Sunday, October 5, 2014

Live by the Customer Satisfaction Ratings and Die By Them




My original intent was to look at the problem of what happens to a group of physicians who are sailing along with very high patient satisfaction ratings.  Then for no particular reason, their ratings drop by about 20-25%.  At the high point they did not question the validity of the ratings.  They just assumed the satisfaction ratings reflected their high quality work.  The problem is that nothing they did changed and suddenly their ratings were significantly lower and people were looking for explanations.  Hence the title of this post.  If these ratings really mean something in the first place the physicians are suddenly thrown into a lot of self doubt.  If they believe the ratings are unscientific, designed by people who don't know much about survey design or sampling, and are actually biased because of the way the staff presents the surveys - they are much less worried.

I posted to above bar graph as an introduction to this post.  It is a composite of the opinions that several primary care physicians have given me about the correlation between benzodiazepine and opiate prescriptions and customer satisfaction ratings.  More prescriptions for controlled substances equals greater customer satisfaction.    Some clinics have adapted to this by letting patients know that they do not prescribe benzodiazepines or deal with psychiatric disorders.  That eliminates physician-to-physician variability in prescribing.  It also demonstrates that certain overprescribed medications are viewed as more serious than others.  I have not for example seen any similar clinic rules for antibiotics even though they are also widely over prescribed.

I hope it is not a news flash to anyone that highly satisfied customers in the health care system have the highest mortality and probability of hospitalization (1).  I know that at least some of the customers out there may be very surprised to hear that doctors can't be rated like a Toyota dealership.  Toyota dealers after all have a product that is high in quality, uniform, and the same irrespective of those pesky human factors that we all have to deal with in human encounters.    I am referring of course to things like communication,  interpersonal skills, thinking capacity, personality traits and personality disorders.  A Toyota dealer is out to satisfy all customer needs in the very circumscribed area of personal transportation.  Even then there will be bumps in the road.  A customer may not like the way the vehicle has turned out or some of the results from the service department.  But generally Toyota dealers have a great product and most of their customers are highly satisfied.

This may be hard to believe but the MBAs that currently run medicine in the USA decided to introduce management principles into the field that were designed for the auto industry.   The details and names of those management principles is irrelevant at this time, but when they were introduced it was a big deal.  I had to listen to several hours of lectures on Six Sigma.  Feel free to read about it and let me know how it possibly applies to the practice of medicine.  After those lectures it was obvious to me that the MBAs running medicine were completely clueless about medical care.  One small piece of evidence in what is now a mountain of evidence that the business emphasis in managing hospitals and doctors is completely off the rails.   Most business concepts are introduced to groups of physicians as a manipulation.  They have to be because no rational person would buy what appears to be Dilbert style management.  It goes something like this:

"Look - we know that physicians don't like the idea that they can measured.   We know you don't like that idea, but let's face it, this is a new era.  Things aren't like they used to be.  The day of the physician running things is over.  You are all going to have to be accountable now.  Some day your reimbursement is going to be tied to these satisfaction ratings."

Administrators like to seethe a little bit when they play the authoritarian act with physicians.  They think it gives them more credibility.  They could also be playing off the collective seething in the room.  The logical questions followed:

"Well what about clinicians seeing patients with cognitive impairment or who are being treated on an involuntary basis.  What can you say about the validity of those satisfaction ratings?"

That led to some laughter, but no explanations.  Everybody would be rated and that was the end of it.  There would be no exceptions.  The irrational authoritarian business model rules.

Before anyone gets too bent out of shape about my view of the business model let me illustrate with an second example of what I mean.  Earlier this evening I consulted with a colleague from another state on an inpatient problem.  When that was over I asked her how things were going in general and she told me:  "It's really kind of tough.  The patients are never really stable, they have multiple psychiatric, substance use, and medical diagnoses and they are very hard to stabilize."  She was thinking about moving on.  She was in a meeting and an administrator said:  "This patient has been here (x number of days) what is the plan?"   She said:  "What do you mean what is the plan?  The plan is what the plan always is - stabilize the patient and discharge them."  Managed care administrators have the uncanny ability to blame the physician for any discrepancy with a pure business approach to medicine.  They apparently believe that hospital treatment and discharges are as predictable as Toyotas rolling off an assembly line.  That is as true for customer satisfaction ratings as length of stay outliers.  It give the administrators leverage against physicians, especially any physician who buys in to the idea that these are valid metrics.

Let me illustrate by considering two different physicians Doc A and Doc B.  Both are very competent psychiatrists, but for some reason Doc A consistently scores lower on customer satisfaction ratings than Doc B.   From the research in this area, it may simply mean that Doc B gives his patients more of what they want than Doc A.  My speculation is that personality is a big factor.  A simple mismatch between extroverts and introverts can fuel a lot of dissatisfaction.  The extroverts on both ends (doctor and patient) like to be engaged and they like the conversation to have no dead air.  A doctor that is too reserved may be perceived as being disinterested or not giving them enough in the interaction.  Some patients want special treatment and others just want confirmation of their perceptions of other doctors and in:  "I was not really impressed with your colleague.  What do you think of him?"  Psychiatrists generally know better, especially psychiatrists who recognize that their organization is set up to facilitate splitting and chaos.  There may be a difference between the doctors in terms of prescribing patterns in terms of my previous analysis of the overprescribing problem.  In this case Doc A may be known for no sleep medications, no benzodiazepine prescriptions, no opiate maintenance prescriptions and no high dose amphetamines for narcolepsy and no stimulant prescriptions for adult ADHD when the patient is functioning well in school or work.  Denying those groups of prescriptions will not only result in low physician satisfaction scores but threats of violence and suicide.  That is not to say that other tests or medication would not result in and extremely dissatisfied patient.  There are thousands of scenarios where the patient does not take the physicians advice in the manner with which it is intended and that is - the best possible advice to diagnosis or treat a problem at a given point in time.

I did not write this post to "prove" that being satisfied with your physician is necessarily a good thing or a bad thing.  If I wanted to approach problems like that I could probably get my own TV show.  The whole point here is that any potential patient-customer needs to know what these things mean.  You may not want to keep hearing the word but politics is the major reason.  People trying to sell their business based idea about medicine versus physicians who have no similar notions.  People trying to sell their idea that medicine is just like making widgets rather than treating people who have tremendous biological variability.  You don't want your Toyota to have tremendous mechanical variability, but for human beings biological variability is both a fact of life and a distinct advantage from an evolutionary standpoint.

And finally what about news from your physician that you don't want to hear.  Certainly there is widespread fear of a dreaded incurable diagnosis.  There is the concern of diagnoses associated with disability and loss of function.  But there is also straightforward advice on how to avoid fatal illnesses and disability.  The way that is presented varies considerably from physician to physician.  You have to ask yourself: "Would I rather hear that I am overweight and need to lose weight or that I should stop smoking or that I should stop using hydrocodone or alprazolam or would I rather be talking with a physician who would keep quiet on those issues?"

I don't think there is a good study of the issue and if somebody knows one please let me know so that I can post it here.  I can provide another anecdote.  I worked with a group of women once many of who consulted a female internist who was bright, attractive and wore very high fashion clothing (their characterization not mine).  Things were generally going along pretty well until this internist told some of them that they were overweight and needed to lose weight.  That elicited a very strong reaction and it seemed amplified by their perception of this physician as being "perfect".  When I thought about my experience with physicians - nobody has ever told me to lose weight even in situations where they should have.  I suggested it to a physician once and he said: "I concur with your recommendation doctor" but never told me that outright.  Social and cultural factors all play a part in the patients perception of the physician and their satisfaction ratings.

It is a good idea to keep all of those factors in mind in attempting to interpret physician satisfaction ratings especially since most consumer web sites focus entirely on these measures.


George Dawson, MD, DFAPA

1:  Fenton JJ, Jerant AF, Bertakis KD, Franks P. The Cost of Satisfaction: A National Study of Patient Satisfaction, Health Care Utilization, Expenditures, and Mortality. Arch Intern Med. 2012;172(5):405-411. doi:10.1001/archinternmed.2011.1662

From the reference:

"Patient requests have also been shown to have a powerful influence on physician prescribing behavior, and our findings suggest that patient satisfaction may be particularly strongly linked with prescription drug expenditures." (p. 408)

"While we do not believe that patient satisfaction should be disregarded, our data suggest that we do not fully understand what drives patient satisfaction as now measured or how these factors affect health care use and outcomes. Therapeutic responsibilities often require physicians to address topics that may challenge or disturb patients, including substance abuse, psychiatric comorbidity, nonadherence, and the risks of requested but discretionary tests or treatments. Relaxing patient satisfaction incentives may encourage physicians to prioritize the benefits of truthful therapeutic discourse, despite the risks of dissatisfying some patients." (p. 409)

Supplementary 1:  If you are a primary care physician I am very interested in your thoughts about how patient satisfaction scores correlate with prescriptions for benzodiazepines, opioids, and stimulant medications as qualitatively depicted in the above bar graph. 

Saturday, October 4, 2014

Life Is Not A Randomized Double Blind Controlled Clinical Trial

Or  what is wrong with placebo controlled clinical trials and transparency?

I was in an imaginary meeting with a bunch of Internists and Psychiatrists.  We were debating the available and meager literature on the use of trazodone for sleep.  We got into one of my favorite topics - the double blind placebo controlled trial and that catch all "Evidence based medicine."  The dialogue went something like this:

Internist:  "The evidence from double blind placebo controlled trials is weak for trazodone....."

Me:  "Do I need a double blind placebo controlled trial to tell me to prescribe trazodone for sleep?"

Internist: "Are you saying you don't need evidence.  Oh wait, I was at a conference where the head of the society stood up and and gave evidence that clinical trials have their limitations.  Like they are subsequently proven to not be true...."

Me:  "That is not what I am talking about.  I am talking about all of the hype out there that only 40% of people recover from antidepressants or that they are no better than placebo........"

Internist: "But you do have the algorithmic approaches that show...."

Me:  "Yada, yada, yada - for every algorithm, there is somebody with a meta-analysis to show it is wrong.  No I am talking about the ridiculous notion that psychiatrists could stay in business or want to stay in business if only 40% of the people they treat got better.  If that was true I would have become a recluse 20 years ago and just walked away."

General laughter

Internist: "I would kill for a 40% response rate for some of the problems that I treat."

And so on........




This informal conversation among colleagues is illustrative of the recent arguments that focus on physicians and generally psychiatrists more than other physicians that treatments are ineffective.  They are based on an oversimplified view of placebo controlled clinical trials and conflict of interest.  Many times there are no clear points of demarcation between what is a scientific issue (the technical aspects of the clinical trial) and the ethical issue (conflict of interest issues that may compromise the scientific results).   You can read all about current technical problems with clinical trials, like the common observation that there is a lack of generalizability to clinical populations compared with the highly selected and trial sample that in the case of psychiatry generally has much milder forms of the illness being studied.  Here are a few of the concerns that I don't see being discussed anywhere, especially when it comes to clinical trials of psychiatric interventions:

1.  The crude state of clinical trials:  Clinical trials in psychiatry are tremendously unsophisticated. The trial result generally depends on rating scale or clinician global rating scale results that grossly oversimplify the condition and measure parameters that are irrelevant in clinical settings.  The best example I can think of is depression rating scales that list DSM criteria for depression and then apply a Likert dimension to those symptoms.  In clinical practice it is common to see hundreds of patients with the same score on this scale who have a full spectrum of disability from absolutely none to totally disabled.  Which population might be more likely to exhibit an antidepressant effect?  It is also common to see medically ill patients with insomnia who may score as mildly to moderately depressed who are physically ill and not depressed at all.   The same problems exist with clinical trials of schizophrenia, anxiety and Alzheimer's disease.   When this weak technology is combined with a selection process that eliminates clinical populations with the most severe illness, it should not be surprising that any treatment being studied has a weak effect.

2.  A weak clinical trials data base:  One of the clarion calls of so-called evidence based medicine is the Cochrane Collaboration.  I have looked up hundreds of their reviews and the majority of those reviews of both medical and psychiatric studies is: "insufficient results and methodologically unsound".  I suppose it is good to have somebody make that statement, but if you have proclaimed that you are an evidence based physician - you have nothing to go on.  In fact, at some point you stop going to Cochrane because the results are fairly predictable.   Even in the case where you have a result does it apply to the patient you are seeing?  I don't see many Cochrane studies depressed patients that have right bundle branch block, ventricular premature contractions, or complex atrial fibrillation - all common patients seen in clinical practice.  How many more research papers do I have to read that conclude that "more research is needed" while continued inadequate trials are being published and analyzed by Cochrane?  From the current trends and political correctness of evidence based medicine this will go on forever.  The practical aspects are the very large costs of trials.  That is the real reason that pharmaceutical companies (Big Pharma) sponsor these trials.  The political system in the US has decided to farm out clinical trials to private for-profit companies in the exact manner that the US government has farmed out management of the entire health care system.  In these systems Big Pharma absorbs a disproportionate amount of criticism relative to managed care companies.  Managed care has equated "medically necessary" care with care that can be provided in the form of a pill.

3.  The politicalization of clinical trials:  No clinical trials of psychiatric medications can be done these days without an eye to the politically relevant dimensions.  A new antidepressant needs to get as many FDA approved indications as possible in order to beat the political restrictions of utilization review by managed care companies.   That would include indications not only for depression, anxiety, panic, and social anxiety but also chronic pain and possibly attention deficit-hyperactivity disorder (ADHD).  The best way to beat utilization review is to have the only FDA approved indication in the class.  That is also applied to atypical antipsychotics and that fact seems to escape the critics who focus on the number of prescriptions and what that implies.  Physicians are pawns in a game when there are no suitable tolerated medications for bipolar disorder depression and there are atypical antipsychotics for that indication.  These current political factors in clinical trials preclude a focus on cognition, functional capacity, and endophenotypes - all potentially much more valuable than a focus on diagnostic criteria or rating scales based on those criteria.

4.  A characterization that the average physician is ignorant - at best:  Any political movement is associated with ugly rhetoric.   There has clearly been an effort to stampede any physicians with reservations about evidence based medicine into a Neanderthal category.  The irony is that the criticism often comes from sources like managed care companies, medical certification authorities and the press (bloggers) - all entities with their own high levels of conflict of interest.  Common rhetoric used against psychiatrists has been: "You just don't want to be measured".  If the criticism originates from a government, managed care company or administrative authority there is often the attached explicit threat: "Those  days are over!".  The obvious implicit observation is that medicine and psychiatry is now being run by people who don't know anything at all about medicine and there is plenty of evidence on this blog to back that up.

Many critics seem to get a lot of mileage out of the position that they seem to be particularly anointed to criticize the field.   That seems especially true if they happen to be a physician as in: "My colleagues certainly seem to be a bunch of chumps and therfore can be rejected on a wholesale basis or of course listen to me for enlightenment".  I have never witnessed that level of incompetence in any group of physicians where I have practiced across multiple settings.

5.  The use of statistics for rhetorical purposes:  At this stage after reading research for that past 35 years, I am convinced that you can come up with a meta-analysis that will show whatever you want it to show.  Several years ago in the New England Journal of Medicine there was a study that looked at how well meta-analyses predict the results of available large scale clinical trials.  That study showed 2/3 times.  It is common to see a result and then see a meta-analysis that "disproves" the clinical trials result.  Nobody seems very interested in looking in detail at how sound that meta-analysis was.

Today we have a large number of questionably valuable clinical indicators or quality care markers that are often based on the political rhetoric of the government and managed care organizations.   They may be invalid on the face of it, but there is a second equally important aspect.   These same organizations have no valid approach to looking at the statistics of longitudinal data.  They will look at clinic results or even results from the same physician and convert them all to a numerator and a denominator.  Whether that fraction means anything or not is anybody's guess, but there is an administrator somewhere who will be happy to tell you all about it.

6.  False assumptions about the expertise of physicians:  Much of the rhetoric above is focused on physicians.   Psychiatrists as the most politically disenfranchised group are a frequent target.  In the past years we have endured the ideas that medical treatments being prescribed are ineffective and overprescribed.  That brings us full circle to the opening imaginary conversation.  Physicians are trained to focus on several goals including acute treatment, treatment of chronic problems, and providing care for the dying.  The psychiatrists and physicians that I have had the pleasure of working with have been highly effective is achieving those goals.  When I look at the modest results of poorly designed clinical trials all I can do is shake my head.  I would have quit a long time ago if my diagnostic or treatment capabilities were accurately described in clinical trials and most physicians would have.  Informed clinical treatment is a series of often rapid changes in course, rejecting poorly tolerated treatments and looking for things that work better along the way.  I can change the course of treatment depicted in a clinical trial in one day.  In the trial that result is carried to the end as a failure.  How is it that a clinical trial or this evidence would predict my treatment results by mean?  If a treatment is ineffective or not tolerated in my practice, I don't stop treatment and call that person an unsuccessful intent-to-treat subject.  I work with them to establish effective treatment - often in the same time frame as a clinical trial.  Is it quite literally absurd to suggest that clinical trials accurately describe what will happen in clinical practice and yet that is the state of discourse.

7.  The false promise of transparency:  Anyone who followed politics knows that disclosing potential conflicts of interest  is meaningless in the case of politicians.  The general idea is that politicians would refrain from either accepting money from sources where they are involved politically or just not be involved in that area of legislation.  In reality that does not happen.  Sometimes the politicians involved will speak out against any suggestion that there is a connection between the money they receive and their legislative record even when their activities are consistent with a financial conflict of interest.  The sunlight of transparency that many of the critics talk about simply legitimizes ongoing involvement in areas of potential conflict of interest.   Disclosure is a stamp of approval for involvement.  All of that can be researched on Congressional watchdog sites.   The new CMS web site that posts payments to doctors is hyped as a way to appease all of the critics who seem clueless about transparency.  For an eye opener take a look at their decision point on conflict of interest.  CMS seems much more charitable than the typical blogger, politician or journalist with this disclaimer:

"Sharing information about financial relationships alone is not enough to decide whether they’re beneficial or improper.  Just because there are financial ties doesn’t mean that anyone is doing anything wrong.  Transparency will shed light on the nature and extent of these financial relationships and will hopefully discourage the development of inappropriate relationships.  Given the complexity of disclosure and the importance of discouraging inappropriate relationships without harming beneficial ones, CMS has worked closely with stakeholders to better understand the current scope of the interactions between physicians, teaching hospitals, and industry manufacturers."

8.  A lack of appreciation of the regulatory environment:  In the rush to condemn Big Pharma and anyone associated with them, critics often have an idealized version of regulation in their minds.  If only they had access to all of the clinical trials data to analyze for themselves.  They would personally be able to hold Big Pharma's feet to the fire and only allow drugs to be approved that they deemed to be safe and effective.   They are smarter and more ethical than anyone doing the actual trials and certainly smarter than the regulators.  This is at the minimum a failure to recognize that pharmaceutical regulation is after all a political process.  Like all politically directed regulation there are broad goals of safety and efficacy but they are relative and the regulatory mandate takes that into account.  On this blog I have pointed out several cases of medications that not only I,  but the Scientific Committee employed by the FDA recommended against based on safety considerations, but that were approved by the FDA.   Many drugs that I approved as a member of a Pharmacy and Therapeutics Committee (P&T) were expensive but had minimal efficacy.  We approved it based on political considerations (small but vocal advocacy group and untreatable illness) rather than pure efficacy or safety considerations.  The regulatory environment is currently designed to get promising agents into the hands of clinicians for clinical use.  The limited exposure of patients in clinical trials means that rare but serious side effects will not be recognized until post marketing surveillance occurs.  Every person taking an FDA approved medication should realize that.  The regulatory process is not designed to provide perfect medications because there are none.

There is a lot more to say about this subject like a detailed analysis of how the politicalized version about how physicians work and think has nothing to do with the way physicians actually work and think.  But for today I am stopping here.

Life is not a randomized double blind controlled clinical trial and that is generally a good thing.

George Dawson, MD, DFAPA

Sunday, September 28, 2014

Neanderthals - Real Human Differences and Stereotypes



That's right - I am 2.1% Neanderthal.  There have been some fascinating developments in human paleogenetics in the past decade including the characterization of genomes other hominins including the Neanderthals and the Denisovans from old remains.  It casts a different light on some of the stories based on stereotypes from the past.  For example, the common view of Neanderthals were that they were strong, but not very intelligent or sophisticated beings.  As as result Homo sapiens could easily outcompete these brutes and as a result modern day man is the only surviving species.  It was quite a surprise to learn that after the Neanderthal genome had been characterized portions of it could be identified in the modern human genome and that ancient DNA may have a role in the HLA (human leukocyte antigen) genes that play a central role in immunity.  There is the related question about whether incorporating the DNA of a new species could lead to certain autoimmune problems.   That fact compounded my interest in this area that was originally piqued by the first NatGeo Genographics project.  That project gave confirmation and graphics to the fact that at some point or another about 60-70,000 years ago, our ancestors walked out of the Rift Valley in East Africa and began their migrations around the globe.  Some of those folks migrating north through Europe encountered Neanderthals and Denisovans along the way.  Contrary to the conventional story that humans "outcompeted" them, they mated and produced offspring.

A quick review on relevant taxonomy.  From zoology, the naming convention is Genus and species.  Modern humans are Homo sapiens.  Considering this convention there were about 16 different species of the genus Homo and apart from Homo sapiens all of the others are extinct.   That includes Neanderthals (Homo neanderthalensis) and Denisovans.  In historical terms, at one time or another there was more than one Homo genus walking the earth.  Looking at a graphic from the Smithsonian suggests that Homo sapiens, Homo floresiensis,  Neanderthals (Homo neanderthalensis), and Denisovans were all walking the Earth sometime in the time zone about 20-30,000 years ago.  Genetic technology has revolutionized this area of morphology based research.  There is a lot of speculation but no good conclusions about why Homo sapiens is the only surviving species.

I don't know if they still teach this in Medical School but in all of my major rotations I was taught to describe the patient in the first sentence by age, sex, and ethnicity based on outward appearance.  There were various rationales provided for that opening sentence but even in medical school (now a long time ago) they did not make a lot of sense to me.  Of course there were cultural and political influences on these descriptions.   The "38 year old black male..." became the "38 year old African-American male..." at some point and back again depending on the politically correct term of the time.  It was all very unscientific, but many physicians seemed to think that it was a more medically precise way to talk about the patient and condense relevant information about that patient.  I did not have to consider anything beyond "male-female" versus "man-woman" to decide that my notes would never start with these words.  The only facts that I capture in my opening lines is the actual age of the patient and whether they are a man or a woman.  Male and female are non-specific terms and don't reflect the fact that I am talking about a human being.  You could say that this is an old convention, but I still see it as present in most medical records that I review.  In fact, it has stretched so that in some cases the characterization of white people has progressed from White to Caucasian to European, even though the person in question and their family has not set foot in Europe in over three or four generations.  I guess I also missed the politically correct convention that white folks were now "European Americans" and yet I have seen that frequently in medical records.

I read a paper in Science about 20 years ago that there were no genetically significant differences based on race or skin color.  It what seemed like a surprisingly simple statement, the authors pointed out that all humans are much more genetically related to one another than to non-human primates.  Genetic differences based on skin color and facial features were trivial to non-existent.  If you look at it that way that opening line:  "24 year old Hispanic female..." becomes little more than an unscientific stereotype.  Why include it in the medical record?  Some might say that it provides the opportunity for the delivery of culturally appropriate health care.  If that is the case, I would suggest including a more accurate description of the patients culture (as described by them) rather than presuming their culture based on their physical appearance or a check off on a standard intake form.  Scientific rather than stereotyped descriptions of people should be the standard.

A related issue is how much people actually know about themselves and their family of origin.  On the average, most of the people I talk with about their family histories know the high points for about 3 generations.  Physicians are typically focused on heritable diseases but most third and fourth generation Americans in this country don't know much about how their families migrated to the US and where they were migrating before that.  The first humans migrated out of the Rift Valley in East Africa about 70,000 years ago.  That is 2800 generations ago, maybe more if we need to correct for the short longevity of prehistoric man.  The fact that we are all Africans to start with and that so-called racial differences were a byproduct of the migration is a huge fact that nobody talks about.  It has far reaching implications and it is why I like to talk about it.

The other issue is what happened to the Neanderthals?  The story used to be that the Neanderthals were typical cave men.  They were squat muscular, and not very bright.  Their fate was considered to be extinction because they were outclassed and outcompeted by Homo sapiens.  Paleogenetics has led to those assumptions being challenged.  An excellent Nova special called Decoding Neanderthals captures some of the surprise and excitement of some of the first scientists who discovered Neanderthal DNA in the human genome.  That program also looks at how inferences can be made about prehistoric beings based on both the archaeological evidence and the genetic evidence.  In the case of archeology, the complexity of Neanderthal flint tool technology was investigated.  They had a method of making flint tools with a broad sharp edge that could be resharpened.  It was termed Levallois technology and the complexity suggests a higher level of intelligence than is commonly assumed.  The second Neanderthal technology that was discovered was using a type of pitch on some of their implements.  To manufacture this early epoxy required mastery of a thermal process again suggesting advanced intelligence.  The final piece of evidence is the presence of the FOXP2 gene.  This gene is responsible for speech and language in humans.  There are FOXP2 variants, but when the Neanderthal DNA was decoded, it contained a copy of the FOXP2 gene identical to modern humans.  That technology and the fact that Neanderthals were also social beings makes it a little more difficult to explain how they were "outcompeted" by Homo sapiens.  I have not seen any theories about how that competition might have included direct incorporation of large numbers of Neanderthals directly into the Homo sapiens population.  What are the numbers of Neanderthals who could have been incorporated into the population given the current DNA percentages?  I suspect that it could have been large.   

 To use an example from my own ancestors, I constructed a table looking at the stated ethnicities of my grandparents.  My maternal grandparents had been in the US for a generation longer.  My paternal grandmother still spoke and read her native language.  My maternal grandfather knew just small bits of Swedish.  He taught me a prayer in Swedish but did not know the translation and neither do I.  Small customs usually having to do with celebrations and food persisted to a small degree but on the balance my family was Americanized.  Comparing the stated ethnicities of my grandparents to DNA markers results in a couple of matches, but as many question marks.







Will there come a time when genetics will allow for better probability statements about who might inherit what disease?  Given the fact that my haplotypes occur in less than 1% of the current NatGeo database of over 650,000 subject - maybe.  But that depends on a lot more study and a medical record descriptor about presumed ethnicity has very little to do with it.  There is a related issue about how the science of paleogenetics can be politicized like any other branch of science.  Chris Stringer wrote an excellent commentary about this in Nature.  He observed a trend speculating that some genomes were more "modern" than others based on their content of "ancient" DNA.  He summarizes this well in two sentences:

"Some of us have more DNA from archaic populations than others, but the great majority of our genes, morphology and behavior derives from our common African heritage.  And what unites us should take precedence over that which distinguishes us from each other."

The current evidence also seems to suggest that the migration out of Africa is only part of the story.  The identical FOXP2 gene found in both Neanderthals and modern humans, suggests a common ancestor long before the African migration.  There are currently 7 billion people on earth.  The processing power of the human brain means that there are 7 billion unique conscious states.  It should not be too difficult to imagine that isolated groups of humans in in recent times will result in different  appearances, customs and practices.  The all too human characteristic of promoting the interests of these groups even to the point of warfare against others seems to be a common element of human consciousness.

A more widespread appreciation that these distinctions are by convention only might moderate a tendency for groups to see themselves as different or "better" than other groups of modern humans.  That leap of consciousness will hopefully happen in future generations.


George Dawson, MD, DFAPA



Supplementary 1:  One of the most striking aspects of this project is the economics of it all.  Over 680,000 people willing to pay $200 apiece for this information.  Researchers take note.  This may be a new way to fund research and generate large amounts of data at the same time.  You probably need a willing department head,  IT department, and IRB.  There is also a question of collaboration.  Is there any correlate between mental illnesses and the genomes of the Neanderthals and Denisovans?  If I have a well characterized sample of research subjects with a specific problem does it make sense to look at that issue?

Supplementary 2:  There are currently only 19 references to the issues of ancient DNA in Medline at this time.  Seems like another good area for research.

Supplementary 3:   My old high school biology text was ahead of its time in another way.  I remember that it predicted that the human race would eventually appear to be uniform due to increased mobility and intermixing of different races.

Supplementary 4:  The infographic at the top of this post was generated by the National Geographic Genographic Project based on my DNA sample.

Supplementary 5:  The evidence of bias against Neanderthals in popular culture is significant.  My first thought was the Geico commercials based on the premise: " three pre-historic men who must battle prejudice as they attempt to live as normal thirty somethings in modern Atlanta".  Even the Wiki piece refers to them as "Neanderthal-like".  Wikipedia has interesting references on this page and also a separate page entitled "Neanderthals in popular culture."

Supplementary 6:  Updated NatGeo infographic accessed on April 9, 2016.  NatGeo knows how to make a world class infographic.  Note that the sample size has gone from 678,632 to 742,652.  The remaining details are about the same but there is more updated information on the web site.





References:

1:  Stringer C.   Evolution: What makes a modern human.  Nature. 2012  May 2;485(7396):33-5. doi: 10.1038/485033a. PubMed PMID: 22552077.



Saturday, September 20, 2014

Lessons From Physical Therapy


I remember the first time I experienced any significant knee pain.  My wife and I had just purchased an old house and as part of the sweat equity that young homeowners do we were going to refinish all of the hardwood floors ourselves.  If you have ever tried that, the most imposing part of the task is sanding all of the floors.  Hardwood floor sanders are very heavy pieces of equipment with cast iron bodies.  My first task was to carry this machine that I guess easily weighed over a hundred pounds up to a high second floor in our old house.  That was about 25 steps and a landing.  By the time I got to the top, it felt like both knees had bottomed out and were starting to creak.  At the time I was a competitive cyclist and training by putting in 200-250 miles on the roads and hills of Duluth, Minnesota.  I had never encountered this type of pain before during cycling, speedskating or weight lifting.   I compensated the best I could by taking the sander down just one step at a time and bringing it up and down again after we ruined the first staining attempt.  Eventually the pain went away, but I had learned several valuable lessons.  Cycling for example, did not cause any knee pain even after this acute injury.  I developed a strong preference for cycling and skating and decided to forget about running.

A couple of years went by and I developed some pain in my lateral knee.  I had already been diagnosed with gout in medical school and compared to gout pain most other musculoskeletal pain is minor.   My experience with physicians diagnosing gout was very mixed and I did not want to get a recommendation for medication if something else would work better.  Instead of seeing a primary care physician, I went in to see a physiatrist who happened to be a sports medicine doc.  He jerked my knee around and was satisfied it was stable and showed me some basic iliotibial band stretching exercises.   Within a week the pain was was gone.

My most foolhardy adventure in knee injuries was trying to extend my usual 40-50 miles training rides to 100 miles with no buildup.  I was out riding the roads in Washington County and remembered a theoretical 100 mile loop that I always wanted to ride.  It was a hot summer day, I felt very fast, and I had plenty of daylight so I took off.  At the 3/4 mark I was coming up a long steep grade and felt some left knee soreness that persisted the rest of the way.  My knee was burning when I stopped and I ignored it and did not ice it that night.  By morning I had developed a significant effusion and could not bend it.   I saw an orthopedic surgeon the next day who jerked my knee around, told me it was an overuse injury, and put my leg in a knee immobilizer.  Within two weeks I was out cycling again.

At other times I have allowed my body to get seriously out of whack.  After years of cycling I started to realize that I ended each session with severe neck and shoulder pain.  After numerous adjustments to the stem length on my bike, a physical therapist figured out I was was extending my neck too far to look up from my riding position and fixed the problem by modifications to my riding position and neck exercises.  At one point, I was almost exclusively cycling and got to the point it was painful to walk around the block.   The solution was again exercise modification and exercises to improve hip flexibility.  

All of this experience has led me to be very conscious of knees and other joints and keeping them in good working order as I age.  Not just my joints but the joints of my wife, family and friends.   It is kind of amazing to hear the emphasis on physical activity at all ages and yet there is no information out there on joint preservation or how to preserve your back.  Many people are surprised to learn that the circulation to intervertebral disks in the spinal column is gone at some point in the late 20s.  That makes biomechanics and muscle conditioning some of the most important aspects of joint and back function as you age.  It also makes physical therapy and exercise some of the most important tools to maintain musculoskeletal function with aging.   When I develop some kind of musculoskeletal pain, the first thing I do is call my physical therapist and schedule an appointment to see her.   She does an examination and an analysis of the biomechanics of the problem and tells me how to solve it.  I have been through the process many times with a physician and the main difference is that there is no biomechanical assessment, no actual manipulation at the time that may be useful, and no specific exercise program to make it go away and stay away.

The results of a medical evaluation are as predictable.  You have a diagnosis of muscle or joint strain.  Use ice or heat whichever one makes you feel better.  I have been told by rheumatologists that there is really no scientific basis for the heat versus ice recommendation only the subjective response.  And of course the recommendation for NSAIDs (non-steroidal anti-inflammatory drugs like ibuprofen) or acetaminophen.  I ignore the NSAID recommendations and take as few tablets of naproxen every year as I can.  I consider NSAIDs to be highly toxic drugs and avoid them even though they are effective.  I had a rheumatologist at a famous clinic tell me that the best evidence that NSAIDs were effective was the negligible amount of joint cartilage that was left when patients came in for joint replacement therapy.   Strong evidence that NSAIDs could knock out the pain as the joint deteriorated.   The only time that I was ever offered an opioid was when I had my first gout attack.  I was seen in an emergency department for severe ankle pain and discharged with a bottle of acetaminophen with codeine - a medication that is totally useless for gout pain.

In clinical practice I see a lot of people with chronic pain.   I notice that many of them are taking NSAIDs on a chronic basis and experiencing complications of that therapy like renal insufficiency.   I notice that practically nobody sees a physical therapist.  I notice that many people are now started on oxycodone or hydrocodone for mild sprains and injuries involving much less tissue injury than many of the injuries I have sustained during sports.   There are also many people who do not receive adequate advice on modifying their activities once an injury or series of injuries has been sustained.   For example, should a person keep running if they have sore knees, are 30% overweight, and have radiographic and physical exam evidence of degenerative joint disease?  Many people seem to have the idea that they can just wear out joints and have them replaced and the replacements will be as good as new.   Some will decide that it is just time to hang it up and start to sit on the couch and watch television.  They are surprised that their pain worsens with months of inactivity.   Some of the patients with back pain decide: "This pain is so bad that physical therapy is not going to do anything.  I am going to get surgery as soon as I can."  The widespread ignorance and neglect of musculoskeletal health is mind boggling to me.

I got into an exchange with an orthopedic surgeon in our doctor's lounge one day - over lunch.  He wanted to talk about narcissistic personality disorder and I wanted to talk about the biomechanics of the knee and hip joints.  It was a lively exchange and in the end he agreed with me about the huge importance of biomechanics during physical activity and as a way to prevent injury and degenerative disease.  It turned out he just wanted to hear about the personality disorder and did not have an opinion on it one way or the other.

I teach a lot about central nervous system plasticity in a neurobiology course that I give several times a year to different audiences.  Widely defined, plasticity is experience dependent changes in the nervous system.  There are a number of mechanisms that can lead to these changes.  Kandel and others have pointed out that these are the mechanisms of animal learning.  Two examples jump out of those lectures.  The first is a physical therapy example of knee extension exercises in the treatment of knee injuries.  It has been known for some time that quadriceps strength and balance through the knee are critical factors in knee rehabilitation and the prevention of future injuries.  Research in this area shows that increased quadriceps strength can occur in the same session.  The other example I use is a guy who wants to go to the gym to increase the size of his biceps.  He starts doing curls and within 6 weeks his strength has increased by 25% but there is no muscle hypertrophy.  His biceps diameter is unchanged.  What do these two examples have in common?

The common thread here is CNS plasticity and everything it allows us to do.  Plasticity will allow your to keep your joints healthy and relatively pain free if you allow it to.  You have to be willing to accept the idea that pain can come from deconditioning and biomechanical problems that are reversible by plastic mechanisms.  The only additional information needed is if it is safe to exercise and that can be provided by a physician and a physical therapist.

And the lesson for psychiatry?  Chronic pain patients certainly need to hear this information especially if they are deconditioned.   People addicted to opioid pain medications who are not getting any relief need to hear this information.  Patients in general with exercise modifiable conditions who see psychiatrists need to hear this message.  There is also a lesson for psychotherapy no matter how it is delivered.  Kandel's original example of plasticity was a psychotherapy session.  If your brain is modified by exercise there is no reason to think it can't be modified by anything from straightforward advice to more complicated therapies.   Success in that area can lead to the limited or no use of medications and a conscious focus on what is needed to maintain health like I discuss from my own experience.  I certainly don't take any medication for pain that physical therapy or exercise adequately treats.  The same argument can be applied to anxiety and depression that can be adequately addressed by psychotherapy or other psychological interventions.  On the other hand if most people don't know that physical therapy, exercise and activity modification successfully treats musculoskeletal pain and other problems they are unlikely to try.    


George Dawson, MD, DFAPA

Supplementary 1:  There are currently only 4 Medline references on biomechanics plasticity sports.  This seems like a promising area for sports medicine, physical therapy, and rehab medicine.

Supplementary 2:   The photo at the top of the page is an exercise I do to alleviate knee pain that I learned from the book The Knee Crisis Handbook by Brian Halpern, MD with Laura Tucker.  The exercise is called the quad set (p. 238) and although the author suggests a towel under the knee, I am doing it on a styrofoam roller.  This book contains a wealth of information on knee health.  I do not recommend doing what you see in the picture without reading the book.  I have no conflict of interests related to this book and purchased it online entirely for my education.

Supplementary 3:  I could not figure out where to fit it in above but after 25 years riding with 175 mm crankarms on my bike, I dropped them back to 172.5 mm.  The bike fit expert for my new bike was convinced it was a good thing to do.  My new bike rides so much differently it is difficult to know what to attribute to crankarm length.  

Tuesday, September 16, 2014

Is SAMHSA a managed care company?

As I read through their flagship document:  Leading Change 2.0: Advancing the Behavioral Health of the Nation 2015-2018 that was what came to my mind especially when I read statements like this:


"Over the past year, SAMHSA leadership with staff to establish a set of internal business strategies that will ensure the effective and efficient management of the Strategic Initiatives. The resulting Internal Operating Strategies serve as the mechanism through which SAMHSA will optimize deployment of staff and other resources to support the Strategic Initiatives. These Internal Operating Strategies (IOS)—Business Operations, Data, Communications, Health Financing, Policy, Resource Investment and Staff Development—articulate SAMHSA’s effort to achieve excellence in operations and leverage internal strengths by increasing productivity, efficiency, accountability, communications, and synergy." 

Being employed at one time in a large managed care organization, I am used to seeing business speak like this.  I learned to cringe when I read it because any Strategic Initiative based on business speak rather than science or clinical expertise typically ends up being a nightmare.  That's just my experience, but any American who survived the last financial debacle has to be sensitized to words like "productivity, efficiency, accountability, communications, and synergy."   I have a previous post on the Orwellian nature of the word accountability in case  you missed it.  But you can substitute any of a number of words in this paragraph - like excellence.  We used to have a term in medicine called quality that actually meant something.  Excellence as used in the business community is a whole new ballgame.  The number of centers of excellence and top hospitals and clinics based on business measures can be astounding.  You can probably drive out in your community and see one of these banners wrapped around some facility right now. 

SAMHSA is supposed to be the federal government's lead agency for the treatment of mental illness and substance use disorders.  There has been some debate, but I think the political strategy of SAMHSA is very clear and that is to continue the rationing and managed care tactics that have been in place for the past 30 years and make them official government policy.  Lately they have been using tactics that I have seen from these companies over the past 10 years.  Here is what I am seeing so far.

Consumer slogans and concepts are identified that are easy (and free) to support.  Micky Nardo, MD posted their pamphlet on their working definition of Recovery .  This is their "primary goal" for the next year and it was supposedly built on among other things: "consultation with many stakeholders" .  The pamphlet goes on to the definition of recovery with no apparent rules for their all inclusive definition.  For example, does everyone in recovery need to have all of the elements of the definition?  Are there exceptions?  If someone is lacking an element would we say their are not in recovery?  Is this just a subjective and totally personal assessment?  Or is this a goal? If so, why is the lead agency for mental health and substance use promoting it and making it a primary goal?  Note the goal here is "behavioral health".  Behavioral health is the managed care version of mental health.    SAMHSA is therefore supporting the managed care view of the world.  That world view has rationed and otherwise decimated resources available for the treatment of mental illnesses.  Just a few observations on the 10 page pamphlet.

Social media is used for marketing purposes.  Well it is the 21st century and this is how everybody including government agencies gets noticed these days.  I got this cheery notification from SAMHSA in an e-mail this morning:



  Nothing like using a standard Internet marketing strategy to discuss a process that has no proven efficacy in treating mental illness.  This is the kind of marketing approach to medicine and mental illnesses that I have seen and expect to see from managed care companies.  It usually happens right before they decide they will financially penalize you for NOT practicing Wellness activities.  In a plan where I was enrolled each employee had to pick a Wellness activity and a counselor would call at intervals and decide if you were in fact compliant with your activity.  Noncompliance meant higher premiums.  In the business world wellness can cost you.

Since SAMHSA is really not a managed care company, why are they using their marketing and political strategies?  The most likely explanation is the unparalleled success of managed care against physicians and other traditional health care organizations.  SAMHSA seems to have surprisingly little expertise in treating significant mental illnesses.  That puts them on par with most managed care companies in the US who if they are honest will flat out tell you that their job is to extract as much money as possible from subscribers who believe that they signed up for some kind of mental health or substance use benefit and send it somewhere else.  That theme is repeated time and time again in corporate America and nobody would fault an American corporation with than attitude.  With a government agency, especially the lead agency there should be a much higher standard than a corporate one.  What is the evidence for my statement?

Let me focus on a section that I lecture on at least a dozen times a year and have more than a passing familiarity with and that is the excessive use of opioids and the current opioid epidemic.  It is a subsection of one of the strategic initiatives for 2015-2018:


The administrators here take the incredibly naive (or cynical) view that what they say will somehow be done.  It is eerily similar to the original statements without proof or scientific backing that were made at the start of the opioid epidemic.  In those administrative guidelines the most compelling feature was that physicians were not doing a good job treating pain and therefore they had to be educated about it.  These guidelines were written by nobody less than the Joint Commission.  Now SAMHSA in their infinite wisdom  is deciding that physicians need more education about this.  Administrators like to play the education card.  They don't seem to understand that this problem, specifically the problem of overprescribing has little to do with education and more about how physicians are being manipulated to provide services that somebody who does not have a clear picture of medical care wants.  Let's remember the SAMHSA track record here.  From the FDA web site, the FDA claims that in 2009 it launched an initiative with SAMHSA "to help ensure the safe use of the opioid methadone."  From that press release (my emphasis added in the underlined section):

"The methadone safety campaign materials provide simple instructions on how to use the medication correctly to either manage pain or treat drug addiction," said H. Westley Clark, M.D., J.D., M.P.H., C.A.S., F.A.S.A.M., Director of SAMHSA’s Center for Substance Abuse Treatment. "Our goal for this training is to support the safe use of methadone by all patients and prescribing healthcare professionals."

The operative term is "all patients and prescribing health care professionals."  In other words SAMHSA was seeing this as an educational deficit.  The detailed program is still available online.  If only the health care professionals could be educated enough by an administrative body that knows more than they do, the epidemic of methadone related deaths from overdose would stop.  The problem occurred when the CDC looked at the epidemiology of single and multiple drug deaths involving opioids and found that the methadone related deaths occurred at much higher rates in both categories than other opioids.  Their recommendation stands in contrast to the SAMHSA educational initiative. From that document - my emphasis added in the underlined section:

  • Between 1999 and 2009, the rate of fatal overdoses involving methadone increased more than fivefold as its prescribed use for treatment of pain increased.
  • Methadone is involved in approximately one in three opioid-related overdose deaths. Its pharmacology makes it more difficult to use safely for pain than other opioid pain relievers.
  • Methadone is being prescribed inappropriately for acute injuries and on a long-term basis for common causes of chronic pain (e.g., back pain), for which opioid pain relievers are of unproven benefit.
  • Insurance formularies should not list methadone as a preferred drug for the treatment of chronic noncancer pain. Methadone should be reserved for use in selected circumstances (e.g., for cancer pain or palliative care), by prescribers with substantial experience in its use.

The CDC does not believe that the problem with the disproportionate deaths from methadone is an educational deficit.  They believe it is a problem inherent in the drug, clinical setting, and experience of the physician.  It should definitely not be prescribed by all physicians, even if those physicians are educated.   SAMHSA apparently still believes in the educational deficit.  As I have posted the associated regulatory problems includes the FDA and their continued approval of high dose opioid products against the advice of their scientific committees, and their plan to educate physicians to safely prescribe these products.  I am using this example to illustrate that SAMHSA's approach, educate the masses and they will accept wellness and their health will improve by practicing wellness is a pipe dream of extraordinary dimensions.  It does not work on a focal issue, why would it work on a population wide basis?

Paul Summergrad's take on the politicalization of wellness/recovery versus psychiatry/medicine was a very accurate statement.  Americans in general are intolerant of probability statements.  Blog discussions are a particularly intolerant environment.  I do not agree with his support of integrated or so-called collaborative care.  It is no surprise that SAMHSA supports and has a leadership role in this managed care strategy.  He stops short of pointing out that SAMHSA has nothing to offer patients with severe mental illnesses.  

Besides being basically a pro-business strategy, the SAMHSA initiative also takes the grandiose approach that there are no psychiatrists out there (I will let other mental health clinicians speak for themselves) who want to see the people they treat recover and lead meaningful and satisfying lives.  They make it  seem like their simple business objectives will be better at this goal than personalized treatment provided by a psychiatrist.   That may provide a rallying point for the detractors of psychiatry, especially when the APA chooses not to counter the insult, but it is not a concept based in reality.  There is nothing more important in the practice of medicine than how a patient does under a physician's care. 

I think it is time for SAMHSA to put up or shut up.  Even though they have probably stacked some of the outcome statistics in their favor ahead of time and some of the outcome measures are as vague as managed care company measures of excellence (both proven business strategies), let's see what happens.  And let's see if the Big Pharma critics are as skeptical of their outcome statistics as they are of a typical pharmaceutical industry funded clinical trial. 

So far they have a solid check minus on the opioid initiative.

George Dawson, MD, DFAPA

Monday, September 15, 2014

Will The Real Neuropsychiatrists Please Stand Up?

Recent dilemma - one of several people around the state who consult with me on tough cases called looking for a neuropsychiatrist.  He had called earlier and I advised him what he might discuss with the patient's primary care physicians that might be relevant.  I suggested a test that turned up positive and in and of itself could account for the subacute cognitive and behavioral changes being observed by many people who know the patient well.  I got a call back today requesting referral to a neuropsychiatrist and responded that I don't really know of any.  I consider myself to be a neuropsychiatrist but do not know of other psychiatrists who practice in the same way.   There is one neuropsychiatrist who practices at the state hospital and is restricted to seeing those inpatients.  There is one who sees primarily developmentally disabled persons with significant psychiatric comorbidity.  There are several who practice strictly geriatric psychiatry.  One of the purposes of this post is to see if there are any neuropsychiatrists in Minnesota.  My current employment situation precludes me from seeing any neuropsychiatry referrals.

Neuropsychiatry is a frequently used term that is the subject of books and papers.  Several prominent psychiatrists were identified as neuropsychiatrists.  I went back to an anniversary celebration for the University of Wisconsin Department of Psychiatry and learned that early on it was a department of neuropsychiatry.  It turns out that the Department of Neuropsychiatry was established in 1925 and in 1956 it was divided into separate departments of Psychiatry and Neurology.  One of the key questions is whether neuropsychiatry is an historical term or whether it has applications today.  The literature of the field would suggest that there is applicability with several texts using the term in their titles, but many don't even mention the word psychiatry.  As an example, a partial stack from my library:



A Google Search shows hits for Neuropsychiatry and basically flat during a time when Neuroscience has taken off.  Both of them are dwarfed by Psychoanalysis, but much of the psychoanalytical writing has nothing to do with psychiatry or medicine.






What does it mean to practice neuropsychiatry?  Neuropsychiatrists practice in a number of settings.  For years I ran a Geriatric Psychiatry and Memory Disorder Clinic.  Inpatient psychiatry in both acute care and long term hospitals can also be practice settings for neuropsychiatrists.  The critical factor in any setting is whether there are systems in place that allow for the comprehensive assessment and treatment of patients.   By comprehensive assessment,  I mean a physician who is interested and capable of finding out what is wrong with a person's brain.  In today's managed care world a patient could present with seizures, acute mental status changes, delirium, and acute psychiatric symptoms and find that they are treated for an acute problem and discharged in a few days - often without seeing a neurologist or a psychiatrist.  There may be no good explanations for what happened.  The discharge plan may be that the patient is supposed to follow up in an outpatient setting to get those answers.  That certainly is possible, but a significant number of people fall through the cracks.  There are also a significant number of people who never get an answer and a significant number who should never had been discharged in the first place.

Who are the people who might benefit from neuropsychiatric assessment?  Anyone with a complex behavioral disorder that has resulted from a neurological illness or injury.  That can include people with a previous severe psychiatric disability who have acquired the neurological illness.  It can also include people with congenital neurological illnesses or injuries.  One of the key questions early on in some of these processes is whether they are potentially reversible and what can be done in the interim.  Some of the best examples I can think of involve neuropsychiatrists who have remained available to these patients over time to provide ongoing consultation and treatment recommendations.  In some cases they have assumed care in order to prevent the patient from receiving unnecessary care form other treatment providers.  Aggression is a problem of interest in many people with neurological illness because it often leads to destabilization of housing options and results in a person being placed in very suboptimal housing.  Treatment can often reverse that trend or result in a trained and informed staff that can design non-medical interventions to reduce aggression.

What is a reasonable definition?  According to the American Neuropsychiatric Association neuropsychiatry is "the integrated study of psychiatric and neurologic disorders".   Their definition goes on to point out that specific training is not necessary, that there is a significant overlap with behavioral neurology and that neuropsychiatry can be practiced if one seeks "understanding of the neurological bases of psychiatric disorders, the psychiatric manifestations of neurological disorders, and/or the evaluation and care of persons with neurologically based behavioral disturbances."  That is both a reasonable definition and a central problem.  In clinical psychiatry for example, if a patient with bipolar disorder has a significant stroke what happens to their overall plan of care from a psychiatric perspective? In many if not most cases, the treatment for bipolar disorder is disrupted leading to a prolonged period of disability and destabilization.  Neuropsychiatrists and behavioral neurologists practice at the margins of clinical practice.  That is not predicated on the importance of the area, but the business aspects of medicine today.  If psychiatry and neurology departments are established around a specific encounter and code, frequent outliers are not easily tolerated.  Patients with either neuropsychiatric problems or problems in behavioral neurology can quickly become outliers due to the need to order and review larger volumes of tests, collect greater amounts of collateral information, and analyze separate problems.  In any managed clinic, the average visit is typically focused on one problem.  Neuropsychiatric patients often have associated communication, movement, cognitive and gross neurological problems.  Some of these problems may need to be addressed on an acute or semi-acute basis.

Where are they in the state?  Neuropsychiatrists are probably located in areas outside of typical clinics.  By typical clinics I mean those that are outside of the HMO and managed care sphere.   They can be identified as clinics that are managed by physicians rather than MBAs.  The three largest that come to mind are the Mayo Clinic, the Cleveland Clinic, and the Marshfield Clinic.  Apart from those clinics there are many free standing neurology and fewer free standing neuropsychiatric clinics.  Speciality designations in geriatric psychiatry or neurology, dementias, developmental disorders, and other conditions that overlap psychiatry and neurology are good signs.  There will also be psychiatrists in institutional and correctional settings with a lot of experience in treating difficult to treat neuropsychiatric problems.  There may be a way to commoditize this knowledge and get it out to a broader audience.  Since starting this blog I have pointed out the innovative pan in place thought the University of Wisconsin and the Wisconsin Alzheimer's Institute (WAI) network of clinics.  They have impressive coverage throughout the state and provide a model for how at least one aspect of neuropsychiatry can be made widely available through collaboration with an academic program.      

What should the profession be doing about it?  The American Psychiatric Association (APA) and just about every other medical professional organization has been captive to "cost effective" rhetoric.  IN psychiatry  that comes down to access to 20 minutes of "medication management" versus comprehensive assessment of a physician who knows the neurology and medicine and how it affects the brain.  The new hype about collaborative care takes the psychiatrist out of the loop entirely.  The WAI protocol specifies the time and resource commitment necessary to run a clinic that does neuropsychiatric assessments.  I have first hand experience with the cost effective argument because my clinic was shut down for that reason.  We adhered to the WAI protocol.

What the APA and other medical professional organizations seems to not get is that if you teach people competencies in training, it is basically a futile exercise unless they can translate that into a practice setting.  The WAI protocol provides evidence of the time and resource commitment necessary to support neuropsychiatrists.   It is time to take a stand and point out that a psychiatric assessment, especially if it has a neuropsychiatric  component takes more than a 5 minute checklist and treatment based on a score.  A closely related concept is that total time spent does not necessarily equate with the correct or a useful diagnosis.  I have assessed and treated people who have had 4 hours of neuropsychological testing and that did not result in a correct diagnosis.

If those changes occurred, I might be able to advise people who ask that there are more than two neuropsychiatrists in the state.

George Dawson, MD, DFAPA

1: Benjamin S, Travis MJ, Cooper JJ, Dickey CC, Reardon CL. Neuropsychiatry and neuroscience education of psychiatry trainees: attitudes and barriers. Acad Psychiatry. 2014 Apr;38(2):135-40. doi: 10.1007/s40596-014-0051-9. Epub 2014 Mar 19. PubMed PMID: 24643397.

Friday, September 12, 2014

A Molecular Basis for Gateway Drugs



The Gateway Drug hypothesis proposes that using a particular drug increases the likelihood that there will be a progressions to using other drugs of abuse.  The competing hypothesis is that there is a general predisposition to using more than one drug in people susceptible to addiction and that it does not depend on any sequence of exposures.  In this Shattuck Lecture in the New England Journal of Medicine, Eric and Denise Kandel examine the epidemiology and molecular biology of nicotine use and the development of addictions.  Most addiction treatment centers recognize the importance of nicotine cessation in improving abstinence rates from the primary drugs of choice.  Most of that depends on series of cases discharged from treatment centers.  The idea of nicotine also has importance because one of the approaches to nicotine cessation depends on nicotine substitution and it is important to know if that treatment intervention might lead to increased risk for ongoing substance use problems.  It also has implications for electronic cigarettes (e-cigarettes).  There is a general idea that any form of nicotine that does not involve exposure to combustible or chewed tobacco components is preferred because of all of the conditions associated with the physical and combustible products of tobacco.  If nicotine alone places one at risk for using another drug like cocaine, the risk/benefit decision will need to be reconsidered.

The authors briefly reviewed the epidemiology showing of all US adults who had ever used cocaine, the vast majority of them (87.9%) smoked cigarettes before using cocaine.  Only 3.5% used cocaine first.   The rate of cocaine dependence was highest (20.2%) among those who smoked cigarettes before using cocaine.  They proceed to use an animal model to examine the possible priming effects of nicotine and to possible elucidate the mechanism.  The animal models of addiction in mice included locomotor sensitization and  conditioned place preference.  In both of these models, micd primed with nicotine first and then treated with nicotine and cocaine showed the expected addicted response with heightened locomotor sensitization and place preference.  Mice primed with cocaine did not.

They proceed to look at the effect on synaptic plasticity and the model used was long term potentiation (LTP) in the nucleus accumbens (NAcc).   The  predominate neurons in the NAcc are medium spiny neurons (MSNs) and they are innervated by dopaminergic neurons projecting from the ventral tegmental area (VTA) and glutamatergic neurons from the prefrontal cortex and the amygdala.  Reducing excitatory (glutamatergic) input to the NAcc reduces inhibitory output to the VTA leading to more dopaminergic input to the NAcc or greater reward.  Repeated cocaine administration leads to reduced LTP in the excitatory synapses of the NAcc.  A single injection of cocaine in a mouse primed with 7 days of nicotine exposure leads to marked reduction in LTP.  Nicotine alone, or nicotine after cocaine had no effect on LTP.  Priming with nicotine causes a change in neuronal plasticity that increases cocaine associated reward.

The authors turned to known gene expression markers of addiction in the striatum specifically the expression of FosB.  They demonstrated that nicotine alone for seven days increased FosB expression and adding cocaine led to a further 25% expression.  The next step was to examine if nicotine alters the chromatin structure  at FosB promotor of the gene and they looked at the acetylation of histones H3 and H4 at the FosB promotor.  Nicotine alone increased the acetylation of both histones, cocaine alone increased the acetylation of H4 only.  They went on to demonstrate that the acetylation was widespread after nicotine exposure throughout the striatum.  Cocaine alone had no similar effect.  They went on to clarify that increase acetylation was due to inactivation of histone deacetylase activity (HDAC) and not activation of acetylases.  They carried out additional pharmacological studies to confirm that the hypoacetylated state (caused by nicotine) leads to depression of LTP associated with cocaine and that further it cannot be rapidly reversed.  The authors investigated if nicotine enhanced cocaine induced LTP in the amygdala and hippocampus and found that it did.

This fairly intensive research program and series of experiments allowed the authors to conclude that nicotine has a unidirectional priming effect and it works through an acetylation mechanism by affecting HDAC activity.  The mechanism explains what is seen in human populations at the epidemiological level and in mice at the experimental level.   That has obvious implications for treatment as well as drug development.  It  also points out that e-cigarettes are potentially as much of a potential gateway drug as combustible cigarettes.  In clinical practice it is also fairly common to see patients with addiction who are continuing to use nicotine substitutes (gum, lozenge, patch) long after they have stopped smoking.  If the mechanism elucidated by Kandel and Kandel is accurate it will be important to discuss the implications of continued nicotine exposure.

Kandel's work is always compelling because of his broad view of science and psychiatry.  He is as comfortable discussing psychoanalysis and Freud as he is talking about molecular biology.  In this case he combines views on epidemiology and molecular biology in a very compelling story and suggests it might be a broader model for how gateway drugs work.  As he is drawing his conclusions there is still room for the competing hypothesis and he makes this explicit.  His work is always a breath of fresh air compared to the current zeitgeist of political arguments about science and psychiatry often from people who know very little about either subject.  Go to the article at the link below and read this paper and compare it to his 1979 article Psychotherapy and the Single Synapse.  That covers at least 34 years of studying synaptic plasticity and it is a remarkable accomplishment.


George Dawson, MD, DFAPA


1: Kandel ER, Kandel DB. Shattuck Lecture. A molecular basis for nicotine as agateway drug. N Engl J Med. 2014 Sep 4;371(10):932-43. doi: 10.1056/NEJMsa1405092. PubMed PMID: 25184865. (free full text).

Supplementary 1:  Drawing depicts nicotine inhibiting HDAC leading to increased acetylation of histones per the above discussion.  CREB-1 = cyclic AMP response-element-binding protein; CBP = CREB-binding protein (acetylates histone H4);  PKA= protein kinase A; A=acetyl groups, P=phosphate groups; H2a, H2b, H3, H4 = histone proteins in chromatin; Pol II = RNA polymerase II (catalyzes synthesis of DNA to mRNA).