APA Misses On The Opioid Crisis - Several Times

The above infographic is courtesy of the CDC (see attribution for the direct link).  To those of us involved in treating addictions talking with many people who are addicted to opioids, getting them to see the problem, and helping them prevent accidental overdoses and death is an everyday occurrence.  The prescription opioid problem is widespread and has been a reality for the last 15 years even though it seems to have hit the news in about the last 5.  That probably coincides with heroin use starting to escalate.  The driving force for that has been economics.  Heroin is generally available in most areas for about a quarter the cost of diverted prescription painkillers.  In the past 5 years I have probably given about 50 lectures on the topic to physicians and graduate students and been actively involved in the clinical care of individuals with heroin addiction only or heroin addiction in addition to a number of other addictions.

When I got a post from the American Psychiatric Association (APA) on my Facebook feed last week it piqued my interest.  Part of what I teach is how failed policy is the root cause of the opioid epidemic and what physicians can do on an individual basis to correct the problem.  I was very interested to see what the APA had to say at a policy level.  Reading through the document that is really a blog post from the Medical Director the answer is "not much".  It appears that the APA has joined a Task Force of other professional organizations that includes that other great laggard the AMA.  They will be working to identify "best practices" and implementing them as soon as possible. Using Prescription Drug Monitoring Programs (PDMPs) is encouraged.  There will also be the focus on stigma.  Dr Levin states: "The APA maintains that substance use disorder is a medical condition that can be successfully treated, and we are actively advocating on behalf of the patients who are too often stigmatized by their community and disenfranchised by insurance carriers who fail to comply with mental health parity laws."

While there is no doubt that most people are biased against people with mental illness and addictions as well as their psychiatrists - I don't think that stigma has any traction in terms of increasing access to care or more importantly access to quality care.  I could argue that the APA support for the collaborative care initiative colludes with stigma-like biases.  That takes the form of "you don't have to see a psychiatrist - take this checklist instead."  I won't get into that today, only to say that I wonder how many people with heroin or opioid addiction are being seen in primary care clinics and being treated for anxiety, insomnia, or depression?  From what I see the numbers are significant.  But it is hard to fault primary care doctors because unless they are the prescribers of opioids, they may not realize that their patient has a problem with them.  There is also the issue of institutional stigma versus public stigma.  Public stigma or the type of stigma that everyday people have is more elastic and it usually depends on their experience with the problem.  If you live in a family where a member has a severe mental illness or addiction - you know that these problems are real, life-threatening, and you are ready to let people know that.  Institutional stigma is the type of stigma that governments and businesses can have, especially health care businesses.  They might grudgingly admit that there is some kind of problem largely because there is such a large secondary impact on medical and surgical services.  In some trauma centers over half of all admissions are primarily due to drug and alcohol problems.  At the same time,  institutional stigma is impervious to change.  It is codified in some texts on healthcare management and as noted in the APA blog post - not even amenable to change when new federal parity laws are implemented.  In terms of managing health care systems there is nothing like having a certain groups of disorders to shift resources away from in a pinch.  Mental illnesses and substance use disorders are that group.  The other considerations would include:

1.  Irrational policy initiatives:  There is no doubt that several policy initiatives to liberalize opioid prescribing were responsible for the start of this epidemic in or around the year 2000.  Making pain the "fifth vital sign", encouraging the use of opioids for chronic non-cancer pain, treating minor conditions with opioids, and a widespread policy initiative that encourage more aggressive treatment of pain even though specific measures were not know are among these initiatives.  I use the word irrational here to mean speculative initiatives that were not based on science.

2.  A serious misunderstanding of the current problem:  When all else fails blame physicians.  That is a highly effective political strategy that worked to consolidate control of the health care system under business and government.  To many of the politicians involved it flowed directly from their negative campaigning experiences.  In this case, the opioid problem is being framed at some level as a problem of inappropriate prescribing by physicians.  Some physicians are being subjected to criminal prosecution for deaths and complications that have resulted from opioid prescribing.  There are no references to the policy changes that occurred in the late 1990's that led to this change in physician prescribing behavior - the loss of gate keep functions in particular.

3.  A misunderstanding of the epidemiology of the problem: The upper decile of opioid prescribers (total number of prescriptions) account for 50-60% of all opioid prescriptions.  These prescribers are almost all family physicians, internal medicine specialists, and mid-level prescribers.  Available databases allow for rapid identification and intervention with these prescribers and that is where resources should be focused and not on all physicians across the board.  A mechanism for feedback on an individual physician's or physician extender's ranking in terms of their prescription of controlled substances is needed as well as individual access to that information.

4.  A serious misunderstanding for the overprescribing problem in general exists: As I have previously pointed out, opioids are one small group of medications that are overprescribed in the US.  Practically everyone who wants this problem to go away sees it as a cognitive problem or knowledge deficit.  If the physician involved just knew more they would not prescribe pain medications this way.  In fact, it is a much more complicated interpersonal, social and intrapsychic problem for physicians.  Until there is a widespread acknowledgement of this - all of the CME courses in the world on appropriate opioid prescribing will not change a thing.

5.  There is a widespread cultural problem:  Opioid hoarding in medicine cabinets across the country, neighbors sharing opioids and neighbors and family members discussing what is the best (translation best = most euphorigenic) is a major problem in the US.  Many politicians have agreed that America's "insatiable appetite for illegal drugs" fuels the international drug trafficking problem.  It also fuels the opioid epidemic.  There are very few initiatives focusing on cultural change.

6.  Misunderstanding the problems inherent in prescribing addictive drugs:  Most physicians are not aware of the unconscious and conscious elements that are activated in susceptible individuals when they take addictive drugs.  There are widespread misconceptions in this area that lead to the prescription of addictive drugs during active addiction,  not assessing the risk of prescribing addictive drugs to a person in recovery, and failing to assess some of the indirect signs of addiction in patients who deny that they have a problem with addiction.  There is also a belief among many physicians that if their goal is to help people that well intended prescribing will not lead to problems in the future.  

These are 6 areas that the APA could be focused on.  I don't think that you will see that analysis anywhere else.  I expect that "best practices" will fall disproportionately on the average physician and be a waste of time on their time and energy.  But it does fall back on the time honored political strategy of taking the heat off of the people who really failed and pretending it is a physician based problem.


George Dawson, MD, DFAPA


Attribution:

The infographic is from the CDC at this URL:  http://www.cdc.gov/vitalsigns/heroin/infographic.html#use

The CDC has done great work in this area and their site should be closely monitored for new data relevant to the problem.

Reductionism Is Not A Dirty Word...

A recent opinion piece in the New York Times, by George Makari, MD has me shaking my head.  The thesis was that a recent headline grabbing story (what's wrong with that criteria?) on the effects of comprehensive treatment of psychosis as opposed to treatment as usual surprised many and highlighted the problem with reductionism.  He bemoans the fact that the reaction to the story was one of surprise.  He doesn't specify who was surprised.  I certainly was not surprised.  I attended recent meeting and somebody in the audience asked Daniel Weinberger if he was surprised.  His response: "They spent $15 million dollars showing that good treatment is better than bad treatment."    He certainly was not surprised.  I have not heard about Eric Kandel's response, but based on his 1979 paper on plasticity and what happens in psychotherapy - I doubt that he would be surprised.  The exact population of who might be surprised by these findings seems poorly defined at this point in time but I doubt that it included any psychiatrists.

Speaking for myself, I will elaborate on why I was not be surprised.  At one point, I was the Medical Director of a community support program of a group of about 100 outpatients in the State of Wisconsin.  According to the state statutes, access to the program depended on diagnosis and degree of psychiatric disability.  You could only apply if you had a diagnosis of Bipolar Disorder, Major Depression, Schizophrenia,  or Borderline Personality Disorder had significant associated disability or were at high risk for hospitalization.  The clinical goal of the program was to reduce hospitalizations, maintain independent living, and facilitate employment.  The program was staffed by a psychologist, 2 social workers, three nurses and me.  When I arrived, one of the early dynamics was to frame problems in terms of medication needs.  That translated to increasing the dose of a medication (typically an antidepressant or antipsychotic) in crisis situations or other emotional crises.  The patients in the program had chronic problems and symptoms that did not necessarily respond to medication.  One of my first steps was to start to discuss problems and solutions with the patients.  I met with all of the patients and did supportive psychotherapy when possible.  We had team meetings every morning and problem solved around the needs of the patients in the community, how to solve any crises, and how to approach people in ways other than medications.  I tracked the total dose of antipsychotic medication and days of hospitalization as outcome measures.  At the end of three years, the days in hospital had gone down from about 14 days per person to less than 1, and the total dose of antipsychotic medication had gone down a total of 600 mg chlorpromazine equivalents.

My point is obviously that comprehensive care of patients with severe problems results in improved outcomes.  In this case lower doses of medications were used and the patients spent less time in the hospital and more time at home.  My orientation and ability to implement such a program was not an accident.  I was trained by Len Stein, MD at the University of Wisconsin.  Dr. Stein was a pioneer in the area defined as community psychiatry.  He was motivated by realizing that once people were in large state hospitals - it was very easy to warehouse them in overcrowded conditions.  Nobody seems to recognize it but overcrowding and suboptimal conditions were the state hospital equivalent of managed care rationing.  Once your state hospital is on the spreadsheet of a state bean counter with no accountability to patients or their families rationing and fewer and fewer resources are the order of the day.   In a community psychiatry seminar, Dr. Stein projected a slide of a gymnasium-sized room populated by male patients with hundreds of cots aligned edge to edge.  There was no room to walk between the cots.  That was his motivation for moving people out of these state facilities and into their own housing.  When I trained, there were three programs with independent living and quality of life as the primary goals and the staff involved in the programs was very good at it.  My effort just extended that skill set.  Contrary to the "surprising" results of the quoted study - I did the same thing back in 1986!

If it is true that we have known for 30 years that comprehensive care for psychiatric disorders trumps "treatment as usual" what is all of the rhetoric about?  Dr. Makari seems to want to make this into a mind-brain argument.  In other words, the biopsychosocial approach and the uncertain effect it has on the mind as opposed to a brain based approach that looks at specific mechanisms of action and seems to be focused on psychopharmacology.  He points out for example that the highlighted study would possible not qualify for current NIMH funding unless it looked at specific brain mechanisms.  He throws around the word "reductionism".  Anytime reductionistic or reductionism is used rhetorically in the same sentence with psychiatry it is pejorative.  My old psychoanalytic teacher would refer to anyone who talked about brain biology as a "dial twister".  The implication is that the reductionists are somewhat simple minded largely because they cannot accept the uncertainty of dealing with an organ that has poorly defined inputs and outputs.  Kind of a double whammy of rhetoric - you are a unsophisticated reductionist and you really can't see the big picture.  Are things really that simple?  Are these arguments accurate?  Are there problems with equating reductionism with "bad".

Of course there are major problems.  The first is the statement that inherent to the proposition that mental illness is a brain disease is "the implication that psychological and social events somehow are not also brain events."  This is a serious misreading of the definition of plasticity or experience dependent changes in the brain.  When I give my neurobiology of the brain lectures. I use Kandel's original New England Journal of Medicine article that discusses brain changes in a patient and a therapist conducting psychotherapy and how those changes are associated with brain plasticity.  I give further examples - weightlifting,  playing the violin, and how the typical stream of consciousness is profoundly altered by drug addiction.  There is no neuroscientist or biological psychiatrist I know who would suggest that psychological and social events are not brain events and there are numerous experimental paradigms that look specifically at how these events occur in the brains of animals.

The second aspect of Dr. Makari's argument has to do with reductionism.  His specific comment is:

"With luck, studies like Dr. Kane’s, which undermine these suppositions, will help move us away from such narrow thinking and embolden the substantial community within psychiatry that has never accepted such reductionism."

The suppositions in this case are that mental illness is a brain disease and that social or psychological events have no brain representation.  The argument is based on that false premise.  But further the use of the term "reductionism" is instructive here as previously noted.  By definition reductionism applies to many proposed etiologies of psychiatric disorders.  Those etiologies can be studied at a molecular level or at a higher level.  Schaffer (2) says that a model is reductive if it "employs standard biochemical and molecular entities to account for psychiatric symptoms and disorders".  Non-reductive models discuss "causal connections at higher levels of aggregation."  He illustrates these definitions by looking at Kendler's non-reductive account of major depression.  Kendler has used path analysis to look at clinical variables relevant to psychiatric disorders and although I do not have access to the one used in the book, here is a typical example.  The model looks at life stages, familial factors and psychological factors and all are higher levels of aggregation than molecular mechanisms.  At the reductive side of things he examines Harrison and Weinberger's proposed genetic susceptibility genes for schizophrenia.  At the time the book was written the author limited the discussion to 5 genes.  He also looked at the continuum of psychiatric genetic models ranging from basic and advanced genetic epidemiology being non-reductive, gene finding partially reductive, and molecular genetics fully reductive.  It seems perfectly logical to me that the study of brain biology proceeds in the same way that the biology of all living organisms proceeds.  The difference is that we are studying an infinitely more plastic organ with significant computational power.  There is clearly a lot of phenotypic heterogeneity that is unexplained in psychiatric diagnostic categories.  It is highly unlikely that refining diagnostic descriptors or applying clinical methods will lead to any significant change in the diagnostic or treatment process.  I don't understand the reluctance to go after more specific mechanisms or treatments.

The idea that a molecular or clinical focus in psychiatry is the problem with psychiatric services is also misleading.  As I hoped to point out by my mental health center example, psychiatrists know all about comprehensive care but they are rarely able to provide it.  They have known about how to provide it for decades.  State asylums became overcrowded and not therapeutic due to the financial management of the system by state governments.  The bean counters have moved out of the asylum and they are now integrated at every level in the health care system.  They all have a very strong bias against the comprehensive treatment of mental illness.  They insist that patients with severe psychiatric problems do not get comprehensive evaluations, that they are discharged before they have been adequately treated, and that any associated addictions are poorly treated.  They do not have the same biases against people hospitalized for medical or surgical illnesses.  They have in effect, moved the poorly run, overcrowded asylum model into the general health care system.  Any comprehensive care for severe mental disorders in such a system is an advertising phenomenon rather than reality.

The reductionism argument is good for New York Times opinion pieces.  It may sell a few more papers or get a few more clicks online.  Unfortunately it perpetuates an old pattern of blaming people and psychiatrists in particular for the shortcomings of a non-system of mental health care in this country that is set up to favor large health care businesses.  You can blame psychiatrists all you want for that - but until people realize that the real problems are the product of business and politics - and not the scientific interests of psychiatrists - nothing will change.


George Dawson, MD, DFAPA

References:

1.   George Makari.  Psychiatry’s Mind-Brain Problem.  New York Times.  November 11, 2015.

2.  Scaffner KF.  Etiological Models in Psychiatry - Reductive and Nonreductive Approaches in  Philosophical Issues in Psychiatry.  Kenneth Kendler, Josef Parnas (Eds), The Johns Hopkins University Press, Baltimore, 2008:  pp 48-98.

Attribution:

Image is Microscope 1 by Bill3t Hughes on Flickr.  Reposted as noncommercial via Creative Commons License on 11/14/2015.  The original work is not modified.

The Myth of "Rescue" Medications

First off a clarification.  I am talking about the specific case where a short acting medication is added to a long acting form of the same medication and not "as needed" medication in order to determine the correct daily dosage.   In my line of work it occurs in two situations, long acting stimulants and their immediate release versions and long acting opioids and their immediate release versions.  I will illustrate that these practices are driven by myths about the medication rather than pharmacokinetics.  There is always the additional consideration about addiction lurking in the background, but the conscious and unconscious determinants of addiction frequently depend on the myths that I will be discussing about medication effects.

The example that I will use here is Concerta (long acting methylphenidate) compared with immediate release methylphenidate.  The graph from the package insert above shows the plasma concentration from a single 18 mg dose of Concerta and three successive 5 mg doses of immediate release methylphenidate.  As noted in the comparison of the curves and additional pharmacokinetic parameters the curve associated with three successive doses of immediate release methylphenidate is nearly identically replicated by a single dose of Concerta.

What is happening when additional doses of a immediate release methylphenidate are prescribed to a person who is already taking Concerta?  I  have seen this happen with sustained release stimulants and sustained release opioids.  I have seen it happen as a single dose of the immediate release preparation or multiple doses over the course of the day.  The patient is usually advised that this is a "rescue" medication that they should take if needed.  The first possibility is that the dose of sustained release medication has not been optimized and a higher dose of the sustained release medication needs to be given.  That is usually not the case.  The most frequent reason for taking the rescue medication is that the patient believes they are experiencing breakthrough symptoms and for a moment they need a higher dose of a medication.  There are serious problems with that concept.  As can be seen from the curves comparing Concerta and methylphenidate it does not make pharmacokinetic sense.  Any additional dose of immediate release methylphenidate on top of Concerta would greatly increase the expected plasma concentration at that point.

The main problem is that both ADHD and non-cancer pain are chronic conditions.  By definition they do not respond well to medications and they will not resolve typically with any amount of the medication.  Many people who take stimulants for ADHD assume that the human brain can be fine tuned with a medication.  There is also a widespread myth that they are cognitive performance enhancing drugs.  The real effects of stimulants are modest at best and there is no good research evidence to support a cognitive enhancing effect.  A similar bias exists for the use of opioids for chronic non-cancer pain.  The person believes that "If I take enough of this medication - my pain will be gone."  Study after study of opioids for chronic non-cancer pain shows that pain relief with opioids is modest at best, with results very similar to what would be expected with non-opioid medications like gabapentin and antidepressants.

There are secondary problems with believing a medication will produce perfect cognition or perfect pain relief.  The first is a tendency to see any medication with such powerful abilities as being able to solve a number of problems that are not the primary indication for the medication.  As an example, with a stimulant - if this medication has such a profound effect on my cognition maybe it can help with with other difficult problems like excessive appetite and weight problems or feeling like I don't have enough energy at certain times during the day.  With the opioid the  thought typically is that it can be used for mental pain as well as physical pain and it is used to treat anxiety, depression, and insomnia.  Whenever a medication is not used strictly for the prescribed indication there is a risk that it will be used for "what ails you."  The danger is dose escalation and addiction.  There is also the risk of attributing too much of an effect to the medication when it does not appear to be doing much.  A person may start to believe that they can't function without the medication but a detailed review of their target symptoms and ability to function shows that there has been a negligible effect.  And finally there is the danger of taking a medication that may produce euphoria, increased energy, and create a sense of well being and not realizing that at some point that is the only reason the medication is being taken.  I have had many people tell me that the medicine did nothing for their pain or cognition but that they kept getting refills because they "liked taking it."

There is what I call the Talisman effect, but probably to a lesser extent than with benzodiazepines.  Many people develop the idea that they are taking a medication that is much more effective than it really is and therefore they have to take it with them wherever they go.  They are conferring what are essentially magical properties to the medication and at some level thinking that they are unable to function in life without it.  They get anxious if they think about not having it or running out.  This not only causes a lot of unnecessary anxiety, but it also prevents the person from using other psychological or conditioning techniques that may work as well or much better than the medication.

These are some of the problems with the idea of taking a rescue medication if you are already on a long-acting form of the medicine.  Physicians in general do not do a good job of explaining these potential problems or even the basic problem of taking a medication that causes euphoria or reinforces its own use.  A more widespread recognition of these problems would go a long way toward curbing overprescription, overuse, and addiction to these medications.    

        

George Dawson, MD, DFAPA

References:

1.  Graph of plasma concentrations of Concerta and methylphenidate is from the package insert on FDA web site at:  http://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021121s014lbl.pdf

Minnesota's Mental Health Crisis - The Logical Conclusion of 30 years of Rationing

It is clear to me that Minnesota doesn't want to hear from any psychiatrists.  Psychiatrists in this state have been complaining about managed care, prior authorization of medications and hospital treatment, managed care medical necessity criteria and mismanagement of the state mental health systems by the State of Minnesota for as long as I have worked here and that is now 27 years.  All of that work at various levels has basically been ignored by the politicians and responsible bureaucrats in this state who are quite happy to address the problems of severe mental illness by progressive rationing at all levels.  That is their only response.  This march toward the managed care approach to mental health has been inexorable and has resulted in major problems with access and quality of care.

I have been writing in various formats about the problem of mismanaging acute care beds in Minnesota for at least 15 years.  What do I mean about mismanagement?  The problem started in the late 1980s when the state of Minnesota gave carte blanche to one of the local insurance companies to start denying alcohol and drug related admissions to inpatient psychiatric units.  Anyone with a sparse knowledge of addiction knows that about 70% of people with addictions have significant psychiatric morbidity and many are at much higher risk of aggression or suicide if intoxicated.  That was not enough of a deterrent to prevent this insurance company (with full collusion of the State) to start denying psychiatric admissions to anyone with an addiction or eventually to anyone with acute alcohol or drug intoxication.  The effects of those denials filtered through the entire acute care system and eventually intoxicated people were held in emergency departments until they were less intoxicated, sent to county detox units where they got no medical or psychiatric care, sent to jail, or discharged to the street.  In some cases people were discharged to the street with a bottle of benzodiazepines and expected to manage their own detoxification.  Many of those patients take the entire bottle the first day.  None of those pathways leads to sobriety or treatment of associated medical and psychiatric conditions and it is not an acceptable level of medical care.

Treatment of mental health conditions has fared no better.  At some point the vague concept of "dangerousness" became the only reason that a person with a severe mental illness could be hospitalized.  In some cases it was a "dangerous enough" standard.  In other words if you happened to have chronic suicidal ideation or self injurious behavior, the gatekeeper (who is usually an emergency department (ED) social worker) has to decide if you are dangerous enough to admit.  That combined with bed availability, other persons needing admission, the availability of psychiatrists to cover the beds, any associated intoxication states, and even the likelihood that a probate court would hold or commit the person led to a gauntlet that even outpatient psychiatrists could not negotiate.  Outpatient psychiatrists from the same clinic could not admit their outpatients to hospitals run by their colleagues.  That led to more and more psychiatrists advising patients and their families to just go the the ED and "let them sort it out."  The ED provides no psychiatric care - only a triage decision on admissions.  This quasi-system of care results in a large circulating pool of people who are never stable, at risk for incarceration or victimization, and who never receive standard care for their problems.

The unstated toll that this chaotic system takes is on the psychiatrists and nursing staff who work in it.  They are frequently the first ones to be blamed for a lack of beds and timely discharges.  A completely unrealistic bed situation becomes a psychiatrist not discharging people soon enough.  Psychiatrists and nursing staff end up treating the consequences of patients being held too long in hospitals that are not equipped to be long term care hospitals.  Patients and family members can become frustrated or irate as a result of this situation and the only people to blame are not the people who caused the problem in the first place.

The quasi-system of mental health care was well described by Karl Olsen, a Hennepin County Crisis Intervention nurse in the Star Tribune about three weeks ago.  He describes the backlog of patients in the ED and crisis centers due to a lack of psychiatric beds.  He describes the risk to both the patients and staff in this setting as well as the impossibility of trying to provide care that can only occur in a hospital setting in an emergency department or crisis unit.  But most of all, he describes the ongoing active discrimination against people with severe mental illnesses by insurance companies and the state.  A more recent article is written by a reporter interviewing a state bureaucrat who reports that the situation is "the worst I have seen it in 20 years."  How can representatives of the State get away with these remarks when the State of Minnesota is largely responsible for the problem?  The article describes the lack of beds in State hospital facilities as being the problem and the State has made no secret of the fact that they are closing down State Hospital facilities and until very recently planned to close the last facility.  This article goes on to conclude:

"Hennepin County Sheriff Rich Stanek was in Washington, D.C., Thursday, helping brief members of Congress about mental health issues and seeking additional funding for treatment beds in a state that has the 50th lowest rate of mental health beds for its population..."

It is truly a sad state of affairs when a county sheriff is advocating for treatment of the mentally ill in Congress.  On the other hand it is also a direct result of the opinions of psychiatrists being actively ignored in this state for decades.

We have seen the bottom of the managed care rabbit hole - and it is called Minnesota.  We take the prize with the lowest rate of psychiatric beds in the US.  There are only two groups of people in this State with any credibility when it comes to critiquing this failed system of care - psychiatrists and psychiatric nurses.  There is no politician or bureaucrat interested in proposed solutions - they are directly responsible for the 30 years of rationing that led to this problem.   One of the retorts by state officials has been: "What's your solution?".  It is time to acknowledge that this is little more than political rhetoric.  They have ignored the solutions including many that have been proposed right here on this blog.

Until the psychiatrists and psychiatric nurses are heard - expect continued deterioration in the treatment of mental disorders that we have witnessed here over the past 30 years.


George Dawson, MD, DFAPA



References:

Jeremy Olsen.  Shortage of state psychiatric beds leaves local hospitals jammed.  Star Tribune. November 2, 2015.

Karl Olsen.  Minnesota's mental health system is in crisis.  Star Tribune.  October 16, 2015.


Supplementary:

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.

UW 3rd Annual Update - Treatment Resistant Depression

There were two presentations relevant to depression that were given at the UW conference this year.  The first was from Karen Dineen Wagner, MD, PhD from the University of Texas Medical Branch in Galveston, Texas.  Her message was a mix of the old and the new.  The old is the state of pharmacology of depressed children seems to have changed very little over the past 20 years.  This seem largely due to the fact that there have been few successful antidepressant trials in children.  This has led to the state where there are only two FDA approved medications fluoxetine and escitalopram based on a total of 4 clinical trials.  She  showed an additional 14 clinical trials of typical antidepressants including 3 that were positive for citalopram and sertraline but an additional negative study for the FDA approved medication escitalopram.  The difficulty in many of these trials is a high placebo response rate in the trials (40% greater than in adult clinical trials).  She recommended an informed consent approach explaining to the parents any time an off label approach was being used and the rationale for using any medication based approach.  She also recommended starting with the FDA approved medications for pediatric depression.

Her suggested approach to depression in children and adolescents is to start out with an FDA approved SSRI plus cognitive behavior therapy (CBT).  This is the most evidence based approach with the evidence rapidly disappearing at subsequent levels where the usual augmentation and substitution steps that are typically used in adults were suggested.  The Treatment for Adolescents with Depression (TADS) study was presented with the recovery rates for fluoxetine, fluoxetine + CBT, and CBT alone at 12, 18, and 36 weeks were presented.  The fluoxetine + CBT arm had superior results at 12 and 18 weeks but at 36 weeks the recovery rates were similar at 86% versus 81%.  Those are good results for any antidepressant trial and the placebo response rate in this study was more similar to the adult placebo response rate.  The results of this study were presented as a rationale for using antidepressants in adolescents with severe depression and/or suicidal ideation since the response rate for fluoxetine + CBT were faster than fluoxetine or CBT alone at 12 and 18 weeks and essentially the same at 18 and 36 weeks.

The issue of strategies for addressing SSRI resistant depression were presented in the form of a previous trial where 334 adolescents with SSRI treatment failures were randomized to a different SSRI or venlafaxine or SSRI + CBT or venlafaxine + CBT.  The trial done by Brent, et al showed that there was no difference in response rates switching to another SSRI or venlafaxine but switching antidepressants and adding CBT produced superior results.  Sides effects were greater for the venlafaxine arm with a slight increase in diastolic blood pressure and heart rate and a four fold increase in skin rashes - a complication that I have rarely seen in adults.  The overall impression was that CBT was the most effective intervention for adolescent depression but I am sure that most psychiatrists in the crowd were left wondering: "If I can't find CBT therapists for my adult patients with depression - what are the odds I can find them for my adolescent patients?  To me that has always been the critical shortage in psychiatry - not the number of people who can prescribe medications.

Others trials of medical interventions (omega-3 fatty acids, ECT, TMS, bright light therapy), psychotherapies (Interpersonal Therapy(IPT), family based IPT), and exercise were sparse.  Computer-based CBT has always been an underutilized modality and it showed that there were similar response rates between treatment-as-usual and an interactive fantasy based CBT called SPARX (Smart, Positive, Active, Realistic, X-factor thoughts).  In the game the child chooses an avatar and the goal is to restore balance in a fantasy world dominated by GNATS (Gloomy Negative Automatic Thoughts).  The SPARX game is available free online to residents of New Zealand.  New Zealand and Australia have been pioneers in the area of online CBT.  To find resources just Google "SPARX virtual therapy for depression".

Paul Holtzheimer, MD provided the adult perspective in the topic Management of Treatment Resistant Depression in Adults.  He made the epidemiological point that treatment resistant depression (TRD) is present in 10-33% of patients with major depressive disorder and in the U.S. that is about 1-3% of the population.  He had a fairly comprehensive agenda covering pharmacotherapy and augmentation strategies, electroconvulsive therapy, more recent non-invasive electromagnetic therapies and deep brain stimulation.  There was nothing new on the medication front.  After reviewing the basic medication groups, he suggested that the newest antidepressants offered no advantage over earlier medication.  He suggested that monoamine oxidase inhibitors (MAOIs) were being underutilized as a treatment for depression unresponsive to standard agents.  In the moderated discussion Ned Kalin, MD - the head of the department of psychiatry at the University of Wisconsin agreed.  The speaker said that he typically used phenelzine and tranylcypromine.  I personally have not prescribed either of these agents in some time.  I recall using them in situations where the person has treatment resistant depression and did not have any responders.  In those situations, response rates tend to be low anyway.  The other problem is that you have to think that your chronically depressed patient is going to be motivated and cognitively intact enough to adhere to the necessary diet, report what could be significant side effects and not try to kill themselves with the medication.  During the discussion there was a report of one patient who decided to eat high tyramine content food (prohibited on this diet due to a the risk of a hypertensive reaction) - have a stroke and die.  The patient in this case did have a stroke but did not die.  I personally know of situations where strokes have occurred, so this strategy is not without risk.

The augmentation strategies discussed were right out of STAR*D with the exception of using atypical antipsychotics with antidepressants.  Dr. Holtzheimer said that this was probably the most common augmentation strategy and the risks were discussed.  He and Dr. Kalin were advocates of augmentation with lithium and triiodothyronine (T3).  There were three slides on STAR*D showing cumulative remission and remission rates across all levels of care.  Those rates were 33% with initial monotherapy and 66% after 4 treatments and as expected less remission rates at each level of treatment change.  Dr. Holtzheimer made the point that the current rates of remission with medication and psychotherapy have really not changed since the 1950s and that makes electroconvulsive therapy (ECT) the most effective antidepressant treatment with a 50-75% remission rates and a >50% relapse rate in the first 6 months.  He touched on novel pharmacological agents categorized by neurotransmitter, neuroendocrine, or immunological systems.  He did not say much about ketamine (there is an intranasal preparation in clinical trials right now) but did mention that there is a IL-6 (cytokine) antibody trial going on right now.

He moved on to talk about more invasive therapies.  He presented a graphic that was a drawing by Papez.  To anyone trained in neuroanatomy around the time I was in medical school, many anatomy professors would present a saggital section of the brain and refer to the limbic structures as the Papez circuit.  At first I thought the drawing had a surprising amount of detail for a 1937 publication but then I went to the original article online (AMA web site) and found that the original drawing was not used.  The 1937 drawing had the surface anatomy correct but no tracts.  Papez mentions the amygdala three times in the last few paragraphs of his article but does not label it in the drawing.  Dr. Holtzheimer used this slide as a prelude to an article by Mayberg (3) providing a rational for deep brain stimulation as treatment for depression.  I plan to come up with a separate post in this technology based on several sources but right now there are a number of centers looking a deep brain stimulation for depression and addiction.  Dr. Holtzheimer briefly commented on transmagnetic stimulation (TMS).  There are apparently 4 FDA approved devices, use is expanding and insurance reimbursement is expanding.  He said it was 50% effective for treatment resistant depression.  I am highly skeptical of that number based on the people I see, but I also realize that I am seeing a highly treatment resistant with multiple comorbidities.  Seizure risk was listed as the most significant side effect.

Vagus nerve stimulation (VNS) has been around for about a decade.  I have seen a few of these patients and never referred anyone for placement of this device.  There is limited third part reimbursement and in my opinion waning enthusiasm for this technology.  The last time I interviewed a person with VNS, their speech quality changed every time the stimulator was active.  That is a significant side effect and I don't know if that has been addressed with current technology.   Transcranial direct current stimulation (tDCS), transcutaneous vagus nerve stimulation, and cranial electrical stimulation were all listed as having limited data.

Deep brain stimulation (DBS) was clearly the main focus of Dr. Holtzheimer's presentation.  The first article suggesting that it may be effective for obsessive compulsive disorder (OCD) was in the Lancet in 1999.  Based on that research DBS of the anterior internal capsule is an FDA approved indication for DBS.  An open label study suggested that it may also be effective for TRD and there were no adverse effects or neuropsychological effects.  Three additional pilot studies of DBS to the nucleus accumbens suggested that it may be useful for TRD and features of TRD like anxiety and anhedonia.  Since then there have been two randomized controlled trials of DBS to the ventral striatum subcallosal cingulate gyrus (SCC).  The first study (ventral striatum) was negative and the second (SCC) was stopped after a futility analysis.

The overall conclusion had to be that TRD was still a common and disabling condition.  The mainstays of treatment at this point are still the medications and ECT that we have had throughout my career.  My experience is that I can help most people get well, but there are significant obstacles even to standard care.  Every lecturer here emphasized the utility of cognitive behavioral therapy.  Like most psychiatrists, I can do cognitive behavioral therapy but by myself I can't meet the demand.  The people responsible for mental health policy and insurance standards certainly do not want to fund the recommended research courses of CBT for chronic depression.  There is no distinction for TRD versus non-TRD depression and no differential resource allocation.  That leaves most patients with TRD and non-TRD depression looking for "prescribers" who can see them for 10-30 minute appointments to get advice on how to recover and try various prescriptions.  None of the available care matches what top researchers recommend in these CME seminars, in articles, or in books.

We could do a lot better trying to live up to that standard while additional diagnostic and treatment strategies are developed.          


George Dawson, MD, DFAPA

References:

1:  David Brent Adolescent depression references  

2:  Papez JW. A proposed mechanism of emotion. 1937. J Neuropsychiatry ClinNeurosci. 1995          Winter;7(1):103-12. PubMed PMID: 7711480.

3: Mayberg HS. Targeted electrode-based modulation of neural circuits for depression. J Clin Invest. 2009 Apr;119(4):717-25. doi: 10.1172/JCI38454. Review. PubMed PMID: 19339763

Should Science, Engineering and Math Majors Go In To Psychiatry?

I got an e-mail from a young electrical engineer the other day who was interested in psychiatry and asked me about some ideas he had to increase his exposure to the process of talking with patients.  He was interested in some experience with this before considering a change to medical school and psychiatry.  As I thought about it today, it brought back some memories about how science and math majors have been discriminated against at times in the medical school admissions process.  Back in the day when I was initially considering an application to medical schools, there was a General Knowledge section on the MCAT - (Medical College Admissions Test).  It was there purportedly to select people who were "well-rounded" and not just science majors with their shoulder to the wheel studying math and science.  Well rounded seemed to mean liberal arts majors and people with a broad exposure to art galleries, museums, theatre and culture in general.

There were a couple of things wrong with that theory.  First of all, it biased the test toward anyone who lived in a major city.  If you were a hayseed like me, you made a school trip to the Guthrie Theatre in Minneapolis exactly once in your high school career.   For everything else - you better be paying close attention to what happened in your English literature class.  Not a very dynamic approach to learning.  Contrast that experience with a friend of mine who is a New York born and raised Internist.  He had very broad experience with all forms of art including opera and ballet before high school and is one of the most brilliant people I have ever met when it comes to discussing and critiquing art of all forms.  All of that most likely originating in a childhood and adolescence steeped in the artistic milieu of New York City.  I know he didn't learn it in medical school.  Who do you think would do better on the old General Knowledge test?

The second problem is the general assumption that people involved in the humanities are more likely to be interested in people and take a humanistic approach to medicine.  There seems to be a bit of a loose connection there between temperament, personality and your intellectual pursuits.  People in the hard sciences must be rigid, lack warmth, be oblivious to the human condition, and lack empathy - right?  I have never found any solid evidence to support this.  I will concede that Communications majors do an outstanding job at weddings.  I recall going to a wedding where I knew the groom since he was an infant.  When he grabbed the microphone and launched into 30 minute impromptu act, I asked him where that came from.  His answer: "Communications major."  Apart from that, I have asked many good psychiatrists what their major was as an undergrad and a surprising number were Chemistry majors.  Those chemistry majors had no defects at all as physicians or psychiatrists.   They did as well as anyone else and I was glad that they were in the field.

As far as I can tell, the previous bias against science majors getting into medical school did not have a rational basis.  I can't be certain about whether or not it exists today but I can be sure that administrators keep manipulating the entrance exam.  In this commentary from a couple of years ago I point out that the stated goals of aspiring to think like a scientist is probably very congruent with being a senior level science major.  But I don't think that will translate to an admissions bias in favor of science majors.

Are there reasons to encourage engineering, math and science majors to go into medicine and psychiatry?  I think that there most definitely are.  At the highest levels, the technical aspects of brain science are exploding and future physicians and psychiatrists with a grounding in scientific thought and information science will be able to make the best use of it clinically and at the research level.  All of medicine is currently in the throes of very crude clinical trials that are often limited by a lack of specificity.  Most medications prescribed have limited efficacy and significant side effects.  That means just from the medical side, physicians in the forseeable future will be managing these medications and their side effects.   I think that a few dimensional comparisons across medicine and science and engineering may be useful:

1.  Economics - physicians are currently overworked and much of that work has little to do with patient care.  Practically all of the people managing physicians are right out of a Dilbert cartoon.  Most of medicine has been reduced to a rapid prescribing paradigm and businesses are recruiting non-physicians to do it.  That has already led to a reduction in the quality of care in psychiatry largely by eliminating psychotherapy, time spent with individual patients, and systems considerations of care.   Engineering in particular may be a more financially sound career with the opportunity to escape the fate of Dilbert.  Economics are not the only consideration.  I recently encountered a young petroleum engineer involved in oil exploration who was very successful and decided to go into medicine.  When I asked her about her motivation she said she wanted to work with and help people - even if it meant a significant hit to her salary and autonomy.

2.  Intellectual Satisfaction - scientific endeavors especially at the business level produce clear measurable results and the process frequently incorporates the theory that you learned along the way if you are an engineer.  Medicine and psychiatry are much more diffuse.  There are administrators and politicians ordering you around under the mantle of science who clearly know nothing about it.  You may find colleagues that are really not interested in the cerebral aspects of the field only the practical.  In medicine and psychiatry that can be stultifying when you realize that this involves a series of political arguments about conflict of interest and drug trials.

3.  Conflict of Interest -  Medicine and psychiatry have been under attack for some time by people who believe that there should be no contact with private industry, at least at the level of reimbursement for work being done.  All payments from private industry need to be reported in a national database and needless to say that discourages physicians from working with with the pharmaceutical or medical device industry.  This is a significant difference with engineering. As an  example, I contacted the IEEE and asked them about their policy on standards and was told that they encourage the participation of industry in the discussion of standards because of the expertise distributed within the industry and the need for those active discussions.  Medicine and psychiatry, largely due to the questionable theory that the industry will affect treatment decisions has embarked on a period of isolation from medical industries that may be alien to technical fields - especially to engineers.

4.  Politics - We are in a 30 year period of unprecedented discrimination against physicians by state and federal governments.  Like most American politics the implicit goal seems to have been to bring all physicians under the management of companies that are proxies for governments and on the face of it that strategy has been highly successful.  Practically all physicians are employees of large health care companies and supervised by people who know practically nothing about the work they do, but who are quite content to tell them how to do it.  Many of these policies, like recertification have a significant impact on physicians and their families.  They are not conducive to the idyllic balanced lifestyle.

5.  Subjectivity/Uncertainty - There is a high degree of subjectivity in medicine and in many circles that is considered a dirty word.  Most non-physicians fail to see the importance of subjectivity and how it relates to information transfer in biological systems.  The least creative try to pretend that it doesn't exist and they try to reduce everything to a 10 point scale.  They mistake these "scales" for objectivity and some sort of measurement.  They don't really understand what scientific measurement is.   They base entire systems of care on these failed measurement systems.  They can't be reasoned with and there has been a large proliferation of measurements that are quasi-scientific at best but that are used to assess physicians and processes.  Frequently meaningless data is collected and used to make decisions about care and how systems of care operate.  Physicians in these settings with a knowledge of science and measurement can be very frustrated.

6.  People - I have posts about the interpersonal dimension of treating people as a psychiatrist.  It is more rigorous than the interpersonal landscape of other physicians.  Psychiatrists treat a broad spectrum of problems and in some cases there are significant conflicts with the people you are trying to help that are based on an underlying mental illness.  Some of these conflicts affect some physicians more than others.  You may already be able to tolerate interpersonal conflicts better than your peers and that may make psychiatry easier for you.  Psychiatrists are also unique in that they are the only medical speciality that has groups of people who dislike them and routinely disparage them whenever they have the chance.  Being able to tolerate that will also make it easier for you to go into psychiatry.

These are some of the issues to consider if you are thinking about switching careers and going into medicine or psychiatry.   Medicine and psychiatry are not sciences - but we need scientists, engineers, and mathematicians.  They make good doctors and I am hoping that they can help medicine move out of the morass of political regulation and business theories and back toward the light.  At the same time, it is only fair to consider that in engineering it may be more possible to find a better work environment, a better lifestyle, more intellectual stimulation and better reimbursement.

That's about all I can think of tonight.  If you are a science or engineering student with additional questions - please feel free to post here and I will try to answer them about any specifics.  Please see the disclaimer below.



   George Dawson, MD, DFAPA          


Supplementary 1:   The e-mail I received suggested that I was an electrical engineer.  I am not an electrical engineer.  My major was biology and chemistry, but I am  member of the IEEE largely though my work with a number of electrical engineers on electroencephalgraphy.  I have been an IEEE member for 18 years.

University of Wisconsin 3rd Annual Update

I just finished the 3rd Annual Update and Advances in Psychiatry at the University of Wisconsin in Madison Wisconsin.  It is familiar turf to me because that is where I finished psychiatric residency training.  I was impressed with the first two updates and have covered my experience at the 1st Annual and 2nd Annual Updates on this blog in the past.  During the introductory comments, the Department Chair Ned Kalin, MD paid tribute to John Greist, MD and James "Jeff" Jefferson, MD who ran the conference for 37 years before it was taken over by the Department of Psychiatry.

The absolute high point of day one was a discussion of schizophrenia by Daniel Weinberger, MD.  I had seen him speak before.  In talking with Dr. Kalin about the conference Dr. Weinberger gave a more research oriented talk the day before in the department that was focused on more science and neuroscience that I wish I had seen, but the lecture he gave to clinicians at this conference was outstanding.  From the introduction Dr. Weinberger had apparently left the NIMH and is now working as Director and CEO and  for the Lieber Institute for Brain Development.   They have quite a unique website and faculty.  The title of his discussion was Neurobiology of psychosis in the era of genetic medicine and he offered some unique perspectives that I doubt are available in many places.  It was useful to see a focus on schizophrenia in a conference of this nature and a focus on how at least some of the cutting edge research is looking at therapeutic modalities that are unique rather than the usual isomeric approach to drug discovery.  It was also refreshing to hear that there is optimism out there rather than the usual doom and gloom about the the "pipeline" from Big Pharma is running dry and there will be limited options for the future.

The Weinberger lecture had an interesting introduction that focused on brain imaging studies in psychiatric disorders.  It was well done, well argued, and based on his American J Psychiatry article that was published earlier this year (2).  He points out that while brain imaging has been the "centerpiece" of neuropsychiatric research that it is still fraught with technical difficulties.  In many of the articles that seem to make the lay press there is almost nothing that is not associated with brain changes.  He showed examples attempting to correlate viewing pornography with the frontostriatal network, increased gray matter volume secondary to lithium use, and other common artifacts and he concludes that most illness associated imaging findings are likely epiphenomenal.  To anyone trained as a chemist in their undergrad major who has experience with nuclear magnetic resonance (NMR) scanning of organic molecules a lot of this comes as no surprise.  To anyone used to reading decades of similar research (like quantitative EEG) and realizing that the pilot studies never panned out even after some were published in very prestigious journals this should also not come as a surprise.  Weinberger offered the technical explanations for why these issues occur and also some studies that seemed to be sound.

The bulk of his lecture was dedicated to the genetics of schizophrenia.  The opening slide not only contained a lot of information it was a tutorial in how to present information in PowerPoint format.  It was titled "The emerging genetics of schizophrenia".  In the upper left corner was a graphic from Gottesman's work with 11 bar graphs above the same axis showing risk for schizophrenia based on relationship to the index case.   Right below that was a table of Exome Sequencing: Rare Variants showing rare structural variants in schizophrenia with the title of a report to the right.  In the upper right hand corner was a Manhattan plot of 108 GWAS loci on all human chromosomes and the reference to the report in Nature.  It was a beautiful slide in terms of presentation and information content.

He went on to discuss genome-wide association studies (GWAS) and what they imply for the genetics of schizophrenia.  Inheritance of schizophrenia is widely considered to be polygenic and has been for some time.  He framed this issue as there being no psychiatric disorder gene and I thought that was a useful reframing because it speaks to studies that are looking at a very few point mutations associated with schizophrenia, and it is easy to think that this gene is the cause of schizophrenia rather than conferring risk for the disorder.  He demonstrated this with a risk profile score (RPR) for developing schizophrenia based on an additive count of all risk alleles.  In the example given the risk profile for the highest risk score had an odds ration of 15-20 to 1 for developing schizophrenia.  He went on to review the evidence for schizophrenia as a neurodevelopmental disorder.  That included some epidemiological data such as artificially imposed famine in China and the Netherlands and the subsequent increase in the incidence of schizophrenia in the respective birth cohorts (1).  He showed that de novo mutation in schizophrenia overlap with more traditional neurodevelopmental disorders like autism spectrum disorder and intellectual disability.  He showed that genes from all three disorders are overexpressed during the fetal period and this is a pattern seen in neurodevelopmental disorders.  

This was compelling stuff.  I come to this conference very year to get rejuvenated and it worked again this year.  The only regret I had was that time has just about run out for me.  I am no longer a young science major with an interest in human behavior and how the brain works.  I don't have time to go back and do a fellowship with Dr. Weinberger or a sleep fellowship or any number of other interesting things that I see at conferences.  I can understand the concepts,  teach them, and advise younger colleagues and residents on what is available and why this is a compelling field whenever I can.  I can also continue to get the word out that psychiatry is alive and well, that the best critics of psychiatry are trained as psychiatrists, and what passes for psychiatric criticism on blogs and in the press lacks a critical element called scholarship.  And as important - you don't have to be Kandel or Weinberger to be scholarly and apply what you know about the science to what you do every day as a psychiatrist.  Equally important - knowing the theory and what can and cannot be applied yet - is an important aspect of being a physician.

It was a good weekend.


George Dawson, MD, DFAPA


References:


1:  Schizophrenia and famine collection (original articles on the Dutch and Chinese famine are references number 39 and 59):

http://www.ncbi.nlm.nih.gov/sites/myncbi/1-MAvBcofi/collections/48942475/public/

2:  Weinberger DR, Radulescu E. Finding the Elusive Psychiatric "Lesion" With21st-Century Neuroanatomy: A Note of Caution. Am J Psychiatry. 2015 Aug 28:appiajp201515060753. [Epub ahead of print] PubMed PMID: 26315983.