The Problem With Benzodiazepines.....

I want to thank David Allen for the inspiration for this post when he commented that as an addiction psychiatrist, I was probably seeing a skewed sample of people addicted to benzodiazepines and that might be why I have such a jaundiced view of them.  I use the above bubble diagram to illustrate how benzodiazepines are prescribed by docs like me with a strong bias toward preventing addiction compared with physicians who have no such bias.  To make sure that we are on the same page, benzodiazepines are all technically tranquilizers or sedatives.  They marked a therapeutic advance from the earlier barbiturate class  in that their therapeutic index (ratio of the drug that produces toxicity in 50% of patients to the dose that produces a therapeutic response in 50% of patients) is much greater than earlier tranquilizers like barbiturates.  The practical measure is that it takes much higher doses to produce respiratory arrest and death.  Despite the increased safety these drugs are addictive.  People can develop a tolerance and in some people they produce a euphorigenic effect, very similar to the effect of alcohol.  Some people describe benzodiazepines as "alcohol in a pill."  Unfortunately we do not know the percentage of people where that occurs or how to detect them. There are many common clinical situations where the safety margin of benzodiazepines is cancelled out by other factors.  Mixing them with alcohol and opiates are two of the most common dangerous situations and if you are treating addiction - you see that happen all of the time.

Rather than list the entire table of benzodiazepines, I am going to list the commonest ones that I see being abused.  In order from the most frequently abuse that group would include alprazolam (Xanax), lorazepam (Ativan), clonazepam (Klonopin), and diazepam (Valium).  Of those compounds Xanax Bars or 2 mg alprazolam tablets seem to be the most commonly abused by far.  The maximum recommended dose of alprazolam is 4 mg/day and I frequently have seen people taking 8-20 mg/day in combination with other street drugs.  Benzodiazepines have all been generic for a long time so they are very inexpensive to purchase if you have a prescription.  If you don't have a prescription and acquire them illegally the "street value" of a drug is a sign of abusability.  The average street value of alprazolam is about $5 for a 2 mg bar.  The immediate risk of using benzodiazepines excessively is accidentally overdosing on the single drug or in combination with alcohol and other drugs of abuse.  There is also a significant seizure risk from abrupt withdrawal when the supply of medications have been used.  The abuse of benzodiazepine like compounds that are more typically used for sleep like zolpidem (Ambien) or eszopiclone (Lunesta) does happen but it is more likely to occur in combination with alcohol for alcohol related insomnia.  A common example would be a person with alcohol dependence who takes zolpidem at night so that they can sleep through the entire night.  Without it they would predictably wake up at 2 or 3 AM from the withdrawal effects of alcohol.  Chronic use of benzodiazepines whether by prescription or acquisition from illegal sources can lead to tolerance and chronic withdrawal symptoms that can last for months if the drug or medication is stopped.  That fact alone should be considered as part of the risk of taking benzodiazepines - even in the situation where the person does not have an addiction and has anxiety that they do not believe can be treated by any other means.  In my experience, I am not sure that kind of anxiety exists.

Another common problem with benzodiazepines is that they can be psychologically debilitating, even if the person affected never takes the pill.  It is all part of the behavioral pharmacology of addicting drugs.  It usually starts out with a panic attack.  That panic attack can result in people going to the emergency department once or twice because they believe they are having a heart attack.  Somewhere along the line a physician prescribes alprazolam to take "in case of a panic attack."  That starts to happen and even if the panic attacks are rare, brief, and situational - the person affected starts to believe they need to carry alprazolam around with them wherever they go "in case" of another panic attack.  They may not have had a panic attack in years, but they are more anxious about whether they are carrying a pill when they get on a plane, cross a bridge, etc.  The pill have taken on Talisman-like features based on their using it for a condition that for most people fades away over time.  Some  who don't know the sequence of events might suggest "what's the harm" if somebody develops such a belief system around a pill.  In my estimation the harm is that the person's normal conscious state has been transformed and they have exchanged one form of anxiety for another.  The debilitating effects of anxiety depend on the illusion that your life needs to be modified in a certain way to accommodate it.  Proving to yourself that is not true is one of the best ways to adapt.        

Despite those reservations, I have prescribed a lot of benzodiazepines in my career.  They are very good medications to use in controlled environments for acute alcohol and sedative hypnotic withdrawal, acute seizures, catatonia,  akathisia, and various agitation syndromes associated with acute psychosis and mania.  The goal is typically to get the patient off the medication before they are discharged and to avoid treating patients with addiction with benzodiazepines.  Benzodiazepines are also useful for the first month in treating panic attacks, but that typically takes a lot of work.  The work involved is convincing the patient that a medication that seems to work rapidly is not a good one to take for the long haul.  The other dimension that is operating here that is rarely commented on and never explicit is whether the person receiving the benzodiazepine enjoys taking it.  Medications that are potentially addictive lead to an array of problems that are not there with drugs than are not addicting.  The main one is that they tend to be viewed as solutions for everything.  Instead of just anxiety or panic people will take them for insomnia, stress, or just to wind down at the end of the day.  Medications that reinforce their own use have the problem of inventing new uses that they were never prescribed for and that can lead to escalating doses of the medication.  In some complicated situations benzodiazepines are added to treat anxiety.  They have been used in psychiatric patients with multiple problems and been shown to add no benefit.  They are commonly added to multiple medications including opioids in patients with chronic pain with no additional benefit.

Benzodiazepines are a big problem in primary care.  The NSDUH survey illustrates that most people with an addiction are not aware of it and further that only a small minority seek treatment and find it.  That same survey suggests that about 1.5 million Americans start using tranquilizers and sedatives (they do not have a unique benzodiazepine category) for non-medical use very year.  Even if it is apparent to a primary care physician and their patient that an addiction to benzodiazepines exits, there are significant obstacles to reversing the process.  Although there are protocols for slowly tapering the medication on the Internet, it takes a very highly motivated person and ideal circumstances to accomplish this.  Outpatient detox from urgent care, the emergency department or an outpatient clinic is problematic because the same medication that the patient is not able to control is being given to them to self administer at home.  It is common that the detox medications are all taken the same day or in some cases at once.  Structured detoxification in the American health care system is practically impossible to find, especially in the case of benzodiazepines that require careful attention to seizure prevention, the prevent of withdrawal delirium, and adequate treatment of chronic withdrawal symptoms when they emerge.  Some primary care clinics are taking the preventive approach of not starting benzodiazepines in the first place.

Substance Abuse and Mental Health Services Administration, Results from the 2012 National Survey on Drug Use and Health: Summary of National Findings, NSDUH Series H-46, HHS Publication No. (SMA) 13-4795. Rockville, MD: Substance Abuse and Mental Health Services Administration, 2013.

There is a lot of resistance to the ideas of addiction docs when benzodiazepines and their long term effects are discussed among physicians.  There is always a physician who claims that they have successfully treated a person with an alcohol use disorder with benzodiazepines or they have people who have stayed on low doses for decades in order to treat their anxiety.  I see the failures.  It leads to the question of how many people are capable of staying sober, not developing a tolerance to benzodiazepines, and not experiencing a negative impact on their life.

As far as I know there are no good studies that address that question and I would not expect that there will be.  Any study that allowed subjects to mix alcohol, opiates, and benzodiazepines would be unethical and should not be approved by any Human Subjects Committee.


George Dawson, MD, DFAPA


Supplementary:

This article was subsequently edited and modified for the Psychiatric Times.  The edited version reads better.

Is President Obama Reading This Blog?

Not really, but you can find the mass shooting links on this blog at this link.  They extend back three years and they overlap with a number of posts on homicide prevention.  They also overlap in many areas with the President's speech.  This was President Obama's 15th address to the nation following a mass shooting incident.  A couple of other landmarks - this was the 40th time this year that a gunman opened fire in a school and the 294th mass shooting incident this year.  Both of these markers illustrate how tragic but absurd this problem is in America.  How can responsible people allow this to happen?

The President is coming to the only logical conclusion that a person can come to about mass shootings and the relationship to firearms.  That point in this speech was when he said that our thoughts and prayers for the families and survivors are not enough.  We cannot keep making these pat statements in response to continuous mass shootings as though nothing can be done to prevent them.  We cannot treat mass shootings like they are routine:

"Earlier this year, I answered a question in an interview by saying, “The United States of America is the one advanced nation on Earth in which we do not have sufficient common-sense gun-safety laws -- even in the face of repeated mass killings.”  And later that day, there was a mass shooting at a movie theater in Lafayette, Louisiana.  That day!  Somehow this has become routine.  The reporting is routine.  My response here at this podium ends up being routine.  The conversation in the aftermath of it.  We've become numb to this."

 The familiar refrain about condolences to everyone and now it is time to move on needs to stop.  With governments that regulate what a lot of us do at work every day - right down to how we cross the Ts and dot the Is - it is difficult to believe that more functional gun control laws cannot be passed.  In his speech he points out that this is possible and there are laws that have been shown to work in other countries and in specific counties and municipalities in the United States.

At one point he speaks to the mind of the perpetrator:

"We don't yet know why this individual did what he did. And it's fair to say that anybody who does this has a sickness in their minds, regardless of what they think their motivations may be. But we are not the only country on Earth that has people with mental illnesses or want to do harm to other people. We are the only advanced country on Earth that sees these kinds of mass shootings every few months."

People tend to get hung up on whether specific perpetrators have a diagnosable mental illness and whether it is treatable.  They tend to get hung up on whether the behavior of violent individuals can be predicted over time.  They tend to be very pessimistic about the nature of the problem and whether insightless people will ever be able to get the kind of help that they need to prevent mass shootings.  It might be easier if there was some education about the types of situations that lead to these problems and the fact that in most of those cases, help is available.  That specific help will prevent homicides and prevent the unnecessary loss of lives of both the perpetrators and the victims.  

The President ended with a comment on the political process and an appeal to gun owners on the issue of whether they are being supported on this issue by an unnamed organization or not.  It was a compelling speech and the arguments are powerful.  As a politician, he is focused on political action and on common sense gun safety laws.  I have stated that it might be best to proceed from a public health standpoint and a focus on violence prevention and forget about legal approaches largely because there has been no political will on this issue.  President Obama has given one of the most compelling speeches on this issue that I have ever witnessed and it will be interesting to see the result.

From the medical and psychiatric side, our advocacy still needs to be on the public health side of the equation.  For me that comes down to seeing the problem to a significant extent as violence and homicide prevention.  We need more public education on the predisposing mental states and how to get assistance when these states are recognized.




George Dawson, MD, DFAPA


References:

Statement by the President on the Shootings at Umpqua Community College, Roseburg, Oregon.  October 1, 2015.  Transcript

High Intensity Movement Disorders Conference

I have been a member of the Movement Disorder Society since 1993.  I decided to join after having nothing but positive experiences at the annual Aspen courses led by Stanley Fahn, C. David Marsden, and Joseph Jankcovic.   Although Dr. Marsden has passed away, the course is still being given by two of the original lecturers with additional faculty.  The level of scholarship and expertise in this conference is really not approached by many venues these days.  Each conference provided participants with a 700 page textbook like syllabus on everything that you ever wanted to know about movement disorders.  Once you attend a conference like this it is a life transforming event.  Suddenly you are following the lecturers, you read what they write and you acquire some of their books.  I changed my Neurology text to Neurology in Clinical Practice because both Jankcovic and Marsden were editors.  I also received the video material and text of Movement Disorders,  the official journal of the International Parkinson and Movement Disorder Society.

People often ask why I am member of what is predominantly a neurological society?  In Minnesota there were only three psychiatrists who were members of the organization. Stan Fahn asked me that himself at one of the conferences.  I don't remember exactly what I said, but he thought my answer at the time was acceptable.  It comes down to clinical expertise and with the confluence of the dorsal and ventral striatum - neuroanatomy.  Back in the days that I went to medical school, nobody talked about the ventral striatum only the dorsal striatum and even back then, the main clinicopathological correlate was movement disorders.  As medical students we learned primarily about Huntington's Disease, Wilson's Disease, and Parkinson's Disease.  Nothing at all about dystonias or other disabling movement disorders and their treatments.  Nothing about the last members of the generation afflicted by what we called in those days post-encephalitic Parkinson's and all of the associated neuropsychiatric morbidity.   In my rotations at Milwaukee County Hospital and affiliated institutions I saw all kinds of undiagnosed or poorly diagnosed movement disorders.   There were no movement disorder specialists in those days and no treatments except for Parkinson's.  The quality of care is slightly improved today in that referral to movement disorder specialists and an appropriate diagnosis can occur, but the total number of these specialists is very small.

That is where psychiatrists need to fill in the gap.  My initial interest was tardive dyskinesia and describing the motor disorders of patients who in many cases had never been exposed to a medication.  But it quickly became recognizing the early manifestations of idiopathic and iatrogenic movement disorders and using these diagnoses in a comprehensive diagnostic approach to the patient as well as the treatment plan.  When you take that approach it is an eye opener.  In my role as a consultant it is amazing how much undiagnosed movement disorder pathology is out there.  A couple of examples will illustrate the problem.  About 50% of young adults with childhood diagnoses of Attention Deficit-Hyperactivity Disorder (ADHD) who have been treated with stimulants have a movement disorder usually in the form of vocal tics, motor tics, or Tourettes.  About 100% of those patients tell me that nobody has ever told them about those diagnoses before.  Of course there is an exhaustive list of medication and environmental exposures that can lead to tic disorders, so there is a question of whether something occurred since childhood.  In the same population there are a group of people with choreiform movements and predominately extensor muscle tone.  They are not aware of the movement disorder and nobody has mentioned it before.  It is as though clinicians consider these movements to be part of ADHD.  One of my observations about tardive dyskinesia has been that the overall prevalence of the disorder has dropped off significantly with the advent of atypical antipsychotic medication.  That does not mean that is has gone to zero and the augmentation of antidepressants with aripiprazole seems to be a new source of that disorder.  Most significantly, the people who are at greater risk for the problem do not seem to have been carefully screened ahead of time.  They are not routinely assessed for akathisia or other early motor symptoms like micrographia, diminished arm swing,  or hypophonia.

The course was presented by three neurologists Cynthia Comella, MD; Rajesh Pahwa, MD; and Jerrold L. Vitek, MD, PhD.  It was presented by the University of Kansas Medical Center and all of the brochures and specific courses are available on this web site.  The course was unusual in its rapid presentation of topics and strict adherence to that schedule.  There were ten presentations by the faculty varying in length from 20 to 55 minutes in duration.  The morning presentations covered Parkinson's and Parkinsonism, Restless Leg Syndrome, Tremor Disorders, and Movement Disorders in Psychiatry.  The afternoon covered Dystonia, Chorea, Tics, Neurotoxin and Deep Brain Stimulation for Neurological and Psychiatric Disorders.  The entire set of PowerPoints (without the videos) was included in the course syllabus.  The slides were all very readable in a standard format.  The Psychiatric Aspects of Movement Disorders was a very interesting presentation because it covered a wide range of problems that acute care and geriatric psychiatrists come in contact with including Parkinson's Disease and the associated psychiatric comorbidity, Tardive Dyskinesia, Neuroleptic Malignant Syndrome, Serotonin Syndrome, and Psychogenic Movement Disorders.  Interest in these topics may reflect exposure to the problem.  In seeing patients with Parkinson's and psychosis for example one of the commonest problems is that antipsychotic medications will generally make their psychosis worse.  The only exception to that is clozapine and that comes with a host of comorbidities and monitoring issues itself.  One of the presenters suggested that quetiapine is a default choice in many cases even though it is not ideal and efficacy is low.  A new medication for the treatment of psychosis in PD was mentioned called Pimavanserin.  It is a selective serotonin 5-HT2A inverse agonist without significant activity at dopaminergic, histaminergic, muscarinic, or adrenergic receptors.  Practical approaches to treating dementia, anxiety, and depression associated with PD were also discussed.

The most fascinating part of the course was the section on deep brain stimulation (DBS).  A fairly detailed description of the procedure was given.  Deep brain stimulation is currently FDA approved for Essential tremor and Parkinsonian Tremor and Parkinson's Disease with humanitarian device exceptions for Primary Dystonia and Obsessive Compulsive Disorder.  This section was presented by Dr. Vitek who has a wide range of experience with this method.  Before and after videos of children and adults with disabling movement disorders were presented and the results were striking.  The general concept presented was that any "circuit disorder" was a potential candidate for DBS and that is consistent with the current literature on the subject.  The other important concept is that with DBS there are no permanent changes in the brain apart from the low risk of placement complications.  That is not true for neurosurgical techniques that have been used for the same neurological and psychiatric complications.  In the case of DBS the stimulator can be reprogrammed, turned on or off in a number of configurations, and turned completely off.  An unexpected benefit of the DBS presentation was a look at brain images from a 7 Tesla MRI scan.  The resolution of these images was incredible arguably as good as artistic renderings of brain anatomy.  Take a look at the side by side comparisons to what is currently clinically available.

Everything considered this was an excellent conference and I recommend it to anyone if it comes to your area.  I think it could be used by practicing psychiatrists who want to get up to speed on movement disorders, residents wanting to do the same thing, and psychiatrists studying for their boards in geriatric psychiatry.  It also raises a larger question of just what psychiatrists should be able to diagnose and treat?  What should they know at a theoretical level?  Based on my experience, psychiatrists seem to be the specialists that are most likely to be confronted with an undiagnosed movement disorder in patients who have seen primary care physicians or pediatricians.  Psychiatrists are also specialists who should be the experts in how to recognize and prevent motor complications of medications used to treat psychiatric disorders.  Psychiatrists have also been using the same interview and mental status exam technology for the past 50 years.  Changes need to be incremental and the logical first change that seems in order is to be able to recognize, diagnose, and treat or refer movement disorders encountered in standard psychiatric practice.  Psychiatrists interested in neuroscience with also find this a very interesting area for ongoing study.  And subspecialists like geriatric psychiatrists are probably going to need to know the difference between tauopathies and synucleinopathies.

This course is a good one to get you on that road.


George Dawson, MD, DFAPA        


Attribution:  My own picture shot at the John Rose Oval in Roseville, Minnesota.



  

Cochrane Distances Self from Critic

The Cochrane Collaboration came out with this press release to point out that one of their collaborators was posting his psychiatric criticism outside of his role in that organization.  The critic mentioned in this release has written this blogger in response to my critique of his criticism of psychiatry.  My response elicited a significant amount of derision directed at me from his apparent supporters.  That led me to modify my policy on posting comments. I believe that he posted a response to my response on another blog or blogs that I never read.

While I am no great supporter of Cochrane and consider their site to be somewhat redundant, non-productive, and lacking creativity and innovation, it is obviously in their interest to distance themselves from statements that they do not consider to be in their best interest.  For links to the exchanges on this blog with this critic, they are included in these two posts:

http://real-psychiatry.blogspot.com/2014/02/an-obvious-response-to-psychiatry-gone.html

http://real-psychiatry.blogspot.com/2014/02/the-proud-critics-of-psychiatry.html

Apart from the obvious, the more I thought about the last sentence in this release, the more it bothered me:

"There is a wide range of views within Cochrane on the benefits and harms of psychiatric drugs...."

That is an interesting perspective from an organization that is supposed to objectively interpret the evidence.  Are there an equally number of "wide range of views" on other types of medication or just the ones used by psychiatrists?  It leads to questions about whether there are psychiatric experts and people who actually prescribe the medications writing these reviews or if anyone can do it?  I could make the argument that many if not most of the summary statements seem like they are written by the same person or committee.  It also leads to the question about the political nature of these documents.  Could the specified critic for example reformulate his criticism according to the Cochrane format and publish it in their library?  Are Cochrane documents ever a compromise of a "wide range of views"?  Is there anyone at Cochrane who is aware of the additional levels of criticism that psychiatric practice is subject to and the rhetorical nature of that criticism?  I think that these are all important questions if you are concerned about being perceived as having a partisan position.  Of course most critics of psychiatry could care less about being partisan or even the appearance of being partisan, but they are generally not selling objective analysis.

Just this year, I lost access to a library database that I had previously accessed for years. I had to try to access Cochrane Reviews directly through a large publisher's web site. I was confronted with the prospect of purchasing the individual articles or an entire year long subscription through that publisher. They also have an open access model where authors can pay significant fees to have their articles published in an open access mode.   The Cochrane Library is a published product just like anything else, subject to all of the conflicts of interest of a published product.

That is an additional perspective to have when reading the release.


George Dawson, MD, DFAPA

Ioannidis - Why His Landmark Paper Will Stand The Test of Time

John P. A. Ioannidis came out with an essay in 2005 that is a landmark of sorts.  In it he discussed the concern that most published research is false and the reasons behind that observation (1).  That led to some responses in the same publication about how false research findings could be minimized or in some cases accepted (2-4).  Anyone trained in medicine should not find these observations to be surprising.  In the nearly 30 years since I have been in medical school - findings come and findings go.  Interestingly that was a theory I first heard from a biochemistry professor who was charged with organizing all of the medical students into discussion seminars where we would critique research at the time from a broad spectrum of journals.  His final advice to every class was to make sure that you kept reading the New England Journal of Medicine for that reason.  Many people have an inaccurate view of science, especially as it applies to medicine.  They think that science is supposed to be true and that it is a belief system.  In fact science is a process, and initial theories are supposed to be the subject of debate and replication.  If you look closely in the discussion of any paper that looks at correlative research, you will invariably find the researchers saying that their research is suggestive and that it needs further replication.  In the short time I have been writing this blog asthma treatments, the Swan Ganz catheter, and the diagnosis and treatment of acute bronchitis and acute chronic obstructive pulmonary disease are all clear examples of how theories and research about the old standard of care necessarily change over time.  It is becoming increasingly obvious that reproducible research is in short supply.

Ioannidis provided six corollaries with his original paper.  The first 4 regarding power, effect size, the greater the number of relationships tested, and the greater the design flexibility are all relatively straightforward.  The last two corollaries are more focused on subjectivity and are less accessible.  I think it is common when reading research to look at the technical aspects of the paper and all of the statistics involved and forget about the human side of the equation.  From the paper, his 5th Corollary follows:

"Corollary 5: The greater the financial and other interests and prejudices in a scientific field, the less likely the research findings are to be true. Conflicts of interest and prejudice may increase bias, u.  Conflicts of interest are very common in biomedical research [26], and typically they are inadequately and sparsely reported [26,27].  Prejudice may not necessarily have financial roots.  Scientists in a given field may be prejudiced purely because of their belief in a scientific theory or commitment to their own findings.  Many otherwise seemingly independent, university-based studies may be conducted for no other reason than to give physicians and researchers qualifications for promotion or tenure.  Such non-financial conflicts may also lead to distorted reported results and interpretations.  Prestigious investigators may suppress via the peer review process the appearance and dissemination of findings that refute their findings, thus condemning their field to perpetuate false dogma. Empirical evidence on expert opinion shows that it is extremely unreliable [28]"  all from Reference 1.

The typical conflict of interest arguments that are seen in medicine have to do with financial conflict of interest.  If the current reporting database is to be believed they may be considerable.  A commentary from Nature earlier this month (5) speaks to the non-financial side of conflicts of interest.  The primary focus is on reproducibility as a marker of quality research.  They cite the facts that 2/3 of members of the American Society for Cell Biology were unable to reproduce published results and that pharmaceutical researchers were able to reproduce the results from 1/4 or fewer high profile papers.  They cite this as the burden of irreproducible research.  They touch on what scientific journals have done to counter some of these biases, basically checklists of good design and more statisticians on staff.  That may be the case for Science and Nature but what about the raft of online open access journals who not only have a less rigorous review process but in some cases require the authors to suggest their own reviewers?  A central piece of the Nature article was a survey of 140 trainees at the MD Anderson Cancer Center in Houston, Texas.  Nearly 50% of the trainees endorsed mentors requiring trainees to have a high impact paper before moving on.  Another 30% felt pressured to support their mentors hypothesis even when the data did not support it and about 18% felt pressured to publish uncertain findings.  The authors suggest that the home institutions are where the problem lies since that is where the incentive for this behavior originates.  They say that the institutions themselves benefit from the perverse incentives that lead to researchers to accumulate markers of scientific achievement rather than high quality reproducible work.  They want the institutions to take corrective steps toward research that is more highly reproducible.

One area of bias that Ioannidis and the Nature commentators are light on is the political biases that seem to preferentially affect psychiatry.  If reputable scientists are affected by the many factors previously described how might a pre-existing bias against psychiatry, various personal vendettas, a clear lack of expertise and scholarship, and a strong financial incentive in marshaling and selling to the antipsychiatry throng work out?  Even if there is a legitimate critic in that group - how would you tell?  And even more significantly why is it that no matter what the underlying factors - it seems that conspiracy theories are the inevitable explanations rather than any real scientific dispute?  Apart from journalists, I can think of no group of people who are more committed to their own findings or the theory that monolithic psychiatry is the common evil creating all of these problems than the morally indignant critics who like to tell us what is wrong with our discipline.  Knowing their positions and in many cases - over the top public statements why would we expect  them sifting through thousands of documents to produce a result other than the one they would like to see?  

I hope that there are medical scientists out there who can move past the checklists suggested to control bias and the institutional controls.  I know that this is an oversimplification and that many can.  Part of the problem in medicine and psychiatry is that there are very few people who can play in the big leagues.  I freely admit that I am not one of them.  I am a lower tier teacher of what the big leaguers do at best.  But I do know the problem with clinical trials is a lack of precision.  Part of that is due to some of Ioannidis' explanation, but in medicine and psychiatry a lot has to do with measurement error.  Measuring syndromes by very approximate means or collapsing some of the measurements into gross categories that may more easily demonstrate an effect may be a way to get regulatory approval from the FDA, but it is not a way to do good science or produce reproducible results. 


George Dawson, MD, DFAPA




References:  

1:  Ioannidis JPA (2005) Why Most Published Research Findings Are False. PLoS Med 2(8): e124. doi:10.1371/journal.pmed.0020124

2:  Moonesinghe R, Khoury MJ, Janssens ACJW (2007)  Most Published Research Findings Are False—But a Little Replication Goes a Long Way. PLoS Med 4(2): e28. doi:10.1371/journal.pmed.0040028

3:  Djulbegovic B, Hozo I (2007)  When Should Potentially False Research Findings Be Considered Acceptable? PLoS Med 4(2): e26. doi:10.1371/journal.pmed.0040026

4:  The PLoS Medicine Editors (2005) Minimizing Mistakes and Embracing Uncertainty. PLoS Med 2(8): e272. doi:10.1371/journal.pmed.0020272

5:  Begley CG, Buchan AM, Dirnagl U. Robust research: Institutions must do theirpart for reproducibility. Nature. 2015 Sep 3;525(7567):25-7. doi: 10.1038/525025a. PubMed PMID: 26333454.

Subtext of "The Autism Spectrum"

I was free associating to public radio a while ago as I listened to Terry Gross interviewing actor Timothy Spall on playing J.M.W. Turner (1775-1851).  Turner was an English artist in the 1800s, renowned for his use of color and light.  His painting above from 1839 was voted Britain's favorite painting in a 2005 BBC Radio poll.  I placed it here to illustrate these techniques that are visible looking toward the sun as it illuminates the cloud cover and some outlines at the horizon as it sets.  Some of the technical aspects of his painting that distinguish him from his contemporaries include the use of a white primer, limited use of underdrawing (sketching before the paint is applied), painting fast with a hard brush and palette knife, and parsimonious use of pigments (see reference 1 for details).  Spall studied art for two years in preparation for this role and was eventually able to recreate a Turner painter.  He describes Turner as possibly one of the greatest landscape painters of all time.  He also teaches how words change in meaning over time when describing how the sublime art movement grew out of the romantic and had as its goal "to capture the beauty of nature, as well as its terror and its horror."

The actual film Mr. Turner as described in the Fresh Air episode seemed somewhat different than the one described.  It did cover the last two decades of Turner's life.  In it we meet Turner, his ex-wife and two adult daughters, his housekeeper, several of his colleagues, and a woman who he meets when she is married and marries when her husband dies.  We see enough of these relationships to develop an impression of what may be going on.  The relationships are set against a visually stunning backdrop of the cinematographer shooting Turner as he travels to sketch seascapes and eventually convert them to paintings.  In many cases, such as the painting at the top of the post we see the scene blend into the painting.  The cinematography of these scenes is some of the best that I have seen anywhere.

I think the key about whether you might enjoy the film or not depends a lot on whether you can appreciate Turner's eccentricities and the attempt at portraying the depth of his character.  He certainly does things that many would find repugnant.  The impression that I had about his relationship to his family was that he had abandoned them.  His ex-wife was somewhat intrusive in attempting to get him to show some interest.  She did not seem to impress him in the least and he would typically walk away.  He did not attend the funeral of his daughter and when asked told people that he had no children, while his father had a facial expression of disapproval in the background. On the other hand he did marry a widow and stayed with her until his death.  Along the way he had a sexual relationship with his housekeeper.  There was one scene of perfunctory sexual intercourse between Turner and his housekeeper.  No words were spoken between them during that scene or at any point to suggest that they had any emotional intimacy but the actress in this case projects a strong sense of caring for him and eventually travels to see him when he is dying in his new home.  She appears saddened when learning he has a new wife and walks away without seeing him.

Throughout the film Turner communicates at times with a series of grunts, even though he has communication skills as good as anyone else in the film.  He has a characteristically gruff and unkempt appearance and only seems to smile when he is in the midst of a deathbed delirium.  I think that presentation is what led Terry Gross to ask the question about whether he might be on the autism spectrum and Spall's excellent response on subtext.  Spall speaks to the fact that he portrayed Turner's inner anguish after hearing that one of his children had died despite his overtly dismissive relationship with them.  He expands on the relationship with his housekeeper and what that means.  He describes his intellect as implosive as a reason for the communication in grunts at times, even though he could be quite articulate at others.

That response was a great one in so many ways.  It explodes the idea that observable behaviors mean much of anything out of context.  If I am gruff appearing or eccentric does that mean much of anything by itself?  Probably not.  Being gruff or eccentric appearing is not really a risk factor for seeing a psychiatrist and it is unlikely that those features mean much of anything.  And what about the communication style and the frequent grunting?  The first time I heard it I had the impression that it was the equivalent of the modern day English expression "oi"  or the American expression "hey".    I did not see it as the typical communication problems in autism.  It also speaks to the larger headlines of famous people who either think they are "on the spectrum" or somebody else thinks there are.  That comes from a number of sources - not the least of which is the popular notion that reading the DSM without being trained in psychopathology means much of anything.  Should a person get evaluated for congestive heart failure by a doctor who has just pulled up an internet site that lists the diagnostic criteria for congestive heart failure or is it better to see a doctor who has made the diagnosis many times, and by learning those patters of illness can successfully parse cases that are in the grey zone (eg. is this congestive heart failure or asthma?).

That is the ultimate value of Spall's comment on subtext.  There is not a lot that is explicitly known about this character in the film.  Certainly nowhere near as much explicit content as Spall discusses in his interview.  And yet he is pointing out that there is something implicitly there to suggest that Turner is not autistic (whatever that might be).  One of the many misconceptions about psychiatrists is that we want to diagnose everyone with some kind of disorder.  A substantial number of the people I have seen over the years want to know that they don't have a problem.  They either ask me up front or at the end:  "So do you think I have (bipolar disorder, Alzheimer's Disease, alcoholism, OCD, borderline personality disorder, etc.)?"  They are relieved that I know the subtext and can say no.  Some people will just ask the generic question: "Do you think I am crazy?" and I explain why that is not a relevant question.  In many cases I just have to tell people:  "I know that you are being treated for this disorder (usually bipolar disorder or ADHD), but there is no real evidence that you have it.  I have treated hundreds of people with this problem and there are a number of reasons why you don't have it.  And by the way, if you don't have the disorder - I would not recommend that you take medications for the disorder."  In rare cases I will see a person who asks a very specific question: "I have been in psychotherapy for 5 years now.  That is a long time.  Do I need to keep going?" and I am obliged to give them my opinion.

Often the observations have to do with non-verbal behavior like Sprall's comment on Turner.  What does silence mean from one meeting to the next?  In one meeting it means tacit unanimous agreement.  In the other it means just the opposite.  What happens if I see a young man thrashing about on the floor and the people around him are panicked and implore me to "Do something doctor?"  Instead of calling a code I reach out and pull him up off the floor and he stands there looking mildly anxious.  And what about that anxious patient who has a piece of pipe in his hands and says: "Do you want a piece of this?"  Instead of confronting him and telling him what to do, I explain what is really happening here - he is scaring the hell out of people (including me) and it is unlikely that an old man with glasses is going to fight him or anybody else.  He apologizes and drops the pipe.  I can recall walking into a gas station in Northern Wisconsin on brisk winter morning at about 7 AM.  A large man crashed into me and my wife right in the front doorway.  I grabbed him by the jacket, he went limp and I lowered him to the ground.  "What are you doing?  What's wrong with him?" my wife asked excitedly.  He was drunk at 7AM and in a stupor on the ground.  In all of these situations things are not what they seem to be.  We all act quickly based on limited information and the chances for error are great.

One of the more critical subtexts is what happens when a person you know very well appears to be different in some subtle way but there is no clear way to describe it.  The standard mental status exam including their cognitive screening turns out to be a very blunt instrument in this situation.  I have talked with people and done complete cognitive screening and when I see them again, they have no recollection of ever seeing me again despite a perfect score on the cognitive exam.  The only differentiating points were the smell of whiskey in the air and a coarsening of affect.  In other cases, a person may deny all problems including the ones that are the focus of treatment and exhibit a slight clouding of consciousness as a prelude to serotonin syndrome or neuroleptic malignant syndrome.

All of that commentary, representing a significant part of psychiatric practice has to do with subtext and not reading a diagnostic manual.  I thank Timothy Spall for his response on the issue of the Autism Spectrum, because it is really about a lot more than that.  I have always been impressed with the observations of artists and my English professors in looking at theories of human behavior and the applied metaphors.  It is also an indication of how difficult it is to be an actor.



George Dawson, MD, DFAPA                



References:

1:  Antonino Cosentino.  Cultural Heritage Science Open Source.  J. M. W. Turner (1775–1851).  Technical Art Examination.  March 24, 2014.

2:  Terry Gross.  Fresh Air.  Timothy Spall Takes On Painter J.M.W. Turner A "Master of the Sublime."  December 14, 2014.  Be sure to listen to the audio to appreciate Spall's voice and accent in this role.




Supplementary 1:

The painting here is: "The Fighting Temeraire tugged to her last berth to be broken up" by J.M.W. Turner.  It was downloaded from the WikiArt web site that advises that the copyright expired because the painter died more than 70 years ago.

Supplementary 2:

Don't try any of the interventions described in this post at home.  They are likely to backfire.

Supplementary 3:

Definition of Subtext from Theatrecrafts.com:

"Subtext or undertone is content of a book, play, musical work, film, video game, or television series which is not announced explicitly by the characters (or author) but is implicit or becomes something understood by the observer of the work as the production unfolds.  Subtext can also refer to the thoughts and motives of the characters which are only covered in an aside. ...."

Is Mental Health Legislation Really The Joke That I Think It Is?

The above graphic is a headline search of mental health parity going back to 2004.  I was in the thick of things from 2009-2012 as the transitioning President of a District Branch of the American Psychiatric Association - the Minnesota Psychiatric Society.  Not that it gave me the inside track on anything.  I think officers in district branches spend most of their time trying to get members motivated to do something.  My strategy was basically to approach things in the way I do on this blog.  I don't think that is was any more or less successful than the dialogue promoters, but at one point some people became uncomfortable when I suggested that one of the hospitals could have been managed better.  It was apparent to me at that time that professional organizations do not tolerate disagreement very well.  As far as I can tell, there can be no real changes in organizations without disagreement and disagreement should be expected anytime there are people who want to talk endlessly and people who want action.  On the other hand nobody has to take it personally.  That may not be possible in Minnesota or in professional organizations.  I have previously referred to it here as the "big tent" approach where multiple goals are tolerated even some that conflict with the overall goals and ethics  of the organization.  An example would be prior authorization of medications.  The vast majority of members find it extremely intrusive and a waste of their time, but the members who are executives in managed care organizations do not.  Accepting both of those positions is a tacit acceptance of prior authorization while working with the members to change it.  How do you think that will work out?

Parity or equal coverage for mental illness and physical illness was a legislative initiative of two U.S. Senators Paul Wellstone and Peter Domenici.  Both had personal experience with the problem having family members with severe mental illness.    That personal experience remains critical in the political and cultural landscape.  There are still plenty of people pushing the "myth of mental illness" fallacies.  Some have moved on to just blame psychiatrists.  People with experience recognize those arguments for what they really are and can try to proceed with real solutions.  I never met Paul Wellstone, but I liked him a lot.  He was one of a handful of US Senators who voted against authorizing the invasion of Iraq based on the flawed weapons of mass destruction argument.  He was vilified by some for the vote and referred to as an ultra-liberal.  That is a glib characterization during an era where there are no liberals.  In Minnesota he was widely known as a populist.  People perceived him as a common man who cared about the common people.  He was tragically killed in a in a plane crash in northern Minnesota in 2002 while campaigning for his fourth term in the Senate.  Senator Domenici retired from the Senate in 2009, after the longest tenure at that position by anyone from the state of New Mexico.  My guess is that the final form of this bill and the way it is implemented was not the intent of either of these Senators.

I read through several iterations of their bill until it became The Paul Wellstone and Pete Domenici Mental Health Parity and Addiction Equity Act of 2008 (MHPAEA).  All of those versions are available on the Congressional web sites, but the factsheet is available from CMS.  It should be fairly obvious by any casual read of the factsheet that there are so many exceptions and vagaries associated with this law that it would not take the insurance industry and their government affiliates long to shred it.  I pointed this out at the APA 2011 Annual Meeting in Hawaii.  There was a meeting about how the MHPAEA was going to revolutionize the care of people with addictions.  A prominent psychiatrist and government official was scheduled to be there to explain how this was going to happen.  At the time, the impact of the law was not apparent on any of the acute care services where I was working.  At the meeting after listening to an overenthusiastic presenter explain how funding all of these programs were going to greatly increase bed capacity and services for all, I asked the simple question: "What would prevent any managed care company from providing a screening test and calling that assessment and treatment?"  The answer was "Nothing would prevent that."  No elaboration.  No discussion of how employers can just opt out of mental health and substance use treatment.

That introduction allows me to flash forward to the current time.  I was recently interested in referral for an acute psychiatric hospitalization in the Twin Cities - a metropolitan area of 3.8 million people.  According to a 2007 state report there were a total of 563 acute care beds for that area or 14.8 beds per 100,000 population.  According to the Organisation for Economic Co-operation and Development (OECD), the US ranks about 30th of 35 ranked industrial countries in terms of psychiatric beds per 100,000 population and the Minnesota metro is significantly below the US average of 25/100,000.   Based on those factors it should not be surprising that I was advised that there were no available beds and that the emergency department we could refer to had a 30 hour wait for assessments.

Compare that to Cardiology services in the same area.  Any middle-aged person (or younger) with chest pain would be immediately admitted to a coronary care unit or telemetry and have a standard evaluation completed even if they were discharged or undergo emergency catheterization and angioplasty/stenting.   I have never heard of a wait for acute Cardiology services.  I have never heard of a 30 hour wait in the emergency department for Cardiology services.   My point here is that the MHPAEA or parity legislation has done exactly nothing for the availability of acute psychiatric services.  These same numbers and waiting times in the ED have been there for the past 15 years.  There is no parity as long as there is no equal funding, and mental health services are funded at a fraction of what Cardiology services are.  Walk through any modern Cardiology Department or Heart Hospital and ask yourself: "Where are the equivalent psychiatric or mental health services?"  There are a few exceptions but generally not many and even then, a new facility is still managed by rationing strategies that result in people being discharged with inadequate plans and before their problems are completely addressed.  Inpatient psychiatric services are in effect behind a firewall and accessible only through the bottleneck in the ED.

The grim picture of acute care mental health services is only exceeded by the state of acute care addiction services.  As early as 1988, I was being advised by managed care companies that I could not detoxify patients with alcohol dependence on inpatient psychiatric units,  even if they had significant psychiatric comorbidity like suicidal ideation and depression.  The picture has gotten progressively worse since then.  It is common practice these days to send alcohol dependent people home with benzodiazepines and expect them to manage their own detox.  The lack of functional detoxification services keeps many people in the cycle of addiction to benzodiazepines, opioids and alcohol.

Confirmation of my skepticism about parity came in the form of the Mental Health Reform Act of 2015.  It is also a bipartisan bill introduced by Senators Bill Cassidy (R-Louisiana) and Chris Murphy (D-Connecticut).   There are House and Senate versions.  Both establish a new assistant secretary position for mental health and substance use disorders under the Department of Health and Human Services (HHS).   The fate of the Substance Abuse and Mental Health Services Administration (SAMHSA) hangs in the balance and getting rid of this highly flawed agency should be a priority.  SAMHSA has been the lead agency for mental health during this time of no parity and has not said anything about it.  The remaining description of the bill has to do with education people about HIPAA (do we really need that?) and insurance company accountability for a lack of parity.  The fanfare for this bill including praise from the APA is the exact same way the parity legislation started.  It should be evidence to every American by now that Congress is really interested in appearing to do something and appearing to want reform rather than getting the job done.

I don't think that there is anyone in Washington who knows the meaning of the word reform.  Until politicians everywhere realize that mental health services and substance use services have been an easy way for health care companies to make money by denying reasonable services nothing will happen.   It would help legislators to realize that they also have the highly flawed idea that managed care actually saves money and it is a conflict of interest for them to continue to promote this middle man on that basis.  I am not holding my breath, but it should be obvious that when a reform bill happens every 7 years, and there are still 30 hour emergency department waits and no acute care beds for admissions - there is no parity and there has been no reform.

George Dawson, MD, DFAPA