big thing, small package

Posted on Monday 2 January 2017

Sometimes big things come in small packages. This is from a research letter published last month in JAMA Intern Medicine. The author’s data comes from the Agency for Healthcare Research and Quality. Medical Expenditure Panel Survey MEPS HC-160A: 2013 prescribed medicines:
hat tip to James O… 
by Moore TJ and Mattison DR
JAMA Intern Medicine. Dec 12, 2016. [Epub ahead of print]
That report they summarized is a bear, but they’ve pared it down into two tables that are manageable. First, how widespread is the use of prescribed psychiatric medication [expressed as % of the population]?
Next, which drugs are being used?
If you work in a public clinic like I do, none of that will come as any great shock. The only thing that surprised me was that Zoloft® and Ambien® are so high up on the list. I prescribe neither so it was just a surprise. Reasons? I had no success with Zoloft® at all, and later, when I looked at the FDA approval documents, they looked beyond shaky to me [zoloft: the approval I…, zoloft: the approval II…, zoloft: the approval III…, zoloft: beyond the approval I…, zoloft: beyond the approval II…, zoloft: the epilogue…]. Ambien®? When the second patient showed up with bruises from falls while sleepwalking on Ambien®, it came off of my formulary for good. But otherwise, no big surprises. However, the authors went further and took a reasonable stab at quantifying something that I’ve thought about [and struggled with] ever since I started at the clinic about 8 or 9 years ago – long term use of these medications. Here are a few quotes from their letter:
"Long-term use was defined as 3 or more prescriptions filled in 2013 or a prescription started in 2011 or earlier…"

"Most psychiatric drug use reported by adults was long term, with 84.3% [95% Cl, 82.9%-85.7%] having filled 3 or more prescriptions in 2013 or indicating that they had started taking the drug during 2011 or earlier. Differences in long-term use among the 3 drug classes were small. The long-term users filled a mean [SE] of 9.8 [0.19] prescriptions for psychiatric drugs during 2013…"

"These data show 1 of 6 US adults reported taking psychiatric drugs at least once during 2013, but with 2- to 3-fold differences by race/ethnicity, age, and sex. Moreover, use may have been underestimated because prescriptions were self-reported, and our estimates of long-term use were limited to a single survey year…"

"Among adults reporting taking psychiatric drugs, more than 8 of 10 reported long-term use…"
Having taken something of a 25 year long sabbatical from mainstream psychiatry after leaving academia for a private psychotherapy practice, I started volunteering in local charity clinic after I retired. I was unprepared for the psychiatry I encountered there. I expected that I’d have to bone up on my psychpharmacology [and I did], but I sure didn’t care for what I found. It seemed like over·medication, poly·pharmacy, inappropriate drug choices, continual use of time·limited medicines, all were standard operating procedures. So I started reading the clinical trials and learned about, Drugs@FDA, PubMed, and the push·back – the blogs and literature that were developing around these topics [and I started this one of my own].

This report by Moore and Mattison well documents what I found returning to general psychiatry. I still find the figures staggering, but the one that makes the least sense is that these medications are being taken long term. Depression, even in its mest malignant format is time limited for the most part. There’s evidence that in some depressions, maintenance medication can be a relapse preventive, but hardly in 80% of the cases. All of this has happened in a period where psychiatry has been telling itself and the rest of the world that it’s medicalizing, but there’s nothing about those figures that’s medical. It’s contaminated by profiteering, plain and simple, and at the expense of patients who’ve come for help.

I hear from patients who are caught up in a carousel  of medications trying unsuccessfully to find something that helps but getting nowhere or even seeing their symptoms worsening:
    "… insanity is doing the same thing over and over again expecting different results"
There was a time that the best advice would be to forget what they’ve been told to date and start over, tapering any medication that isn’t clearly helping. Check out the hardware [a medical condition or medication that might be contributing]; likewise with the firmware [a major psychiatric syndrome like Melancholia or Manic Depressive Illness]; and then the software [find a reputable therapist to help them explore their lives, past and present, looking for the tangles]. That’s the same advice they would have gotten forty years ago. And it’s still good advice.

This coin has another side. While the figures quoted in this article telegraph the clear message that these medications have been over·promoted and over·prescribed, they also raise another potential concern. When we became disappointed with mental hospitals, we shut them down rather that right-size them. When we were disillusioned with antipsychotic medication and community care, we did the same thing [and filled our jails]. Similarly, when the various psychotherapies didn’t live up to their early promises, they were vilified. And while we currently remain in a situation where the medications on that list are over·prescribed, that’s not to say that there aren’t a significant number of patients who are genuinely benefiting from taking them. Something about the:
    "… baby with the bathwater"
Mickey @ 8:00 AM

so long 2016…

Posted on Saturday 31 December 2016

Mickey @ 4:00 AM

whodunit? theydunit…

Posted on Thursday 29 December 2016

    The active voice is usually more direct and vigorous than the passive:
         I shall always remember my first visit to Boston.
    This is much better than
         My first visit to Boston will always be remembered by me.
    The latter sentence is less direct, less bold, and less concise. If the writer tries to make it more concise by omitting "by me,"
         My first visit to Boston will always be remembered,
    it becomes indefinite: is it the writer, or some person undisclosed, or the world at large, that will always remember this visit?

I come from a generation schooled in the ways of Strunk and White, though the only suggestion I really remember is Don’t use the passive voice as my take-away [in case I forget, the grammar-checker in Microsoft Word is there to remind me]. As a kid, I could see that the active voice sounded better. But later, I saw that the passive voice was often used to obscure agency – a way of avoiding saying directly whodunit?. So writing "The primary outcome variables were changed in the published version of Paxil Study 329" just isn’t the same as writing "Martin Keller and his coauthors changed the primary outcome variables in the published version of Paxil Study 329."

One encounters patients who appear to live their lives in the domain of the passive voice. Things just happen in the world. Things happen to them [usually bad or disappointing things], but there’s no agent causing them. And invariably, they leave out their own participation in the things that happen. This was once known as the Fate Neurosis. While it may keep them from blaming others, or keep them from shouldering blame themselves, it’s part of a long-suffering view of life that has a sticky persistence that maintains their dysphoria [and often drives their therapists and acquaintances to distraction]. One of the goals of their psychotherapy is to help them see their own part in making things happen, even if it’s negative – to help them see a world in which they are actors rather than victims of obscure forces like fate, destiny, or bad luck. Whodunit? is of major importance in understanding anything that happens to these people [often times theydunit].

Oddly, my mind goes down this path when reading some of the language used to describe the various sources of bias in Clinical Trial reporting. There’s a long-suffering quality to the lamentations, as if we are victims of a maleficant  universe. It’s in the language we use. Publication Bias refers to trials with unfavorable outcomes that don’t get published. That italicized phrase happens to be an example of the use of the passive voice in that the actor who didn’t publish the study is missing in action – literally. Selective Reporting? Somebody did the selecting. And so it goes. The culprit isn’t in the language. All these sheenanigans that have so garbled our Clinical Trial literature aren’t mistakes, or sloppiness, or something overlooked, or random acts of a perverse deity. They’re not coming from incompetent or poorly trained statisticians. They’re the conscious, motivated acts of a person or persons who’ve got something very specific in mind. And again, the important question is whodunit?

We all know that these distorted trial reports are motivated actions. The goal is to exaggerate efficacy and downplay toxicity, to sell these drugs, but that knowledge doesn’t make it into our descriptive language or our policies. We routinely relate to them in the passive voice, but then wrack our brains trying to think up things that might respond to their happening rather than stopping people from doing them in the first place. We request minimal information and give industry a long time to provide it. Then we don’t levy fines when the required information doesn’t show up. We lament the things that are happening and rarely go after the agents except to extract inadequate fines long after the fact. Many say it won’t stop until we start sending people to prison, but that just hasn’t happened, in part because it’s so difficult to prosecute and often impossible to prove.

Instead of chasing instances where various biases have colored  the reported results after the fact, we could face the reality that distortion and non-compliance are the the expected response. The a priori protocol and declared outcome variables are unlikely to be available a priori. So we could say that no trial can begin until the outcome variables are posted in the registration section on Why not? They’re already available from the Institutional Review Board submission. Similarly, we could say no FDA review of an NDA will be initiated until the Results Database is publicly available filled out on for all submitted trials. Why not? They’re being submitted to the FDA so they’re available. Why not submit them to the rest of us?

So no more it happened to us. We need to act on they do it. We already know whodunit!
Mickey @ 11:54 AM

an explanation and a surprise…

Posted on Sunday 25 December 2016

So, picking up from explanation would be welcome… and looking at the enrollments in RAP-MD-01, RAP-MD-02, and RAP-MD-03 that seem so high in those Rapastinel Clinical Trials. The way trialists pick their sample size is to do a Power Analysis. Using the Standard Deviation from a previous similar study, then pick the difference in means between the control and experimental values you would consider meaningful, and it spits out a sample size. Here’s the formula:

These studies use Montgomery-Asberg Depression Rating Scale [MADRS], and I can’t find any data to give me a Standard Deviation for Rapastinel using MADRS, nor do I know that scale well enough to select a mean difference. But, if you’ll allow me a bit of numeric mojo, I can use the Z Scores for p=0.05 and an 80% power [both standard], si I simplified the equation. I noticed that it has a clause that contains the formula for the Cohen’s d Effect Size so I substituted and come up with a formula that calculates the sample size for the group for any given Effect Size [could that be right?]. The table on the right gives some example values:

Looking at the group sample sizes for RAP-MD-01, RAP-MD-02, and RAP-MD-03, we have 700÷2 = 350, 2333÷3 = 778, and 1556÷2 = 778 respectively. Applying the formula, that gives Cohen’s d values of 0.21, 0.14, and 0.14. So if my formula works, using Cohen’s rough guidance [0.25 is a weak Effect, 0.50 is moderate Effect, and 0.75+ is a strong Effect] these studies are powered to detect statistically significant differences at Effect Sizes that are for all intents and purposes no Effect at all, clinically insignificant. By this read, these studies are dramatically overpowered.

And as to the question, why three different clinical trials that are close to identical? That one’s easy. They need two statistically significant RCTs to be eligible for an FDA Approval. Instead of doing a trial, and if it’s positive, trying to replicate it, they are doing them simultaneously because it’s faster. Sinilarly, why so many sites? I really speeds up recruitment.And how are they going to come up with 4589 depressed subjects that are treatment failures [<50% response to an SSRI] and get this study done in two years? I haven’t a clue. But the point is clear, this is a race to the finish line, to be the first company to have a Ketamine-like product on the market.

Surprise/Flash: So I just went to to look up something about RAP-MD-04 that I was about to write about, and there’s another whole trial! posted on Christmas Day! It’s called Long-term Safety Study of Rapastinel as Adjunctive Therapy in Patients With Major Depressive Disorder [RAP-MD-06]. And this is what I had just typed, "But those things aren’t the most alarming piece of this suite of clinical trials. The fourth trial [RAP-MD-4] is a longer term clinical trial looking at relapse prevention…" I was about to talk about the potential harms. They were talking about an extension study where they were giving an intravenous drug weekly that is a kissing cousin to Ketamine, a hallucinogen. They’ve reported that Rapastunel isn’t a hallucinogen based on one published single shot trial. Now they’re going to give it weekly for up to two years as a preventative, but there’s no contingency for any continued monitoring over the long haul. And Flash, there’s appears a safety analysis. Thought broadcasting? I hope not. Anyway, here’s the new study…

which looks for all the world like yet another trial using that same cohort. Is that kosher? Basing multiple trials on a single group of subjects? I guess the right thing to do at this point is to back off until Allergan settles down and lands on a scenario that suits them. Is this their first CNS drug trial? They’re sure making one fine mess of things so far…

So Merry Christmas already!…
Mickey @ 6:00 PM

season’s greetings…

Posted on Sunday 25 December 2016

Mickey @ 12:01 AM

explanation would be welcome…

Posted on Friday 23 December 2016

I’ve been writing about Rapastinel, an NMDA receptor partial blocker touted to have Ketamine’s antidepressant effects without being a psychomimetic [see a touch of paralysis… and a block-buster-in-training…]. It was developed by a Northwestern University neuroscientist who formed a private company [Naurex], later purchased by industry giant Allergan for $560 M. They’ve recently registered four phase 3 clinical trials – all now recruiting. Before discussing these trials, here’s a bit of a review.

A properly conducted clinical trial has a number of essential elements related to the efficacy analysis:

  1. Subjects are assigned to the various arms at random.
  2. It is blinded – neither subject nor rater knows the subject’s assigned arm.
  3. The outcome variables [primary and secondary] are declared a priori [before the study begins] as is the plan for later analysis.
Many clinical trials have been misreported in journal articles, and a common modus operandi for distorting the results has been to base the report on the outcome variable that give the most favorable results rather than those declared a priori. Since the pharmaceutical companies that sponsor these trials insist that the raw data is proprietary [a secret], we don’t have the IPD [Individual Participant Data], the CRFs [Clinical Report Forms], the Protocol, or the SAP [Statistical Analysis Plan]. So our only shot at knowing what outcome variables were designated primary and secondary a priori is the registration on And even registration is only useful if it’s before the study starts and the outcome variables are clearly stated.

And so to the Rapastinel Phase 3 trials. Three of the four are virtual clones of each other, differing only in the number of subjects [why?] and one has a second dose level. They all have the same cohort – subjects in a Major Depressive Episode that "[h]ave no more than partial response [< 50% improvement] to ongoing treatment with a protocol-allowed antidepressant." These three trials call for 4589 total subjects who have failed to respond to SSRIs, documented by a less that 50% response on some unspecified rating scale after a course of an antidepressant from some unspecified list of drugs. That’s a huge cohort and it’s unclear why so many. There’s no power analysis included to explain it. Likewise, there’s a huge number of sites [134]. I even wondered if they are piggy-backing on the end of a bunch of somebody else’s antidepressant trials to get cases? Some kind of explanation would be welcome.

This is a medication that is given intravenously and the antidepressant effect lasts ~one week in the proof-of-concept study [see a block-buster-in-training…], so they call for weekly injections. Here’s all they have to say about the conduct of the study and the primary and secondary outcome variables:

  • Primary Outcome Measure: Change from Baseline in Montgomery-Asberg Depression Rating Scale [MADRS] Total Score [Time Frame: Baseline and 1 Day]
  • Secondary Outcome Measure: Change from Baseline in MADRS Total Score at the End of Study [Time Frame: Baseline and 3 Weeks]
That’s it for RAP-MD-01, RAP-MD-02, and RAP-MD-03. Bear in mind that this is a medication that’s going to be given weekly intravenously to over 4000 subjects for several years [explained below]. It’s a cousin to Ketamine [Special-K], a drug that people take to hallucinate, certainly not with anything like this kind of chronic frequency. Based on a single one injection proof-of-concept trial, the claim is that it has the antidepressant effect of  Ketamine, but not the club drug effects. But we have no idea if that holds true with long term use. And yet there’s no plan about how harms are to be assessed, no PANSS to look for subtle psychotic symptoms, no global well-being scale, no "self assessment" by the subjects themselves mentioned. Safety should come before efficacy.

How long does the study last? It doesn’t really say. I’m presuming three weeks based on that Time Frame comment in the Secondary Outcome Measure. They say the Primary Outcome Measure is the MADRS Score on day 1. After the first injection? or after each injection? And why day 1? After studying it a while, this was my best guess about what they were going to do,,,

Looking at the only published study [see a block-buster-in-training…], it seems important to take a look later in that week. That’s the whole reason the drug’s being given – for its presumed ability to last the week. And there are any number of Baselines. Which one is used? When? Is there a minimum MADRS score for entering the study? I could go on and on [and so could you].

And the 4th trial? RAP-MD-04? While it doesn’t say it in the registration document, this trial apparently follows some subset of the subjects from the other three trials [responders?] on either continued Placebo or Rapastinel [weekly or every two weeks] as a relapse prevention trial for two years. And though it presumably follows some group from RAP-MD-01, RAP-MD-02, and RAP-MD-03, the criteria for that determination isn’t specified. Again, there’s no self rating depression scale, no PANSS, no adverse event plan mentioned.

In September, the NIH, FDA, ad announced their long studied reforms for and its place in our clinical trial reporting system [see a blast off… and The Final Rule]. If this is an example of what they had in mind, they failed. To be continued
Mickey @ 9:16 PM

Klerman 1978: schizophrenia…

Posted on Monday 19 December 2016

Psychiatry was obviously ripe for the the medicalization ushered in by the neoKraepelinians and the DSM-III released two years after this article. Changes in reimbursement schedules, a burst of new psychotropic drugs certified by industry funded clinical trials, and a focus on neuroscience research soon followed. The disappearance of the public mental hospitals was matched by similar closings in the private sector. And the boundaries between academic psychiatry, guild organizations, and the pharmaceutical industry became increasingly indistinct.

In the period since this chapter was written, the large mental institutions closed for good, replaced, with the reinstitutionalization of many chronic mental patients in our jails and prisons. Psychiatry did indeed medicalize to the point that most psychiatrists became primarily involved in pharmacologic and other biological treatments. And the neuroleptic drugs used in the treatment of psychosis in Klerman’s time were for the most part forgotten, replaced by a string of new Atypical Antipsychotics.

Although The Evolution of a Scientific Nosology] is a broad commentary about nosology in general, it’s in a book called Schizophrenia: Science and Practice, sandwiched among a number of different perspectives [though it would soon become the dominant point of view]. Here’s what Klerman had to say about Schizophrenia in 1978:
What has been the influence of the disease approach on understanding schizophrenia? The neo-Kraepelinian answer has been another question: Does the concept of schizophrenia have any meaning, and if it does, what are the data that give it meaning? In other words, the concern has been with what one might call the epistemology of diagnosis; namely, what are the rules of the game? In the disease approach, there are six steps toward validating a concept of an illness such as schizophrenia.
  1. Define the theoretical bases with clarity. It is very important to make explicit the assumptions on which the many conceptual views of schizophrenia are based. But unfortunately much of psychiatric discourse until the middle of this century* has never moved beyond these theoretical debates. In order to move psychiatry beyond philosophy and into science, the second step must be taken.
  2. Translate the general concept into specific hypotheses that can be operationally tested. For example, what is the meaning of borderline schizophrenia? What are its components? How does it manifest itself?
  3. Put the hypothesis to empirical testing to determine its reliability. How well do several observers agree that a borderline patient does have ego deficits, is using splitting or denial?
  4. Subject the data to various statistical tests to determine whether we are dealing with one syndrome alone or a mixture of syndromes.
  5. Attempt to validate the statistics by follow-up studies, family and genetic investigation, correlates in childhood development, and so on
  6. Undertake epidemiological studies to ascertain the patterns of incidence and prevalence.
How well, then, does schizophrenia meet the criteria of a chronic disease in the medical model? It meets it well but not completely. Before one can conclude definitively that schizophrenia is a disease, conclusive evidence will have to be presented as to etiology and clinical course. While such evidence exists for many other disorders in psychiatry, it does not yet exist for schizophrenia — nor for many other clinical conditions with which medicine deals, such as hypertension, arthritis, and leukemia. That is to say, it is an obviously disordered state with multiple determinants in which there is not certainty as to the exact etiology. Moreover, schizophrenia as we now’ define it is similar to hypertension in that it is likely to comprise various disorders. As the specific etiological principles come into scientific investigation, we will probably reaffirm Bleuler’s concept of a group of schizophrenias. Nevertheless, it is likely that within this group of schizophrenias there is a core group that has a strong genetic component. This genetic factor creates a vulnerability that becomes manifest in psychosis when precipitated by environmental stresses.
In his introduction to the chapter, Klerman had said of Emil Kraepelin…
His textbook was significant in tlie history of psychiatry not because it was the first textbook of psychiatry but because it was one of die first to approach mental illness in terms of causation and etiology, using the principles of modern scientific medicine.
After classifying as many cases of mental illness as possible by etiology — those due to infection, to endocrine disorders, and so on — Kraepelin was left with a large group of patients whose psychoses began in young adulthood and went on for many years but who had relatively few deaths… Kraepelin proposed that these psychotic conditions with no established etiology be further divided into two groups, which he called “dementia praecox” and “manic-depressive insanity.” He justified this division on the basis of clinical features during the acute illness, long term course, and outcome.
… capturing the conundrum that continues to haunt these discussions – from among the psychotic cases with no established etiology, Kraepelin was a pioneer for approaching them in terms of causation and etiology. In the snippet from his section Schizophrenia as a Disease quoted above, he lays out a pathway to define such Diseases.

Most psychiatrists have traditionally accepted the disease model based on the syndromatic constellation and predictable course, suspecting a biological etiology to show itself sooner or later. The critics are less taken with the homogeneity of the syndromes [see a guest post from Sandy Steingard…], many seeing guild hegemony and medical training as unacknowledged complicating factors. That conflict is, if anything, more intense now than it was in 1978.

Gerald Klerman and the neoKraepelinians had an unprecedented impact on the subsequent course of psychiatry itself. On the other hand, the plight of the patients with the schizophrenias, particularly those with its chronic forms, have not seen much change in the four decades that followed.
Mickey @ 3:21 PM

Klerman 1978: the critics…

Posted on Saturday 17 December 2016

[continuing from an interesting read…, Schizophrenia: Science and Practice, Chapter 5: The Evolution of a Scientific Nosology, and Klerman 1978: on the medical model…].

In 1978, criticism of psychiatry was in full bloom. At the radical pole were people like R. D. Laing and Thomas Szasz who questioned whether psychiatry should even exist. In 1974, Thomas Szasz had published The Myth of Mental Illness, asserting that Mental Illness was a made-up construct used to control aberrant behavior eg an agency of the  State. And there were other criticisms to deal with. In the US as opposed to the rest of the world, psychoanalytic training was largely limited to physicians. They were prominent in academic and organized psychiatry, and had exerted a strong influence on the DSM-II classification of non-psychotic mental illness. The criticism from both within psychiatry and at large was that psychoanalytic theory and practice was subjective without an evidence or research base; that precise classification was of little interest with no distinction between normal and abnormal; that psychoanalysts were elitist; and that they were charging long therapies on the walking wounded to medical insurance carriers. All of these criticisms were obviously strong influences on Klerman’s neo-Kraepelinian Credo:
American, British, and Canadian psychiatry is today in the midst of a Kraepelinian revival that is becoming the dominant force among research and academic leaders, In contrast, the Meyerian school is currently in a phase of decline in American psychiatry. The Meyerian approach stresses the importance of personal experience and the uniqueness of the individual in his social context, in contrast to the Kraepelinian emphasis on categorizing diseases, an emphasis derived from continental European medicine, The neo-Kraepelinian credo includes nine propositions:
  1. Psychiatry is a branch of medicine.
  2. Psychiatry should utilize modem scientific methodologies and base its practice on scientific knowledge.
  3. Psychiatry treats people who are sick and who require treatment for mental illnesses.
  4. There is a boundary between the normal and the sick.
  5. There are discrete mental illnesses. Mental illnesses are not myths. There is not one but many mental illnesses. It is the task of scientific psychiatry, as of other medical specialties, to investigate the causes, diagnosis, and treatment of these mental illnesses.
  6. The focus of psychiatric physicians should be particularly on the biological aspects of mental illness.
  7. There should be an explicit and intentional concern with diagnosis and classification.
  8. Diagnostic criteria should be codified, and a legitimate and valued area of research should be to validate such criteria by various techniques. Further, departments of psychiatry in medical schools should teach these criteria and not depreciate them, as has been the case for many years.
  9. In research efforts directed at improving the reliability and validity of diagnosis and classification, statistical techniques should be utilized.
… In this country the neo-Kraepelinian point of view has been most strongly identified with the group at Washington University in St. Louis, whose leading spokesman are Eli Robins, Sam Guze, and George Winokur. Recently, they have been joined by a New York contingent including Donald Klein, whose book on diagnosis and drug treatment has probably been the most influential textbook of psychopharmacology in this country.  Klein has repeatedly asserted that psychiatrists cannot prescribe drug treatment appropriately without a careful description of the patient’s symptoms and syndromes.  Another New York investigator identified with the neo-Kraepelinian approach is Robert Spitzer, chairperson of the American Psychiatric Association Task Force that is drafting the third edition of the Diagnostic and Statistical Manual. The first draft of this volume has been met with controversy over the strongly descriptive approach it takes to psychopathology…
Note: While Adolf Meyer’s thinking had indeed heavily influenced the original DSM [1952], it was the psychoanalytic influence in the DSM-II [1968] that was the target to be supplanted here. Another omitted major player was Mel Sabshin, Director of the American Psychiatric Association from 1974-1997, who initiated and shepherded many of the changes being discussed here. To change sources for just a moment, this is a quote from Dr. Sabshin’s book, Changing American Psychiatry: A Personal Perspective, about the task they had undertaken:
How could a professional organization engineer a scientific revolution that changed its core? According to conventional wisdom, organizations respond; they do not initiate By Ihe 1970a psychiatry in the United States had begun to undergo massive changes. The postwar glow had been replaced by the new pressures for accountability on all of medicine. Many leaders in psychiatry deplored the ideological rifts that had divided the field and they called far a more unified, scientifically based profession. They deplored the "demedicalization" of psychiatry and its severe loss of credibility . I was one of the young leaders who had criticized the ideological divisions within psychiatry and had been searching for ways to improve its scientific status throughout my career. The field’s ideological schisms had weakened us serious, and psychiatrists bitter public disagreements were self-destructive To cover up these differences or to act solely because of the criticism was not in itself sufficient; psychiatry had to adopt a genuine commitment to science rather than to ideology, It needed to change the profession fundamentally if it was to become a respected part of medicine. To accede to the pressures without radical modifications of the field would not have convinced others that the profession had changed. A new strategy was essential! Producing the DSM-llI stated emphatically that psychiatry in America chose an evidence-based practice rather than ideology.
So now back to the Klerman chapter. Klerman is clear on where this was all headed:
The Kraepelinian revival is part of the general movement of psychiatry towards greater integration with medicine. This movement has multiple sources, professional, economic, social, scientific. Whatever its sources, the consequence for psychiatry is a greater concern for medical identity Applied to schizophrenia, there is greater attention to diagnosis in the classical medical tradition and to biological causes and treatments of this disorder.
This chapter by Gerald Klerman and the release of Robert Spitzer’s DSM-III two years later became the rallying texts of record for the dramatic changes in psychiatry that soon followed. The point of this post is to flesh out some of the criticisms of that time that helped shape what happened and what came to be…
Mickey @ 5:13 PM

Klerman 1978: on the medical model…

Posted on Friday 16 December 2016

Some of Gerald Klerman’s comments from 40  years ago [an interesting read…, Schizophrenia: Science and Practice, Chapter 5: The Evolution of a Scientific Nosology] could’ve been written yesterday, and you wouldn’t see any difference. After reviewing the oft told history of diagnosis and treatment of psychotic illness and discussing the neoKraepelinian Credo, he turns to the medical model:
The medical model has become a code word for controversy and debate, a slogan with which to rally one’s allies or to castigate one’s enemies. To psychiatrists concerned about defending their health insurance prerogatives, the medical model is an umbrella to justify continued support from Blue Cross, Blue Shield, or Aetna. To psychologists and other nonmedical practitioners anxious to be included under health insurance, the medical model refers to a narrow biological approach to the treatment of psychological problem. To behavior therapists, who apply the methods of B. F. Skinner, the medical model applies to dynamic psychotherapy and psychoanalysis, which they attack for postulating “underlying conflicts” of which symptoms are only manifest behaviors [It is ironic that this extension of the medical model to psychoanalysis would be rejected by a substantial group of nonpsychiatric physicians]. To black militants in an urban ghetto, the medical model is a term of contempt for the futile attempt of the community mental health center to treat social ills by treating individuals, whom the militants regard as victims rather than patients.
That is the way it felt in 1978. I’d never even heard the term medical model of disease as an internist – first encountering it as a psychiatry resident as I was being berated by a behaviorist trainee for believing in it. Klerman goes on to say how he understands the term:
[1] The disease concept. This is a theory of illness that evolved in the eighteenth century and is now held throughout Western industrial civilization.
[2] The sick role. As sociologists such as Parsons [1951] and Fox [1968] and anthropologists such as Fabraga [Fabraga et al. 1968] have pointed out, every known society has a category of the “sick role” for a special class of deviance, even non-Western societies that do not have modern notions of biology such as bacteriology or catecholamines. The sick role carries with it a set of rights and prerogatives, and mechanisms are specified whereby this role can legitimately be conferred on certain individuals by another group within society, the “healers.”
[3] The health care system. As society becomes more specialized and differentiated, the roles of both the sick and the healer become more complex. In modern industrial society there is a complex health care system that includes various kinds of specialists among healers, such as nurses, doctors, technicians, as well as complex institutions such as hospitals and universities and, recently, fiscal mechanisms such as health insurance and Social Security. In part, the debate over whether or not schizophrenia or anxiety are “diseases” is a conflict over whether individuals exhibiting such behaviors are legitimately to be given the rights and prerogatives of the sick role and whether or not the complex and powerful apparatus of the health care system shall serve their needs…
1978 was a very different time from the days of Emil Kraepelin when psychiatry was still associated with the asylum whose population who could be classified by the syndromes he so carefully described. By 1978, there were a treatments for a broad range of behavioral and emotional conditions  that had unclear boundaries and didn’t easily groups treated by psychiatrists, psychoanalysts, psychologists, social workers, etc. Those in non-medical specialties were not reimbursed by medical insurance and were vocal about being excluded. Also, the insurance carriers balked at including these patients in the "sick" role along with those with physical ailments or even the classic psychiatric syndromes. Thus, Klerman’s comments about legitimacy – an issue that was very much on the front burner in those days. Klerman goes on:
Looked at in these terms, mental illness and the medical model are social constructs; they are inventions of modern society that attempt to make sense of and deal with the real phenomena of pain, distress, anguish, and disability experienced by certain individuals. However, to say that the medical model or the concept of mental illness is a social construct is not to say that it is a myth or that it is invalid. All social constructs are not myths and they are not necessarily untrue. After all, “the rights of man,” the electron, and the university are also social constructs. They are not facts given in nature, but rather are complex ideas developed by historical forces and legitimated by consent. The concept of illness is not arbitrary but reflects areas of shared consensus, embodying truths arrived at by rules of evidence.

The application of the medical model to mental illness was an achievement of the nineteenth century, when Philippe Pinel at the Salpetriere was responsible for bringing medical leadership to the asylums. For centuries Western Europe had had institutions for lunatics, but these asylums had not been considered appropriate for medical supervision. Usually they were run by religious orders or were parts of jails or prisons. Furthermore, the courts had not distinguished “madness” and “badness” as clearly as became the norm in the early part of the nineteenth century, as a result of the eighteenth century Enlightenment. This distinction between being mad and being bad was regarded as a major humanitarian gain, motivated by humane and benevolent intents.
The psychiatry of 1978 was also very different from the 2016 version. Psychoanalysts at that time were all physicians and heavily represented in the upper levels of the Departments and Professional Organizations. Schizophrenia was one of the least conflicted areas, but even then, you can see the difference just by looking at the chapter headings of this book.

    Historical and Philosophical Perspectives
  1. Approaches to Understanding Schizophrenia – John C. Shershow
  2. The Manifest and the Scientific Images – Etiology: The Nature-Nurture Interaction
  3. Heredity and Environment – Seymour Kety
  4. A Developmental Theory – Theodore Lidz
  5. Bioscientific Research
  6. The Evolution of a Scientific Nosology – Gerald L. Klerman
  7. Biochemical Investigation – Ian Creese and Solomon II. Snyder
  8. Psychopharmacology – Leo Hollister
  9. Care and Treatment: The Human Dimension
  10. The Patient and the Community – Jonathan F. Boras and Elaine Hatow
  11. Psychotherapy – Daniel P. Schwartz
  12. The Surrogate “Family,” an Alternative to Hospitalization – Loren II. Mosher and Alma Z. Menn
And while Klerman’s chapter was about Schizophrenia, it was also about nosology for the whole of mental illness. Reading this section about the medical model, I doubt that many psychiatrists or physicians would disagree with much of it. It certainly fits my understanding [then and now], though it wouldn’t sit well with psychiatry’s critics – then or now. They would argue that to call something a Disease, you needed a known cause and a biomarker. They would likely see his notion of a social construct as a rationalization or worse, and go on to talk about why it’s harmful to think that way. So on to the critics in 1978 in the next post…
Mickey @ 4:31 PM

an interesting read…

Posted on Thursday 15 December 2016

I came to psychiatry from practicing Internal Medicine with something specific in mind to learn about – and it wasn’t psychiatric patients. It was the subset of medical patients whose problems were clearly mental – and there were plenty of them. But in a psychiatry residency, that’s not where you start. It’s on the wards of a beleaguered City/County hospital populated with psychotic people and an emergency room called the Crisis Intervention Service [throw in that it was the end of the de-institutionalization period]. I found myself in the middle of interesting times, to say the least. By 1978, I was one year out of residency, in a psychoanalytic training program, in charge of that Crisis Intervention Service, and having a fine time. There was a book published that year that I didn’t know about, but it was a harbinger of a really big change coming to psychiatry:

Schizophrenia: Science and Practice, Edited by J. C. Shershow. [Pp. 248]; Harvard University Press: Cambridge, Massachusetts. 1978. Chapter 5: The Evolution of a Scientific Nosology by Gerald Klerman.

A couple of years later [1980], there was another book that nobody missed [the DSM-III], ushering in that big change – the medicalization of psychiatry.

I’ve quoted Klerman’s neoKraepelinian Tenets frequently but never had the whole chapter in hand. Some time back, I ran across a dogeared copy of the Shershow book for $2.53 online and ordered it. In the holiday, post-election lull, I opened it up and ended up reading the whole book. It was a window into to state of psychiatry at the dawn of the new era, the dawn of my own psychiatric career. The Klerman chapter was a lot more that just the neoKraepelinian Tenets. I’m going to write about it some, but I thought others of you might want to read what he had to say, so I Scanned/OCR’d it, and it can be downloaded here as a .doc file.

Trust me. It’s an interesting read [11 pages]…
Mickey @ 2:02 PM