practically all psychiatric care in this country is now dictated by these companies and the arbitrary rules they have set in place to ration it.  The APA made some initial attempts to explain managed care and advise their members about how to "get along" with these methods.  At no point was it suggested that there was a severe ethical problem with allowing for profit companies to dictate psychiatric care.  At no point was there any strategy to illustrate the difference between quality care and rationed care.  Instead, we read stories of the mentally ill being incarcerated by the thousands and the inappropriate care they receive in jail.

3.  Managed care - PBMs -

Billions of dollars are wasted every year as pharmaceutical benefit managers ration generic drugs and tie up physicians and their office staff in order to make more profits.  There is no other group of professionals anywhere who are basically forced to work for a managed care company for free in order to help them ration medications and turn a profit.  The only action I have seen from organized psychiatry was a half measure about a standard prior authorization form that for some reason could never be adequately enacted.  There is always something within federal law that favors managed care companies and gets in the way of addressing this.

4.  Organization wide support for models of care other than collaborative care -

There are massive problems with the collaborative care model that is being promoted by the APA along with SAMHSA, the managed care industry and their partners in government.  The hype is at about the same level as the promotion of the managed care industry was in the 1980s and '90s.  It is obvious how that turned out.  The reason people train as specialists is to provide specialty care, not to sit in a primary care clinic and supervise the prescription of antidepressants based on a rating scale without personally assessing patients.  The real pipe dream here is that primary care clinics under the accountable care organization model will hire psychiatrists to provide the academically proven cost savings to their primary care clinics.  I guess that was a media moment lost on the APA; the models used to hype the care model and sell it to politicians are not the ones eventually implemented by the "managers".   Expect the same rationing and either the complete elimination of psychiatric services to save money or psychiatrists offering their services on their own.  The APA should at least be prepared for that and be involved in preparing their members.

5.  Lack of recent professional guidelines -

Contrary to what a lot of people think, the DSM-5 has nothing to do with treatment.  The APA has treatment guidelines, most of which are in need of a serious update.  They also need guidelines to cover most specific practice situations such as the treatment of aggressive or suicidal patients.  A serious update and an ongoing effort to stay current is necessary in order to prevent the illusion that some guidelines put together by a business organization is as good as and somehow represents professional standards.


These are a few of the things that psychiatrists and the members of the APA need right now!  I doubt that any of us are going to be impressed with the sign on to the AllTrials initiative.  I would not be surprised to find out that most APA members haven't heard about it.  I am a member and I am on the APA listserv and the APA Facebook feed and did not get any notification about this happening.

I don't see anything wrong with the APA signing on to a feelgood initiative on the face of it.  But over the years the membership has paid a lot of money for an organization that supports professional education, standards and advocacy.  Signing a mass petition for an initiative that is not likely to do anything to advance the science or patient care is a politically correct symbolic gesture.

We need a lot more than that and we have for years.



George Dawson, MD, DFAPA

A Garage Door Lesson

I learned a valuable lesson from a garage door today that I thought I would pass along to some posters who think they know something about psychiatry and psychiatrists.....

I came home early this afternoon and hit my garage door remote, like I had done thousands of times in the past.  This time the door went up and seemed to hesitate and drop back about 2 inches, then it went all the way up.  I stepped out and noticed a bolt laying on the floor.  I picked it up and it was a 5/8 x 1 1/2 inch self-tapping bolt.  Looking around, I noticed that it has fallen out of the plate that fastens the garage door to the door itself.  The plate was bent and there was only one bolt left holding the door.  I grabbed a socket wrench and a ladder and headed up to where the door was suspended to fix it - about 5 or 6 feet off the floor.  It was immediately evident that the plate was bent at such an angle that I could not gain any purchase in the door with the free end of the bolt - or it was stripped.  Without thinking, I thought I would pull the emergency door release hanging just to my right to give me just enough slack to fasten the bolt.

In an instant, the arm assembly jerked my left hand very hard toward the door opening as the door crashed from fully open to fully closed in a less than a second.  I was propelled about ten feet through the air landing on the floor at the base of the door with some serious neck strain and a few sprains but otherwise, none the worse for wear.  I was somewhat stunned by all of this.  When I looked up I noticed the coil spring over the left side of the double garage door was snapped in half.  Directly in front of me was a warning that I had read many times before:

The universal "Don't turn your own wrench" sign.  I apparently ignored some pretty basic information that any professional garage door mechanic would not have.  It resulted in me getting knocked around pretty good and putting me at serious risk for a head injury, a spinal injury or death.  A few data points and I ignored them.  I also knew that garage doors were dangerous.  Just a few years ago, my brother showed me a healed scar across his palm that resulted when he attempted to repair a snapped garage door spring.  But where in all of this is the lesson for the inappropriate criticism of psychiatrists?

I should probably define at least part of what I consider inappropriate criticism and what a poster here has touched on as important dynamic.  On the sites where it is common for psychiatrists to post or sites that claim some legitimacy in the area of criticism, there are also some thoroughly hostile and malignant posts that are at the minimum inappropriate and at their worst pathological.  I have received a few directly here last week, but have decided that posts such as these will not appear on this blog.  I am aware that some people think that anyone should be allowed to criticize psychiatrists in any manner.  They are wrong.  People suggesting that I should "burn in the hottest part of hell" of course would be one example, but there are many more.

The garage door incident is instructive for at least some of them.  I recently saw a number of anonymous posts saying that psychiatrists can "just say anything" and that psychiatric credibility could be "shredded" in forensic settings.  Interspersing those arguments among supposedly legitimate critics takes the level of their arguments way down.  If these types of posts were always the case, it would be very easy to ignore a thread inhabited by barbarians.  I could certainly come up with a neat little definition of the barbarians but what is the point?   A related question is why those sites feel compelled to include this posts?  I don't think that is a passive or well thought out decision.  Once the discussion has headed into abusive, threatening, or irrational territory and it remains in fair play - that says a lot about the intent of the administrator.  At the very minimum, the intent is no longer a reasonable discussion.  Granted that it is often difficult to determine what is reasonable, given the overall tenor of the site.  For example, if I wrote a book bashing all psychiatrists and was promoting it on a site, why wouldn't I include every possible irrational post as evidence that I am correct?

It is much more instructive to look at the garage door example and what it implies for the basic argument that there is no such thing as mental illness and the closely related arguments - psychiatrists are not needed for the diagnosis and treatment of mental illness or that they have simply made up mental illness so that they can all be rich and drive expensive cars (another e-mail from one of the fans).  The garage door is a simple scenario with three critical points of information that any experienced person could observe - arm plate screw missing, arm plate bent, and left main garage door coiled spring snapped in half.  As an additional historical point I should add that in my experience these springs snap about every 15 years and this one was only 5 years old.   I observed 2/3 of the points thought I could make the repair and nearly had a catastrophic result.

In the case of a psychiatrist seeing a new patient, there are hundreds of relevant points that all have to be acquired and examined in the initial evaluation.  The total number of critical points is unknown, but to use just the example of a basic instrument for the assessment of suicide potential they number in at least the 20-30 range.  This assumes that the patient is able to respond appropriately to the questions.  There are at least another 20 or 30 points when it comes to the prescription of medications and coming up with a treatment plan.  As any affected family member can attest, severe mental illness or addiction is at least as serious as a crashing garage door that knocks you off a ladder.  It leads to trying to shake off the acute effects and prevent any long term harm.  In that event many people are seen and treated successfully by psychiatrists.  As I have posted here before, we are the people who are trained to see significant problems and the psychiatrists I know do a good job.

In practically all of the irrational criticism of psychiatry, none of these information points are covered.  People seem quite content to tar and feather psychiatrists with whatever seems fashionable at the time.  So this lesson is really one about the information content not typically being covered and how missing even a small point in any information set can be potentially problematic, and in my analogy, not just in terms of my own safety but the liability issue if anyone had been working with me.

I know that this lesson may be a stretch for some and in that case consider this a public service announcement for not trying to fix your own garage door.  Do not try it at home like I did.  Leave it to the professionals.

Oh - and I am not sorry to disappoint those who would have just as soon seen another psychiatrist bite the dust.

As far as I know - I am OK.



George Dawson,  MD, DFAPA

Indignation Bias

"Moral indignation in most cases is 2% moral, 48% indignation, and 50% envy." - Vittorio De Sica


The New England Journal of Medicine has started a new series on conflicts of interest that should prove to be enlightening if the rest of the articles are as good as the first one.  In this article, Lisa Rosenbaum, MD  takes on typical cases that appear to be straightforward conflict of interest cases and thoroughly debunks the common thought process.  She provides a clear link between the outrage over the behavior of the pharmaceutical industry and an indignation based approach to regulation and conflict of interest considerations.

In the first example she looks at the issue of the 2013 cholesterol guidelines and the expansion of the target population for statin therapy.  There was the standard New York Times editorial by two physicians who concluded that the guideline "would benefit the pharmaceutical industry more than anyone else."  They referenced an article by one of the authors on the frequency of statin side effects that was later withdrawn due to an overestimate of the frequency of side effects.  They challenged the credibility of  the guideline writers suggesting that they needed to be free from "influence, conscious or unconscious".  Rosenbaum reviews the checks and balances in place for the writing of this guideline in a manner reminiscent of my analysis of a Washington Post commentary on the DSM-5 diagnosis of depression.  In both cases, the safeguards in place are overlooked, the benefit to the pharmaceutical industry  overestimated, and the authors of these critical articles are never challenged.  She asks the important question: "So why the rush to conclude that the guidelines were an industry plot?"  It is also interesting from the perspective of psychiatry where the field would never get that kind of break.  The question for psychiatry is:  "Why the rush to judgment to conclude that the guidelines were a plot between psychiatrists everywhere and industry?"

The Jesse Gelsinger case was examined next.  Mr. Gelsinger was an 18 year old man with ornithine transcarbamylase deficiency.  He volunteered for a research protocol examining gene therapy for the disorder.  The ethical considerations included the fact that the researchers were advised that it was not ethical for them to test the protocol in affected babies who might benefit if it was successful because that would be considered coercion.  There was also an issue relating to the reporting of a complication of the therapy by basic science researchers.  Rosenbaum points out that after Jesse Gelsigner's death due to the research, the popular explanation for what happened was that the lead researcher had an equity position in a gene-therapy company.  There were numerous safeguards in place including a lack of a direct connection between sponsorship of the trial, a university prohibition of the lead researcher in patient enrollment or interaction,  and that same researcher asking a colleague to be the lead investigator in that trial.  The research had also been approved by more than one Institutional Review Board (IRB).  Most IRBs require a review of the scientific merit of the research before considering it on ethical grounds.   Since this was a protocol for the first human experiment in gene therapy, the vetting was unusually rigorous:

"The OTCD gene therapy protocol and the associated consent document underwent extensive review including IRBs at three institutions, the Recombinant DNA Advisory Committee, the Oversight Committee of the General Clinical Research Center of the University of Pennsylvania, and the FDA."  (reference 2)

 Please read the entire paper on line for the complexities of this case.  For the purpose of the NEJM article the relevant section had to do with Wilson recommendations of why the appearance of conflict of interest maybe all that counts.  After disclosing everything that he did  to minimize financial conflicts of interest Wilson concludes:

"I conclude that it is impossible to manage perceptions of conflicts of interest in the context of highly scrutinized clinical trials, particularly where there is a tragic outcome....." (reference 2, p 155).

That is where Rosenbaum's article gets interesting.  She introduces a concept that gets very little play in clinical medicine and one that has not had much play in psychology until the past decade and that is emotional reasoning.  There are physiological and evolutionary reasons why emotions play a large role in day to day reasoning.  In patients with a pathological loss of emotional reasoning there are significant problems in day-to-day decision making.  Diagnostic reasoning in medicine on the other hand is often described as a purely intellectual  process.  Psychiatrists  encounter this in our colleagues.  I can recall for example, confronting a Cardiology resident with the fact that her agitated patient did not have an acute exacerbation of bipolar disorder like she suspected and  did not need transfer to Psychiatry, but in fact had just had a stroke and was aphasic.  "What the hell do you know about strokes?  What do psychiatrists know about neurology?"  she stated forcefully as she rapidly escalated herself.   I calmly back pedaled and said: "Get your attending to confirm the findings and the diagnosis and if he doesn't - call me back.  But right now your patient has aphasia and has right upper extremity weakness and needs to go to the Neurology service."  Within an hour that patient was under the care of the Neurology service.  My point being that level of emotion or in this case emotional biasing really doesn't show up in any of the case records or diagnostic reasoning in the New England Journal of Medicine.  Everything is cool, dry, and pure Bayesian analysis.

Rosenbaum likes the work of a social psychologist Robert Zajonc who was one of the pioneers in this area.  If most decisions begin with a feeling, what persisting feeling may be there in the case of decisions about conflict of interest.  She had previously cited numerous legal infractions and penalties against most of the major pharmaceutical manufacturers.  It should not be surprising that the persistent emotional decision making involving that industry is going to be rather negative and miss the complexities and information that runs counter to that emotion.  I think back to one of the basic admonitions of grandmothers everywhere from my generation: "If there is one thing I can't stand it is a liar!"  I reflected on that over the course of my years in medicine as I realized that the reality is that everybody lies and they lie all the time.  But if you are indoctrinated to that rule and you have a definite emotion associated with it, you should be able to predict the direction of the decision.  You only have to look as far as Cognitive Appraisal Theory (4) for the predictable results when anger is that emotion.  To make it real, in the case of ongoing problem with the pharmaceutical industry you will see their responsibility as high and any adverse outcomes as being totally in their control.  You will be very certain about your decision, irrespective of what the reality is.  One example previously mentioned is the idea that the new cholesterol guidelines would be a windfall for the pharmaceutical industry when the vast majority of the prescriptions are for generic statins.  There will be a contamination effect on everyone associated with those companies and as long as the underlying emotion persists the associates will be predictably condemned with the same level of certainty and any negative events will be perceived as being under the complete control of the individuals involved.  There can be no unanticipated adverse outcomes or complications.        

The most concerning aspect of this kind of emotional bias is that people seem to be completely unaware of the fact that they have been swept up in it.  To them, their decisions all seem reality based.  The biasing effect in emotional reasoning has the same predictable effect in paranoid psychotic states, road rage, and Little League parents.  It is certainly alive and well in practically all aspects of public opinion when it comes to psychiatry.  Many blogs and Internet sites seem nothing more than a lens to focus rageful commentary against the profession, and further indignation if any psychiatrist dares to speak out against many of these practices.

I think indignation bias explains a lot, particularly attitudes toward psychiatry but also overly rigid thinking in the case of complex decisions and unpredictable negative outcomes.  It has allowed an irrational connection between Big Pharma and psychiatry and for many people to profit from focusing anger against the profession.  And per Dr. Rosenfeld it is not conducive to rational regulations of the industry, but it seems that at least the marketing end of those businesses seem content to see their "pushback" as being the cost of doing business.  Even marketers could benefit from educating themselves about the negative future effects of emotional decision-making against their industry.


George Dawson, MD, DFAPA


References:


1:  Rosenbaum L. Reconnecting the Dots - Reinterpreting Industry-Physician Relations. N Engl J Med. 2015 May 7;372(19):1860-1864. PubMed PMID: 25946288.

2:  Wilson JM. Lessons learned from the gene therapy trial for ornithine transcarbamylase deficiency. Mol Genet Metab. 2009 Apr;96(4):151-7. doi: 10.1016/j.ymgme.2008.12.016. Epub 2009 Feb 10. PubMed PMID: 19211285.

3:  Lerner JS, Li Y, Valdesolo P, Kassam KS. Emotion and decision making. Annu RevPsychol. 2015 Jan 3;66:799-823. doi: 10.1146/annurev-psych-010213-115043. Epub 2014 Sep 22. PubMed PMID: 25251484.

4:  Lerner JS, Keltner D. 2000. Beyond valence: toward a model of emotion-specific influences on judgment and choice. Cogn. Emot. 14(4):479.



Supplementary 1:  According to UpToDate, the gene therapy trial mentioned in the above reference was cancelled after the death of Jesse Gelsinger.  He was the 19th patient in the trial and metabolic correction of the other 18 patients did not occur.  (Topic 2923)

Supplementary 2:  Image used at the top of this post is a Shutterstock standard license download.

Supplementary 3:  Quote from Vittorio De Sica is from Stereophile June 2015, p 125.

The Heuristic is Dead - Long Live The Heuristic

One of the latest non-scandals to rock monolithic psychiatry and psychiatrists everywhere is David Healy's commentary on serotonin and depression (1).  Certainly nothing new there from the Healian perspective - SSRIs don't work, SSRIs don't work for melancholic depression, no evidence that SSRIs raise or lower serotonin levels, SSRIs pushed tricyclic antidepressants out of the market, and SSRIs forced the abandonment of research on biological disturbances in depression like hypercortisolemia.  The only thing I did not see was the idea that SSRIs are somehow addicting because they cause discontinuation symptoms in a subgroup of people who take them.  Feel free to call that a withdrawal syndrome, but withdrawal does not constitute an addiction.  All of these premises allow him to reject serotonin and it's role in depression on the vaguest possible grounds while stating that it is not irrelevant:

"Serotonin is not irrelevant.  Just as with noradrenaline, dopamine, and other neurotransmitters, we can expect some correlation with personality and temperament."

Indeed - but I expect those to be a very weak correlations probably not on par with the mood disorder work.  I was glad to see his reference to the late Marrku Linnoila (2) or more specifically Linnoila and Virkkunen.  Linnoila had done some of the outstanding work in this area and work on serotonin metabolites (CSF HIAA) in alcohol use disorders remains a classic.  He talks about the serotonin based research running into the sand.  I did a Medline search of serotonin and major depression and plotted the papers per year and there does not seem to be any precipitous fall off (the 2015 references are through March).  If anything I would expect the research to increase with the availability of ligands for additional receptors and the further characterization of serotonin transporter (SERT) variants.

But the main problem with Healy's argument is that he is talking about serotonin as if there is a chemical floating around in the brain and that is it.  He is basically describing his own brand of chemical imbalance theory.  So if he is saying there is no serotonin chemical imbalance theory I would of course have to wholeheartedly agree with him.  And in fact, I would tell him the same thing I told the Prozac rep back in the 1980's:  "The brain is far more than a bag of chemicals.  Unless you can say something about brain structure and physiology naming a neurotransmitter is meaningless."  There is no such thing as a chemical imbalance theory and reading through the index of any psychopharmacology text printed in the past 30 years will confirm that.

Healy can't stop himself at that level.  He goes on to describe the impact of his chemical imbalance theory on clinicians:

"This history raises a questions about the weight doctors and others put on biological and epidemiological plausibility.  Does a plausible (but mythical) account of biology and treatment let everyone put aside clinical trial data that show no evidence of lives saved or restored function?"

Things get very tenuous at that point.  As a clinician who has made a career out of treating patients with the most severe problems  I don't care at all about the "biological and epidemiological plausibility" of a theory of a medication.  I got past that in the 1990s when the elegant Nobel laureate mechanism of action of aminophylline was debunked and the former first line drug for asthma and COPD exacerbations was suddenly relegated to tertiary status.  And even then, with the people I was running up on gurneys from the emergency department while calculating the parameters of their aminophylline drip - not a patient of mine was lost.  I suppose you could say it was all an elaborate placebo response, treating all of those people with acute shortness of breath bad enough to be brought in by paramedics.  I was after all using a tertiary treatment with a disproven molecular mechanism.  But really?  And my living, breathing pulmonary patients did not seem to mind.

The only thing that matters to me is if the medication works in my hands, has few side effects, and I am using it exclusively to save lives and restore functioning.  And without keeping anyone in suspense, I do prescribe SSRIs and they do work, and I do fully acknowledge to anyone willing to listen that the mechanism of action is unknown. Not surprisingly many patients want more than that and I can discuss speculative mechanisms as well as the next psychiatrist.  I don't think that makes me a drug company stooge or an idiot, because I am the only person with any accountability in the entire scheme of things.  It really doesn't matter to me what David Healy or anybody else thinks.  I am seeing very ill people and it is my job to get them better and not cause them side effects with the medication and not have the drug interact with one of their underlying medical conditions.  When you get right down to it, I don't need a mechanism of action to use a medication - only the approval of a regulatory body like the FDA.  At some point somebody may say that  SSRIs are no better for depression than aminophylline was for asthma, but so far (apart from Healy and various sympathizers) that has not happened.  I just attended a CME conference last weekend and they were still recommended.  As far as I know the FDA has not sent out any letter to doctors telling them not to prescribe them any more.

Healy also asks the irrelevant question:  "Do clinical trial data marketed as evidence of effectiveness make it easier to adopt a mythical account of biology ?"  Or I guess the real question is do these data make it easier to accept this strawman?  I strongly encourage any psychiatrist to read and reread the FDA approved package insert on any drug they prescribe and any drug their patient happens to be taking.  I encourage reading and rereading those package inserts especially if they are updated and sent out in a mass mailing by the FDA.  These package inserts need to be studied because they are not the final word in safe prescribing.  If you are an experienced psychiatrist you will routinely be called on to decide if a medication (based on all of the available evidence) is safe to prescribe to a patient with cardiac, liver and renal disease.  You will have minimal data to go by in most cases, because people with significant medical illness are typically eliminated from clinical trials.   Any psychiatrist reading those package inserts will recognize that for some time now, the package inserts have contained clinical trials data and that data is very useful.  It's utility has nothing to do with putative biological mechanisms, it has to do with safely monitoring and prescribing the medication.  The other consideration implicit in this question is that clinical psychiatrists are unaware that clinical trials are really a primitive technology.  Given that awareness exists, why would anyone accept clinical trials data as proof of much of anything.  How in the world does a double-blind placebo controlled study with an intent to treat analysis have anything at all to do with my practice of psychiatry?  It is totally irrelevant clinically and even less relevant theoretically.  Its only use is to get a new drug in my hands that my patients and I will accept as useful or reject as too toxic or worthless.

Why are reasonable people interested in serotonin despite Healy's commentary?

The complexity of serotonin or more appropriately serotonergic signaling for one.  Absolute levels of neurotransmitters are rarely the issue in complex disorders.  In the case of serotonin any bare bones discussion needs to consider the fact that there are 14 serotonin (5-HT) receptor subtypes coded by 18 genes.  Those receptors are organized into 7 families, 6 of which are G-protein receptor linked superfamily.  The remaining family is part of the ligand-gated ion channel superfamily.  The combinatorics of these receptor types, their specific locations, and their genetic variants can lead to a dizzying number of signaling variations that can easily be found in psychiatric research (4).  As an example, this is from a 2013 review of serotonin signaling in depression and suicide by Mann (3):

".......Part of the neurobiology observed in recurrent major depression, that is present between episodes as well as during episodes, is a series of abnormalities in the serotonergic system [19]. Cerebrospinal fluid (CSF) levels of the main serotonin metabolite, 5-hydroxyindoleacetic acid (5-HIAA), are low in more lethal suicide attempters, and predict the risk for future suicide with an odds ratio of 4.6 [20].  Convergent evidence comes from some reports of low CSF 5-HIAA in suicide attempters with other diagnoses such as schizophrenia [21,22], bipolar disorder [23] and personality disorders, although there are fewer studies and less consensus in these other disorders [24,25]. Nevertheless, if correct, such findings suggest that less serotonin transmission, as implied by less 5-HIAA, appears to be associated with suicidal behaviour across psychiatric diagnostic boundaries, as would be expected if it were associated with the diathesis for suicidal behaviour instead a specific psychiatric disorder. A review of post-mortem brain studies of suicides has found much the same thing: most studies find suicides have lower levels of serotonin and/or 5-HIAA in the brainstem serotonin neurons compared with psychiatric-matched groups [26–28]."
   
Apart from all of the disputed technical details, what is the importance of the Healy commentary?  It follows the political tradition of other commentaries mentioned on this blog by prominent psychiatrists.  People have sent me e-mails and asked me: "What do you mean by political?"  In the simplest analysis it is taking one end of a polarized position and running with it and bringing everything that you can to support that position.  That is the classic way that politicians work.  They are fueled by ideology.  On the surface, it seems that science operates like that as well, but ongoing scientific arguments don't include comments about marketing or words like "neurobabble".  They don't make assumptions about how clinicians think or whether they are confusing science and hypothesis testing with clinical work.  The best science encompasses complexity and contradictory data and we are past the point where neuroscience can be watered down for the masses in a 2 minute sound bite.

Neurobabble happens when a neuroscience discussion is reduced to a sound bite and debated the way that Democrats and Republicans discuss just about anything.  That is what happens when we are all polled "Serotonin - yes or no?"

If you really want to get your opinion out in the press that way that is one thing.  Let's not pretend that psychiatrists really think this way or that psychiatrists are just flunkies for Big Pharma talking about some crazy chemical imbalance theory or that we based our clinical practice on heuristics or for that matter marketing.

Psychiatrists are really bright people, time to stop pretending that we are not.


 George Dawson, MD, DFAPA



References:

1: Healy D. Serotonin and depression. BMJ. 2015 Apr 21;350:h1771. doi: 10.1136/bmj.h1771. PubMed PMID: 25900074.

2:  View my collection, "Marku Linnoila" from NCBI

3: Mann JJ. The serotonergic system in mood disorders and suicidal behaviour. Philos Trans R Soc Lond B Biol Sci. 2013 Feb 25;368(1615):20120537. doi: 10.1098/rstb.2012.0537. Print 2013. Review. PubMed PMID: 23440471

4:  KEGG.  The Serotonergic synapse.

5: Albert PR, Benkelfat C. The neurobiology of depression--revisiting the serotonin hypothesis. II. Genetic, epigenetic and clinical studies. Philos Trans R Soc Lond B Biol Sci. 2013 Feb 25;368(1615):20120535. doi: 10.1098/rstb.2012.0535. Print 2013. PubMed PMID: 23440469

6: Albert PR, Benkelfat C, Descarries L. The neurobiology of depression--revisiting the serotonin hypothesis. I. Cellular and molecular mechanisms. Philos Trans R Soc Lond B Biol Sci. 2012 Sep 5;367(1601):2378-81. doi: 10.1098/rstb.2012.0190. PubMed PMID: 22826338