collusion with fiction…

Posted on Thursday 16 October 2014

After the last post [a betrayal…], Psycritic commented that Celexa® had also been approved for adolescent depression by the FDA [I had said "Only Prozac®"]. I had a vague memory that something had happened, but was confused, so I took a look in Drugs @ FDA and got more confused. Then I tried Google and found a 2011 Canadian review of Celexa/Lexapro in adolescents that was illuminating. The part that got my attention was towards the end:
by Carlo Carandang, Rekha Jabbal, Angela MacBride, and Dean Elbe
Journal of the Canadian Academy of Child and Adolescent Psychiatry. 2011 20[4]: 315–324.

FDA Approval Process & Legal Action
While only one RCT for escitalopram was statistically superior to placebo on the primary outcome measure, according to Forest Laboratories, Inc. [US manufacturer of Lexapro] the FDA decision to approve escitalopram was based on two RCTs – the escitalopram RCT with positive results and an earlier trial with citalopram. “Escitalopram is the only active enantiomer of the racemic drug citalopram, so we considered it reasonable to [deem] the positive citalopram study along with the positive escitalopram study as sufficient evidence to support the approval,” said Karen Mahoney, an FDA spokesperson. A 2002 application for a pediatric indication for citalopram had previously been rejected by the FDA, and the US patent for citalopram expired in 2003.

The FDA approval decision for escitalopram came shortly after filing of a federal civil suit alleging Forest Laboratories, Inc. had illegally marketed escitalopram and citalopram for off-label use in children and adolescents from 1998 to 2005. The suit also alleged the company suppressed publication of a negative citalopram trial, and reports of increased suicidality in pediatric patients. This lawsuit was joined with another lawsuit regarding another Forest Laboratories, Inc. product levothyroxine, and was eventually settled in September 2010 for the sum of $149 million.

The citalopram trial [Wagner et al., 2004] that formed part of the basis for escitalopram FDA approval was alleged to have been written and submitted by a medical “ghost-writer” on behalf of Forest Laboratories, Inc. In April 2009, one month after the FDA approval for escitalopram in adolescents was granted, Forest Laboratories, Inc. admitted that a medical communications company, Prescott Medical Communications Group was not acknowledged as a contributor to the article at the time of publication. This practice is not allowed by the American Journal of Psychiatry, and an editor’s note regarding correction of this matter was published in August 2009…

At this point, I will admit that I had lost interest in my initial quest [FDA Approval of Celexa/Lexapro] because I’d run across something that was far more interesting. So let’s start over. The new topic is the 2009 Editor’s Note in the American Journal of Psychiatry about their earlier 2004 article on Celexa:

Editors’ Note

The article "A Randomized, Placebo-Controlled Trial of Cilalopram for the Treatment of Major Depression in Children and Adolescents," published in the June 2004 issue of The American Journal of Psychiatry [vol. 161, pp 1079-1083] is alleged by the United States Department of Justice in an ongoing suit to have been written and submitted to the Journal by a commercial medical writer on behalf of Forest Laboratories, Inc.

We requested responses from Drs. Karen Dineen Wagner, Adelaide S. Robb, and Robert L Findling [authors in their role as investigators in the clinical trial at their respective universities], Dr. William E. Heydom [the senior Forest laboratories study director], and Forest laboratories. Drs. Wagner, Robb, and Findling reported that they had received an initial draft from Dr. Heydom to which they contributed through several drafts, This paper was submitted as a Brief Report, which the Journal’s editors requested be resubmitted as a full-length Article. Drs. Wagner, Robb, and Findling report that they contributed with Dr. Heydorn to the resubmission and that they were not aware that Dr. Heydorn was working with a commercial writer. Dr. Heydorn did not respond to our request for comment.

A Forest laboratory official in a letter of April 17, 2009, acknowledged that: "Forest retained a medical communications company to assist with preparation of the manuscript, a practice we understand to be common among pharmaceutical companies. Following discussion with the article’s named authors, the medical communications company created an initial draft of the manuscript. Over the course of time, however, from the initial draft to the final publication, the manuscript went through multiple iterations with the input of the named authors, as well as others who reviewed and commented on the manuscript; throughout this process, the medical communications company continued to provide copy editing, formatting, referencing and other editorial support. Hie manuscript was then submitted to AJP by Dr. Wagner, who, along with the other named authors, maintained control over the final content of the manuscript."

We are satisfied that the named contributors of this article satisfy the criteria for authorship as set forth in the "Uniform Requirements for Manuscripts Submitted to Biomedical Journals" from the International Committee of Medical Journal Editors. However, the Journal’s Instructions to the Authors in 2004 and our policy today do not allow contributions by unnamed writers to the preparation of a paper. Thus, the editorial contributions of Prescott Medical Communications Croup should have been acknowledged in the published article as required at the time the article was published.

Furthermore, Forest Laboratories failed to disclose to the Journal that it was aware of data from a study by Lundbeck that showed increased suicidality in children and adolescents who were treated with citalopram. Authors and sponsors are expected to disclose the existence of all data that affects the interpretation of their study. This note will appear in Medline and other databases as a Comment on the paper.

The official complaint [United States and Christopher R. Gobble v. Forest Laboratories Inc. and Forest Pharmaceuticals Inc. Civil Action No. 03-10395-NMG] is posted at …

Robert Freedman, M.D.

Michael D. Roy
Editorial Director
American Journal of Psychiatry. 2009 166[8]:942-943.

I’d never seen this before. It’s like a picture window into how much competition there was for the adolescent depression market, and how corrupt the whole enterprise had become. While we can respect Editor Robert Freedman for publishing this Editor’s Note, his certification of authorship is, of course, a sham – as is Dr. Wagner’s claim that she knew nothing of the ghost authoring. In the first place, the paper was presented to her already drafted. Whether it was written by Forest senior study director Dr. William Heydorn or someone else, it certainly wasn’t Wagner’s or her co-investigator’s work. And since she was in the author role in multiple other ghost-written trial reports at that time, her claim of naïveté about hired professional writers holds no water. She was everywhere in those days – Paxil, Prozac, Zoloft, Celexa – an author on each of these of ghost-written journal articles – all four claiming efficacy and safety in depressed adolescents for their respective drug:

Paradoxically, Karen Wagner and some of her co-authors in these studies were later on the ACNP [American College of Neuropsychopharmacology] Task Force convened to report on these questions after the Black Box Warning was added by the FDA in 2004:
And this kind of hyperbole was standard fare whenever ghost-writing was exposed:
    A Forest laboratory official in a letter of April 17, 2009, acknowledged that: "Forest retained a medical communications company to assist with preparation of the manuscript, a practice we understand to be common among pharmaceutical companies. Following discussion with the article’s named authors, the medical communications company created an initial draft of the manuscript. Over the course of time, however, from the initial draft to the final publication, the manuscript went through multiple iterations with the input of the named authors, as well as others who reviewed and commented on the manuscript; throughout this process, the medical communications company continued to provide copy editing, formatting, referencing and other editorial support. The manuscript was then submitted to AJP by Dr. Wagner, who, along with the other named authors, maintained control over the final content of the manuscript."

It’s time to stop arguing with such nonsense as if it might be credible. By now, we all know what happened in these trials. The contract CRO organized and ran the trials. The sponsoring/funding pharmaceutical company analyzed and manipulated the data, then turned it over to the contract medical writers. The named authors may or may not have done some editing along the way after it was written, but their main function was to provide the academic credentials needed for a ticket into the peer-reviewed medical journals or a poster at a meeting. These heavily worked-over studies regularly amplified efficacy while downplaying adverse events. When the FDA finally added the black box warning, it put a glitch in their profit projections, so the involved industries set about publicly debunking the FDA warnings in their now decade-long campaign [as described in a betrayal…].

As for the specific suit that brought this particular bit of ghost-writing into the public eye? The case against Forest Laboratories ultimately settled [see September 15, 2010: Drug Maker Forest Pleads Guilty: Will Pay More Than $313 Million to Resolve Criminal Charges and False Claims Act Allegations]. But even in this instance where the ghost-writing was exposed and admitted, the American Journal of Psychiatry, official journal of the American Psychiatric Association, chose to collude with the fiction that the academics on the by-line were genuine authors, and the journal left the study in place.

The American Psychiatric Association seems to be poised to engineer yet another identity shift in psychiatry [the prequel…, anything but over…, the sequel I…], apparently intending to proceed without acknowledging the misadventures of the last makeover, without participating in the reform efforts like Data Transparency or revised Conflict of Interest policies, without correcting or at least flagging the large fiction sections of our journal libraries. The American Academy of Child and Adolescent Psychiatry meeting in San Diego next week appears to be moving along the same silent path. Beside the obvious moral and ethical tangles involved, it seems to me that there’s an enduring liability being assumed by the professional organizations, the academic community, and our peer reviewed journals when they incorporate this attitude of denial and rationalization. The active participants in the deceit and corruption that accompanied the industrial invasion of academic and organized psychiatry actually represented only a segment of psychiatrists, albeit a segment in high places. Many of their names are already on this page, most are cataloged throughout this blog. And while too many in the specialty followed their lead, it was also the only major highway open to traffic, and it’s easy to forget how little many of us knew of this before the last six or seven years. That’s not intended as an excuse, but rather a commentary on the state of play.

If our professional organizations, our academic departments, and our peer reviewed journals continue to leave this big piece of history and its published record unexamined and uncorrected, the specialty of psychiatry incorporates it as its own rather than seeing it as the foreign body it deserves to be. And any of our current leaders who participate in this strained policy of rationalization and denial might just as well have been among the ranks of the worst of the KOLs, the guest authors, or on the advisory boards and the speaker’s bureau payroll – complicit in creating and perpetuating a fiction in a space reserved for scientific and therapeutic intention…
Mickey @ 1:00 PM
Filed under: OPINION
a betrayal…

Posted on Wednesday 15 October 2014

New York Times
by Robert Gibbons and J. John Mann
October 7, 2014

The changes in treatment and attitude brought on by Prozac prompted two colliding points of view. One was that antidepressants were overprescribed and people were encouraged to turn to a pill to solve all their problems. Another viewpoint was that major depression was one of the most debilitating illnesses in the world and was mostly untreated or undertreated, and even though we were now prescribing a lot of antidepressants there were still too many people with moderate to severe depression that remained untreated.

A third claim intruded into this debate, namely that the efficacy of antidepressant medications is overstated and the best evidence of effectiveness was in only the most severely ill patients. In an effort to shed light on this question, we obtained much of the world’s complete longitudinal data on randomized controlled trials of the antidepressants fluoxetine [Prozac] and venlafaxine [Effexor] in depressed patients conducted by Lilly, Wyeth and the National Institute of Mental Health. We included studies regardless of whether they demonstrated the medications were effective in order to get the clearest picture possible of the efficacy of these widely used antidepressants.

From the statistical model that synthesized these data across all studies separately for each age category, we computed estimated response and remission rates. We found an improvement in depression regardless of age in both medications relative to a placebo pill. Interestingly, the greatest benefit in terms of response and remission rates was seen in children, followed by adults, and then by more modest effects in the elderly. There was no evidence that severity of depression made a difference to how well the antidepressant medication worked. Based on these findings we concluded that antidepressants work across the lifespan, in patients with moderate or severe depression.
In a recent blog post, I reviewed Dr. Gibbons’ most recent paper, yet another assault on the Black Box Warning, this time using commercial databases [gibbons everlasting...] and cataloged his many previous attempts to cast doubt on the 2004 FDA Black Box Warning. He has made similar attempts to debunk the warnings on Neurontin® and Chantix® [very monotonous…].. This recent NYT comment is based on his 2012 articles with the same intent. I had offered a strong criticism at the time of those 2012 articles [an anatomy of a deceit 1… etc.], as did many others. But in gibbons everlasting…, I left out something important, something mentioned by Dr. Bernard Carroll both in his comment here and to the New York Times. So I thought I’d just run it around again:
by Gibbons RD, Coca Perraillon M, Hur K, Conti RM, Valuck RJ, and Brent DA
Pharmacoepidemiologic Drug Safety. 2014 Sep 29. doi: 10.1002/pds.3713. [Epub ahead of print]

PURPOSE: In the 2004, FDA placed a black box warning on antidepressants for risk of suicidal thoughts and behavior in children and adolescents. The purpose of this paper is to examine the risk of suicide attempt and self-inflicted injury in depressed children ages 5-17 treated with antidepressants in two large observational datasets taking account time-varying confounding.
METHODS: We analyzed two large US medical claims databases (MarketScan and LifeLink) containing 221,028 youth (ages 5-17) with new episodes of depression, with and without antidepressant treatment during the period of 2004-2009. Subjects were followed for up to 180 days. Marginal structural models were used to adjust for time-dependent confounding.
RESULTS: For both datasets, significantly increased risk of suicide attempts and self-inflicted injury were seen during antidepressant treatment episodes in the unadjusted and simple covariate adjusted analyses. Marginal structural models revealed that the majority of the association is produced by dynamic confounding in the treatment selection process; estimated odds ratios were close to 1.0 consistent with the unadjusted and simple covariate adjusted association being a product of chance alone.
CONCLUSIONS: Our analysis suggests antidepressant treatment selection is a product of both static and dynamic patient characteristics. Lack of adjustment for treatment selection based on dynamic patient characteristics can lead to the appearance of an association between antidepressant treatment and suicide attempts and self-inflicted injury among youths in unadjusted and simple covariate adjusted analyses. Marginal structural models can be used to adjust for static and dynamic treatment selection processes such as that likely encountered in observational studies of associations between antidepressant treatment selection, suicide and related behaviors in youth.
In gibbons everlasting… I listed Dr. Gibbons previous articles on this topic since the Black Box Warning was issued by the FDA in 2004. While the FDA meta-analysis supported the case that suicidality is an uncommon but dangerous side effect of the use of SSRIs in adolescents, it was the case reports heard by the panel that lead them to append the warning. Dr. Gibbons statistical analyses have chased disproving the warning all over the map – from multi-country comparisons, the CDC statistics, proprietary databases, VAH statistics, drug company clinical trials, etc. always chasing the same hypothesis, the same one recently espoused by Lu et al [all databases are not created equal…]:
    The Hypothesis [my version]:
    The Black Box Warning is wrong. It scared doctors who prescribe fewer antidepressants to adolescents, depriving them of needed treatment, thereby increasing the incidence of suicidality.
In his previous outings, over the last decade, Gibbons has stuck to attempts at using population meta-analyses to show that antidepressants don’t increase the incidence of suicidality. His articles are difficult because they can’t be vetted [not enough information] and they involve complicated statistical analyses that he describes, but does not show. They are invariable followed by media reports, The ones mentioned in the NYT above were followed by a media blitz [the campaign…]. Invariably he finds no evidence of suicidality in adolescence on SSRIs. There are several points to make about these papers:
  1. There is no strong evidence that SSRIs are even effective in adolescent depression. Only Prozac was approved, and that was early on before these questions were raised. So the notion that effective treatment is being withheld is unsubstantiatable.
  2. This syndrome is not common, but once you see it, you have no question of causality [at least I didn't]. It’s not a population study thing, it’s a case report thing. And there are plenty of cases of completed suicides among those reports. I don’t even treat adolescents, but I personally know of several such cases. The cases are substantiatable.
Now to the most recent paper and Dr. Carroll’s point. After a decade of trying to prove it doesn’t happen, in this new study, it seems that it does happen after all:
    "For both datasets, significantly increased risk of suicide attempts and self-inflicted injury were seen during antidepressant treatment episodes in the unadjusted and simple covariate adjusted analyses."
And then Dr. Gibbons undoes it with some kind of factor analysis that is opaquely described and unintelligible to any physician no matter how statistically sophisticated. Carroll calls it "voodoo statistical hand waving," but even that is forgiving because Gibbons’ presentation is effete and insulting to the reader. So the question really comes down to Why do these recurrent articles against the Black Box Warning keep coming? with each study more questionable and convoluted than the last. They are presented as being in the service of child advocacy – hardly likely. One hint about their persistence is in looking at the authorship:
by Nemeroff CB, Kalali A, Keller MB, Charney DS, Lenderts SE, Cascade EF, Stephenson H, and Schatzberg AF.
Archives of General Psychiatry. 2007 64[4]:466-72.
Three authors on Senator Grassley’s list, chairmen who lost their chairs in the following years; four customers of Sally Laden, notorious ghost-writer; and the medical director and emplyees of Quintiles, a major CRO. Then:
News coverage of FDA warnings on pediatric antidepressant use and suicidality
by Barry CL and Busch SH.
Pediatrics. 2010 125[1]:88-95.
These studies were financed by the National Bureau of Economic Research, a think tank founded by a member of the Eli Lilly Board at the time [see pretty loud coi…, the NBER study, and tortured numbers…]. Then there are the numerous studies of Dr. Gibbons who has testified for Pfizer in the cases involving SSRIs, Chantix, and Neurontin. Throw in the recent study by Lu et al [see all databases are not created equal…], employed by Harvard’s Managed Care conglomerate. There are others, but nowhere among them are the expected child psychiatrists or psychologists. This is pretty much an industry effort all the way through.

This is a strange story about an unlikely collection of people diligently pursuing the debunking of a clear, if uncommon, adverse effect of a class of medications when given to youth – a potentially fatal complication. It proposes to be advocacy for teens being denied effective treatment, yet even the evidence for its effectiveness is decidedly underwhelming. The people producing these studies are not from the community of people actively involved in treating the populations studied, and the evidence they present is at some distance removed from the actual patients [claims databases, population statistics, etc.], invariably connected with some industry [PHARMA, Managed Care, etc.], and generally accompanied by some kind of prominent media coverage like the NYT piece I started with above. The important question is Why? Why do they keep at it? Of course we can’t truly know their motives, but it’s a pretty good guess that it’s not what the articles say. And though unprovable, we can easily hypothesize for ourselves what drives this campaign. Almost anyone reading this could come up with a set of motives, but I want to say a few of them out loud:
  • PHARMA: Depressed adolescents are common – a lucrative market for the sale of antidepressants.
  • PHARMA: The suicidality Adverse Event was downplayed in the original reports – a litigation liability.
  • Managed Care: The cost of delivering care other than drugs to depressed teens would be expensive.
  • Psychiatry: The KOL psychiatrists have based their reason d’etre on the effectiveness of the SSRI drugs, talking about ‘depression’ as if it’s a ‘disease entity’ and the SSRIs as the ‘treatment’ for that ‘disease entity’. They essentially define psychiatry by this disease/treatment dyad. 
In my mind, this is an affront to the biological psychiatrists who have given us effective treatments for the subset of depressed people who have the depressions that fit the disease model – eg Manic Depressive Illness, Melancholia. It is an affront to the psychotherapists from a variety of disciplines who work with adolescents who present with depression. It is an affront to psychiatrists who don’t subscribe to the neoKraepelinian dictum that all mental illness is biological. And it is an affront to the scientists who adhere to the scientific method and use its tools carefully – hypervigilant to the introduction of bias, including their own. But first and foremost, it is a betrayal of the trust of the depressed adolescents, their parents, and the practitioners who treat them…
Mickey @ 2:00 PM
Filed under: OPINION
«evidence-based medicine» some evidence

Posted on Tuesday 14 October 2014

In my medical lifetime, I’ve watched medicine turned into a business enterprise. I was fortunate to be able to hide in the cracks and mostly evade that myself – haunting places like training programs, academia, military service, a solo practice off the grid, a charity clinic. It’s not that I’m averse to systems. I’m just specifically wary of systems for-profit being involved with anything that purports to give care. And I’m wary of systems not-for-profit that are funded as start-ups that are slated to later carry the ball on their own. The best medical system I ever worked in was an overseas military hospital. The worst was everything else. These are all acquired feelings at the end of a career, not something I started with.

The top graph tells the story. The relative cost of medical care in the United States has doubled [since the days I first heard of Managed Care around the late 1970s]. And the reasons are obvious everywhere you turn. Fee churning Emergency Rooms in for-profit Hospital Corporation owned facilities; Direct-to-Consumer ads increasing drug sales six-fold; inflated guidelines fueling unnecessary testing and treatment; controlling Managed Care monitors demanding evidence of efficacy but giving no evidence of their own [efficacy]; abusive pharmaceutical advertising and pricing; the constant whirr of the MRI machines in the background pouring out normal studies. The sick and those of us who treat them are a captive audience with no clear alternatives in sight. We’ve been an easy mark for decades. And it’s as if there’s an inertia from a more benevolent time, memories of a different ethic – something that keeps us naive about the impact that the business·i·fi·ca·tion of medicine has had on our lives and our healthcare. And speaking of evidence, the bottom graph is one of the many that make the same indictment – it hasn’t been worth it.

It’s funny, the cynicism in that last two paragraphs is evanescent. I can get to feeling it in spades, work myself up into a righteous froth – and then watch it evaporate within minutes. It happened today. I hadn’t worked in a couple of weeks – weddings, funerals, other things – but when I went to the clinic today, the cynical gloom lifted and I had fun. Maybe that’s not the right word. I got into the problems that came my way and did what I’ve learned to do. Some might say I wrote too many prescriptions. Others might say I didn’t write near enough. Some would say I didn’t need all those years of training to do what I actually spent my time doing today. Since I don’t get paid, it would be hard to say I didn’t earn my keep. My point is that I felt none of that uncomfortable cynicism I can feel at other times. The Licensed Professional Counselor I worked with and I saw several cases together we pass back and forth in our version of Collaborative Care, the same with the Internist and the Nurse Practitioner.

After work, I came home and saw those graphs up there on my desktop, prepared before I left town for the weekend. They seemed far away from the morning’s activities. It took a bit to recall why I’d hunted them down. I’ll get back to that I’m sure. But right now, I think I’ll just let the good feeling linger…
Mickey @ 8:44 PM
Filed under: OPINION
a thing to share…

Posted on Monday 13 October 2014

from ChopstiX restaurant
Raleigh NC
Mickey @ 7:09 PM
Filed under: OPINION
the sequel I…

Posted on Sunday 12 October 2014

The order of things:
  1. the prequel…
  2. unanswered questions…
  3. the sequels
Whether you think the introduction of the DSM-III in 1980 was a necessary specialty-saving intervention, a hostile take-over, a revolution, a bloodless coup d’état, right or wrong, isn’t what this post is about. It’s about the long term ramifications of a professional organization itself orchestrating a major change in the direction of a profession. Here’s what the architect of that change had to say about how that came to be:
    "How could a professional organization engineer a scientific revolution that changed its core? According to conventional wisdom, organizations respond; they do not initiate. By the 1970s 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 for 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 the scientific status throughout my career. The field’s ideological schisms had weakened us seriously, and psychiatrist’s bitter public disagreements were self-destructive. To cover up these differences or to act solely because of the criticism was not in and of 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 pressure without radical modifications of the field would not have convinced others that the profession had changed. A new strategy was essential! Producing the DSM-III stated emmphatically that psychiatry in America chose an evidence-based practice rather than ideology."
    Dr. Mel Sabshin in Changing American Psychiatry: A Personal Perspective
As one who was much younger in the profession at the time, but not in-the-know, I was oblivious to all of that. So what happened over the next several years was dramatic and unexpected, at least to me [irony I…, irony II…, irony III… ]. Independent of the reasons, the correctness, or the content of what happened in those days, the changes resulted in a consolidation of power within the APA [American Psychiatric Association] that persists to the present – a "top down" power structure as described by Dr. Sabshin.

The turn of the century saw a very different psychiatry from the days that produced the DSM-III. Most practicing psychiatrists were doing medication management using a host of new drugs that had poured from the pharmaceutical industry pipeline. The journals were filled with clinical drug trials and biological research articles. What started in the DSM-III as an open question…
    For most of the DSM-III disorders, however, the etiology is unknown. A variety of theories have been advanced, buttressed by evidence – not always convincing – to explain how these disorders came about. The approach taken in DSM-III is atheoretical with regard to etiology or pathophysiological process except for those disorders for which this is well established and therefore included in the definition of the disorder. Undoubtedly, with time, some of the disorders of unknown etiology will be found to have specific biological etiologies, others to have specific psychological causes, and still others to result mainly from a particular interplay of psychological, social, and biological factors.
    DSM-III Introduction – page 7.
… wasn’t so open any more, at least in mainstream psychiatry, and the research thrusts were to solidify the dominant view of biological causality and treatment. An example of the continued centralization of power within the APA was the commissioning of a Task Force at the turn of the century to produce a DSM-5 that was directly keyed to the hypothesized biological substrate of the various disorders.

As mentioned in the prequel…, the 2014 landscape in psychiatry is very different from the year 1980 or even the year 2000. Exposures of scientific and commercial misconduct swept through academic psychiatry and the pharmaceutical industry; the psychopharmacology pipeline ran dry; PHARMA took "a runner" from CNS drug development altogether taking its liberal support of academic institutions and the APA with it; the DSM-5 Revision floundered in something of a public spectacle; and there was a growing backlash against the monocular biomedical directions in psychiatry in general and the efficacy and safety of the widely used medications in specific. Most psychotherapy had been handed off to other disciplines in the 1980s. These days, most medication is being prescribed by Primary Care Physicians. Most Psychiatric hospitals are closed. Many chronically mentally ill patients are in jail, prisons, or shelters. And the ACA [Affordable Care Act] looks to turn the third party system further upside down. After a frantic year or so trying to woo PHARMA back without success, the place and fate of psychiatry are again in question – endangered species? obsolete? severe shortages? train more? train less? train none? are the kind of phrases being thrown around [or hurled].

Most practicing psychiatrists have grown up in the post-1980 era – by which I mean that within the body of the APA, there’s little apparent turmoil or faction. If there’s much of a call for change or reform coming from inside the ranks, I don’t know about it. Incidentally, there are many psychiatrists who are off the grid for a multiplicity of reasons, suggesting that there’s not much room for discord, controversy, or dialog within the APA. And so to the subject: the APA’s continued assumption that it is tasked with defining, rather than representing, the body psychiatric – persistent since the the days of Sabshin and Spitzer.

In unanswered questions…, I was mentioning several articles in the PsyciatricNews where Presidents of the APA are talking about the future of psychiatry being in Integrative Care, Collaborative Care, and Population Health. I added another in which the APA is offering a course on Recovery [with a capital R] meaning Recovery as it is formulated by SAMHSA [Substance Abuse Mental Health Services Agency] or as you might read about it on many websites opposed to the current medication-heavy brief-contact psychiatric practices. That is a huge topic that I’m not going to talk about substantively in this post, not because I don’t have something to say or don’t want to say it, but for the opposite reason. It’s too big for a simple blog post [and there are too many distracting rants along the way]. Right now I want to talk about just one simple thing. There is a growing trend in what’s coming from the upper levels of the APA that the redirection of psychiatry and the redefinition of psychiatrists is what the organization is setting out to do – what it’s supposed to be doing.

That’s a bad habit that needs a great deal of reflection, because that’s what the APA did in 1980 – created a psychiatry that fit the prevailing vision of what physicians should do in the face of Managed Care’s insistence – see sick people, make a diagnosis, give them the treatment for their sickness, then send them on their way. So the APA created a dictionary to catalog those diseases in concrete terms, and industry went about coming up with a compendium of treatments keyed to the catalog. There are some mental diseases that can be classified in that way, and some treatments that can be used in that way. But being the only model in town, it inappropriately generalized to be the model for all comers. Then the medication makers jumped on board, engaged with psychiatry, and made an ill-gained fortune. We now live in a world where the system that the APA actively created, encouraged, and maintained is currently a very big problem – and psychiatrists are villified for going along with it.

Dr. Sabshin’s retrospective above makes it clear he knew that leveraging the DSM-III Revision to change to direction of psychiatric practice was highly unusual…
    "According to conventional wisdom, organizations respond; they do not initiate."
My point is that the resulting consolidation of power persisted to the present along with the role of the APA in a defining psychiatry. And as to the goal of reducing discord …
    "The field’s ideological schisms had weakened us seriously, and psychiatrist’s bitter public disagreements were self-destructive."
… it was achieved in spades. Many psychiatrists converted and others just left – having no place at the table. Third Party payment schedules moved psychiatrists into the medication management slot while psychotherapies and counseling went to panels of other mental health specialties, tightly controlled by Managed Care. There has been little controversy or debate among the membership of the APA since those days. Even in these later years of scandal over conflicts of interest, ghost writing, jury-rigged clinical trial publications, false advertising, speaker’s bureaus, distorted reporting of efficacy and adverse events, etc., the outcry and movements for reform have come from outside the APA, mostly outside psychiatry. And as the chronic mental patients filled up our prisons in the years after de-Institutionalization, the APA has had little to say. We could’ve used a lot more discord along the way.

The APA’s assumption of power may well have been justified in the 1970s, but holding onto it wasn’t. The APA was heavily supported by the Pharmaceutical Industry, and supportive in kind. When the ethical misbehavior, the conflicted commercial connectedness, and the invasions of our literature became crystal clear to the whole world, the APA was silent or defensive. Ironically, the revolution launched with the cry against ideology…
    "Producing the DSM-III stated emphatically that psychiatry in America chose an evidence-based practice rather than ideology."
… has created a professional organization that is a bastion for a particular notion of overall causality and treatment that has all the earmarks of a fixed ideology, and in spite of a massive research effort, an ideology that operates with little in the way of a strong confirming evidence base except in limited areas.

And now the APA is making noises about another major redefinition as we move into the future, and appears to be pitching it to its membership. While there’s much to be said about what’s being pitched [next post], there’s a question that comes before that. Should the APA even be on the pitching mound at this point. The suggested changes aren’t coming from the floor of the membership. They’re not coming from some subgroup of psychiatrists intensely studying a problem, nor a subgroup of practitioners who have long-occupied the suggested roles, nor the halls of physical medicine, nor being introduced as a topic for general debate within psychiatry itself. My premise is obvious, that the centrality of the APA upper echelon in defining psychiatry has been maintained and used to keep psychiatry on a path controlled by industrial and ideological forces – a legacy from Sabshin, Spitzer, and 1980s DSM-III – whether that was their intent or not and it’s being exerted once again.

Now, the APA is pushing a major change in the directions of the profession in the face of the exhaustion of the current paradigm that will have not only an effect on practice and third party reimbursement, it does nothing to deal with the plight of the chronic patients now incarcerated; it does nothing to curb overuse of psychiatric medications particularly by primary care; it moves clinical psychiatry to a non-patient-contact role; it’s based on a theoretical role originating from outside the specialty; and it looks as if it will perpetuate the very things in need of change. These are goals that have been pushed by Managed Care and PHARMA, hardly by psychiatrists or even its opponents – more like retiring the side than reform. And it’s coming from the APA – the only negotiating force in town. Is this to be the legacy from the 1980 revolution? Is the APA representing psychiatry, our patients, or simply itself and some inappropriate assumptions of power and misguided decisions all along the way? Will practicing psychiatrists continue to leave their fate in the hands of an organization that unilaterally lead us down this path?

Undoubtedly, changes need to be made once again. But these changes? as being presented? dictated by the APA? It sounds like the decision of a group that has painted itself into a corner and further abandoned the practice of clinical psychiatry, taking charge at a time it needs to be taking stock, and operating on an anachronistic centralization of power whose utility has long passed…
Mickey @ 9:00 AM
Filed under: OPINION
anything but over…

Posted on Thursday 9 October 2014

Tom Jefferson is a researcher/reviewer with the Cochrane Collaboration. He was involved throughout in the Tamiflu story and the Cochrane meta-analysis of the Tamiflu Trials. He’s as good a resource as we might find for understanding what the EMA’s recent policy decision really says:
British Medical Journal blog
by Tom Jefferson
7 Oct, 14

The European Medicines Agency [EMA] has now released the final version of its policy on the prospective release of clinical reports of trials, which are submitted by sponsors to support marketing authorisation applications [MAAs]. The agency has said that it will—at a future date—determine how to release individual participant data [IPD].

The policy—to become effective from 1 January 2015—explains what will be released and how. Full clinical study reports will not be released. Rather, selected parts of clinical study reports will be released, including the “core report” [although this is not labelled as such in the text], the statistical analysis plan, protocol and its amendments, and a blank case report form. [To those familiar with clinical study reports, these are sections 1-15, 16.1.1, 16.1.2, and 16.1.9 of the ICH E3 guidelines.] The policy document does not explain why full clinical study reports will not be released.
This «core report» for the CSR [Clinical Study Report] is what I was worried about [beyond the blind…]. And it for sure won’t have the IPD [Individual Participant Data]. Having the «statistical analysis plan, protocol and its amendments» is a good thing. But does it pass the Rolling Stones test?
    You can’t always get what you want
    But if you try sometimes
    Well you just might find
    You get what you need
Ask me in February 2015…
The EMA’s policy states: “The Agency respects and will not divulge CCI [commercially confidential information]. In general, however, clinical data cannot be considered CCI.”  That said, commercially confidential information will be redacted, “where disclosure may undermine the legitimate economic interest of the applicant/market authorization holder” and in items that may facilitate identification of trial participants. Sponsors will have primary responsibility for redacting study reports for EMA’s approval prior to their being made accessible under the new policy.
This is the part that got to AllTrials:
    The policy puts primary responsibility for redacting information into the hands of trial sponsors. This means that they get to suggest which information submitted to the EMA should be kept hidden. The EMA has a policy that the information in clinical trial reports should not generally be considered commercially confidential [this is echoed in the EU Clinical Trials Regulation] but it may never become clear which information is being kept hidden.
As it should…

The policy is a landmark, as for the first time it ensures access to clinical study reports of drugs that have obtained a MAA or on which a decision has been made. The EMA may be the first regulator to allow such access and the Nordic Cochrane Centre, the European Ombudsman, and the EMA deserve credit for that.

There’s a lot of good news for researchers in the final version of the policy. Gone is the “Peeping Tom” clause of “viewing only” access to data—described by users of comparable policies as “science through a periscope”—and there is no trace of a threat of legal proceedings for those who produce research that is disagreeable to sponsors.

In a previous post I urged users to adopt Reagan’s maxim of “trust but verify” when reading the EMA’s policies. Ultimately, we will not know how usable and transparent this policy is until it has been in use for some time.
I was prepared to say at this point that Tom’s report adds some disappointments, but that I stick to my guns that it’s a leap forward [beyond the blind…]. But when I went to the AllTrials site to clip their comment, I found this [see also a coup d’état…, the other shoe]:
    Yesterday, the likely European Commissioner for industry who will oversee the regulation of medicines and the EMA said there are risks that need to be balanced with greater clinical trial transparency. MEPs have been questioning the candidates for the new European Commission and, if approved by MEPs, Elzbieta Bienkowska will lead the industry department [DG ENTR].

    The new president of the European Commission, Jean-Claude Juncker, recently moved the responsibility for the regulation of medicines from the health to the industry department. When asked whether this move would allow industry lobbying to affect drug regulations, Ms Bienkowska said, “All my professional experience shows that I am lobbyist-proof. I’m absolutely lobbyist-proof”. Glenis Willmott MEP said, “It is disappointing Ms Bienkowska didn’t answer directly whether or not she thinks pharmaceutical and medical devices should really be in the health commissioner’s portfolio.”

    Ms Willmott also asked Ms Bienkowska if she will ensure the EMA’s commitment to greater clinical transparency will continue. Ms Bienkowska replied that clinical trial transparency is important for Europe; “however, you have to look at the other side and ensure there are adequate levels of safety when it comes to the potential misuse of data.” We’ve heard this claim before and we responded on our “Myths & Objections” page. MEPs will vote to appoint the candidates to the European Commission on 22nd October.

This battle is anything but over.  In the other shoe I ended with a picture of Niccolò di Bernardo dei Machiavelli, the author of The Prince – the Renaissance treatise on how to gain and wield power at any cost. I think of him once again this evening. There is no stopping place for the cause of Data Transparency. PHARMA is always in the background. They have unlimited resources and teams of people being well-paid to spend their days working whatever angles are necessary to win the day and allow PHARMA to hold onto control of the data from clinical trials. It’s not paranoia that leads me to this cynical conclusion, it’s self-evident experience. The only thing to say is that their offering this much consistent resistance says that we’re fighting the right battle. And by the way, endless thanks to MEP Glenis Willmott [see on the right track…]. She’s a true champion for the cause [and it is a cause]…
Mickey @ 12:15 AM
Filed under: OPINION
the prequel…

Posted on Wednesday 8 October 2014

I wrote this before the last post. Even as I wrote it, I knew I was writing it to myself, mainly to get things straight in my own thinking. But I changed my mind about posting it for two reasons. First, many of you aren’t psychiatrists and may not know the chronology so intimately – and I think it might help. History always seems to help me. Second, there’s something I want to say that has to do with George Dawson’s comment to the last post that won’t make sense without this. I apologize for the redundancies, where I lifted phrases to write the last post.

I was only casually aware of matters psychiatric during the 1960s. For me, it was the era of medical school, Internal Medicine training, and bench research. But from what I recall, the psychiatric residents got a generous government bonus for choosing the specialty. There was a shortage, it seems. In retrospect, that was because of de·Institionalization, and psychiatrists were needed to staff the Mental Health Centers that were to take their places as patients were moved from the hospitals into the community. By the latter half of the 1970s when I was in psychiatric training and early on the faculty, public mental health services were in crisis as the community services and hospital resources disappeared, even as the patient load from de·Institionalization grew [it was before they started filling up the jails and prisons]. Within psychiatry, there was a backlash against the prominence of psychoanalysts. Outside of psychiatry, the criticisms of psychiatry had a broad base: the heavy use of medications in treating psychosis; both the psychoanalytic and medical models; charging third party payers for psychotherapies; the question of whether mental illness was disease; the power of psychiatrists in involuntary commitment and medication. It was a tumultuous time. In the background, the revision of the diagnostic manual was marching towards release in 1980, a force that would make massive changes in the specialty and its practice. One part of that oft-told story is that those changes in psychiatry were orchestrated by the American Psychiatric Association [APA] under the guidance of its Board of Trustees, its Medical Director Dr. Melvin Sabshin, the chair of the DSM-III Task Force, Dr. Robert Spitzer, and the strong influence of the neoKraepelinians centered at Washington University in Saint Louis. Dr. Sabshin further consolidated the power of the APA by founding the American Psychiatric Publishing, Inc. [APPI].

The course of psychiatry in the US has been steered by the American Psychiatric Association since those 1980 changes. I don’t know if that central control was present before then, but it has certainly been true during my time. Many of us have withdrawn our membership for a variety of reasons in that time period. The medical·ization and medicine·ization of the specialty built through the ensuing quarter century, an era when much of academic and organized psychiatry was actively engaged with the pharmaceutical industry and the neuroscientific focus of the NIMH. It was a period of dramatic change with third party payers paying psychiatrists for outpatient medication management, and contracting with other specialties for psychosocial treatments. Another change – our prisons filled with chronic mental patients creeping toward the numbers of the confined prior to de·Institionalization.

The first decade of the new century began at the apogee of the now aging new psychiatry. The APA embarked on a DSM Revision that would realize a dream of connecting clinical diagnosis with measurable biology. Dr. Tom Insel of the NIMH advocated reframing psychiatry as Clinical Neuroscience. And the pharmaceutical industry was maintaining a steady pipeline of new medications coming onto the market [along with a publishing arm of its own]. But by the end of the decade, things were once again changing dramatically, as we all know. The involvement of academic psychiatrists with industry came to public attention with the revelations of Senator Grassley about unreported income, but the focus soon generalized to the whole issue of a corrupted alliances between a prominent sector of psychiatry and drug manufacturers – and we began to learn about ghost writing, and guest authorship, and industry financing out-front and in the background. Suits against pharmaceutical companies flourished exposing false advertising, exaggerated efficacy, minimizing of adverse reactions, and the involvement of the "KOLs" with industrial interests which became a source of public shame for us all. Meanwhile, the enthusiasm for a "biologic" DSM-5 choked in a desert of non-confirmation. Then the pipeline dried up, and PHARMA began to exit CNS drug development en masse. Quite an impressive decade of changes in fortune.

Here at the near midpoint of the second decade of the century, it would be hard to summarize the current state of play. We’ve seen several years of intense efforts to reform the clinical trials of drugs through Data Transparency, though at least in psychiatry, at present there’s not a lot of actual action in that arena with a dry pipeline – so, the "closing the stable door after the horse has bolted" adage seems to apply. The DSM-5 effort mercifully limped to its lackluster conclusion, but not before being abandoned by the NIMH, now creating a diagnostic system of its own – the Research Domain Criteria project [RDoC]. If anything, the DSM-5 Task Force process exposed the APA to further scorn – particularly with it’s chairman being exposed as involved in an entrepreneurial enterprise. And to complexify matters further, there’s another huge general issue on the table at the moment, the changing landscape of practice, finance, and health policy coming with the Affordable Care Act [ACA] among other things.

Where is the American Psychiatric Association in all of this? The DSM-5 is certainly not the catalyst for a paradigm shift like its predecessor, the DSM-III. It’s a code book at best, one still haunted by the process of its creation. While there’s continued wide usage of the medications from the earlier decade, the accompanying enthusiasm for psychopharmacology has undergone considerable dampening in recent years. The mainstay triad of promising future biological discovery [proteinomics, neuroimaging, and genomics] has lost some of its star-power. Likewise, the publicity around the ubiquitous conflict of interest issues have taken a heavy toll on the reputation of psychiatry in general, as they should. As I mentioned above, the APA has been the prime driving force for the direction of American psychiatry since at least 1980. While still in the leadership position, the APA is now operating in a dramatically different environment with the only clarity being that change is inevitable, though the shape and direction of that change is unclear…
Mickey @ 4:35 PM
Filed under: OPINION
unanswered questions…

Posted on Wednesday 8 October 2014

In my home town, there was a 19th century bridge across the Tennessee River. It was designed with bolts that were intended to be tightened and loosened with the seasons, but that never happened. Over a 90 year period, the subtle stresses and strains of seasonal expansion and contraction rendered it unsafe for auto traffic – unfixable. It’s now a tourist attraction as a pedestrian bridge.

The APA’s DSM-III revision in 1980 ultimately lead mainstream psychiatry to an exclusively biological focus and a deep entanglement with the pharmaceutical industry. My primary "dog in this hunt" has been the resulting corruption of the industry sponsored clinical drug trials in our peer reviewed psychiatric literature, and the collusion of the academic KOLs who signed on as authors. But the ‘subtle stresses and strains‘ from the ensuing three plus decades of inattention to the traditional domains of psychiatry have taken their toll in many arenas, and left the specialty ill prepared for the challenge of a dramatic change in the healthcare landscape and a growing disillusionment with the medication-heavy approach to matters mental.

Beginning in 2007 when Senator Grassley exposed a number of academic psychiatrists who were failing to report personal drug-company income, there followed a steady stream of revelations of scientific misbehavior and corrupt practices eroding confidence in psychiatry in general. Then, the exit of PHARMA from CNS drug development three years ago took things from bad to worse. The DSM-5 Revision had begun life a decade earlier dreaming of a triumphant transition to a biologically based diagnostic system, but floundered in a desert of non-confirmation – limping to its release barely even revised. Periods of paradigm exhaustion in science are rarely smooth, but this one has been abetted by disillusioning revelations and a reactionary and paralyzed establishment unwilling to deal directly with much of anything.

Comes now Paul Summergrad as an APA President and Saul Levin as Medical Director. I know very little about either one of them. Unlike Jeffrey Leiberman, the immediate past president, Dr. Summergrad isn’t part of the identified KOL establishment that has been such a problem and he doesn’t seem to be writing things like Leiberman’s «Time to Re-Engage With Pharma?» or «DSM-5: Caught between Mental Illness Stigma and Anti-Psychiatry Prejudice». Looking over the From the President blogs for the last several presidents, they seem to see the future of psychiatry in something called Integrative Care or Collaborative Care. Just looking at today’s PsychiatricNews, there are new things these days: a course for psychiatrists on Recovery Oriented Care [as in the Recovery Movement - see the other guy…]…
by Vabren Watts
September 15, 2014
an innovative and heavily jargoned piece on Population Health…
by Mark Moran
September 23, 2014
And a big president’s blog on Integrative/Collaborative Care highlighting the APA’s 2014 Institute on Psychiatric Services at the end of the month entitled, Integrating Science and Care in a New Era of Population Health.
From the President
by Hunter McQuistion and Paul Summergrad
September 26, 2014
and it was there last year…
From the President
by Jurgen Unützer and Jeffrey Lieberman
November 12, 2013
At least they’ve stopped talking exclusively about medications, the coming magical advances around the corner, and using that tiredest of lines about the global burden of depression.

All healthcare specialties are currently trying to figure out how to fit into the new world of the Affordable Care Act – adapting their traditional identities to a new set of rules and a new theater of operations. Psychiatry doesn’t have that luxury – more starting from scratch, trying to create a new brand – a consultative identity that is as yet amorphous and very different from medication manager of recent years or the general psychiatrist of the past. It’s hard to see through the upbeat rhetoric what they envision psychiatrists actually spending their time doing, or if the primary care physicians they plan for psychiatrists to collaborate with are interested, or if psychiatrists are interested in filling that particular role. And it’s unknown how [or if] they intend to address the widespread misadventures of their predecessors – those longstanding ignored stresses and strains.

In 1980, the American Psychiatric Association was able to effect a dramatic, specialty wide change in practice aided by the pharmaceutical industry and the third party payers who, for different reasons, supported the change. Can the APA bring it off again? …going it alone? Will practitioners follow their lead? Should they follow this lead? All unanswered questions with no guarantees…
Mickey @ 8:00 AM
Filed under: OPINION
two weeks!…

Posted on Sunday 5 October 2014

    A response to:

  1. Javier Arnedo, M.S.
  2. Dragan M. Svrakic, M.D., Ph.D.
  3. Coral del Val, Ph.D.
  4. Rocío Romero-Zaliz, Ph.D.
  5. Helena Hernández-Cuervo, M.D.
  6. Molecular Genetics of Schizophrenia Consortium
  7. Ayman H. Fanous, M.D.
  8. Michele T. Pato, M.D.
  9. Carlos N. Pato, M.D., Ph.D.
  10. Gabriel A. de Erausquin, M.D., Ph.D.
  11. C. Robert Cloninger, M.D., Ph.D.
  12. Igor Zwir, Ph.D.
American Journal of Psychiatry. Published in advance on September 15, 2014.
  1. Gerome Breen, PhD [Institute of Psychiatry, King’s College London, London, UK]
  2. Brendan Bulik-Sullivan [Broad Institute, Cambridge, MA, USA]
  3. Mark Daly, PhD [Broad Institute, Cambridge, MA, USA]
  4. Sarah Medland, PhD [QIMR Berghofer, Brisbane, Australia]
  5. Benjamin Neale, PhD [Broad Institute, Cambridge, MA, USA]
  6. Michael O’Donovan, MD PhD [Cardiff University, Cardiff, UK]
  7. Stephan Ripke, PhD [Broad Institute, Cambridge, MA, USA]
  8. Patrick Sullivan, MD [Karolinska Institutet, Stockholm, Sweden]
  9. Peter Visscher, PhD [University of Queensland, Brisbane, Australia]
  10. Naomi Wray, PhD [University of Queensland, Brisbane, Australia]

In this study published on September 15, Arnedo et al. asserted that schizophrenia is a heterogeneous group of disorders underpinned by different genetic networks mapping to differing sets of clinical symptoms. As a result of their analyses, Arnedo et al. have made remarkable and perhaps unprecedented claims regarding their capacity to subtype schizophrenia. This paper has received considerable media attention. One claim features in many media reports, that schizophrenia can be delineated into “8 types”. If these claims are replicable and consistent, then the work reported in this paper would constitute an important advance into our knowledge of the etiology of schizophrenia.

Unfortunately, these extraordinary claims are not justified by the data and analyses presented. Their claims are based upon complex [and we believe flawed] analyses that are said to reveal links between clusters of clinical data points and patterns of data generated by looking at millions of genetic data points. Instead of the complexities favored by Arnedo et al., there are far simpler alternative explanations for the patterns they observed. We believe that the authors have not excluded important alternative explanations – if we are correct, then the major conclusions of this paper are invalidated.

Analyses such as these rely on independence in many ways: among variables used in prediction, absence of artifactual relationships between genotypes and clinical variables, and between the methods of assessing significance and replication. Below we identify five specific areas of concern that are not adequately addressed in the manuscript, each of which calls into question the conclusions of this study.
    A. Ancestry/population stratification…
    B. X chromosome [chrX]…
    C. Linkage disequilibrium [LD]…
    D. SNP selection…
    E. Replication…
Conclusions: Given the remarkable claims made by Arnedo et al., it is essential that alternative explanations be excluded. Unfortunately, the authors do not provide the necessary evidence. As presented, their methodology is opaque [even to experts], meaning that their results cannot be independently validated. Arnedo et al. do not consider alternative explanations for the phenomena that they observe, such as confounding from ancestry and LD, even though these are well-known issues for the statistical methods that they employ and have been studied extensively in the statistical and population genetics literature. In addition, their multistep analysis approach is subject to multiple issues as noted above. We believe that it is highly likely that the results of Arnedo et al. are not relevant for schizophrenia. We urge great caution in the interpretation of the results of study.
Well, that didn’t last very long – just two week. We mortals aren’t really capable of vetting these genetic studies on such large populations, working with so many genes and complicating factors. We’re just spectators in a Colosseum watching a Battle of the Titans. At least that’s where I am when it comes to this kind of research. The criticisms in A-F above that I left out of my summary are far reaching – untested confounding factors like ancestry and gender, faulty analytic and statistical methodology, replication errors. And their conclusion…
    We believe that it is highly likely that the results of Arnedo et al. are not relevant for schizophrenia.
… is almost as definite as that in the original paper, in the opposite direction:
    Schizophrenia is a group of heritable disorders caused by a moderate number of separate genotypic networks associated with several distinct clinical syndromes.
I’m not reporting this with an opinion about who is right here, or if either is right. I just wanted to make a couple of observations. First, this is how the moving edge of science feels – back and forth, confusing, various investigators and groups working on something we don’t know, almost in a competition for who is going to get there first, or if there is even a "there" to get to. In the case of these genetic studies, it’s more like an athletic contest with teams than between individuals – football as opposed to wrestling. The thing that’s a bit different here is that they are so definite. This is not a tentative hypothesis versus a light critique. It’s dogma [a truth] versus dogmatic skepticism [it isn't true]. When I wrote about the original paper [short-list?…], I was tempted to say that the authors would either end up on a podium in Stockholm [Nobel Prize] or in the annals of Retraction Watch [but decided that was a too-tacky comment]. It did seem like an attempt to knock the ball out of the park instead of simply to get a base hit. The modern "Translational Science" motif pushes for that kind of speed to discovery [as if it's possible to push a rope].

But the main thing I wanted to write about was PubMed Commonssomething whose power I hadn’t quite realized Heretofore, once an article was posted in PubMed, it may have had a few things appended over time. Retracted articles were usually annotated. If there were published letters, they might be referenced with links. But it required journal access to see the letters and they were slow in coming. So a questionable article often languished for many months before any sign of the dissent showed up, if it showed up at all. Many of the disreputable industry funded clinical trials have nothing in PubMed to let a reader know of the problems. In the case above, an international consortium was on the case within two weeks. Take a look. Then look at the infamous Paxil Study 329 with the old links above, and the new below, a comment added when PubMed Commons went live a year ago. Here’s Dr. Karen Dineen Wagner’s write-up about an equally questionable pair of Zoloft trials with many links, but no comment [just waiting for the comments it deserves]. Any author indexed in PubMed can open a Commons Account and leave a comment. Among the major contributors to the problem with clinical trials of the psychiatric drugs, first was that no one much was looking, but even if they were, there was no easy public way to post comments to flag the literature.

It’s easy to get discouraged when reforms that seem so obviously right move so slowly or come in only an incomplete form [beyond the blind…, what we claim to be…], but probably the most important thing isn’t necessarily the enduring safeguards, but rather the ongoing awareness and the mechanisms to alert people to instances that need attention. Right now, there’s a heightened awareness of the problems in our literature. But what matters is that the vigilance lasts beyond the news cycle and we don’t have to look at empty spaces like this anymore:

Mickey @ 9:00 PM
Filed under: OPINION
stands on its own…

Posted on Saturday 4 October 2014

by Pat Bracken
World Psychiatry. 2014 13[3]:241-243.

I contend that good psychiatry involves a primary focus on meanings, values and relationships, both in terms of how we help patients as well as identifying from whence their problems arise. This is not to deny that psychiatry should be a branch of medicine, or that other doctors sometimes deal with problems of meaning. However, interpretation and "making sense" of the personal struggles of our patients are to psychiatry what operating skills and techniques are to the surgeon. This is what makes psychiatry different from neurology. When we put the word "mental" in front of the word "illness", we arc demarcating a territory of human suffering that has issues of meaning at its core. This simply demands an interpretive response from us. 1 think that many psychiatrists would recoil from the idea that they should train themselves to be uninterested in the problems of their patients, as the New York Times interviewee described.

Hermeneutics is based on the idea that the meaning of any particular experience can only be grasped through an understanding of the context [including the temporal context] in which a person lives and through which that particular experience has significance. It is a dialectical process whereby we move towards an understanding of the whole picture by understanding the parts. However, we cannot fully understand the parts without understanding the whole. The German philosopher H.-G. Gadamer suggested that the idea of hermeneutics is particularly relevant to the work of the psychiatrist.

By adopting a hermeneutic approach to epistemology, we can attempt to understand the struggles of our patients in much the same way as we attempt to understand great works of art. To grasp the meaning of Picasso’s Guernica, for example, we need to understand what is happening on the canvas, how the artist manages to create a sense of tension and horror through the way he uses line, colour and form. We also need to understand where this painting fits in relation to Picasso’s artistic career, how his work relates to the history of Western art and the political realities of his day that he was responding to in the painting. The meaning of the work emerges in the dialectical interplay of all these levels and also in the response of the viewer. The actual physical painting is a necessary, but not a sufficient, factor in generating a meaningful work of art. A reductionist approach to art appreciation would involve the unlikely idea that we could reach the meaning of a painting through a chemical analysis of the various pigments involved.

I do not believe that we will ever be able to explain the meaningful world of human thought, emotion and behaviour reductively, using the "tools of clinical neuroscience". This world is simply not located inside the brain. Neuroscience offers us powerful insights, but it will never be able to ground a psychiatry that is focused on interpretation and meaning. Indeed, it is clear that there is a major hermeneutic dimension to neuroscience itself. A mature psychiatry will embrace neuroscience but it will also accept that "the neurobiological protect in psychiatry finds its limit in the simple and often repeated fact: mental disorders are problems of persons, not of brains. Mental disorders are not problems of brains in labs, but of human beings in time, space, culture, and history."
hat tip to Mad in America… 
I’m always pleased when I run across something by Dr. Pat Bracken. The last time [a long and lonely wait…], I had this to say:
    So when I read this commentary that mirrors the beginnings of a career that I actually feel like I got to have, I feel a sadness in the place of the sense of joy and hope I would like to feel reading it. Some of the sad is altruistic, thinking about damage done and opportunities lost. But I think a lot of it is personal – about having finally found an identity that fit but then no longer having a place at the table. If you read this blog, you know that my attachment to the ways and means of hard science are clearly still living and well [I never met a graph I didn't like]. And I completely agree that the pre-1980 psychiatry had to change, but if this hasn’t been an example of "throwing the baby out with the bathwater," they ought to retire the saying. I wish this group the best in their attempts "to develop a different sensibility towards mental illness itself and a different under-standing of our role as doctors." If they see that as a new discovery, so be it. But it has been a long and lonely wait for it to come back around…
Pat Bracken is a favorite. I envy his ability to say simply and clearly what I have always thought, but couldn’t come close to saying so eloquently. While I’m about to lodge a minor complaint, or maybe just flag a difference, it doesn’t detract from the wisdom of his words. And as I said in my past commentary, for me it’s not a change in paradigm, rather a welcom reminder of something abandoned by too many along the way.

For most of my career, I was comfortable with the term «mind·brain dichotomy». Actually, it wasn’t anything I gave much thought. It was just a descriptor – a way of separating two areas that I knew something about. I didn’t pay attention to the «mind·brain dichotomy» part, as in mutual exclusivity or contrast. My primary interests were in the «mind·brain dichotomy» part, but that didn’t mean I didn’t care about the «mind·brain dichotomy» part. I was certainly aware that in the halls and meetings of psychiatry and psychology, this was a true «mind·brain dichotomy» and the controversy was endless. Mainstream psychiatrists like APA presidents and NIMH Directors were careful to always say brain diseases or even clinical neuroscience, and critics raled against the bio·bio·bio medical model. I frankly thought it was all a bunch of turf fighting with the many psychiatrists asserting their "medical·ness" and way overdoing the whole neoKraepelinian thing, perpetuating their war with the psychoanalysts, and the critics were on the same tack as Dr. Szasz and the 1970s behaviorists. The battling feels anachronistic, like straw man arguments, to me, and I try to avoid it whenever possible in line with my life rule, "never accept an invitation to go crazy."

But as an older retired psychiatrist, I have had other thoughts. I now think that explicitly or implicitly dichotomizing  brain disease or human psychological processes is only destructive, and that it is a «false dichotomy» in the end. I personally think that the psychotic mental illnesses are likely biologically determined, or at least have prominent biological determinants. I don’t know that like I do about Systemic Lupus Erythematosis [SLE], but it’s what I think. I would be likely to use medications in cases of psychotic illness, but not because I think I’m treating the underlying cause. I would be using them because psychosis can be disruptive to the person’s life and sometimes fatal, and the medicine can help with that. I’m way on the side of using medications only when there’s a reason and not as a maintenance. The drugs are too toxic for maintenance and there’s increasing evidence that less is better in the long term [I think of Lithium as an exception to that statement]. I think the same thing about Lupus. Steroids or immunosuppressives don’t treat whatever Lupus is [like Vitamin C treats Scurvy]. They treat the damage to the body by suppressing the pathological immunological mechanisms. Antipsychotics can suppress psychotic damage, also a mechanism of disease. The analogy goes further in that. Both steroids and antipsychotics are toxic, dangerous, and not for casual or prolonged use. But that has nothing to do with the minds of these patients. I happen to think many patients with the schizophrenic illnesses are candidates for a kind of psychotherapy adapted to their specific mentation – and that it involves their learning to live with the difficulties in abstraction, emotional experience, and their propensity to psychotic reactions in the face of life’s confusions. Those patients have minds too and often need [and want] help with some aspect of their mental life, on meds or not [by the way, adaptive counseling often helps Lupus patients live with their illness as well\.

So as much as I like Dr. Bracken and as much as I agree with "I do not believe that we will ever be able to explain the meaningful world of human thought, emotion and behaviour reductively, using the "tools of clinical neuroscience", and even though I say things like that sometimes, I'm trying to get over doing it. And as much as I am infuriated when Dr. Nemeroff flashes slides that say things like this implying that he knows something the rest of us don't:


I say let him think what he thinks. I doubt that many are listening much anymore.

I realize that in this piece, Dr. Bracken is reacting to people like Dr. Nemeroff, Dr. Insel, and many of the mainstream psychiatrists who have dehumanized psychiatry and tried to make an unleapable leap. He's part of a group that call themselves the Critical Psychiatry Network for that very reason. But I think they make a mistake to even engage with those people on the other side, as destructive as they can sometimes be. There are destructive forces on both sides [and will be so long as the notion of "sides" persists]. Dr. Bracken and others in this group have so much to teach us, to restore a rational balance, but not by arguing with the caricatured enemy. The biologists and neuroscientists have much to teach us too, at least some of them do, and I look forward to learning about it when they get it straight.

The early neoKraepelinians caricatured and destructively wrote off the whole «mind» side of the «mind·brain» equation, and it was neither good for psychiatry nor our patients [nor correct]. The temptation is strong right now to do the same thing in reverse and attack the «brain» side [when they're down on their luck]. I frankly think all of that has more to do with the influence of industry and finance that with the mentally ill – and I’d hate to see us go through another round of straw men and caricatures making yet another version of simplifications analogous to Dr. Nemeroff’s silly slide. A Hermeneutic Shift isn’t the swinging of a pendulum to me, or a dichotomy, it’s the reclaiming and elaboration of a somewhat lost tradition and line of productive thinking that needs no straw man for support. It’s part of the basic science of psychiatry, and it stands on its own. For that matter, it’s a basic science of medicine as Dr. Bracken says in his opening…
Mickey @ 12:00 PM
Filed under: OPINION