A Grand DSM critique from Health Affairs

There is a large Health Affairs article that just became available online.  It criticizes (what else) the DSM 5.  The article and its initiatives all seem to flow from the conclusion:

"Inadequate interdisciplinary review and collaboration translate into missed opportunities to increase the accuracy of explanations for mental disorders.  They also lead to suboptimal care and outcome disparities for millions of patients at a time when dramatic differences in psychiatric diagnosis and treatment rates by sociodemographic status, ethnicity, and geography have undermined public confidence in psychiatry.” (p 7)

I hope that anyone reading this blog knows what the factors are in the mismatch between psychiatric diagnoses and care.  I hope that anyone reading this blog knows the biases against psychiatry and how that influences the allegations of overdiagnosis, diagnostic reliability, overprescriptions and conflict of interest that are typically leveled at psychiatrists and their professional organization.  The most obvious example and a point that seems to be completely lost on these authors is the rationing of psychiatric services and the resulting fact that most of the diagnostic disparities that they are complaining about are not due to psychiatrists or the DSM.   I hope that any reader here has also noted my running commentary about the real causes of “suboptimal care and outcome disparities”.  It is directly related to managed care, pharmacy benefit managers, and the adoption of these same rationing practices by local, state, and federal governments charged with the provision of mental health and substance abuse services.

The authors seem to lack an understanding of some of the basic social processes that they believe to be impacted by the DSM.  They cite the New York Times as a source for the issue of whether the DSM committee backed down on diagnostic revisions that would have disqualified “half of those who currently receive benefits for autism spectrum disorders” and various other changes.  As a psychiatrist who is intimately familiar with the disability process, the determination of disability is a political process at the level of the Social Security Administration.  A diagnosis is an entry point but it does not assure a disability award or even ongoing disability payments.  I have seen patients who were hospitalized for severe problems who did not get a disability determination in their favor.  I have seen people who clearly misrepresented themselves, did not believe they have a mental disability, and who received disability determinations that they requested.  As far as I can tell, the system is currently set up to favor people with mental illnesses who have been hospitalized at least three times in two years.  There are companies who facilitate applications.  It generally takes a series of two or three appeals that can drag out over a year or two.  If it comes to a hearing, those hearings are uncontested and they are not adversarial in that the government does not have an attorney present to oppose the application and the decision is made by a judge and not a jury.  The most  significant political event in this process occurred about 15 years ago when the government decided it would not consider alcoholism and drug addiction a disability.  Prior to that alcoholism was a leading cause of disability in many states.  With all of those political variables how can a DSM diagnosis be seen as the rate limiting step in that process?

The authors also conclude “Psychiatric conditions result from a combination of biological and environmental factors”.  The arguments that follow suggest that psychiatrists are basically clueless about these phenomenon.  I did not see George Engel or the biopsychosocial model of illness referenced.  In Engel's seminal 1977 paper in Science, he directly addressed the limitations of the biomedical model and changed the paradigm for the future by proposing a biopsychosocial model.  This paper is dramatic in its intellectual scope and it addresses practically all of the issues brought up in the Health Affairs article including several areas that are not addressed such as the experience of the patient.  Engel also addressed the issue of “When is grief a disease?”, a popular current DSM critique:

“…Hence the physician’s basic professional knowledge and skills must span the social, psychological, and biological for his decisions and the actions on the patient’s behalf involve all three.  Is the patient suffering normal grief or melancholia?  Are the fatigue and weakness of the woman who recently lost her husband conversion symptoms, psychophysiological reactions, manifestations of a somatic disorder, or a combination of these.  The patient soliciting the aid of a physician must have confidence that the MD degree has indeed rendered that physician competent to make such differentiations.”  

A reference to Engel would seem appropriate but it detracts from the authors’ contentions that physicians seem to need to have their biopsychosocial horizons broadened and acknowledging that a physician discussed this definitively 35 years ago would detract from their argument.

The authors more direct arguments about the role of “social and institutional influences on diagnosis” can be similarly addressed.  Although they don’t acknowledge the DSM, they discuss post traumatic stress disorder as an example of environmental exposure.  They cite evidence gathered in the psychiatric literature as their proof.  In fact, any psychiatric evaluation should contain a formulation section that considers social, biological, and consciousness based factors in the overall evaluation of the person seeking help.  This is nothing new and every competent psychiatrist is trained to do this.  The now abandoned oral Board exam, used to test these skills.  The idea that these factors are relevant to psychiatric diagnosis have been taught to psychiatrists for decades.  Do we really need to learn that from a panel of social experts who don't talk with people about that information every day like we do?

The idea that social context,  is a relevant factor has also been obvious to psychiatrists for a long time.  Psychiatrists are routinely asked to evaluate and treat patients from various socioeconomic and cultural groups and frequently work with interpreters in the process.  There is no basis in fact for their speculative comment that “Identifying and understanding the causes of diagnostic disparities can lead to improved diagnostic criteria and their more accurate application.”

On the issue of institutional and policy factors the authors also miss the mark.  They make the previous mistake about diagnosis and Social Security disability by suggesting that a specific diagnosis results in a disability check.  They do not point out how the Social Security process rather than a DSM diagnosis may be more important in the issue of disabilities for mental health. Interestingly they are concerned about the “major consequences for payers and patients" and reference a study looking at the prescription of atypical antipsychotic medications for children.  They ignore the fact that the actual treatment of mental illnesses are outside of the purview of the DSM and that overprescription (if this is actually overprescription) is a widespread problem that extends well beyond the field of psychiatry.  As is the case with all critics of psychiatry and the DSM, they give a pass to the real causes of systemic poor treatment and a focus on medications rather than psychosocial therapies and that is the managed care industry and its supporters at all levels in the government.

Their final focus on publicity and marketing is certainly not a problem specific to psychiatry.  It is also a process that is not DSM dependent.  Restless leg syndrome or insomnia do not need to be in the DSM to end up being treated on a large scale by primary care physicians.  All it takes is a pharmaceutical company web site with a checklist.  They provide no insight into why the political process of direct-to-consumer advertising as determined by lobbyists, politicians, and the associated exchange of money should be part of a DSM oversight process.

The authors proposed Psychiatric Diagnosis Review Body and its potential benefits are equally speculative.  Their idea that there would be “greater sophistication” in the explanations of mental illness is doubtful, especially considering the impact that Engel’s biopsychosocial model has had on both the field and DSM development.  Their idea that the work of a review body would “heighten mental health practitioners’ awareness of population level differences in diagnoses, in some instances improving their ability to tailor diagnoses to patient’s demographic characteristics and cultural backgrounds…” is also problematic.  First off, the DSM is written for psychiatrists and a psychiatric diagnosis and formulation is much more than looking at a list of symptoms that possibly identifies a person as being a statistical outlier in a group.  Any person can pick up a copy of the DSM and presume to make a "diagnosis" based on these criteria, but that is not a psychiatric diagnosis.  Secondly, cultural, demographic characteristics, and demographic factors have already been incorporated into psychiatric evaluations for decades.  An even greater question is what broad scale social data would add to the evaluation of the individual patient given the biases that are usually present in those studies.

The authors suggest that the incorporation of feedback from the review body would “increase public confidence in the manual and psychiatry as a medical profession”.  The single most important factor that would enhance psychiatry’s image would be the recognition that rhetorical negative arguments against the profession abound and need to be corrected.  That could start by recognizing what psychiatrists actually do and what a DSM is actually used for.  It would also take a critical look at why 20 years of rationing of psychiatric services by the managed care industry and the government is the single largest factor in why these services have deteriorated and now operate on the premise that getting people on one medication or another is the best way to treat mental illness.  The authors in this case banter about million and billion dollar amounts that are typically used to suggest the impact of the DSM or significant conflicts of interest in psychiatry.  Nobody is focused on the fact that the managed care industry makes far more money than that by denying medical care.  Psychiatric services make up a disproportionately large amount of denied care.

If you are really interested in improving the care of people with mental illness in this country it would seem logical to attack those who routinely deny them care and interfere at all levels with the provision of care rather than those providing the care and trying to improve it.   That is the most important social problem affecting the provision of mental health services and access to psychiatry.  Social scientists seem to be as disinterested in that fact as the average journalist.

George Dawson, MD, DFAPA

Hansen HB, Donaldson Z, Link BG, Bearman PS, Hopper K, Bates LM, Cheslack-Postava K, Harper K, Holmes SM, Lovasi G, Springer KW, Teitler JO.  Independent Review Of Social And Population Variation In Mental Health Could Improve Diagnosis In DSM Revisions. Health Aff (Millwood). 2013 Apr 24. [Epub ahead of print] PubMed PMID: 23614899.

Engel G. The need for a new medical model: a challenge for biomedicine. Science 1977; 196:129-136.

George L. Engel, MD. JAMA.2000;283(21):2857. doi:10.1001/jama.283.21.2857

Homicide Debate Goes Further Off the Rails

Apparently broadcast news is about as reliable as the Internet these days.  I was watching an "expert" on the weekend discuss the connection between homicide and antidepressant medications.  He apparently believed that there was one.  I understand that Sanjay Gupta made a similar comment today on CNN.  The misinformation is flying out there.  There are several political interests that would like that statement to be true and they appear to be out in full force. What is the short answer to the association between antidepressants and homicide?  Who can you believe?

Well there is always the scientific approach and a review of the medical literature.  Admittedly the literature is a lot drier and less entertaining than Dr. Gupta.

There is also simple arithmetic   The American media like to give the impression that violent crime and homicide are at epidemic levels.  It is always a shock when people discover that in fact we are at a 30 year low:

The homicide rate has actually declined from 10.2 per 100,000 in 1980 to 5.0 per 100,000 in 2009.  What are the odds of that happening if a major new cause of homicide is being added at the same time (namely antidepressants).  How does that compare with antidepressant use?  A recent study estimated that from 1996 to 2005, the number of Americans older than 6 years of age in surveyed households who received at least one antidepressant in the year studies increased from 5.84% in 1996 to 10.12% in 2005.  From the table there was a 24% reduction in the homicide rate during a time that antidepressant use nearly doubled.  One in ten Americans received an antidepressant prescription   The authors of this study noted this trend was broad based and correlated with a lower percentage of people receiving psychotherapy.

But what does that tell us about the observation that antidepressants cause homicide?  Technically there is no current way to demonstrate causality from a negative correlation between homicide rates and the rate of people taking antidepressants.  A large scale significant negative correlation between antidepressant use and lethal violence over a 15 year period has already been reported in the Netherlands.

What about the commentator suggesting that the toxicology of homicide perpetrators shows that they can have psychiatric drugs present that explain their homicidal behavior.  In fact, a study looking at that issue showed that 2.4% of 127 murder-suicide perpetrators had toxicology that was positive for antidepressants.  That is a lower than expected rate of antidepressant use than in the general population.   In a study of elderly spousal homicide-suicide perpetrators, depression was seen as an antecedent to this act but none of the perpetrators tested positive for antidepressants.

Given these observations any claim that antidepressant or any psychiatric drug causes homicidal behavior needs to be backed up with some hard data.  I don't mean a series of cases reported by somebody to make a point and I don't mean a legal decision where lawyers and judges can pretend that scientific data do not exist and make a decision about what they hear in a court room.  I also do not mean listening to somebody claim that we will never know the real relationship until we conduct "prospective double blind placebo controlled studies" of homicidality as a medication side effect.  If it isn't obvious, that study would by definition be unethical and would not pass the scrutiny of any human subjects committee.

Anyone with potential homicidal thinking needs close supervision and treatment.  They may need inpatient treatment in a unit that specialized in treating homicidal thinking and behavior.  Any clinician working in these settings will tell you that the people being treated generally come in with aggressive and violent thoughts and behavior before they take any medication.  If they have positive toxicology associated with homicidal thinking it is generally alcohol or an illicit drug like cocaine or methamphetamine.  Anyone with this problem also needs close monitoring and management of medication side effects.  Antidepressants can cause agitation and restlessness.  There are some people who do not benefit from antidepressants.  In the case of persons with the potential for aggression and suicide the medication response may need to be determined in a controlled environment before they can be safely treated.  Like all medications antidepressants are not perfect medications and they need to be administered by an expert who can provide effective treatment while managing and eliminating any potential drug side effects.

George Dawson, MD, DFAPA

The diagnosis of anosognosia

Follow up on another blog today where the author proclaims "It is not possible to diagnose anosognosia in schizophrenic patients on brain scan."

No kidding.  Here is another shocker and you can quote me on this - it is not possible to diagnose anosognosia in stroke patients based on a brain scan.  Quoting an expert: "Anosognosia refers to the lack of awareness, misbelief, or explicit denial of their illness that patients may show following brain damage or dysfunction.  Anosognosia may involve a variety of neurological impairment of sensorimotor, visual, cognitive, or behavioral functions, as well as non-neurological diseases."  I  encourage anyone who is interested in this topic to find a copy of this book chapter listed in the references below.  The author thoroughly discusses the fascinating history of this disorder, specific protocols used to make the diagnosis, various neurological subtypes with heterogeneous lesions and the fact that no specific mechanism has been determined.

In a more recent article available online, Starkstein, et al provide an updated discussion in the case of stroke.  They discuss it as a potential model of human awareness, but also point out the transient nature and difficulty in developing research diagnostic criteria.  They provide a more extensive review of instruments used to diagnose anosognosia and conclude: "Taken together, these findings suggest that lesion location is neither necessary nor sufficient to produce anosognosia, although lesions in some specific brain areas may lower the threshold for anosognosia. Strokes in other regions may need additional factors to produce anosognosia, such as specific cognitive deficits, older age, and previous strokes."

The experts here clearly do not base the diagnosis of this syndrome on imaging.  It is based on clinical findings.  For anyone interested in looking at the actual complexity in the area of anosognosia in schizophrenia I recommend reading these free online papers in the Schizophrenia Bulletin in an issue that dedicated a section to the topic in 2011.  You will learn a lot more about it than reading an anti-biological antipsychiatry blog.  But of course you need to be able to appreciate that this is science and not an all or none political argument.

George Dawson, MD, DFAPA.

Patrik Vuilleumier. Anosognosia in Behavior and mood disorders in focal brain lesions.  Julien Bogousslavsky and Jeffrey L. Cummings (eds), Cambridge University Press 2000, pp. 465-519.

Medscape Has Not Stopped Anonymous Postings

I had to put this comment here because my attempt to post it on the Psychiatric Times was unsuccessful.  I tried to put this comment in response to an article by Ronald W. Pies, MD on anonymous posters that are abusive and in some cases threatening.  He discusses situations where psychiatrists who are not anonymous are subjected to these tactics by anonymous posters.  He  goes on to say:

"It was therefore with great satisfaction that I learned of a new (6/27/12) policy on the popular medical Web site, Medscape; ie"we have removed the ability to post comments anonymously in our physician-only discussion forum, Medscape Connect, and in all Medscape blogs."

I am familiar with the discussion area on Medscape for quite a long time.  There are anonymous posters there who are somewhat disagreeable.  There are anonymous posters there who clearly have a lot of time on their hands.  There are posters there whose main goal is to denigrate psychiatry and psychiatrists.  Interestingly posts against psychiatrists and psychiatry have never been censored, no matter how off the wall they are.  One psychiatrist fighting back, made several posts that were pulled.  The abusive anonymous posters there usually fall back on "freedom of speech" as their right to say whatever they want about psychiatry.  As far as I know only a psychiatrist was ever censored in that forum - but in that case an entire series of posts was pulled.

I have always advocated for physicians posting under their own name in any Internet discussion by physicians.  When that does not happen there is always a predictable amount of rhetoric and name calling.  At times the posts on Medscape were at such a level it was difficult to believe that they were made by physicians.  Of all the specialty discussion boards on Medscape, it is probably no surprise that psychiatry was the only specialty under attack.

The problem currently is that despite their advertised policy, posting on Medscape's physician discussion forums really have not changed.  I just looked at the forum and anonymous posting is alive and well.  Bashing psychiatry is alive and well.

Old antipsychiatry habits die hard.

George Dawson, MD, DFAPA

Ronald W. Pies, MD.  Is it time to stop anonymous (and abusive) posting on the Internet?  Psychiatric Times; August 16, 2012.

On the Validity of Pseudopatients

Every now and again the detractors and critics of psychiatry like to march out the results of an old study as "proof" of the lack of validity of psychiatric diagnoses.  In that study,  8 pseudopatients feigned mental illness to gain admission to 12 different psychiatric hospitals.  The conclusion of the study author was widely seen as having significant impact on the profession, but that conclusion seems to have been largely retrospective.  I started my training about a decade later and there were no residuals at that time.  I learned about the study largely through the work of antipsychiatrists and psychiatric critics.

Several obvious questions are never asked or answered by the promoters of this test as an adequate paradigm.  The first and most obvious one is why this has not been done in other fields of medicine.  It would certainly be easy to do.  I could easily walk into any emergency department in the US and get admitted to a Medicine or Surgical service with a faked diagnosis.  I know this for a fact, because one of the roles of consulting psychiatrists to Medicine and Surgery services is to confront the people who have faked illness in order to be admitted.  Kety (9) uses a more blunt example in response to the original pseudopatient experiment (1):

"If I were to drink a quart of blood and, concealing what I had done, come to the emergency room of any hospital vomiting blood, the behavior of the staff would be quite predictable. If they labeled and treated me as having a bleeding peptic ulcer, I doubt that I could argue convincingly that medical science does not know how to diagnose that condition. "(9)

I also know that this happens because of the current epidemic of prescription opiate abuse and the problem of drug seeking and being successful at it.  An estimated 39% of diverted drugs (7) come from "doctor shopping."  By definition that involves presenting yourself to a physician in a way to get additional medications.  In the case of prescription opioids that usually means either faking a pain disorder or misrepresenting pain severity.  So it is well established that medical and surgical illness well outside of the purview of psychiatry can be faked.  And yet to my knowledge, there is hardly any research on this topic and nobody is suggesting that medical diagnoses don't exist because they can be faked.  Does that mean the researchers consider the time of these other doctors too valuable to waste?  More likely it did not fit a preset research agenda.

The second obvious question has to do with conflict of interest.  It is currently in vogue to suggest that psychiatrists are swayed in their prescribing practices by incentives ranging from a free pen to a free meal.  Compensation as a company employee or to give lectures is also thought of as a compromising incentive. The free pen/free meal incentive is pretty much historical at this time.  What about intentionally misrepresenting yourself?  What is the conflict of interest involved at that level and how neutral can you stay when you are trying to escape detection in order to prove a point?  A vague script like a mono-symptomatic presentation of schizophrenia should suggest that the intent is to escape detection.  How should a person with a vague script act when they are face to face with a real clinician?  The logical conclusion is that they would be as evasive as possible even if they were adhering to that protocol.

The bottom line is that the pseudopatient experiments were seriously flawed out of the box.  Continuing to promote them as meaningful reflects a serious lack of scholarship in reading the relevant literature and a need to suspend the reality that in fact mental illness does exist, that distinctions can be made among various types of mental illness, and that those distinctions are useful to psychiatrists trying to help people with those problems.

George Dawson, MD, DFAPA

1: Rosenhan DL. On being sane in insane places. Science. 1973 Jan 19;179(4070):250-8. PubMed PMID: 4683124.

2: Fleischman PR, Israel JV, Burr WA, Hoaken PC, Thaler OF, Zucker HD, Hanley J, Ostow M, Lieberman LR, Hunter FM, Pinsker H, Blair SM, Reich W, Wiedeman GH, Pattison EM, Rosenhan DL. Psychiatric diagnosis. Science. 1973 Apr 27;180(4084):356-69. PubMed PMID: 17771687.

3: Bulmer M. Are pseudo-patient studies justified? J Med Ethics. 1982 Jun;8(2):65-71. PubMed PMID: 7108909; PubMed Central PMCID: PMC1059372.

4: Spitzer RL, Lilienfeld SO, Miller MB. Rosenhan revisited: the scientific credibility of Lauren Slater's pseudopatient diagnosis study. J Nerv Ment Dis. 2005 Nov;193(11):734-9. PubMed PMID: 1626092

5: Spitzer RL. More on pseudoscience in science and the case for psychiatric diagnosis. A critique of D.L. Rosenhan's "On Being Sane in Insane Places" and "The Contextual Nature of Psychiatric Diagnosis". Arch Gen Psychiatry. 1976 Apr;33(4):459-70. PubMed PMID: 938183.

6: Zimmerman M. Pseudopatient or pseudoscience: a reviewer's perspective. J Nerv Ment Dis. 2005 Nov;193(11):740-2. PubMed PMID: 16260928.

7: Inciardi JA, Surratt HL, Cicero TJ, Kurtz SP, Martin SS, Parrino MW. The "black box" of prescription drug diversion. J Addict Dis. 2009 Oct;28(4):332-47.  PubMed PMID: 20155603; PubMed Central PMCID: PMC2824903.

8: Millon T. Reflections on Rosenhan's "On being sane in insane places". J AbnormPsychol. 1975 Oct;84(5):456-61. PubMed PMID: 1194506.

9: Kety SS. From rationalization to reason. Am J Psychiatry. 1974 Sep;131(9):957-63. PubMed PMID: 4413516.

A Positive Review of DSM5? In the New York Times?

I know it is hard to believe.  Something about psychiatry in the NY Times that is not spun as negatively as possible.  One blogger referred to the phenomenon as "New York Times Psychiatry".  But today there is a positive review of the addiction section of DSM5.  No spin on how the DSM is a carefully crafted plot by psychiatry to diagnose all Americans with a mental illness or collude with Big Pharma to sell more drugs.  Instead an author suggesting that there may be a scientific basis for these decisions.  And as we all know, science is a process and not a set of definitive answers.  Could science actually be the organizing force in the DSM rather than what we typically hear in the media?

Probably.

This is a brief scholarly essay on the history of the concept of addiction and the current neurobiological underpinnings.   It should be no surprise that with the accumulation of knowledge that the concepts of what is an addiction and what is not changes over time.  Just like everything else in the DSM and just like everything else in the field of medicine.  It is not a conspiracy or a plot - it naturally happens as knowledge accumulates and we get more sophisticated.

George Dawson, MD, DFAPA


Howard Markel.  DSM 5 Gets Addiction Right.  NY Times June 5, 2012.

Some Psychiatrists Continue to Obsess - Time for Action

In an editorial in this month’s British Journal of Psychiatry, Peter Tyrer contemplates the future of the profession.  It seems that pieces like this happen every 6 months or so in psychiatry and never in other medical specialties.  Tyrer discusses a recent conference in Belgrade where one of the speakers predicted that psychiatry would vanish and be absorbed into neurology.  That is after he develops the theme that neurology is so different from psychiatry that he could not possible entertain the idea of being a neurologist.    He would not have gone into psychiatry if it was a branch of neurology.  I think the problem for psychiatry and psychiatrists is really encapsulated in a single sentence in this editorial and it is also one of the main reasons I keep writing this blog:

"We live in turbulent economic times and may have a right to be gloomy, but I was quite disturbed to hear speaker after speaker predicting the demise of our profession or its absorption into neurology or some other discipline, as the funding for mental illness and respect for psychiatrists gets progressively less."

There is probably no better recipe for the demise of a profession than continuing to obsess about the future.  Pick a direction, any direction and the critics be damned.  It seems that the personality of most psychiatrists does not allow for that action.  We can dissect how psychiatrists as a group may be different from other specialists but I think the problem is that introspection and the need to understand motivations and emotions has translated into a lack of action and a really very annoying tendency to never take a stand.  I have also observed and equally annoying trait of uncritically accepting any criticism that comes down the pike as though it is generally legitimate.  All of the maladies in Dr. Tyrer’s piece including stigma, decreased funding, and a lack of respect for psychiatry come from those places.  Tyrer goes on to say that he sees no connection between stigmatization and discrimination and psychiatry’s lack of direction.

Let me suggest that at many levels this is the perception of a lack of direction.  The psychiatrists I know are trained to high levels of competency, technically skilled and care about what happens to their patients.  They successfully treat mental illness, save lives, correct misdiagnoses, and improve the lives of millions of people.  What they do every day differs considerably from what is written in the American press.  The sensational and inaccurate headlines can only be countered by aggressive political activity against all of the distortion that is typically being passed about psychiatrists.  For a moment, I was going to write that this is an American phenomenon, but then I recalled the work of Claire Bithell in the UK,  showing that coverage of psychiatry was less often than other specialties and when it did happen it was four times as likely to be negatively framed.

How about at least getting the word out that this trend exists and it biases people at all levels including the people who are responsible for funding treatment?  Here in the US, an unrealistically negative press feeds into a health care system that is set up to exploit patients with mental illness and the mental health professionals trying to treat them by providing disproportionately less funding.  It was so blatant that a parity law had to be passed to attempt to counter that discrimination.  But even as I type this note, large health insurance companies are trying to figure out a way to avoid paying for specific treatment settings, therapies, and drugs recommended by psychiatrists.   Nothing helps their cause more than propaganda against psychiatrists. 

  

So let’s break the deadlock of continuing to obsess about the future of a specialty when the current practitioners know what they are doing and treat people as successfully as they get treated by any other specialists.  This is not about the difference between psychotherapy or medications or treatment philosophies.  This is about the difference between a stroke and a psychiatric disorder.  I have had to educate many practitioners about that difference over the years, always when they were misdiagnosed with a mental illness.  Some of those practitioners were neurologists.  That is proof of an unique skill set that nobody else in medicine seems to have and for psychiatry that is just the tip of the skill set iceberg.

George Dawson, MD, DFAPA   

Radicals and Reformers for Managed Care

I was struck by a post on the Critical Psychiatry blog this AM.  Duncan Double discusses his experience at a meeting of the radical caucus at the APA on Sunday.  His main argument was the need to abolish psychiatric diagnostic systems - specifically the DSM, but he mentions that you can apparently provide psychiatric services without an ICD diagnosis in the UK.  But then he makes this astonishing comment: " The American psychiatric system has become very dependent on DSM for billing purposes, but I'm sure the insurance companies could develop an alternative system unrelated to DSM. "


I am positive that the American insurance industry would like nothing better than to establish their own "alternative system unrelated to the DSM'.  In fact, they are doing it already with a host of measures that they can use to basically deny care or dismantle systems of care.  The managed care industry in the US has selectively discriminated against psychiatric services for the past 20 years to the point that most states have little service availability.  The motivation for managed care is clear - shift hundreds of billions of dollars away from providing care to persons with mental health and chemical dependency problems and into the pockets of the insurance industry.  We are talking about an industry where the CEOs can make an annual salary of millions of dollars and in a famous case the CEO received a $1 billion dollar bonus.


Stated in another way, the "American psychiatric system" is no system at all.  There is hardly any availability of psychotherapy services.  Most people are restricted to a handful or less of 15 minute visits with a psychiatrist every year.  The length of stay in hospitals is appallingly short by UK or European standards and people are asked to leave if they are no longer "suicidal".  It is psychiatrists on the one hand being severely restricted in attempting to provide care and a predatory insurance industry trying to make disproportionately more money off policy holders with mental health problems on the other.   The government is not a passive player in this effort with most state governments abdicating their role in caring for the indigent and the uninsured often by using managed care tactics.  All of this happens independent of any DSM or ICD diagnosis.  At the national level, there is a long list of interests who favor the same tactics in order to maintain leverage over doctors and the clinical care advocated by doctors.


Critical psychiatry would rather "Occupy American Psychiatric Association" rather than "Occupy Wall Street" .    I guess we can add them to the managed care  list.  That is exactly the type of reform that the politicians want.

Does the FDA discriminate against antidepressants?

The FDA came out with a new warning on citalopram on 3/28/2012.  The main point of the warning is that citalopram may lead to electrocardiogram changes that can be associated with an abnormal heart rhythm or arrhythmia that is potentially fatal.  The specific change is prolongation of the QTc interval or the interval that correlates with the total duration of ventricular activation and recovery.

Citalopram is a widely used antidepressant medication and it widely used for three reasons.  It is not likely to have a lot of interactions with other drugs.  Citalopram figured prominently in the STAR*D algorithm from the largest study done on enhancing antidepressant effectiveness.  A third reason is that it is a generic medication and it is very inexpensive.  Psychiatrists have broad experience with the drug and the general experience is that it is well tolerated with little toxicity.

Flecainide is a Type IC antiarrhythmic agent indicated for the prevention of paroxysmal atrial fibrillation (AF), paroxysmal supraventricular tachycardia (PSVT), and the prevention of life-threatening ventricular  arrhythmias like sustained ventricular tachycardia. The FDA warnings on the drug include proarrhytmic effects and excess mortality.  The excess mortality was directly observed in a clinical trial done to suppress ventricular arrhythmias.

The black box warnings for each drug listed below are directly from Medline:

Looking at the safety concerns for both medications - important differences emerge.  First, the FDA recommends maximum doses for the citalopram not just for the a maximum dose for adults but in specific conditions including aging.  Searching the FDA web site shows exactly 25 references for safety concerns of flecainide and none of them contain that level of information.  Second, the citalopram warning shows a table of QTc interval changes by dose for both citalopram and escitalopram.  There is no information in FDA documents (that I could find) for flecainide even though it is widely accepted that flecainide causes dose related changes in not just the QTc interval but also the QRS and PR intervals  along with a host of additional effects on cardiac pacemakers and conduction.  The  overall tone of the release is  that citalopram is a potentially cardiotoxic drug.  Third, the ECG monitoring recommendations are not internally consistent.  The absolute cut off of a QTc interval of 500 ms is highly unlikely - even in cases where the patient is taking 60 mg per day or more of citalopram.  It is also unlikely that the QTc intervals in the citalopram warning will lead to a QTc interval of greater than 500 ms.  This will result in tens of thousands of ECGs done because that is the only way that the QTc interval can be determined.

The black box warnings and the recently issued warning all considered, serious questions are raised relative to drugs with known cardiotoxicity and the whole issue of QTc warnings in all psychiatric drugs.  Certainly nobody wants a rare severe complication as a result of a prescription medication but can it really be avoided?  What good would ECG screening do?  There have not been any trials to address that issue of whether all patients taking citalopram need baseline ECGs.  All the patients taking flecainide have probably had multiple ECGs done that indicate a possible need for treatment but there is little guidance on the ECG issue.  In many patients taking flecainide, patients get serial ECGs and they do exercise stress tests to rule out proarrhythmic effects.  Are the same precautions needed for patients on citalopram?

Are the thresholds for treatment different given the fact that flecainide caused increased mortality during clinical trials and citalopram did not?  There would be an argument that flecainide is used to treat life-threatening arrhythmias, but the other indication is for prevention of atrial fibrillation and atrial fibrillation is not a life threatening arrhythmia.  With regard to the seriousness of the diagnosis, major depression carries a lifetime mortality of 10%.  Finally, where is the table on the relationship between flecainide dose and QTc prolongation like we see for both citalopram and escitalopram?  Is it possible that flecainide has more of an effect throughout the dosage range than citalopram?

These are serious questions given that I have already established that there is a significant bias in the media against psychiatry, psychiatrists and psychiatric medications.  The most recent FDA warning has created a lot of anxiety for psychiatrists and any patient taking citalopram.  The majority of those patients are being seen by primary care physicians.

  

If citalopram is that cardiotoxic, let's see the evidence and let's see how it compares to a medication with known cardiotoxicity.  Let's have the same level of warning for both medications and some concrete ideas about what needs to be done to manage that risk.

George Dawson, MD, DFAPA

The Lancet has it about 40% right

The Critical Psychiatry blog listed a brief editorial in the Lancet commenting on the current state of affairs in psychiatry. The commentary describes psychiatry's current "identity crisis" as an international problem and cites recent comments by the American Psychiatric Association and the Royal College of Psychiatrists suggesting that psychiatry is not "scientific" enough, that it does not have a central role in medicine, that the image of psychiatry with other professionals is negative, and that the therapeutic interventions are weak. The conclusory statement is: “But more fundamental still, it is time for the specialty to stop devaluing itself because of its chequered history of mental asylums and pseudo-science, and to realign itself as a key biomedical specialty at the heart of mental health.”

The Lancet has it right in concluding that psychiatry has a long history of self-flagellation that continues right up until present times. The Lancet is also correct in concluding that the image of psychiatry is negative, and that was well-documented in the journal Psychiatric Treatment showing that press coverage for psychiatry is four times as negative as any other specialty. The remarks about the science of psychiatry, the lack of a central role in medicine, and weak therapeutic interventions miss the mark entirely. In fact, I think the only way an editor can lump all of those negatives together is the uncritical acceptance that all of the negatives about psychiatry must be true.

What the critics of psychiatry can never explain away is the fact that psychiatric treatment is effective. I have personally gone to work every day for over 20 years confident that I have been doing far more good than harm. When you are doing the same work for a span of decades rather than the time it takes someone to do a clinical trial and you are personally responsible to your patient and their family you need to realize that you are effective. If I did not think I was effective and doing a reasonable job for people I would have quit a long time ago.  I also work with hundreds of competent psychiatrists in my home state where being competent is the rule not the exception.

My personal sense of effectiveness is built on decades of watching people suffer. That happened before I was a psychiatrist. Many of those people were my own family members and neighbors with severe problems who did not have access to psychiatrists. They were treated by generalists and the treatment did not go well. In many cases it was worse than no treatment at all. When I was growing up, it was also a fairly common practice for counties to sequester people with mental illness at subpar facilities that were designed for containment.  In some cases that meant that people were placed in facilities that were also tuberculosis sanatoriums or “poor farms” for the indigent.  I think that many of us in the mental health field got into it to compensate for the deficiencies of the past.  Much of that “chequered” past has nothing to do with psychiatry at all.

Although the Lancet associates psychiatry with asylums it leaves out the fact that psychiatry invented the paradigm to care for people with severe mental illnesses in the community. That was the direct product of psychiatrists and their collaborators realizing that state-funded institutional care was completely inadequate. Psychiatry moved people out of asylums on a massive scale and helps them stay out.  At this time many of these programs have been in place for over 30 years.  These same programs are actively working on the health problems of the people that they serve.

The scientific basis of psychiatry has exploded in the past two decades.  The criticism of the “lack” of science in the field always astounds me.  The criticism often seems to flow from the lack of understanding of the process of science and how the scientific accomplishments within psychiatry are on par with other fields of science.  It also seems to ignore the fact that many prominent scientists like Kandel, Snyder and others are psychiatrists.

The idea that psychiatrists are ineffective seems to flow from the same biases.  Details about the effectiveness of primary care physicians are usually left out of that argument.  It is well known that 30-50% of complaints presenting to general medical and specialty outpatient clinics have no medical explanation even after extensive investigation. Other studies have shown that primary care physicians deliver error free care in uncomplicated situations 73% of the time and in complex situations 9% of the time.  It is really not possible for psychiatry to be worse than that and yet there are no movements critical of other specialities and those are specialities that generally have far more toxic treatments.

So we are left with an abundance of critics. The critics all have various motivations but one thing is clear and that is at least part of their agenda is not to recognize the fact that psychiatrists are currently effective,  care about their patients, and that their clinical practice really is not removed from the rest of medicine.  In order to recruit more psychiatrists, the best thing to do is expose students to psychiatrists working with patients and to follow those patients while they recover. It might be useful to expose them to the biases against psychiatry and why a lot of the criticism does not match reality.  The fundamental work for many psychiatrists is to stop devaluing themselves, but it also requires recognition that much of that devaluation occurs due to the uncritical internalization of criticism that is far from the reality of clinical practice.

George Dawson, MD, DFAPA

Psychiatrists work for patients - not for pharmaceutical companies

That should be obvious by anybody reading this post but it clearly is not. I have already established that there is a disproportionate amount of criticism of psychiatry in the popular media compared with any other medical specialty. The most common assumption of most of those critics is that psychiatrists are easily influenced by pharmaceutical companies or thought leaders who are working for pharmaceutical companies. There are many reasons why that assumption is incorrect but today I want to deal with a more implicit assumption that is that there is a drug that is indicated and effective for every medical condition.

In the field of psychiatry this marketing strategy for pharmaceuticals became prominent with the biological psychiatry movement in the 1980s. Biological psychiatrists studied neuropsychopharmacology and it followed that they wanted to apply their pharmaceuticals to treat human conditions. At the popular level initiatives like National Depression Screening Day were heavily underwritten by pharmaceutical companies and the implicit connection was that you could be screened and be treated with a medication that would take care of your depression.

From the perspective of a pharmaceutical company this is marketing genius. You are essentially packaging a disease cure in a pill and suggesting that anyone with a diagnosis who takes it will be cured. The other aspects of marketing genius include the idea that you can be "screened" or minimally assessed and take the cure. We now have the diagnosis, treatment, and cure neatly packaged in a patent protected pill that the patient must take.  The role of the physician is completely minimized because the pharmaceutical company is essentially saying we have all the expertise that you need. The physician's role is further compromised by the pharmaceutical benefit manager saying that they know more about which pill to prescribe for particular condition than the physician does. That is an incredible amount of leverage in the health care system and like most political dimensions in healthcare it is completely inaccurate.

The pharmaceutical company perspective is also entirely alien to the way that psychiatrists are trained about how to evaluate and treat depression.  Physicians in general are taught a lot about human interaction as early as the first year in medical school and that training intensifies during psychiatric residency. The competencies required to assess and treat depression are well described in the APA guidelines that are available online.  A review of the table of contents of this document illustrates the general competencies required to treat depression. Reading through the text of the psychopharmacology section is a good indication of the complexity of treating depression with medications especially attending to side effects and complications of treatment and decisions on when to start, stop, and modify treatment. Those sections also show that psychopharmacology is not the simple act that is portrayed in the media. It actually takes a lot of technical skill and experience.  There really is no simple screening procedure leading to a medication that is uniformly curative and safe for a specific person.

The marketing aspects of these medications often create the illusion that self-diagnosis or diagnosis by nonexperts is sufficient and possible. Some people end up going to the website of a pharmaceutical company and taking a very crude screening evaluation and concluding that they have bipolar disorder. In the past year, I was contacted by an employer who was concerned about the fact that her employee had seen a nonpsychiatrist and within 20 minutes was diagnosed with bipolar disorder and treated with a mood stabilizer, an antidepressant, and an antipsychotic medication. Her concern was that the employee in question could no longer function at work and there was no follow-up scheduled with the non-psychiatrist who had prescribed medication.  Managed care approaches screening patients in primary care settings increase the likelihood that these situations will occur.

The current anti-psychiatry industry prefers to have the public believe that psychiatrists and their professional organization are in active collusion with the pharmaceutical industry to prescribe the most expensive medications.  In the case of the approximately 30 antidepressants out there, most are generic and can be easily purchased out-of-pocket.  Only the myth that medications treat depression rather than psychiatrists keeps that line of rhetoric going.

George Dawson, MD

American Psychiatric Association.  Practice Guideline for the Treatment ofPatients With Major Depressive Disorder, Third Edition. 2010

How Can Psychiatry Save Itself? Part 2.

Ronald Pies, MD just published his second article in a two-part series on "How American Psychiatry Can Save Itself". This essay contains specific recommendations for change. I was surprised to see that it was written from the perspective of "the American public is disenchanted with psychiatry and how the profession needs to address these issues". He attributes the public relations problem to a number of factors including the lack of "robustly effective, well-tolerated treatments", ties to the pharmaceutical industry, the declining use of psychotherapy, the public's lack of understanding of current effective treatments, and essentially political attacks by anti-psychiatry groups and other sources.

It is disappointing to see the formulation of the problem as basically one of public relations. Dr. Pies observes that the public really doesn't care about what was or what is in the DSM or the model that is used for mental illness. It is historically obvious that the only reason that psychiatry has been tolerated over the years has been our availability to treat people with obvious problems. It is difficult to deny that mental illness exists when you have brought your catatonic family member into the emergency department because they have not been able to eat or drink for two days. That fact alone is the reason that decades of anti-psychiatry abuse has been a nuisance but has not destroyed the profession. The main problems these days is that it has morphed into a brisk business for many of our detractors and whatever legitimate media is out there does not seem to be able to separate the wheat from the chaff.  In the case of psychiatry there is an incredible amount of chaff.

Dr. Pies has six fairly specific recommendations based on this public relations problem. I have listed them in table below along with my responses. This places him at a distinct advantage because I am in the position of reacting to his statements. I will offer my solutions further along in the article and hope for his rebuttal or the rebuttal of anyone else reading this article.

Dr. Pies	Dr. Dawson
1. Change the name of the DSM to the Manual of Neurobehavioral Disease or MND. Another option would be Manual of Psychiatric Disorders.	I generally avoid the term "behavioral" because it is a political term used by managed care companies to disenfranchise psychiatry or behavioral neurologists to suggest that they know more about human behavior than psychiatrists do.  Every time we use the word "behavioral" rather than psychiatry we lose to somebody.  Neuropsychiatry anyone?
2. Emphasize the importance of suffering and incapacity as hallmarks of disease and eliminate any condition that lacks those features.	I don't think the DSM is that confused in the "Cautionary Statement" or "Definition of Mental Disorder" (xxi) when it describes mental disorders as "a clinically significant behavioral or psychological syndrome or pattern that occurs in individual and that is associated with present distress or disability or with a significantly increased risk of suffering death, pain, disability, or loss of freedom.” There are additional details.
3. Separating clinical descriptions of disease from research oriented criteria using prototypes for the clinical descriptions.	This might be a useful public relations move but experienced clinicians already do this and there is some movement in DSM5 to already capture this, namely the elimination of schizophrenia subtypes.
4. Understand diagnostic categories as tools in the service of medical-ethical goals.	I think that experienced clinicians also currently do this.
5. Biological data is regarded as supporting but not finding disease categories and the diagnoses would remain clinical.	That is probably a state-of-the-art, but biomarkers may be fast approaching that can define more homogeneous categories of disease and more specific and successful treatments can be offered.
6. Parsimony with regard to the number of diagnostic categories.	Agreed and at some point we should be able to use mechanisms of disease to parse the categories. A hopeful but at this point speculative example would be the role of the ventral tegmental area in both addictions and amotivational syndromes.

From the opinions I have offered it should be apparent that I think this plan is a fairly weak one. In order to come up with a strong plan, the major problem affecting psychiatrists and the delivery of psychiatric services needs to be in clear focus. When I look at Dr. Pies suggested solutions he has public relations and the diagnostic manual in his focus. I suppose you could argue that public relations is always important and that the diagnostic manual is essentially a public relations nightmare particularly when you're considering the arguments of people who are not trained clinicians and who have their own agendas and are looking for easy press.  I don't think the American Psychiatric Association has the resources to engage the thousands of anti-psychiatry and special interest groups who want to make headlines by critiquing the DSM5.

In order to save American Psychiatry the problem needs to be clearly recognized. The single most destructive force to American Psychiatry without a doubt is managed-care and that includes managed care companies that are for-profit, managed care companies that are not-for-profit, pharmaceutical benefit managers, and government agencies that are using managed care strategies to ration psychiatric care.   Within the space of two decades they have essentially shut down half of the inpatient bed capacity, they have turned inpatient units into high-volume and very low quality discharge mills, they have created a similar assembly line in outpatient clinics, they have added hours of free work from physicians frequently to justify their financial decisions, and they claim to be one of the great purveyors of quality treatment in medicine in the United States. How can that travesty possibly be ignored? All of the other threats to American Psychiatry pale in comparison.  We have become a profession that is essentially defined by the managed care industry.

To reverse that trend and actually save psychiatry the following steps need to be taken:

1. Managed care, pharmaceutical benefit managers, and managed-care tactics being applied by the government and government proxies need to be clearly identified as the problem. There needs to be a concerted effort to reverse the political and tactical gains made by this industry and most importantly reclaiming the quality ground. The managed care industry is currently represented by NCQA, and its role as an accreditation entity. Anyone who has looked at their standards for mental health care should be appalled. Every professional organization that has psychiatrists as members should be critiquing this organization and posting their own quality standards.

2. Professional psychiatric organizations need to maintain the edge in terms of quality and standard of care guidelines. We cannot afford to have guidelines that are 5 to 10 years out of date they need to be up-to-date and current. If the American Psychiatric Association is not up to the task, other professional societies should post current guidelines in their areas of expertise. You cannot possibly win political battles against an industry special interest group by using dated and incomplete guidelines and standards of care. An excellent example of psychopharmacology guidelines is available on the British Association of Psychopharmacology website.

3. The education of future psychiatrists is critical and that makes the issue of managed care and assembly-line psychiatry an even more immediate problem. We cannot possibly expect psychiatrists to train for an additional one or two years if they are going to be paid $22 or less to see a patient. There are not enough "medication management" visits in the world to fund for that additional training and a professional salary. Unless concrete changes occur in the practice landscape the future of current psychiatric training is at risk and there is no point in speculating on how it can be enhanced.

4. In the event that adequate funding is available for training and the future profession I would recommend changes in the total time of residency and psychotherapy training but in a different manner than that suggested by Pies.  I would opt for adding a two-year neuroscience rotation and pool resources with departments of neurology and neurosurgery for a joint rotation to focus on the latest neuroscience applications to psychiatry, neurology, and neurosurgery. In the near future genomics and neuroscience will be required training and the associated philosophy can be taught at the same time during discussions of modeling at various levels.

In terms of psychotherapy, the first thing that we can do is recognize the progress that has been made in residency programs as well documented in the Archives article by Weissman, at al.  It was not that long ago that a number of "biological psychiatrists" were walking around and annoying the rest of us by proclaiming that "I don't do talk therapy".  A psychiatrist trained in psychotherapy applies that continuously in their work and uses it to inform the structure of treatment. Some of the best psychiatrists that I have encountered do psychotherapy in as little as 10 or 20 minutes and the patients they saw during that time found those discussions to be very beneficial.

Psychotherapy today can also be informed by the New England Journal of Medicine article written by Kandel over 30 years ago when he described how neuronal plasticity is affected by human encounters. The teaching of psychotherapy today can be used both as a technical tool to teach patients and a heuristic tool to teach staff and residents about human consciousness and its biological basis. Newer forms of psychotherapy such as Acceptance Commitment Therapy and Mentalizing therapy provide theories and an explicit roadmap and how to provide research proven and effective psychotherapy that takes human consciousness into account.

5. Political attacks by prominent government officials cannot be tolerated. It is no longer acceptable to suggest that all psychiatrists are corrupted because some psychiatrists are being paid to give presentations for drug companies or to do research. The suggestion that the DSM5 is corrupted, by ties to the pharmaceutical industry can be dealt with. There are clear strategies to deal with some of the blanket claims by Congressional critics.  I can never understand how an entire profession became criticized because of the fact that some members were legitimately being paid to work by the pharmaceutical industry. I cannot understand how a member of Congress can decide to investigate private employment arrangements between an employee and employer or say nothing when no problems are found. I cannot understand how member of Congress with significant conflicts of interest is allowed to treat our profession with impunity when his conflicts of interest are never discussed.

6. Board certification has become a business that is rapidly aligning itself with the business of running medical boards and managed-care corporations. The goal of ongoing professional education should be to bring all practitioners up to the same standards and there is no reason that board examinations are necessary. There is no evidence that they can achieve that goal. This was clearly an arbitrary political decision by the American Board of Medical Specialties and it should not be tolerated by practitioners in the field. There is precedent for forming independent boards and I would refer to the American Society of Addiction Medicine as a clear example. If the ABMS, is no longer relevant - a better solution would be to form a new board that meets the needs of clinicians instead of purported political goals.

7. Quality based standardization of local practice is an attainable goal. One of the practical problems in any medical specialty is the fact that there are outliers. There is a robust solution to this and the best example I can think of is the Wisconsin Alzheimer's Institute Dementia Diagnostic Clinic Network.  The network is a statewide collaboration of independent clinics that receive guidance and updates from a central university-based clinic specializing in the diagnosis and treatment of dementias. Patients anywhere in the state of Wisconsin or their physicians can refer to a local clinic to receive state-of-the-art diagnostics and treatment recommendations. This model solves two problems for psychiatry. The first is access to state-of-the-art psychiatric treatment and the second is practice drift by practitioners especially the outliers. It also solves a third problem of ongoing education.  There is no reason why collaborative networks like this one could not be established for mood disorders, addiction, schizophrenia, anxiety disorders, and personality disorders. Training at all levels could be guided by the principle that psychiatric residents need to have the necessary skills to get into these networks and implement the guidance suggested by the central academic center.

That is the path I would take to save American psychiatry. It is not an easy path but it is a realistic one. Any psychiatrist who has been practicing for the past 10 or 20 years realizes that the practice environment has deteriorated rapidly and despite all of the talk about a shortage of psychiatrists, the current lot of psychiatrists is being worked to death and they are trapped in a paradigm that results in high volume and low quality work.  The main problem is that there is no foreseeable professional organization that can carry it out. The APA does not have the political will, expertise, or leadership to do it and in that regard the future does not look good. I think that also implies that the APA has really underestimated how far psychiatry has fallen and how much they have played a role in that fall.  I see an occasional glimmer of hope, but as long as we have an ineffective structure and an election process that rewards academic achievement rather than a vision for psychiatry in the 21st century, progress will remain difficult if not impossible. We have already been replaced by a generation of "prescribers" in some areas and managed-care and the government would not complain if that occurred everywhere.

George Dawson, MD

Ronald Pies, MD.  How American Psychiatry Can Save Itself: Part 2.  Psychiatric Times March 2012, vol XXIX, No 3: 1, 6-8.

Myrna M. Weissman; Helen Verdeli; Marc J. Gameroff; Sarah E. Bledsoe; Kathryn Betts; Laura Mufson; Heidi Fitterling; Priya Wickramaratne. National Survey of Psychotherapy Training in Psychiatry, Psychology, and Social Work.  Arch Gen Psychiatry. 2006;63(8):925-934.

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