1 Boring Old Man

Psychiatrists protest against disgraced academic’s lecture at research centre
^{The decision by the Institute of Psychiatry to invite US professor, Charles Nemeroff, has split the profession
The} Independent
by Jeremy Laurance
11 June 2013

Britain’s premier institute for the study of mental illness has become embroiled in a damaging row over its decision to invite a disgraced US academic to give the inaugural lecture for a new research centre. The decision by the Institute of Psychiatry at Kings College, in central London, Europe’s largest psychiatric research organisation, to invite Professor Charles Nemeroff, an expert in the treatment of depression, has split the psychiatric profession and been attacked by members of the institute itself. Professor Nemeroff, a leading authority on the biological causes of mental illness, is one of the highest profile doctors to have been exposed for concealing large payments from pharmaceutical companies.

He was forced to resign his post at Emory University, Atlanta, in 2008 after an investigation revealed that he had failed to report more than $1.2m of payments from GlaxoSmithKline, despite having signed an undertaking to limit payments to $10,000 a year. He received the payments whilst undertaking a study on behalf of the National Institutes of Health into drugs made by GSK.

In 2009, Professor Nemeroff was appointed chair of psychiatry at the University of Miami and was subsequently awarded a research grant of $400,000 a year for the next five years by the National Institutes of Health. In 2012 it emerged that US Senator Charles Grassley, whose 2008 investigation triggered Professor Nemeroff’s  downfall, had written to the National Institutes of Health to ask why they had given him a grant when he was still under federal investigation.

Now a group of UK psychiatrists have written to the Institute of Psychiatry protesting against its decision to invite Professor Nemeroff to give the “inaugural annual lecture for the new Centre for Affective Disorders”, which is due to take place at the institute next Monday. The group representing the radical Critical Psychiatry Network claims the Nemeroff case is frequently cited as “one of the starkest examples of the financial corruption of medicine” through its “overly cosy relationship with the pharmaceutical industry”. “Many medical institutions have recognised this relationship is unhealthy and is bringing the profession into disrepute. We find it surprising therefore that the Institute of Psychiatry has seen fit to invite Nemeroff to deliver this important lecture,” they wrote.

Separately, Derek Summerfield, honorary senior lecturer at the Institute, wrote in the BMJ, formerly called the British Medical Journal, last week that the Institute of Psychiatry’s lauding of Professor Nemeroff as “one of the world’s leading experts” showed how psychiatric academe “sails blithely on as if such revelations beg no broader questions about its associations and supposed scientific independence.”

In a response, the Institute said it was “aware of the concerns” and took the issue of declaring financial conflicts of interest “extremely seriously”. “We have been informed by Professor Nemeroff that he will not be presenting any research that was funded by commercial companies or affected by commercial implications. Obviously, he will be declaring any relevant conflicts of interest prior to his lecture.” Professor Nemeroff could not be contacted for comment. He has previously said that his payments from GSK were for talks about GSK drugs now on the market, while his research funded by NIH involved basic laboratory studies of GSK chemical compounds that were years away from market.

Dr. Nemeroff was exposed for recommending treatments where he had a financial interest without disclosure in a review article in 2004. In 2006, he was again exposed when he published a ghost-written article reviewing a treatment that he and other authors had a financial interest in without disclosure in a journal that he, himself, edited. He was asked to step down as editor and censured by Emory University where he was Chairman. In 2008 after the US Senate investigated him for unreported pharmaceutical income, he was removed as Chairman at Emory. On the left above are the number of outside PHARMA consulting jobs he held per year and on the right the number of promotional talks he gave for GSK per month. Below, the journal articles he published per year…

There is no rational explanation why the Institute of Psychiatry at Kings College would select Dr. Charlie Nemeroff to give an annual lecture to inaugurate a new Affective Disorders Centre. His quirky research hinges around proving that childhood trauma reverse engineers the brain and predisposes to later depression – or that people are genetically loaded to be harmed by psychological trauma. He uses trendy terms like epigenetic or neurogenesis and all the latest technologies to come at these hypotheses from a variety of directions – always on the cutting edge, always seeing amazing breakthroughs just around the corner. Self reference punctuates every presentation [even his jokes are grandiose - as in his assertion that he's somehow connected to Jan Evangelista Purkinje, the famous Czech neurophysiologist, in a recent grand rounds @23:00]. He chases and then jumps in front of every fad that washes over the world of bio·psychiatry – a man for all seasons. But if he’s actually excelled at something, it’s making funny money for his corporate sponsors, his departments and universities, and for himself. So there’s simply no rational explanation why they would select Dr. Charlie Nemeroff to give an annual lecture to inaugurate their new Affective Disorders Centre – leaving us to ponder in disbelief that the Institute of Psychiatry at the prestigious Maudsley would voluntarily don the shroud that is Dr. Charlie Nemeroff?

^{The Hamilton Rating Scale for Depression[HRSD], also called the Hamilton Depression Rating Scale [HDRS], abbreviated HAM-D, is a multiple item questionnaire used to provide an indication of depression, and as a guide to evaluate recovery. Max Hamilton originally published the scale in 1960 and revised it in 1966, 1967, 1969, and 1980. The questionnaire is designed for adults and is used to rate the severity of their depression by probing mood, feelings of guilt, suicide ideation, insomnia, agitation or retardation, anxiety, weight loss, and somatic symptoms.}

I can reminisce about the tricyclic antidepressants too. As a psychiatric resident when I saw hospitalized patients, I saw many whose severe depressions responded to the tricyclics. They were used some in the outpatient clinic at Grady, our charity hospital in Atlanta, but I never personally saw a patient there get much better on them. I usually saw them discontinued because of anticholinergic side effects. There were some older doctors who worked in the clinic as volunteers, and they prescribed a lot of Doxepin. It was a lighter·weight antidepressant that I never saw used in the hospital, but it also had anti·anxiety properties and I presumed that’s why it was being used.

The long and short of it is that I don’t think I wrote a single prescription for an antidepressant in the decade between the time I finished training and the time I left the University – which happened to be around the time that Prozac was introduced. Part of the story was that my University practice was all referrals – personality disorders, eating disorders, students with problems of one sort or another. Since I had never seen antidepressants as much help in that kind of patient, they never came to my mind. I enjoyed my practice and the results, but through the retrospectascope, it even seems strange to me that I didn’t use antidepressants.

Thinking back even further to my days in Internal Medicine, most of what I learned about medications was OJT [on the job training], more on the apprentice model than from books and articles. I’ve always been a reader, but I don’t recall reading a lot about drugs. I recall talking a lot about drugs, or poring through the PDR, therapeutics manuals, and calling people up when I had a case where I needed to get up to speed on some unfamiliar medication. But as the years passed, it was my own experience with a particular medication that mattered the most. I think I grew up with the model that we all did our own "clinical trials." Again, as strange as it sounds today, that was almost a code of honor. Learning to use medications was like learning to discriminate heart murmurs with a stethoscope or palpate the gall bladder in a jaundiced patient. And that model followed me into psychiatry.

But when I first read about people criticizing clinical trials, what they said didn’t compute. The idea of a controlled and protocol driven clinical trial makes total sense – more along the lines of the research in psychology than my former more ethological approach. Vetting a number of clinical trials and finding their deceitful ways on my own made the detractor’s point more palatable. But over time, other things became apparent – obvious things. Here’s a clinical trial where I had the actual raw data available to plot the HAM-D for every subject:

It’s not a great example because it’s Paxil Study 329 which was, in my reading, a negative study presented otherwise, but I think I can still make my point. When I’m in the room with a single patient, which line matters? They only get one. In a world of such small differences, even a non-jury-rigged trial that is statistically significant doesn’t necessarily help. Should I show my patient the plots of these raw results for placebo and drug responses? How about showing them on a Direct-To-Consumer television ad rather than the beautiful smiling people?

I’d feel a lot better holding up a graph from the 1959 trial by Drs. Ball and Shiloh whose results were a doctor/patient consensus [and would have stood on their own with no statistics involved]. In that case, I’d be sticking close to the clinical question that the patient wants to ask, "What will it do for my depression?" The modern clinical trials in psychiatry are way too sensitive to correlate with palpable clinical improvement. I don’t question that they measure a drug’s antidepressant properties, but in lots of cases, clinical relevance is another matter.

So what to do? What to do? I’d personally like to see the NIMH get over Dr. Insel’s obsession with developing novel new targets and inventing virtual new diagnostic schemes, and focusing on the off-patent old antidepressants we already have that are so widely prescribed. How about some well designed, comparative clinical trials with help-seeking patients in academic centers with both the rating scales and actual hands-on, eyeballs-on, ears-open clinician evaluations [circa 1959]? How about a data-base of subjects to follow with extensive life and family histories, psychometrics galore, and symptom profiles in a setting that approximates clinical practice to replace the dead-end, sterile data from STAR*D? We could even draw some blood for the geneticists of the future. Here’s another novel idea – put the raw data in the public domain for all to see and play around with. There’s enough question in everyone’s mind about these heavily prescribed medications to more than justify the expense. And frankly, the last twenty-five years of research has left us with more questions than answers. Who knows? Maybe we’d see the contested Akathisia after all, or precisely characterize the withdrawal syndromes and relapse rates. Plus, all these academic centers need something to keep them occupied and funded now that the pharmaceutical money is evaporating.

Revealed: US dirty tricks to win vote on Iraq war
^{Secret document details American plan to bug phones and emails of key Security Council members}
The Observer
by Martin Bright, Ed Vulliamy in New York, and Peter Beaumont
1 March 2003
Read the memo

Katharine Gun: Ten years on what happened to the woman who revealed dirty tricks on the UN Iraq war vote?
^{In the runup to the critical vote on war in Iraq, Katharine Gun exposed a US plot to spy on the UN. As a film of her story is planned, she tells of her anger and frustration – but not her regrets}
The Observer
by Martin Bright
2 March 2013

That came to light a lot faster than the back story of the Iraq War, since it was such a felt presence in all of our lives. But then [no rest for the weary], the chairman of the very Department of Psychiatry I had been affiliated with was investigated by the US Senate and removed from his position for unreported income and conflicts of interest – Dr. Charles Nemeroff. And I was off and running again as I learned about how much deceit and corruption was right under my nose in my own specialty of psychiatry.

I have no intention of going backwards and spending my time following the ins and outs of the recent whistle-blower’s [speaking of whistle blowers…] leaks or how it all plays out. I expect it will blanket our news all by itself. The NSA’s capacity to eavesdrop is well known to me from last time around. It should be no surprise to any of us in a post 911 world. The issue then, and now, isn’t that it can be done. It’s the oversight that matters. What was missing back in 2003 was oversight. What was missing in the financial collapse in 2008 was oversight. And what was missing in the pharmaceutical invasion of academic psychiatry and the psychiatric  literature that got so out of hand was oversight. This latter piece is much more suited to me than my former preoccupations, so no political regressions coming. If you care about the NSA and its goings on, follow emptywheel, and her fellow bloggers. They have a wellspring of moral outrage and a political agenda, but they’re also truly amazing investigative people who will unearth the back story in this recent revelation. Another resource is Glen Greenwald, the interviewer in the video in the last post, now with The Observer. He got going back in the days of the Plame Affair, a bit before I did on a blog Unclaimed Territory and never looked back to his career as a litigator.

I’ve wondered aloud and privately about why one of my retirement hobbies has been deceit, secrecy, and lack of oversight. I sort of know the answer. It’s what my job was for forty years – helping people see how having oversight of their own mental processes was worth it in the long run in the conduct of living. And it wouldn’t take a rocket scientists to figure out why that’s what I ended up doing for a career. The great discovery of my own life halfway back was realizing that I didn’t have enough oversight in my own mind, and doing what I could muster to make some progress in that area. I’d heard the saying, "We’re only as sick as our secrets" all my life, but I didn’t really even know what it meant until I saw it in the mirror. What I learned early was that any progress on that front was progress nonetheless, and I also never looked back.

Decline in placebo-controlled trial results suggests new directions for comparative effectiveness research.
^{by Olfson M and Marcus SC.}
Health Affairs. 2013 32[6]:1116-1125.

^{The Affordable Care Act offers strong support for comparative effectiveness research, which entails comparisons among active treatments, to provide the foundation for evidence-based practice. Traditionally, a key form of research into the effectiveness of therapeutic treatments has been placebo-controlled trials, in which a specified treatment is compared to placebo. These trials feature high-contrast comparisons between treatments. Historical trends in placebo-controlled trials have been evaluated to help guide the comparative effectiveness research agenda. We investigated placebo-controlled trials reported in four leading medical journals between 1966 and 2010. We found that there was a significant decline in average effect size or average difference in efficacy [the ability to produce a desired effect] between the active treatment and placebo. On average, recently studied treatments offered only small benefits in efficacy over placebo. A decline in effect sizes in conventional placebo-controlled trials supports an increased emphasis on other avenues of research, including comparative studies on the safety, tolerability, and cost of treatments with established efficacy.}

1. National Trends in the Office-Based Treatment of Children, Adolescents, and Adults With Antipsychotics. Archives of General Psychiatry. 2012 69[12]:1247-1256.
2. National Trends in the Antipsychotic Treatment of Psychiatric Outpatients With Anxiety Disorders. American Journal of Psychiatry 2011 168:1057-1065.
3. Proportion Of Antidepressants Prescribed Without A Psychiatric Diagnosis Is Growing. Health Affairs [2011] 30:1434-1442.
4. National trends in the outpatient diagnosis and treatment of bipolar disorder in youth. Archives of General Psychiatry. 2007 Sep;64[9]:1032-1039.

I graphed some of their tabular data to make it easier to see [all were significant]. On the left is the percent of Clinical Trials where PHARMA funding was acknowledged. This figure is confusing as that only became a requirement during the study period [NEJM 1985, JAMA 1989, BMJ 1994, Lancet 1994]. On the right, the number of authors rose from a median of 2-3 to 8-20 over the study period! Who knew?

The left graph below shows the median number of sites used in the clinical trials. The trend to multiple sites is a striking phenomenon of the recent past, I presume reflecting the ascendency of of the Clinical Research Organizations. Similarly, in the center the median number of study subjects has soared over the last two decades [chasing significance]. And on the right, another way of showing the falling effect size – the mean odds ratio.

And finally some miscellaneous stats from their tables. In this study the % of non-US studies, studies with insignificant Primary Outcomes, and drop-out rates did not change significantly. Intent-to-treat analysis means all subjects that start the study are included including drop-outs etc [corrected for missing data]. Studies reporting number of subjects screened and ITT analysis increased significantly.

^{[reformatted]}

Substantial investments are made in clinical trials. In the United States, for example, more than $100 billion is spent each year on biomedical research, with most of the funding devoted to clinical trials.  Concern over a slowdown in the discovery of innovative medical treatments has prompted calls for new public policies to stimulate drug development, including incentives for novelty drugs. During difficult economic times, however, private research sponsors may be tempted to take a cautious approach that favors incremental research focused on follow-on or “me too” drugs that offer little additional efficacy over more speculative high-risk/high-reward strategies.

The Affordable Care Act mandates a new national comparative effectiveness research agenda. Its great promise is to build the scientific foundation of clinical practice. Yet forty years of declining effect sizes in traditional placebo-controlled trials underscores the increasing challenge of discovering breakthrough interventions. Where established treatments achieve comparable efficacy, comparative effective research can help identify the safer, less expensive, and better-tolerated alternative. By placing clinical decision making on firmer footing, it is hoped that comparative effectiveness research will help patients receive the best possible care and save them from unnecessary risks, inconvenience, and costs.

I obviously liked this study – well-done, timely, well-analyzed. I’m not sure I’m through digesting it, but several things occurred to me. First, my focus has been on the deceit in the psychiatric clinical trial world and I tend to see the problems with clinical trials as localized to psychiatry. This study widens that lens to all of medicine. I was surprised by that. Besides deceit, I’ve also tended to blame the falling effect sizes on the Clinical Research Industry using recruited subjects often in far-away lands with culturally diverse subgroups. So I wouldn’t have expected the same decline in trials of biomarker-confirmed physical diseases. But there it is.

It’s the rare clinical trial article that doesn’t comment on the small effect sizes these days – blaming the placebo effect or other karmic forces. And this paper makes it very clear that they are escalating the number of subjects [requiring multiple sites] to chase significance with smaller effect sizes. But I find it impossible to look at this data and conclude anything except that, on the whole, they’re testing weaker and weaker drugs.

^{hat tip to Pharmagossip…}

Declining Differences in Response Rates with Antidepressants versus Placebo: A Modest Proposal for Another Contributing Cause.
^{by Preskorn SH.}
Journal of Psychiatric Practice. 2013 19:227-233.

^{This column discusses declining differences in response rates between sequentially introduced selective serotonin reuptake inhibitors [SSRI] and placebo. Although discussions of this phenomenon in the literature have largely focused on increasing placebo response rates, the author proposes that another factor may be responsible. That factor is an order effect, meaning that response rates have been declining as a function of the number of SSRIs on the market when the next SSRI is in development. The rationale is that the pool of potential clinical trial participants likely to respond to a drug with this mechanism of action [MOA] becomes progressively smaller with the introduction of each new agent with the same MOA, because many patients will already have been treat- ed and responded to an earlier member of the class. This phenomenon is not limited to the SSRIs but generalizes to any class of treatments that shares the same MOA.}

^{hat tip to Helge…}

This week, a man died who had a profound effect on my close friends and the part of the world I live in. His name was Will Campbell [Rev. Will D. Campbell, Maverick Minister in Civil Rights Era, Dies at 88]. When I met him in the late 1970s, he was already the stuff of legend, but when he started back in the 1950s, no one ever would have predicted that. He was just a young white preacher in Mississippi who saw that there was something very wrong and he could never stop seeing it, at a time and in a place where it was a very lonely thing to see.

HEALY: Dr. Nemeroff came up to me in the course of the meeting in what was a very scary meeting between him and me and told me that my career would be destroyed if I kept on showing results like the ones that I’d just shown, that I had no right to bring out hazards of the pills like these.

MACINTYRE: In a written statement, a doctor who witnessed the confrontation told us, when it became clear that David Healy would not back down from his points of view, Nemeroff said that what Healy was publishing might harm the drug industry, specifically Eli Lilly. He, Charles Nemeroff, said that these people were ruthless and would go to great lengths to make life hard for academics who published articles associating suicide with Prozac.

HEALY: It was a fairly short encounter. It lasted about two or three minutes but a very scary one.

The first footnote was at the end of a post on Dr. David Healy’s blog [We have a Dream: Getting engaged to a doctor] that says, "I have recently been disinvited from a Catholic Church linked meeting on psychotropic drugs and children apparently for using an analogy between child abuse in the Church and pharmacotherapy abuse in clinical care." [see Vatican to Hear Debate About Psychotropic Meds for Children and STUDY MEETING: THE CHILD AS A PATIENT]. It’s really a shame. They’re having some real luminaries on the topic [Robert Whitaker, Irving Kirsch, Joanna Moncrieff, Pat Bracken, Giovanni Fava, etc.], but they’re excluding the guy that got the whole topic on the table in the first place twenty plus years ago because he made an obvious analogy.

The second was added to a response letter in the British Medical Journal [academic psychiatry, research ethics and the pharmaceutical industry] that I referenced Tuesday [coffee-house science…]. In 2000 when Dr. Healy had his confrontation, Dr. Nemeroff was at the top of his game, referred to "the boss of bosses" and "bling-bling." Since then, he lost a major editorship, has been investigated by the US Senate, and removed from the chairmanship at Emory all over gross conflicts of interest. He’s been referred to as the "poster child for conflicts of interest" and "so toxic he glows," yet the Institute of Psychiatry, King’s College London, has invited him to give the inaugural Annual Lecture at its new Centre for Affective Disorders. The article in the BMJ was critical of that decision. I don’t know what prompted the footnote ["Editorial note: This response was modified on legal advice on 7 June 2013"] or even what was modified in the letter, but my fantasy is that Dr. Nemeroff or those that invited him complained. When POGO exposed him as having signed on to a ghost-written textbook several years ago, he and Dr. Alan Schatzberg mounted a legal attack rather than admit the obvious [roaches…, enter the lawyers…].

[Somehow, that last sentence didn't quite fit the flow of things]. Next came the editorial [Workplace Depression: Personalize, Partner, or Pay the Price] with the opening lines I quoted above [I can pretty much guarantee you that Diego Rivera would rise from the grave if he could and denounce this editorial, throwing red paint on as many copies as he could get his hands on]. The editorial ends with:

^{[WPAI: example from Irritable Bowel Syndrome]}

Increase in Work Productivity of Depressed Individuals With Improvement in Depressive Symptom Severity
^{by Madhukar H. Trivedi, M.D.; David W. Morris, Ph.D.; Stephen R. Wisniewski, Ph.D.; Ira Lesser, M.D.; Andrew A. Nierenberg, M.D.; Ella Daly, M.B., M.R.C.Psych.; Benji T. Kurian, M.D., M.P.H.; Bradley N. Gaynes, M.D.; G.K. Balasubramani, Ph.D.; and A. John Rush, M.D.}
American Journal of Psychiatry 2013 170:633–641.

Objective: The authors sought to identify baseline clinical and sociodemographic characteristics associated with work pro- ductivity in depressed outpatients and to assess the effect of treatment on work productivity.

Method: Employed depressed outpatients 18 – 75 years old who completed the Work Productivity and Activity Impairment scale [N=1,928] were treated with citalopram [20 – 40 mg/day] in the Sequenced Treatment Alternatives to Relieve Depression study. For patients who did not remit after an initial adequate antidepressant trial [level 1], either a switch to sertraline, sustained-release bupropion, or extended-release venlafaxine or an augmentation with sustained-release bupropion or buspirone was provided [level 2]. Participants’ clinical and demographic characteristics and treatment outcomes were analyzed for associations with baseline work productivity and change in productivity over time.

Results: Education, baseline depression severity, and melancholic, atypical, and recurrent depression subtypes were all in- dependently associated with lower benefit to work productivity domains. During level 1 treatment, work productivity in several domains improved with reductions in depressive symptom severity. However, these findings did not hold true for level 2 outcomes; there was no significant association between treatment response and reduction in work impairment. Results were largely confirmed when multiple imputations were employed to address missing data. During this additional analysis, an association was also observed between greater impairment in work productivity and higher levels of anxious depression.

Conclusions: Patients with clinically significant reductions in symptom severity during initial treatment were more likely than nonresponders to experience significant improvements in work productivity. In contrast, patients who achieved symptom remission in second-step treatment continued to have impairment at work. Patients who have demonstrated some degree of treatment resistance are more prone to persistent impairment in occupational productivity, implying a need for additional, possibly novel, treatments.

What bothered me more was what always bothers me when STAR*D is in the picture – the drop-out rate and missing data rate is extremely high. And in Table 3, they didn’t use the start values that they had exit values for. They used all of the start values [1924] compared with the exit values [1097]. So the results suggest a continuity that’s not really there [1-(1097/1924)=43% missing exit values from drop-outs or failure to phone home]. It becomes even more tangled because with the Level 2 data, they only reported subjects if they had both start and exit data.

They say this Level 2 table shows non significance. I guess I’ll take their word for it [I couldn't figure out a way to vet it]. And with STAR*D papers, we must always include this part:

In case you don’t recall, Jon Kilner is a medical writer whom I presume to be the ghost-writer/editor for the whole STAR*D enterprise when he’s not writing science fiction. Look here for what I could find a couple of years back:

I’ve already concluded the the STAR*D Trial was a $35 M misunderstanding for countless reasons and wouldn’t have bothered with this iteration had it not been displayed so prominently. But going through it, it has the same kind of internal flaws and non-transparency as so many of its predecessors. Even if taken at face value, the changes in missed hours and subjective self-reported impairment are small. I suspect that the always-missing primary outcome variable [HDRS] and the huge drop-out and missing data rates in STAR*D resulted from the impersonal and mechanized way the study was conducted [check lists done over the phone]. Had I been a subject, I would have felt like a depersonified part of an algorithmic treatment machine. And the list of the authors’ industry connections [in spite of being a NIMH Study] just adds to its industrial feel.

The accompanying editorial feels the same way – a pitch to Managed Care and industry in general to support the pharmaceutical industry [and its academic allies] in developing drugs to increase productivity in the workplace, following the future-think motif so prevalent in the psychiatry of the last three decades [Workplace Depression: Personalize, Partner, or Pay the Price].

^{"Rivera’s politics and his publicity seeking are detestable. But let’s get the record straight on what he did here. He came from Mexico to Detroit, thought our mass production industries and our technology wonderful and very exciting, painted them as one of the great achievements of the twentieth century. This came after the debunking twenties when our artists and writers found nothing worthwhile in America and worst of all in America was the Middle West. Rivera saw and painted the significance of Detroit as a world city. If we are proud of this city’s achievements, we should be proud of these paintings and not lose our heads over what Rivera is doing in Mexico today."}

The oldest map of the world shows Babylon [the rectangle] and its surrounding countries.

^{British Museum 6th Century BC}

^{Hecataeus of Miletus – 500 BC}

^{Ptolemy – 150 AD}

^{al Idrisi – 1154 AD}

^{Martellus – 1490 AD}

^{Waldseemüller - 1507 AD}

^{Ribero – 1529 AD}

^{Mercator – 1569 AD}

And so the maps just kept getting more accurate as technology and exploration advanced. But, as anyone who was near a television set in 1968 would be glad to tell you, no map ever equaled that first glimpse of the real thing from space as Apollo 8 went around the Moon and sent the first photos of the "earthrise." 1968 was a year of assassinations and political upheaval in the US, but those pictures ended the year with a much-needed ray of hope.

These are some of the great maps along the two thousand plus year road to an accurate rendition of our world [Wikipedia]. Some of the advances were technological – the Astrolabe, Quadrant, Sextant, ship and sail design, accurate time-pieces. Others were conceptual – Latitude, Longitude, a spherical earth, cartographic advances. Many were commercial – funded exploration in search for gold, trade routes, conquest. At times there was no progress for centuries. At other times, each new map improved over the last.

Meet the Doctor Big Pharma Can’t Shut Up
AlterNet
By Tamara Straus
May 30, 2013

For the last 33 years, David Healy, an Irish psychiatrist and professor at Cardiff University School of Medicine in Wales, has written heavily researched university press books and academic journal articles on various aspects of psychopharmaceuticals. His output includes 20 books, 150 peer-reviewed papers and 200 other published works. He is not only well-pedigreed, with degrees and fellowships from Dublin, Galway and Cambridge medical schools, he is a widely recognized expert in both the history and the science of neurochemistry and psychopharmacology.

Yet Healy says his output and reputation have had little to no effect — both on the pharmaceutical industry he argues buries relevant information about prescription drug harms, and on the psychiatric and medical professions he claims are being “eclipsed” by drug companies. “It’s been clear to me that writing books or articles banging on the risks and hazards of drugs is just going to increase the sale of drugs,” said Healy, who speaks calmly, dresses mostly in black and looks a bit like Rod Serling.

Rather than write another university publication, Healy has taken his frustration to the street. In November, he launched a nonprofit website called Rxisk.org with a group of like-minded and highly credentialed international colleagues. The site aggregates FDA data about prescription drug side effects and urges patients to submit a detailed report on their own pharmaceutical drug reactions.

Healy is not the first psychiatrist to express boiling frustration with the pharmaceutical industry or to pen dire warnings about drug-based healthcare. He is joined by people like American psychiatrist Peter Breggin, who has written several books critical of “biological psychiatry,” and Irving Kirsch, who directs the Program in Placebo Studies at Harvard Medical School/Beth Israel Deaconess Medical School and is best known for The Emperor’s New Drugs: Exploding the Antidepressant Myth. Healy is the author of such dire sounding titles as Pharmageddon and Let Them Eat Prozac: The Unhealthy Relationship Between the Pharmaceutical Industry and Depression.

For years, it was fairly easy for people in the pharmaceutical and medical industries to label Healy, Kirsch and Breggin as alarmists. But two summers ago, one of the most prominent members of U.S. medical establishment, Marcia Angell, former editor-in-chief of New England Journal of Medicine, published an article damning the over-prescription of psychoactive drugs. In two essays in the June 23, 2011 and July 14, 2011 New York Review of Books, Angell backed arguments by the university clinician Kirsh, the mental heath journalist Robert Whitaker, and Boston psychiatrist Daniel Carlat that there is something extremely suspicious about the following trends: the number of people treated for depression has tripled since the launch of Prozac® in 1987; 10 percent of Americans over age six are taking antidepressants; and 30 antipsychotics like Risperdal, Zyprexa and Seroquel are replacing cholesterol-lowering agents as the top-selling class of drugs in the U.S., largely because they are being prescribed to children.

Angell’s articles should have been a bomb on the medical establishment. She wrote:

“The industry-sponsored studies usually cited to support psychoactive drugs—and they are the ones that are selectively published—tend to be short-term, designed to favor the drug, and show benefits so small that they are unlikely to outweigh the long-term harms. … Both the pharmaceutical industry and the psychiatry profession have strong financial interests in convincing the public that drug treatment is safe and the most effective treatment for mental illnesses, and they also have an interest in expanding the definitions of mental illness.”

But like Healy, Angell’s warnings have fallen on deaf ears. Recent data indicates that U.S. prescription drug use is growing. The September 2012 Consumer Reports National Research Center report found that among the 46 percent of American adults taking prescription drugs, a fourth of those ages 18 to 39 regularly take two prescription drugs, indicating that multiple drug use is no longer confined to older Americans. Congressional testimony in 2012 by the American Society of Interventional Pain Physicians revealed that Americans consume 80 percent of opiate painkillers produced in the world. And a January 2011 report from Stanford University Medical School warned that antispychotics are now regularly being prescribed to treat conditions for which they have not been approved, including anxiety, attention-deficit disorder, sleep difficulties, behavioral problems in toddlers and dementia.

According to a Feb. 7, 2013 report from Drugs.com, the No. 1 best-selling U.S. drug [in dollar volume] is an atypical antipsychotic for schizophrenia treatment called Abilify. Sales for the last quarter of 2012 soared to $1.5 billion, because Abilify is widely prescribed off-label—i.e., not for schizophrenia in adults, but, for example, for irritability in children. Although Bristol-Myers Squibb, the maker of Abilify, was fined $515 million in September 2007 for recommending off-label uses of Abilify, doctors are still doling out the drug. Why?…

Top Five Drugs by Sales, Q4 2012
Drug Name	Sales [$000]	% Change [previous quarter]
Abilify	$1,478,301	5.20%
Nexium	$1,441,472	1.45%
Crestor	$1,275,483	2.41%
Cymbalta	$1,227,484	5.97%
Humira	$1,206,377	4.70%

As I read the Alternet article, I got stuck on the opening line, "For the last 33 years, David Healy, an Irish psychiatrist and professor…" The calculator in my head felt a jolt since 2013 – 33 = 1980. In 1980, there was no Prozac® or SSRI in existence. I thought it was probably just some fuzzy math but I looked up Dr. Healy and found the quote that started this post ["In 1990, Healy became a Senior Lecturer in Psychological..."] which made more sense. 1990 was when he took his faculty position, some 3 years after Prozac® was approved. That would make it "For the last 23 years, David Healy, an Irish psychiatrist and professor…" That would mean that Healy’s focus on the pharmaceutical industry started at the very beginning of his academic career and has persisted to the present. But being the follow-your-nose type, I pulled down his 2004 book, Let Them Eat Prozac, and ended up rereading Chapter I – Take One [which is available on the Internet here as a Google Book preview]. If you haven’t read it, it is still more than worth the time. This is the terse PubMed version of the report Dr. Healy read back then [in 1990] reinforcing his own experiences with his cases:

Emergence of intense suicidal preoccupation during fluoxetine treatment
^{by Teicher MH, Glod C, and Cole JO}
American Journal of Psychiatry. 1990 147[2]:207-210.

^{Six depressed patients free of recent serious suicidal ideation developed intense, violent suicidal preoccupation after 2-7 weeks of fluoxetine treatment. This state persisted for as little as 3 days to as long as 3 months after discontinuation of fluoxetine. None of these patients had ever experienced a similar state during treatment with any other psychotropic drug.}

Around that time, I had left-or-been-sent-away-or-both from an academic position as a dinosaur and was in practice. In 1991, I read two documents pertinent to this topic. The first was a Time Magazine article that blamed the concern about suicidality and Prozac® on Scientology [covered by Dr. Healy here], and the exceedingly thick résumé of our new Chairman of Psychiatry at Emory, Dr. Charlie Nemeroff. At the time, I knew nothing about Scientology, or Prozac®, or Dr. Healy, or Dr. Nemeroff. I sure didn’t know that in that year, Dr. Nemeroff was testifying for Eli Lilly in an FDA hearing on this very topic that Prozac® was absolutely safe [see an anatomy of a deceit 6…]:

FDA Hearing

September 20, 1991

I would suggest to you that I have as little confidence in these anecdotal reports as I do in the anecdotal report of Teicher, and that, in fact, there is no substitute for controlled prospective double-blind clinical trials…

In conclusion, there is simply no scientific evidence whatsoever, no placebo-controlled double-blind study that has established a cause-and-effect relationship between antidepressant pharmacotherapy of any class and suicidal acts or ideation. As Drs. Potter and Fawcett have suggested, limiting the availability of antidepressants could have a very profound adverse effect in terms of increasing the morbidity and, in fact, mortality associated with untreated depression.

Dr. Charles Nemeroff,
Professor and Chair, Department of Psychiatry,
Emory University, Atlanta Georgia

What is this post about with all of its old stories? It was so refreshing to me to read Dr. Healy’s case reports in Let Them Eat Prozac, Dr. Teicher’s case reports in the full text of Emergence of intense suicidal preoccupation during fluoxetine treatment, the case reports on the Rxisk site, and the case reports on the blog Dr. Healy started. And it was so infuriating to read Dr. Nemeroff’s pronouncement "I would suggest to you that I have as little confidence in these anecdotal reports as I do in the anecdotal report of Teicher, and that, in fact, there is no substitute for controlled prospective double-blind clinical trials…" It was the spirit of that quote that lead me to leave my job at Emory so long ago, a job I really loved. Back then, I had no idea that the depersonified clinical trial would replace the case focus that brought me to psychiatry in the first place. I thought it was just what was happening in the department I was leaving.

I’m not opposed to clinical trials per se. What I oppose is that they became the sine qua non of truth rather than ancillary information. And I am beyond outraged that they became such a regular conduit for manipulation and obscuring the truth as time went on. It was through those very depersonified and deified clinical trials that psychiatry handed over the reins to the Managed Care bean counters, the Pharmaceutical Companies, and the Dr. Nemeroffs in academia.

Those of us coming into adolescence in the 1950s were too young to be Beatniks, but we knew something about the rules. It was kind of hard work. Go to the coffee house and talk about the really deep things in the universe, expressing unique and novel opinions without being committed to doing anything except keeping the conversation going. And even though you knew you weren’t going to be actually involving yourself, you couldn’t just say that. You actually had to know the topic pretty well so you could say wise things along the way, otherwise, you were labeled as the worst thing imaginable – a pseudo-intellectual. [which was as bad as working at DOW Chemicals]. In the coffee house, you had to know your stuff to go nowhere. After all, the point wasn’t to say or do anything that mattered – but just sound that way. The point was to fit in and keep up with the other unique and clever people at the coffee shop.

We have a lot of coffee house science, particularly in psychiatry – people who take the results of clinical trials [they didn't design] on patients [they haven't seen] and give presentations of papers [they didn't write] that sound wise and novel – fitting into a world that always ends the same way, needs further study. They don’t look like Beatniks, but they play the same game. They’ve stayed in the coffee house for years by knowing the rules about how to stay, but accomplish little of note. There are some prime examples in my recent posts about STAR*D [a whole lot better than this…] or Vortioxetine [way past time…, the squeaky wheel…].

Decreased Cortical Representation of Genital Somatosensory Field After Childhood Sexual Abuse
^{by Christine M. Heim, Ph.D. Helen S. Mayberg, M.D. Tanja Mletzko, M.S. Charles B. Nemeroff, M.D., Ph.D. and Jens C. Pruessner, Ph.D.}
American Journal of Psychiatry. 2013 170:616–623.

Objective: Sexual dysfunction is a common clinical symptom in women who were victims of childhood sexual abuse. The precise mechanism that mediates this association remains poorly understood. The authors evaluated the relationship between the experience of childhood abuse and neuroplastic thinning of cortical fields, depending on the nature of the abusive experience.

Method: The authors used MRI-based cortical thickness analysis in 51 medically healthy adult women to test whether different forms of childhood abuse were associated with cortical thinning in areas critical to the perception and processing of specific behavior implicated in the type of abuse.

Results: Exposure to childhood sexual abuse was specifically associated with pronounced cortical thinning in the genital representation field of the primary somatosensory cortex. In contrast, emotional abusewas associated with cortical thinning in regions relevant to selfawareness and self-evaluation.

Conclusions: Neural plasticity during development appears to result in cortical adaptation that may shield a child from the sensory processing of the specific abusive experience by altering cortical representation fields in a regionally highly specificmanner. Such plastic reorganization may be protective for the child living under abusive conditions, but it may underlie the development of behavioral problems, such as sexual dysfunction, later in life.

I can’t tell you what their data was because it wasn’t there, at least not in any way an expectable reader of the American Journal of Psychiatry might understand. I’m afraid an expert would be in the same boat. So all I can do is tell you what they did. They recruited 51 women some with abuse histories and some not. With this group, it’s been traditional to recruit from the Grady Hospital [Atlanta Georgia] waiting room or from bus advertisements, but in this paper they don’t say. The women filled out questionnaires about childhood abuse and had structured interviews to rate the extent of the abuse. Structured DSM-IV Interviews provided Psychiatric Diagnosis. They had MRIs ["a high resolution T1 three-dimensional magnetization-prepared rapid gradient echo sequence (TR=2,600 ms, TE=3.02 ms, flip angle=8°, field of view=2563224 mm, in-plane resolution isotropic, 1 mm3)"]. All of this happened in Atlanta, GA, US. Here’s my new hobby – a world map of the study:

^{Cortical thickness analysis was performed using the automated analyses pipeline developed at the Montreal Neurological Institute. In brief, anatomical MRIs are corrected for nonuniformities, registered into standard stereotaxic space, and classified into gray matter, white matter, and CSF using a neural-net classifier. At the core of the cortical thickness analysis, a constrained Laplacian anatomical segmentation using proximities is applied to determine white and gray matter surface boundaries using a surface deformation algorithm. This procedure computes 40,000 vertices of white and gray matter surfaces that are linked. Cortical thickness is computed as the distance between these linked vertices. In a final step, individual cortical thickness data were smoothed using a blurring kernel of 20 mm.}

^{"… emotional abuse specifi cally affects the areas of the left (x= -3, y= -61, z=45; F=7.8, p , 0.05) and right (x=6, y= -49, z=51; F=6.2, p , 0.05) precuneus and the left anterior (x= -4, y=40, z=11; F=6.9, p , 0.05) and posterior cingulate cortex (x= -2, y= -47, z=28; F=8.1, p , 0.01). We also observed thinning in the face region of the somatosensory cortex (x= -56, y= -12, z=45; F=22.7, p , 0.001). Hence, emotional abuse, which likely represents experiences of parental rejection and is often considered most detrimental in terms of altered concept of ‘self,’ is associated with the cortical thinning of regions implicated in mediating self-reflection, self-awareness, and first-person perspective."}

^{"we investigated the effect of age at onset of any abuse on cortical thickness in the group of women reporting moderate to severe exposure. This analysis revealed that earlier exposure was associated with thinning of the left temporal pole (x= -49, y=22, z= -26; F=19.9, p , 0.001), the left parietal lobe (x= -63, y= -32, z=45; F=18.9, p , 0.001), the left frontal pole (x= -28, y=63, z=12; F=16.8, p , 0.001), and the right frontal pole (x=11, y=69, z=4;F=18.6,p , 0.001), areas associated with autobiographic memory, as well as thinning of the anterior cingulate cortex (x= -2, y=21, z=22; F=8.13, p , 0.01). This finding is concordant with reports that abuse occurring earlier in childhood is often associated with absence of memories concerning the abuse. We did not see an effect of duration of the abuse, which supports the assumption that the observed effects reflect developmental programming rather than consequences of cumulative exposure to maltreatment over time."}

So even if we accept the methodology used to measure cortical thinning at face value and accept that the questionnaires and structured interviews actually give an accurate index of the type and magnitude of the child abuse in the subjects, we’re still left entering the world of multiple regressions with no direct access to any data other that the significance corrected in multiple ways we can’t see. Anyone who has done multiple regressions with large data sets using a statistical package knows that if you play with the data enough, you can make it sing any song. It’s where the saying, "Torture the data long enough, and it will tell you anything you want to hear." And then the authors speculate on complex abstract concepts like "self-reflection" or "parental rejection" without actually assessing these things in the subjects  of the study as if the outcome of a given experience is an index of its impact – a clinically indefensible position. We are supposed to be thinking that the childhood sexual trauma resulted in cortical thinning of the genital sensory area of the brain without asking the subjects about their adult sexual history or experience. If there are subjects with cortical thinning of the clitoral area, are they sexually anesthetic? All of that behind us, we are then teleported into the realm of neuroplasticity, the brain changing anatomically based on experience – a concept on the outer edge of our understanding at best.

So everything said in this study may be absolutely correct or it may all be a fantastic coffee house poetry reading. What’s included in this paper itself doesn’t help us make that distinction. Rather than giving us a narrative we can’t possibly vet on the way to conclusions filled with speculation, how about a scatter-plot of the various trauma indices against the cortical thickness in different parts of the cortex. Maybe we can’t grasp the methodology completely, but we could at least see something concrete that gave us a sense of what we’re being asked to believe.

I’m not sure what part Dr. Nemeroff actually played in this study, but his track record doesn’t support anyone asking us to accept things he publishes on faith alone. There’s too much consistent dodgy science in his former outings to ask us for that – particularly when the conclusion has so many conceptual ramifications. This is the kind of study where the raw data, at least the various values of cortical thickness by cortex area and the results of the associated subject data should be available for validation by some kind of outside source. I can’t imagine how a peer reviewer could evaluate this paper.

^{Neural plasticity during development appears to result in cortical adaptation that may shield a child from the sensory processing of the specific abusive experience by altering cortical representation fields in a regionally highly specific manner. Such plastic reorganization may be protective for the child living under abusive conditions, but it may underlie the development of behavioral problems, such as sexual dysfunction, later in life.}

• Critical Psychiatry Network Calls on Institute of Psychiatry to Cancel Charles Nemeroff
• Letter from the Critical Psychiatry Network
• academic psychiatry, research ethics and the pharmaceutical industry

"The Nemeroff case tells us something about how the psychiatric establishment and the biomedicine-driven research world work, and about their relationship with the pharmaceutical industry that has a vested interest in the biologisation of human experience – indeed in the disease – mongering Jonathan Gornall reprises. Nemeroff’s appointment to another chair of psychiatry as if nothing had happened and when the case against him was not closed, his receipt of substantial new grants, and the Institute of Psychiatry in London continuing to laud him as “one of the world’s leading experts”, all show how psychiatric academe sails blithely on as if such revelations beg no broader questions about its associations and supposed scientific independence, about research ethics, and specifically how conflicts of interest must inevitably contaminate the integrity of the research data informing publications in the scientific literature."

"It is worth adding that in fact no clinically meaningful “neurobiology of depression” has been discovered- and perhaps never will be, given that “depression” is merely a syndromal category, subsuming a very heterogeneous range of patients and circumstances,and whose widely differing understandings of their distress point rather more often to social space than to the space between their ears."