in a guilded cage…

Posted on Tuesday 5 May 2015

There is much to say about the semi-debate documented in guilding the lily… [in fact, this is my third attempt at writing what comes next]. I think I’d like to frame the essence of the issue being debated. That’s most easily done in this quote from the first article:
  • Bruce Levine’s Question: In Anatomy of an Epidemic, you also discussed the pseudoscience behind the "chemical imbalance" theories of mental illness – theories that made it easy to sell psychiatric drugs. In the last few years, I’ve noticed establishment psychiatry figures doing some major backpedaling on these chemical imbalance theories. For example, Ronald Pies, editor-in-chief emeritus of the Psychiatric Times stated in 2011, "In truth, the ‘chemical imbalance’ notion was always a kind of urban legend – never a theory seriously propounded by well-informed psychiatrists." What’s your take on this?

    Robert Whitaker’s Answer: This is quite interesting and revealing, I would say. In a sense, Ronald Pies is right. Those psychiatrists who were "well informed" about investigations into the chemical imbalance theory of mental disorders knew it hadn’t really panned out, with such findings dating back to the late 1970s and early 1980s. But why, then, did we as a society come to believe that mental disorders were due to chemical imbalances, which were then fixed by the drugs?

    Dr. Pies puts the blame on the drug companies. But if you track the rise of this belief, it is easy to see that the American Psychiatric Association promoted it in some of their promotional materials to the public and that "well informed" psychiatrists often spoke of this metaphor in their interviews with the media. So what you find in this statement by Dr. Pies is a remarkable confession: Psychiatry, all along, knew that the evidence wasn’t really there to support the chemical imbalance notion, that it was a hypothesis that hadn’t panned out, and yet psychiatry failed to inform the public of that crucial fact…
After that, the articles are a back and forth about the place of Institutional Psychiatry in the whole issue of "Chemical Imbalance" and Serotonin depletion. Did Institutional Psychiatry promulgate it? Ignore it? Fail to refute it? Is it an example of Institutional Corruption? Was it PHARMA? There are two articles in the series that defend psychiatry:
Each countered by Philip Hickey of Behaviorism and Mental Health and Mad in America with examples:
Whitaker further clarified his perspective in his comment on this blog last week:
As for my new book, co-written with Lisa Cosgrove, Psychiatry Under the Influence, this came out of a fellowship I had at Harvard University, in a lab devoted to studying institutional corruption. And while we do write about pharmaceutical influence on psychiatry, the real focus of the book is how the APA and academic psychiatry—the institution of psychiatry we were asked to study — were corrupted by psychiatry’s own guild interests since the publication of DSM-III. The pharmaceutical influence is a distraction from this internal problem within the profession, and I have to say, we believe that the “institution of psychiatry” remains quite oblivious to how this guild influence has corrupted its behavior, in terms of fulfilling its ethical duties to serve the public, over the past 35 years.
Whitaker is talking about the Safra Center at Harvard where he and LIsa Cosgrove did fellowships [see a heady collection…]. That’s also where Paul Thacker went when he left POGO and Senator Grassley’s staff. I got this today from Roy Poses of Healthcare Renewal:
It is really too bad the project on institutional corruption was only meant to last five years.  It was the only game in town, and one of the few concerted academic initiatives to address systemic corruption, specifically including health care corruption, of which I know.  The project produced some innovations – a word that has become overused business-speak, but is appropriate in this case – to improve disclosure and even somewhat discourage conflicts of interest, and some good ideas – that are unfortunately unlikely to gain any traction – to reduce corruption.  If only this torch will be picked up now that the project is over.  And if only there could be other projects like this in the US and around the world.  But corruption produces a lot of money with which to sustain itself, and the honest are increasingly poor these days.
It’s unlikely that either of the defensive articles [Pies and Alexander] listed will win many new followers. We’ve all been around through these last decades and we know that the Serotonin hypothesis or the "Chemical Imbalance" meme have lasted for years. I still see patients who say, "I’ve been told I have a chemical imbalance." And, surely by now, there’s no one reading this blog who couldn’t wax eloquent about institutional corruption in the upper echelon of psychiatry in dealings with the pharmaceutical industry.

Although the title of his new book [Psychiatry Under the Influence] suggests some outside force; he says, "the real focus of the book is how the APA and academic psychiatry — the institution of psychiatry we were asked to study — were corrupted by psychiatry’s own guild interests since the publication of DSM-III." And he sees attempts to move the blame for the Chemical Imbalance meme to PHARMA as an attempt at weaseling out of responsibility. Some of Whitaker’s critics propose that his criticism is motivated by his own alliance with other guilds or movements [like in the old Spy vs Spy cartoons in MAD]. Guild vs Guild. I tend to agree with both perspectives.

Speaking of guilds, it was an outburst by Jeffrey  Lieberman, recent past President of the APA, that got this discussion started [see just stop…]:
“Is [Whitaker] wrong? What he says is preposterous. He’s a menace to society because he’s basically fomenting misinformation and misunderstanding about mental illness and the nature of treatment. What he just said in that clip you ran about, if you’re taking an antidepressant and you go off it and you get sick again… the same thing could be said about insulin for diabetes and asthma medication… Whitaker, he ostensibly considers himself to have been a journalist, God help the publication that employed him, but he has an ideological grudge against psychiatry for whatever reason and there’s no, what he calls research is simply his opinion and his construction of information"…
Lieberman said that in a radio interview promoting his own book, but I wouldn’t be surprised if he sold more books for Whitaker than himself that day. Robert Whitaker has inserted himself squarely into the national dialog about psychiatry and its practices over the last decades, a force to be reckoned with. My own complaint about Whitaker and his followers is that they use the word «psychiatry» as if it represents a personified unitary entity, but I’ll clarify that point later. Right now, I think he’s earned the right to be listened to and is unlikely to be dissuaded by articles downplaying the behavior of academic and organized psychiatry in the current mess [or, for that matter, Lieberman’s carping]. The new book [Psychiatry Under the Influence] is out now [with a hefty $100 price tag!]…
Mickey @ 10:53 AM

guilding the lily…

Posted on Sunday 3 May 2015

It really is impossible to start this story at the beginning. And who knows where the middle is before the end is in sight? So all that is clear is the lead-in and general directions. The loose debate in the articles below picks up with an interview in Truthout of Robert Whitaker by one of the Mad in America bloggers, Psychologist/Activist Bruce Levine. It came long after Senator Grassley’s investigations of prominent psychiatrists [2008], four years after the publication of Whitaker’s Anatomy of an Epidemic and PHARMA’s exiting CNS drug development [2010], and a year after the publication of the DSM-5 and the tumult that came before [2013]. Here’s Levine’s intro to the interview:
… Whitaker’s sincerity about seeking better treatment options, his command of the facts and his lack of anti-drug dogma compelled all but the most dogmatic psychiatrists to take him seriously. In the past four years, the psychiatry establishment has pivoted from first ignoring Whitaker to then debating him and attempting to discredit him to currently agreeing with many of his conclusions. But will Whitaker’s success in changing minds result in a change for the better in treatment practices? I was curious about Whitaker’s take on the recent U-turns by major figures in the psychiatry establishment with respect to antipsychotic drug treatment, the validity of the "chemical imbalance" theory of mental illness and the validity of the DSM, psychiatry’s diagnostic bible. And I was curious about Whitaker’s sense of psychiatry’s future direction.
As one progresses through these articles, the argument builds over the institution of psychiatry’s participation in spreading the "Chemical Imbalance" explanation of depression [including the idea of Serotonin depletion that is reversible by the SSRIs]. Did psychiatry push the idea? or was it picked up in the culture? or promoted by PHARMA? But in the background, the real debate is about whether psychiatry knew the Serotonin theories were false and promoted them anyway as a method to sell drugs? The reason to read these articles in toto is that the latter accusation isn’t so apparent in individual extracted quotes…
  1. Psychiatry DID Promote the Chemical Imbalance Theory
    Mad in America; by Philip Hickey; June 6, 2014.
  2. Chemical Imbalance
    Slate Star Codex; by Scott Alexander; April 5, 2015.
  3. Psychiatrists Still Promoting Low-Serotonin Theory of Depression
    Mad in America; by Rob Wipond; April 15, 2015.
  4. The Spurious Chemical Imbalance Theory is Still Alive and Well
    Mad in America; by Philip Hickey; April 27, 2015.
While not directly part of this dialog, David Healy’s recent editorial on this topic is pertinent to the discusion:
The impetus for this post was Robert Whitaker‘s comment here last week:
As for my new book, co-written with Lisa Cosgrove, Psychiatry Under the Influence, this came out of a fellowship I had at Harvard University, in a lab devoted to studying institutional corruption. And while we do write about pharmaceutical influence on psychiatry, the real focus of the book is how the APA and academic psychiatry—the institution of psychiatry we were asked to study—were corrupted by psychiatry’s own guild interests since the publication of DSM-III. The pharmaceutical influence is a distraction from this internal problem within the profession, and I have to say, we believe that the “institution of psychiatry” remains quite oblivious to how this guild influence has corrupted its behavior, in terms of fulfilling its ethical duties to serve the public, over the past 35 years. Anyway, that is what is “new” about this book: It really focuses on the guild interests of psychiatry, once it promoted its biological model, and how guild influence has led the institution astray. It is also meant to be a “case study” of institutional corruption, as opposed to a story only about psychiatry.
My own thoughts about this sequence are multidimensional, and I think I’ll just stop here for the moment and let them sort themselves before proceeding…
Mickey @ 2:45 PM

can’t argue…

Posted on Saturday 2 May 2015

Two of the videos in the last  post came from Evidence-Live, a partnership between The BMJ and the Centre for Evidence-Based Medicine in the University of Oxford’s Nuffield Department of Primary Care Health Sciences and their conference two weeks ago. The timing couldn’t have been better, coinciding as it did with the WHO‘s announcement of their new policy on Data Transparency [see now, back to basics!…]. In many ways, the meeting itself was a celebration of the success of the AllTrials campaign, amazingly only just over two years old [see click it and sign it…]:
PharmaTimes
by Peter Mansell
January 10, 2013

James Lind MD [1716-1794]The push from the UK for wholesale transparency of clinical-trial data has taken on a new dimension with the launch of the AllTrials public campaign. An accompanying petition – already close to 3,000 over 7,000 signatures at the time of writing – calls on governments, regulators and research bodies to put in place measures ensuring that “all trials past and present” are registered and “the full methods and the results” reported. The initiative follows last month’s call by the UK House of Commons Science and Technology Committee for submissions on transparency and the disclosure of study data as part of a broader inquiry into clinical trials.

Among the campaign backers are some familiar names in the recent drive for clinical-data transparency: Bad Science – i.e., epidemiologist and Bad Pharma author Dr. Ben Goldacre; the BMJ; the James Lind Initiative; and the Centre for Evidence-Based Medicine. Joining them in the campaign is Sense About Science, a UK-based charitable trust that works in partnership with scientific bodies, research publishers, policymakers, the public and the media to change public discussions about science and evidence.

Sense About Science director Tracey Brown commented: “Everybody agrees that all clinical trials should be registered, and that we should at the very least have access to the basic results, and ideally the full Clinical Study Reports. But there have been years of foot-dragging and non-compliance with requirements.” Government and regulators “must listen to what the public thinks about this”, Brown insisted. “It’s a vital matter of public interest for the medicine we have now and the medicines we might have in the future”…

Who is James Lind? He’s the 18th centery British Naval Surgeon who did the first real controlled clinical trial – citrus fruits for Scurvy [he published his data and did a literature review]…

Among all the things I’ve learned blogging about all of this stuff, the one that most amazed me was my research into The Proprietary Data Act. I was awed at how quickly the AllTrials campaign caught on in spite of the active resistance from PHARMA. There were glitches along the way and skirmishes at every turn, but even with that, it put meaning to the phrase "catches on like a wildfire." At some point along the way, about 9 months ago, I got to wondering about how the Clinical Trial Data had been declared proprietary, wondering what legal hurdles lay ahead. I started looking for what I called The Proprietary Data Act on the Internet, and I got nowhere. Here’s what I said last June about my research on this topic:
So I thought I’d go back to the Proprietary Data Act and see why they were given that right in the first place. Only I couldn’t find the Proprietary Data Act anywhere no matter what I put in Google®. That happens, so I wrote everyone I knew asking for leads. They kindly agreed to help, but they couldn’t quite recall – Was it Congress back in 1962? Just not sure. So they looked and couldn’t come up with anything either. So how am I going to mount a campaign to Repeal the Proprietary Data Act if I can’t even find it?
And the punch line:
I finally heard from some people-in-the-know who had obviously gone on the same Hegira and found nothing either. It just happened apparently. The pharmaceutical companies had the data from the CROs they hired, and they kept it to themselves. There is no Proprietary Data Act. Never was. I guess it’s something like staking a claim in the Klondike during the gold rush or squatter’s rights. So much for my Repeal the Proprietary Data Act Movement..
It turned out to be a little more complicated than that [except where necessary to protect the public…, spellbound…], having to do with trade agreements, but it sure wasn’t anything like a Law. I’m still awed that we’ve allowed PHARMA to keep their data under lock and key for so long [50+ years!], or that the regulatory agencies have worked so hard to protect it for them. And I don’t mean to diminish the accomplishments of the AllTrials campaign. It was the right campaign, at the right time, done the right way. You just can’t argue with success…
Mickey @ 8:00 AM

net·flix…

Posted on Friday 1 May 2015

hat tip to pharmagossip…
Mickey @ 4:02 PM

chunk of change…

Posted on Wednesday 29 April 2015

Pharmalot: WSJ
By Ed Silverman
04/29/2015

Otsuka Pharmaceuticals was dealt a setback yesterday when the FDA approved four generic versions of its best-selling Abilify® antipsychotic pill, following an unusual and protracted legal battle. Shortly thereafter, Teva Pharmaceuticals announced that it was launching a copycat medicine. The move comes after Otsuka cited complex regulatory law to thwart generics, but the agency rejected the argument and decided that generic versions meet the standard for approval… And Otsuka also has a great deal at stake – Abilify® generated $4.9 billion in U.S. sales last year.

As we wrote previously, the FDA late last year approved Abilify® for treating children with Tourette syndrome, a neurological disorder that causes tics. Since Abilify® had a so-called orphan designation, which refers to a drug used to treat a rare malady like Tourette’s, Otsuka won another seven years of exclusive marketing rights – through late 2021 – before low-cost generics could appear.

But in February, the FDA surprised Otsuka by approving Abilify® to treat adults with Tourette syndrome. This widened the market, but Otsuka contends FDA law would trigger a labeling change that could usher in generics. Otsuka filed a lawsuit claiming the FDA isn’t allowed to approve an indication for which a drug maker didn’t apply and charged the agency was actually attempting to usher in generic copies.

For its part, the FDA backpedaled and earlier this month told Otsuka that Abilify® was now approved to treat Tourette syndrome, but only for children. However, the agency also indicated it may use a so-called carve-out approach to approve generics for treating psychiatric disorders, but not Tourette syndrome. And that is what the FDA did Tuesday…
Well, speaking of Abilify®, just as I was starting to look up how much it brought in per year, Ed Silverman to the rescue – $4.9 B! which explains why there’s so much noise. No small chunk of change by anybody’s standard. Thus, there’s the rush to anchor Abilify®Maintena and Brexpiprazole to hold onto some of that cash, and the move to hold onto Abilify® itself, if possible [apparently not]. I’ve never prescribed Abilify® and know nothing about it from experience. Here’s what Johanna Ryan on Rxisk had to say about it:
Personally, I wonder the same thing I thought about with Seroquel®. When it was in-patent, people asked for it. Out of patent, and I don’t hear about it anymore or run into anyone taking it. Are they all taking Abilify® now? Will Abilify® go out of style too? I don’t get it…
Mickey @ 10:11 PM

machiavellian medicine lives…

Posted on Wednesday 29 April 2015

I missed something. In the spice must flow…, I was looking at the two papers recently published about Brexpiprazole, a new Atypical Antipsychotic and found the the only academic authors were from the same faculty and research institute:
by Correll CU, Skuban A, Ouyang J, Hobart M, Pfister S, McQuade RD, Nyilas M, Carson WH, Sanchez R, and Eriksson H.
American Journal of Psychiatry. 2015 Apr 16 [Epub ahead of print]
by Kane JM, Skuban, Ouyang, Hobart, Pfister, McQuade, Nyilas, Carson, Sanchez, and Eriksson.
Schizophrenia Research. 2015 Feb 12. [Epub ahead of print]
Towards the end of writing that post, I looked up the chemical structures and realized what a clone Brexpiprazole was of Aripiprazole [Abilify®] [the number one overall seller in the US] that’s about to go off patent:
But something was nagging at me, and it just occurred to me what it was. A month and a half ago, I wrote a post about a CME for Aripiprazole [Long Acting Injectable] which is Abilify®Maintena [see a crying shame…] – which I saw as a patent-extender move now that Abilify® is going generic [analogous the same ploy with Seroquel®XR or Paxil®CR]. What I didn’t notice was the authorship on the Abilify®Maintena paper or the presenters of the CME.
by W. Wolfgang Fleischhacker, Raymond Sanchez, Pamela P. Perry, Na Jin, Timothy Peters-Strickland, Brian R. Johnson, Ross A. Baker, Anna Eramo, Robert D. McQuade, William H. Carson, David Walling and John M. Kane
The British Journal of Psychiatry. 2014 205:135–144.
Funding
This study was supported by Otsuka Pharmaceutical Commercialization, Inc. [Tokyo, Japan]. Editorial support for the preparation of this manuscript was provided by Suzanne Patel at Ogilvy Healthworld Medical Education and Amy Roth Shaberman, PhD, and Brett D. Mahon, PhD, at C4 MedSolutions, LLC, a CHC Group company; funding was provided by Otsuka Pharmaceutical Commercialization, Inc. and H. Lundbeck A/S.
Acknowledgements
The authors would like to thank Svetlana Ivanova, PhD, Otsuka Pharmaceutical Development & Commercialization, Inc., Rockville, MD, USA, for her contribution to the analysis and interpretation of data.
and [from a crying shame…]…
So we wonder who is on the faculty of this Free CME?  I clicked on the link to Adherence, Recovery, and the Role of LAIs in Schizophrenia:
Faculty
  • Christoph U. Correll, MD
    Professor of Psychiatry and Molecular Medicine
    Hofstra North Shore – LIJ School of Medicine
    Medical Director of Recognition and Prevention (RAP) Program
    The Zucker Hillside Hospital
    Glen Oaks, NY
  • John M. Kane, MD
    Professor of Psychiatry
    Hofstra North Shore – LIJ Health System School of Medicine
    Vice President
    Behavioral Health Services of the North Shore – LIJ Health System
    Chairman of Department of Psychiatry and Chief of Staff
    The Zucker Hillside Hospital
    Glen Oaks, New York
  • John Lauriello, MD
    Chancellor’s Chair of Excellence in Psychiatry
    Executive Medical Director of the Missouri Psychiatric Center
    School of Medicine, University of Missouri Health System
    Columbia, MO
Take a look at the Learning Objective and guess what you’re going to learn – for free. Oh by the way, John Lauriello, MD is the senior author of a glowing handout review of Abilify®Maintena.
Familiar? All the authors in blue are Lundbeck or Otsuka employees. The three academic authors are all on Bureaus or Boards for both Lundbeck or Otsuka. John Kane, listed as senior author wrote was a listed author on one of the Brexpiprazole papers and is on Bureaus or Boards for both Lundbeck or Otsuka. And the Abilify®Maintena CME has both of the Academic Authors from the Brexpiprazole papers on the faculty.

In the spice must flow…, I joked "[it was one·stop shopping for both ghost·writers and KOLs]," but it was bigger than I knew. The Hofstra faculty provided not only authors for both Brexpiprazole  papers, but also the Abilify®Maintena paper  and the Abilify®Maintena CME – all of which were aimed at holding onto the market as Abilify® becomes generic. This was one·stop shopping-maximus [though Abilify®Maintena did get different ghost-writers]. The Abilify®Maintena study had 98 sites!

Lest  you’re getting excited about all the reforms, this is Academic·Industrial·Complex all the way – complete with KOLs, ghost-writers, CRO-style Trial with many sites and foreign sites, industry stats, ignoring the results database, COI everywhere you turn, commercial rather than scientific motives [replacing Abilify® as a cash cow], no primary data posted, etc.:
  • Guest Authors: In this case, the articles are no longer crammed with academics like a decade ago. I guess it only takes one to be the ticket into an academic journal. In this case, the main authors came from Hostra [The Feinstein Institute] for the articles and C.M.E. Their C.V.s and C.O.I. are heavily weighted with Clinical Trials of drugs.
  • Ghost-Writers: All articles had the characteristic writing/editorial support usually indicating the paper being ghost-written [and some ghost-statisticians].
  • Multiple International sites [60+57+98=215] and large subject cohorts [636+674+662=1972; 1972÷215=~9 subjects/site] ["fast" "sensitive" trials].
  • Selective Presentation: eg effect sizes reported in Correll et al [high] but not Kane et al [low].
  • Results Database on ClinicalTrials.gov: Missing in Correll et al and Kane et al.
  • And: a bunch of stuff I can’t see through the haze…
Machiavellian Medicine at its finest…
Mickey @ 2:17 PM

just stop…

Posted on Tuesday 28 April 2015

Well, this can’t be a book review of Lieberman’s and Ogasi’s Shrinks, the Untold Story of Psychiatry or Whitaker’s and Cosgrove’s Psychiatry under the Influence because I’ve read neither, but we all have a pretty good take on what they’re about. What struck me is that the titles could be interchanged, and they would still work. Lieberman’s book continues the well worn theme that the 1980 revolution ushered in by the DSM-III in which Psychiatry was liberated from Psychoanalysis and put on the path of true science – so he could’ve worked with a title like Psychiatry under the Influence. And Whitaker and Cosgrove could’ve gone with Shrinks, The Untold Story of Psychiatry to illustrate how much the post-1980 version of Psychiatry has been  influenced  dominated by the pharmaceutical industry. This weekend we were offered a tête-à-tête between the two with Dr. Lieberman’s appearance on the Canadian radio program – CBC: The Sunday Edition – promoting his book [the operative comments come at around 51:30]. The host, Michael Enright, had interviewed Robert Whitaker previously, and played the transcript, asking Dr. Lieberman to comment:
Lieberman: “Is [Whitaker] wrong? What he says is preposterous. He’s a menace to society because he’s basically fomenting misinformation and misunderstanding about mental illness and the nature of treatment. What he just said in that clip you ran about, if you’re taking an antidepressant and you go off it and you get sick again… the same thing could be said about insulin for diabetes and asthma medication… Whitaker, he ostensibly considers himself to have been a journalist, God help the publication that employed him, but he has an ideological grudge against psychiatry for whatever reason and there’s no, what he calls research is simply his opinion and his construction of information."
Enright: "What about his contention that the unmedicated patients did better than the medicated patients?"
Lieberman: "I’d say that’s absolutely wrong. If you do a controlled study with various illnesses, whether it’s schizophrenia, depression, bipolar disorder, obsessive compulsive disorder, and you do a randomized study, assign one group to receive whatever the state of the art is in psychiatry including medication and you assign the other to some innocuous, non-medical type of supportive therapy or whatever, and you follow the people for a period of time the outcomes will be extraordinarily superior in the treated group. The magnitude of the difference we can sort of quibble about, but there’s no doubt about it."
By that afternoon, there was a post about it on Mad In America, Lieberman Calls Whitaker “A Menace to Society”, and shortly thereafter, another by Robert Whitaker, A Challenge to Dr. Lieberman, saying:
So here is our challenge to Dr. Lieberman. Please provide a list of randomized studies that show that medicated patients have a much better long-term outcome than the unmedicated patients. Please note that we are asking for studies that measure outcomes over the long-term, say for at least two years or longer, and are randomized, since you indicate there are many such studies. Please point out the “extraordinarily superior” outcomes for the medicated group. We presume the studies will focus not just on symptom control, but also functional outcomes…
adding:
This is not the first time Lieberman has denounced me as a crappy journalist. [See CV here.] After Mad in America was published, we were on a National Public Radio show together, where he said that my book was a travesty that set journalism back decades [as apparently I had failed to get in line with the rest of journalists writing about the wonders of modern psychiatry]. He has written other things very similar to what he told Michael Enright on Sunday, but I have to confess, I took extra pride in being called a “menace to society.” I think one day I will put that on my gravestone.

Dr. Lieberman obviously sees himself as the champion and spokesman for Psychiatry. It seems to antedate his tenure as APA President. In September 2011, not long after the DSM-5 Task Force had to abandon the attempt to create a "biological" classification and it became apparent that PHARMA was closing its CNS Drug research labs, Lieberman recorded a MedScape video [Psychiatric Diagnosis in the Lab: How Far Off Are We?] about the neuroscience breakthroughs that were just around the corner. He has continued to be a cheerleader for APA and his own brand of Psychiatry [DSM-5: Caught between Mental Illness Stigma and Anti-Psychiatry Prejudice, Our Time Has Come, Psychiatry Hits its Stride as Brain Science Informs Treatment], and has continued to push for a strong relationship with PHARMA [Don’t Turn Your Back on Industry, but Keep It Honest, APF Convenes Unique Pipeline Summit, Time to Re-Engage With Pharma?]. One could make the case that he is the leading [or at least the loudest] voice for the Guild of Psychiatry.

The outbursts at Robert Whitaker are not Dr. Lieberman’s only ventures onto the slippery slope of contemptuous ad hominem attacks. In February when the British Psychological Society released Understanding Psychosis and Schizophrenia, Tanya Luhrmann, an anthropologist, wrote a New York Times op-ed supporting the BPS report [see Redefining Mental Illness and which side of the street?…]. Dr. Lieberman responded in another MedScape piece with a similar ad hominem that indicted both Luhrmann for writing  it and the New York Times for publishing it [What Does the New York Times Have Against Psychiatry?]. Said Liebermann:
The article about mental illness was an incredibly unscholarly, misinformed, confused — at worst, unhelpful, and at best, destructive — commentary that will add to the confusion about the diagnosis of mental illness, enhance the stigma, and may lead some patients to doubt the veracity of the diagnoses that they have been given and the treatments that they are receiving…

Finally, when I read the article, disappointed and annoyed as I was, I tried to write a serious, responsible, and constructive letter to the editor, which I submitted within 24 hours. Seventy-two hours have elapsed since the article’s publication. I haven’t heard from the Times about their interest in publishing my response, so I assume they won’t publish it. The name that I publish under is my own. My credential is the Chairman of Psychiatry, Columbia University College of Physicians and Surgeons, one of the leading departments of psychiatry in the country, past president of the American Psychiatric Association, and author of the forthcoming book for the lay public called Shrinks: The Untold Story of Psychiatry.

Assuming that my letter was not completely uninformed or incoherent, I would think that there would have been reason to accept it, given my credentials and the fact that I made a reasonable point. Let’s see if they print it. If they don’t, that adds further to my dismay over what I consider to be journalistically irresponsible behavior by this once-respected newspaper.
It’s hard to comment on Dr. Lieberman’s remarks without following the Talion Law [an eye for an eye, and a tooth for a tooth] like saying that he attacks and discounts, but doesn’t address the content of the criticismor by pointing out the arrogance of his comments about Robert Whitaker as a journalistor his petulant remark about the New York Times’ journalismor his believing that his credentials entitle him to speak for psychiatry at large. All of those are ad hominems. And that’s all I can think of to say, so I’ll just stop. I wish he had…
Mickey @ 10:18 PM

feels like old times…

Posted on Saturday 25 April 2015

I don’t actually believe that most of the patients who showed up in my office looking for help were afflicted with a biologically determined brain disease, but from the first case I ever saw of melancholic depression to the present, I never doubted that biology was the major player in that condition. One of the paradoxical consequences of the biological revolution in psychiatry with the DSM-III in 1980 was that it shut down substantive research on Melancholia by eliminating it altogether [see political sabbatical… – Feb 2015]. In that post, I mention an editorial [Issues for DSM-5: Whither Melancholia? The Case for Its Classification as a Distinct Mood Disorder – Jan 2010], a plea to the DSM-5 Task Force to reinstate it written by an impressive cast of researchers. There was another excellent paper mentioned in my post that demonstrated separation among the depressive syndromes on clinical grounds [Cleaving depressive diseases from depressive disorders and non-clinical states – Jan 2015]. The first author of both papers was Gordon Parker, Director of the Black Dog Institute in New South Wales, Australia. And now we’re treated to another nuclear paper from that group about Melancholia, this time a neuroimaging study:
by Matthew P. Hyett, Michael J. Breakspear, Karl J. Friston, Christine C. Guo, and Gordon B. Parker
JAMA Psychiatry. 2015 72[4]:350-358.

IMPORTANCE Patients with melancholia report a distinct and intrusive dysphoric state during internally generated thought. Melancholia has long been considered to have a strong biological component, but evidence for its specific neurobiological origins is limited. The distinct neurocognitive, psychomotor, and mood disturbances observed in melancholia do, however, suggest aberrant coordination of frontal-subcortical circuitry, which may best be captured through analysis of complex brain networks.
OBJECTIVE To investigate the effective connectivity between spontaneous [resting-state] brain networks in melancholia, focusing on networks underlying attention and interoception.
DESIGN, SETTING, AND PARTICIPANTS We performed a cross-sectional, observational, resting-state functional magnetic resonance imaging study of 16 participants with melancholia, 16 with nonmelancholic depression, and 16 individuals serving as controls at a hospital-based research institute between August 30, 2010, and June 27, 2012.We identified 5 canonical resting-state networks [default mode, executive control, left and right frontoparietal attention, and bilateral anterior insula] and inferred spontaneous interactions among these networks using dynamic causal modeling.
MAIN OUTCOMES AND MEASURES Graph theoretic measures of brain connectivity, namely, in-degree and out-degree of each network and edge connectivity, between regions composed our principal between-group contrasts.
RESULTS Melancholia was characterized by a pervasive disconnection involving anterior insula and attentional networks compared with participants in the control [Mann-Whitney, 189.00; z = 2.38; P = .02] and nonmelancholic depressive [Mann-Whitney, 203.00; z = 2.93; P = .004] groups. Decreased effective connectivity between the right frontoparietal and insula networks was present in participants with melancholic depression compared with those with nonmelancholic depression [χ² = 8.13; P = .004]. Reduced effective connectivity between the insula and executive networks was found in individuals with melancholia compared with healthy controls [χ² = 8.96; P = .003].
CONCLUSIONS AND RELEVANCE We observed reduced effective connectivity in resting-state functional magnetic resonance imaging between key networks involved in attention and interoception in melancholia. We propose that these abnormalities underlie the impoverished variety and affective quality of internally generated thought in this disorder.
[This is a rough stab at introducing their methodology from one boring old psychoanalyst – so be gentle]. 25 years ago, Seiji Ogawa discovered that the MRI could detect the difference between oxygenated and deoxegenated hemoglobin. Since neuronal activity uses oxygen, it meant that we could actually see areas of increased neuronal activity in the brain – the blood-oxygen-level dependent contrast imaging or BOLD technique. We’ve all seen the pictures of areas in the brain lighting up in response to various stimulus. Attention then turned to the brain at rest, without stimuli [Resting state fMRI] where a number of consistent functional areas have been identified. These functional areas in the resting fMRI are connected, detected by timeline studies of simultaneous activity, so connection [and the direction of these connections] can be determined by some statistical/mathematical analyses beyond comprehension by most of the earth’s population – certainly mine. These connections [networks] may be visible [eg connectomes] or functional. Thus ends my stab at an intro to their methodology.

What Matthew Hyett et al did was to run resting fMRIs on 16 subjects each, from three cohorts – normals, non-melancholic depressed people, and a group with Melancholia. They identified five of the functional areas and studied their connectivity in each group. What they found was a clear separation among the three groups – documenting "reduced effective connectivity in resting-state functional magnetic resonance imaging between key networks involved in attention and interoception in melancholia."

This article begins with:
Despite advances in pursuing the neurobiological causes of clinical depressive conditions, the literature is characterized by divergent findings, likely reflecting their heterogeneity and varying causes. One such condition, melancholia [previously termed endogenous depression], has long held consistent ascriptions: being genetically weighted, having prominent biological perturbations, evidencing overrepresented clinical features, and showing a greater response to physical therapies than to psychotherapy. As psychiatry strives toward a diagnostic nosology based on genetic, behavioral, and neurobiological criteria, melancholia arguably represents a canonical test case…
Melancholia was already canonical test case way back when I started psychiatry in forty years ago, being hotly pursued by biological researchers hunting for biomarkers [eg Bernard Carroll’s Dexamethasone Suppression Test, David Kupfer’s REM Sleep Latency]. I now know some of the story about how and why this time-honored disease disappeared from the psychiatric diagnostic manual, but knowing the story doesn’t make it any less senseless than it was in 1980 [or in 1988, 1994, and 2013 when the diagnostic system was revised]. So in the intervening years, mainstream psychiatry has pretended that all depression fits Major Depressive Disorder with some kind of biologic substrate while ignoring this one diagnosis [Melancholia] where that’s most likely to actually be true. So this group studies this obvious candidate. They go on to lay out their hypothesis:
Historical failure to identify specific neurobiological correlates of melancholia is consistent with recent advances in cognitive neuroscience that regard the brain as a complex network, whereby psychiatric conditions reflect changes in functional integration rather than perturbations within an isolated region. Large-scale brain networks supporting mood regulation, interoception, and cognition [eg, concentration and attention] are thus likely candidates for furthering understanding of melancholia’s neurobiology…
Then they present their data in a matter-of-fact way, and conclude:
Conclusions: We position the neurobiological features of the spontaneous dysphoria of melancholia as a weakening of interactions among regions that subserve attention,mood regulation, and interoception. Computational accounts of internally generated thought highlight the importance of a critical homeostatic balance between stable self-regulation and dynamic instability. We propose that our findings reflect a loss of this optimal balance, undermining the adaptive role of interoception.
I obviously really liked this research. In my mind, it is a definitive affirmation that Melancholia is a distinct clinical entity with demonstrable brain abnormalities. The article goes about "furthering [the] understanding of melancholia’s neurobiology." The neuroscience parallels our traditional clinical diagnosis. As a matter of fact, it probably wouldn’t be funded by our NIMH these days: it’s an uncommon illness that doesn’t fit the RDoC [more like DSM-5 Major Depressive Disorder with Melancholic Features] and it doesn’t Translate into anything. Even though I don’t really understand the vicissitudes of all of the analytic techniques, they’re clear enough to follow and one of the authors [Karl J. Friston] was involved in their development. Likewise, Dr. Gordon Parker’s work has been consistently solid science. And then there’s this:
    Conflict of Interest Disclosures: None reported.
    Funding/Support: This study was supported by grants from the National Health and Medical Research Council of Australia [program grants 510135 and 1037196] [Mr Hyett and Drs Breakspear and Parker], Queensland Health [Mr Hyett and Dr Breakspear], and the Wellcome Trust [Dr Friston].
it feels like old times…
Mickey @ 4:19 PM

the spice must flow…

Posted on Wednesday 22 April 2015

And so another atypical antipsychotic may be dripping from the FDA Approval pipeline…
Lundbeck Press Release
September 24, 2014

H. Lundbeck A/S [Lundbeck] and Otsuka Pharmaceutical Co., Ltd. [Otsuka] today announced that the US Food and Drug Administration [FDA] has determined that the New Drug Application [NDA] for brexpiprazole for monotherapy in adult patients with schizophrenia and for adjunctive treatment of major depressive disorder [MDD] in adult patients is sufficiently complete to allow for a substantive review and the NDA is considered filed as of 9 September 2014 [60 days after submission]. The PDUFA date is July 11, 2015…
PsychiatricNews
April 17, 2015

New findings from a phase 3 clinical trial, published today in AJP in Advance, suggest that a recently developed antipsychotic may prove to be one of the next treatments for schizophrenia. Researchers from the Department of Psychiatry at Hofstra North Shore-LIJ School of Medicine conducted a randomized, double-blind, placebo-controlled study with 636 patients with schizophrenia to investigate the efficacy, safety, and tolerability of brexpiprazole—a  serotonin-dopamine activity modulator that acts as a partial agonist at serotonin 5-HT1A receptors and dopamine D2 receptors, while antagonizing serotonin 5-HT2A receptors and noradrenaline alpha receptors…

“It is important for clinicians and patients to have a range of treatment options to manage symptoms effectively and safely … as response to therapy can vary greatly from individual to individual and from one medication to the next.” Correll informed Psychiatric News that the Food and Drug Administration will make its final decision about the approval of brexpiprazole for the treatment of schizophrenia as well as major depressive disorder in July…
I thought it might be interesting in the light of all of our enthusiasm for Data Transparency and other reforms to take a look at the Clinical Trials for Brexpiprazole and see how they stack up with some of the suggested changes:
Clinicaltrials.gov has 30 entries for Brexpiprazole, 25 being Phase 3. They’re obviously aiming for the adjunctive-antidepressant market [which must be much larger than the schizophrenia market]. They don’t get high marks in the Clinical Trial Results Database in that none of the completed studies have results posted [at least 8 completed over a year ago]. Here are the two recently published studies in Schizophrenia which I presumes are the ones being submitted to the FDA for approval [each study listed 60 locations as clinical sites!]:
by Correll CU, Skuban A, Ouyang J, Hobart M, Pfister S, McQuade RD, Nyilas M, Carson WH, Sanchez R, and Eriksson H.
American Journal of Psychiatry. 2015 Apr 16 [Epub ahead of print]

OBJECTIVE: The efficacy, safety, and tolerability of brexpiprazole and placebo were compared in adults with acute schizophrenia.
METHOD: This was a multicenter, randomized, double-blind, placebo-controlled study. Patients with schizophrenia experiencing an acute exacerbation were randomly assigned to daily brexpiprazole at a dosage of 0.25, 2, or 4 mg or placebo [1:2:2:2] for 6 weeks. Outcomes included change from baseline to week 6 in Positive and Negative Syndrome Scale [PANSS] total score [primary endpoint measure], Clinical Global Impressions Scale [CGI] severity score [key secondary endpoint measure], and other efficacy and tolerability measures.
RESULTS: The baseline overall mean PANSS total score was 95.2, and the CGI severity score was 4.9. Study completion rates were 62.2%, 68.1%, and 67.2% for patients in the 0.25-, 2-, and 4-mg brexpiprazole groups, respectively, versus 59.2% in the placebo group. At week 6, compared with placebo, brexpiprazole dosages of 2 and 4 mg produced statistically significantly greater reductions in PANSS total score [treatment differences: -8.72 and -7.64, respectively] and CGI severity score [treatment differences: -0.33 and -0.38]. The most common treatment-emergent adverse event for brexpiprazole was akathisia [2 mg: 4.4%; 4 mg: 7.2%; placebo: 2.2%]. Weight gain with brexpiprazole was moderate [1.45 and 1.28 kg for 2 and 4 mg, respectively, versus 0.42 kg for placebo at week 6]. There were no clinically or statistically significant changes from baseline in lipid and glucose levels and extrapyramidal symptom ratings.
CONCLUSIONS: Brexpiprazole at dosages of 2 and 4 mg/day demonstrated statistically significant efficacy compared with placebo and good tolerability for patients with an acute schizophrenia exacerbation.

First off, in the PsychiatricNews article above, the comment "Researchers from the Department of" isn’t accurate. It should read "A researcher from the Department of" since all the other authors on the by-line are employees of either Lundbeck or Otsuka [in blue].The PHARMA companies seem to have dropped the multiple academics on the by-line method and settled for only one. Dr. Christoph Correll made the following COI declaration:
Dr. Correll has been a consultant and/or advisor to or has received honoraria from Actelion, Alexza, American Academy of Child and Adolescent Psychiatry, Bristol-Myers Squibb, Cephalon, Eli Lilly, Genentech, Gerson Lehrman Group, IntraCellular Therapies, Lundbeck, Medavante, Medscape, Merck, National Institute of Mental Health, Janssen/J&J, Otsuka, Pfizer, ProPhase, Roche, Sunovion, Takeda, Teva, and Vanda; he has received grant support from Bristol-Myers Squibb, Feinstein Institute for Medical Research, Janssen/J&J, National Institute of Mental Health, NARSAD, and Otsuka; and he has been a Data Safety Monitoring Board member for Cephalon, Eli Lilly, Janssen, Lundbeck, Pfizer, Takeda, and Teva.
And did he [they] have any help writing the paper?
Funded by Otsuka Pharmaceutical Development & Commercialization, Inc., and H. Lundbeck A/S. Jennifer Stewart, M.Sc. [QXV Communications, Maccles field, U.K.] provided writing support that was funded by Otsuka Pharmaceutical Development & Commercialization, Inc., and H. Lundbeck A/S.
So far, we’re not getting a lot of reform-is-in-the-air vibes. How about the other paper that’s part of the FDA NDA submission?
by Kane JM, Skuban, Ouyang, Hobart, Pfister, McQuade, Nyilas, Carson, Sanchez, and Eriksson.
Schizophrenia Research. 2015 Feb 12. [Epub ahead of print]

The objective of this study was to evaluate the efficacy, safety and tolerability of brexpiprazole versus placebo in adults with acute schizophrenia. This was a 6-week, multicenter, placebo-controlled double-blind phase 3 study. Patients with acute schizophrenia were randomized to brexpiprazole 1, 2 or 4mg, or placebo [2:3:3:3] once daily. The primary endpoint was changed from baseline at week 6 in Positive and Negative Syndrome Scale [PANSS] total score; the key secondary endpoint was Clinical Global Impressions-Severity [CGI-S] at week 6. Brexpiprazole 4mg showed statistically significant improvement versus placebo [treatment difference: -6.47, p=0.0022] for the primary endpoint. Improvement compared with placebo was also seen for the key secondary endpoint [treatment difference: -0.38, p=0.0015], and on multiple secondary efficacy outcomes. Brexpiprazole 1 and 2mg also showed numerical improvements versus placebo, although p>0.05. The most common treatment-emergent adverse events were headache, insomnia and agitation; incidences of akathisia were lower in the brexpiprazole treatment groups [4.2%-6.5%] versus placebo [7.1%]. Brexpiprazole treatment was associated with moderate weight gain at week 6 [1.23-1.89kg versus 0.35kg for placebo]; there were no clinically relevant changes in laboratory parameters and vital signs. In conclusion, brexpiprazole 4mg is an efficacious and well-tolerated treatment for acute schizophrenia in adults… BEACON trial.


[recolored to match the graph above]
Again, there is only one academic author, Dr. John Kane, with the following COI declaration:
Dr Kane has been a consultant for Amgen, Alkermes, Bristol-Meyers Squibb, Eli Lilly, EnVivo Pharmaceuticals [Forum] Genentech, H. Lundbeck. Intracellular Therapeutics, Janssen Pharmaceutica, Johnson and Johnson, Merck, Novartis, Otsuka, Pierre Fabre, Proteus, Reviva, Roche and Sunovion. Dr Kane has been on the Speakers Bureaus for Bristol-Meyers Squibb, Eli Lilly, Janssen, Genentech and Otsuka, and is a shareholder in MedAvante, Inc.
Writing help?
Ruth Steer, PhD, [QXV Communications, Macclesfield, UK] provided writing support, which was funded by Otsuka Pharmaceutical Development & Commercialization, Inc. [Princeton, USA] and H. Lundbeck A/S [Valby, Denmark].
Does QXV Communications sound familiar? And speaking of sounding familiar, in case you didn’t follow the author links, Dr. John Kane is Chairman of Psychiatry at Hofstra where Dr. Christoph Correll is on the faculty [it was one·stop shopping for both ghost·writers and KOLs]. Both authors are at the Feinstein Institute for Medical Research. Both articles say:
From the Zucker Hillside Hospital, Glen Oaks, N.Y.; Otsuka Pharmaceutical Development & Commercialization, Princeton, N.J.; and H. Lundbeck A/S, Valby, Copenhagen, Denmark.
I know this is getting long, but let me add one other tidbit. The top article referenced a 2013 meta-analysis in the Lancet [Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis] of the Effect Sizes and Discontinuation Rates of the Atypical Antipsychotics which I liked, by authors who do Cochrane meta-analyses. I lifted one of their figures and added the results from these Brexpiprazole studies for comparison. The Effect Size is an index of the magnitude of the drug’s effect. It was included in the AJP article but not the Schizophrenia Research article [I didn’t calculate the 95% Confidence Limits for the Brexpiprazole studies]. It shows a problem in replicability [2mg]:
First, I apologize for going on and on about this. When I started, I had no intention of writing a blog·epic. I didn’t know that the academic authors were from the same department; or that the ghost·writers were from the same firm; or that they were ignoring the Clinicaltrials.gov Results Database; or that there were 60 sites for each study. I guess they are taking advantage of the formula used by their predecessors to maximize their impact on launch with slick writing and optimized choices in data presentation. If you read the actual papers, they even read like advertisements. They’re obviously going to be handout reprints for the drug reps to give out to primary care physicians. They are in some of the top journals, quickly published after submission, and presented together as a poster at the American College of Neuropsychopharmacology [ACNP] meeting in December.

I just wrote a three part series on the Academic·Industrial·Complex that was as overly detailed as this post – which is yet another example of what that phrase means. I think I’ve been chasing down the details, looking in vain for something that breaks out of the mold of scientific enterprise being used as a commercially driven advertising platform. And what I find is that the further I look, the worse it gets. I was tempted to say that Brexpiprazole is a weak sister Atypical Antipsychotic with a low Adverse Event profile, but I’m not even sure that’s defensible with just two six week trials. And unmentioned here, they used some idiosyncratic analytic techniques that were unfamiliar to me, but I just didn’t have the libido to look into them further [because there was no primary data to test them with].

This is pitiful, in my humble opinion. We’ve clearly still got a long way to go to reclaim our academic literature, in spite of the good news coming from various directions…

Afterthought: Looking at all of those sites on the two clinical trials, it is highly unlikely that any author ever even met a single subject in either trial…

Another Afterthought: They could call Brexpiprazole son of Abilify
 
Mickey @ 10:05 PM

Academic·Industrial·Complex III…

Posted on Monday 20 April 2015

In Academic·Industrial·Complex II… I was implying that the $700,000 spent on the study of Seroquel XR® in Borderline patients was a waste of money, but another way of looking at that is that their various trials of Seroquel XR® were overall worth it, because Seroquel® stayed in the Blockbuster range even after the patent expired thanks to Seroquel XR®. That’s an easy mistake to make – from drugs.comto forget how much money is involved in the commerce of these drugs. Abilify® is currently involved in a similar patent extension scheme, and Johanna Ryan has a first-person blog on RxISK about the pressure to take Abilify®. Even in this era when the pharmaceutical industry has all but abandoned CNS drug development and their patent protections are disappearing, we still feel the rumblings of the now passed golden era of psychopharmacology. The KOL class in academic psychiatry is still playing the only tune they’ve known. And that far right point on the Abilify® chart [on the right] represents the number one best selling drug in the US.  The Academic·Industrial·Complex is still very much a major player.

When a new Chairman arrived at my university in the early 1980s carrying the banner of the new psychiatry, he traveled around meeting the faculty as is customary. He didn’t ask questions, but instead talked about the need for the faculty to do research. When it came my turn, I told him I’d looked forward to finally having some time to finish several papers. I was about to tell what they were, but he interrupted and talked about psycho-immunology, because I had been an Immunologist. I’d never even heard the word. It took me several months to figure out that what he really wanted us to do were Clinical Trials for drug companies. And if you read Dr. Schultz’s interview twenty five years later describing his vision of his Minnesota department, the topic had changed very little:
"How many people had been imaged at the CMRR by faculty in the Department of Psychiatry in 1999? Zero. The Department of Psychiatry now images more people in CMRR than all other departments on the campus combined…"

"I developed an idea to focus our academics on imaging, genetics, and clinical trial research, and the rationale for that being we had one of the greatest imaging centers and that’s what the NIH wanted to do. Genetics were emerging. There hadn’t been a person imaged in CMRR, there hadn’t been a blood drawn for genotyping in the department, and I said – We have to get going in these areas. Both of those areas, I thought, could interact with doing very good clinical trial studies…"

"So, like Dr. [David] Mrazek at Mayo says – "Let’s draw your blood and find out what’s going on in your serotonin or your transporter genes or your metabolic genes and that’ll help us with your treatment. The same is also true for imaging, where we’re now imaging at baseline, giving them medicine, imaging after the study is over, and seeing where does the drug act in the brain…"

"We are now 25th out of 135 medical schools, and that puts us in a good position, but we still have a ways to go. We went from 39th in 1999 to 25th now, and we tripled our NIH funds and expanded the breadth and scope of what we’re able to do. But I’m hoping we’ll be able …  to take it up a notch, and move up maybe another ten spots…" 
Dr. Schulz doesn’t mention industry funded Clinical Trials, but there were plenty along the way. I’m aware that such metrics are common among academic administrators, but in academic psychiatry as I’ve known it since the 1980s, this is most all of what there was. When the next new Chairman showed up [Charlie Nemeroff], they sent around his CV. It was a bound book with hundreds of publications. I’d never seen anything quite like it. Research became the most important thing – but not for what it discovered, but rather how much was being done. Schulz’s string of Clinical Trials of Atypicals in Borderline Personality Disorder mentioned earlier wasn’t really about treatment – it was about the income stream [A Drug Trial’s Frayed Promise]. That happens to be the way things work in an Academic·Industrial·Complex. And as a matter of fact, in the early 1980s, we heard about imaging and genetic studies even back then [that’s why it has been so hard for me to accept that PHARMA was just opportunizing on the 1980 revolution in psychiatry rather than having been a prime mover]. But whichever the case, in an Academic·Industrial·Complex, Academia prospers, but only if Industry prospers.

Here’s the part where I’m speculating [but for what it’s worth, I happen to believe this speculation]. In the course of too many training programs and too many fellowships, I’ve worked in or been affiliated with a number of clinical research units and their staff. They have been the most cracker-jack support staff I’ve ever had the pleasure to work with – the crème de la crème, inspired by the possibility of advancing medical science and care – loyal to the researchers as part of the team. But in an Academic·Industrial·Complex, they’re grinding out Clinical Trials that don’t have such lofty goals – "just making a buck." The researchers are less available. For example, Dr. Olson saw Dan Markingson just "four or five times" during his six month’s stint in the CAFE trial, and I don’t know that Dr. Schulz ever met him. My speculation is that the "just making a buck" attitude filters down the ranks – manifesting as a disillusioned "just going through the motions" mentality.

Dr. Faustus' pact with the Devil...But whether my speculations are true or not, Drs. Elliot and Turner have opened a window into the world of psychiatry’s Clinical Trials and the whole Academic·Industrial·Complex that goes much further than the tragic case of Dan Markingson, than the Department of Psychiatry, than the State of Minnesota. We need even more than just the Data Transparency we’re seeking. We need Transparency for the whole Clinical Trial process. While I’m personally sensitive to the problem of financing psychiatric education, an area I left reluctantly – no matter what problems the Academic·Industrial·Complex tried to fix, it didn’t justify the obvious lapses in medical ethics that arose out of the solution. Faustian contracts with the Devil rarely do…
Mickey @ 5:59 AM