don’t take sides…

Posted on Wednesday 12 August 2015

While it’s not fashionable these days to acknowledge that Sigmund Freud even existed other than as a caricature, a container for the things he got wrong, this is one of those places where I would evoke something he got right – neutrality. Actually, his daughter Anna wrote it down in the most frequently quoted form, saying the analyst "takes his stand at a point equidistant from the id, the ego, and the superego." In just plain English that means, "Don’t take sides."
by Renée Binder, M.D.
July 13, 2015

… In June, I arranged for the Board of Trustees to tour San Quentin in northern California. It was a powerful, moving, and formative experience, and I’m thankful to Dr. Paul Burton, the chief psychiatrist, and to the California Department of Corrections and Rehabilitation for giving us that access. Our visit was important because, if one wants to understand firsthand the toll mental illness is taking on our country, one just needs to peer beyond the bars of our nation’s jails and prisons. It’s also important to have a detailed and nuanced understanding of the situation. Our tour was a no-holds-barred look at San Quentin State Prison. For three hours, we were shown various aspects of prison life…. We specifically saw the psychiatric facilities, which are highly used by the inmates. In many ways they are state of the art. As you’d expect, sharp angles in the halls and cells, down to the door hinges and door handles, were filed smooth to prevent inmates from using them to aid in a suicide attempt. Many cells provided a sanctuary for inmates, nearly always curled up on a plain bed with a blanket covering them head to toe.

But the rooms that captivated our group were the group therapy rooms. Separate enclosures or “modules” formed a semi-circle for people who are at once both dangerous and needing and deserving of help. We briefly observed one group. Those participating highly praised the care they were getting. One patient’s body language told us when he had enough of our interruption; in a visceral way, it was clear he valued his treatment.

The four psychiatrists with whom we interacted were obviously compassionate and concerned about each of their patients. At each stop, it was abundantly clear that the care provided by the staff psychiatrists was superb and professional. Even if incarceration itself is likely a detriment to many individuals’ mental health, the physician-patient interactions we witnessed gave us hope…

Jails and prisons have become the front lines of treatment for mental illness. The data indicate that San Quentin is an anomaly in the quality of care that’s available in such a setting. This is likely due to its proximity to a highly desirable metropolitan area and its affiliation with the University of California, San Francisco, Department of Psychiatry.

According to a 2010 study by the Treatment Advocacy Center and the National Sheriff’s Association, there was one psychiatric bed for every 300 Americans in 1955. By 2005, that rate dropped to one psychiatric bed for every 3,000 Americans. Over time mental illness has been criminalized, and our jails and prisons take up the slack, despite being seriously ill-equipped to do so. Our jails and prisons have turned into warehouses for those with mental illness; the number of people with mental illness in jails is three to six times higher than that of the general public.

This is why APA and the American Psychiatric Association Foundation have joined forces with the National Association of Counties and the Council of State Governments Justice Center in the “Stepping Up” Initiative. The initiative seeks to reduce the number of people with mental illness in our prisons and jails by promoting the use of mental health courts and diverting minor offenders who have mental illness to treatment resources rather than incarceration…

We must reduce the use of our jails and prisons as warehouses for Americans with mental illness, partly to help our patients, but also because of what this tragedy says about the kind of nation we are. This is an effort for our patients, for our profession, and for our nation.
I personally couldn’t be more pleased that Dr. Binder wants to do something about this very real  problem, but this reporting doesn’t acknowledge the layers of history and controversy that lie embedded in this particular mustard seed – dating all the way back to Philippe Pinel and beyond. It frames the problem from one particular vantage point. But as soon as one does that, you hear:
… psychiatry’s concern about the imprisonment of the mentally ill is being used by advocates of forced outpatient treatment as a Trojan Horse.  The advocates for forced treatment in outpatient settings [such as the Treatment Advocacy Center] argue that forced drug treatment would prevent the mentally ill from ending up in prison, and thus their legislation, which in fact curbs the civil rights of citizens in profound ways, comes cloaked in the rhetorical garb of “humanism.” If we are going to have an honest societal discussion about the shame of imprisoning the “mentally ill,” then it needs to be completely decoupled from that legislative agenda. Indeed, an argument can be made that the growing imprisonment of the “mentally ill” is yet another example of how our drug-based paradigm of care has failed us. The use of psychiatric medications in our society has exploded over the past 25 years; there is great societal pressure put on people diagnosed with schizophrenia or bipolar disorder to take their medications; and yet we now have this problem of hundreds of thousands of “mentally ill” in prisons and jails…

However, I do agree with Allen Frances on this point: Any effort to remake mental health care in this country needs to include a focus on what can be done to help the multitudes of poor people and disenfranchised people who show up in distressed emotional states in emergency rooms and homeless shelters, and the eventual routing of many such people to jails and prisons.  But, in my opinion, if we want to find a solution, we should focus on providing housing, social support and jobs that help people lead meaningful lives. If we want to reduce the number of people said to be mentally ill and in jail, then we should focus on reducing poverty in this country. Substantially raising the minimum wage would, undoubtedly, be a good first step in addressing this problem…
Sound familiar? Here’s another version from the last time around:
For some time now I have maintained that commitment—that is, the detention of persons in mental institutions against their will—is a form of imprisonment; that such deprivation of liberty is contrary to the moral principles embodied in the Declaration of Independence and the Constitution of the United States; and that it is a crass violation of contemporary concepts of fundamental human rights. The practice of "sane" men incarcerating their "insane" fellow men in "mental hospitals" can be compared to that of white men enslaving black men. In short, I consider commitment a crime against humanity. In the first place, the difference between committing the "insane" and imprisoning the "criminal" is the same as that between the rule of man and the rule of law: whereas the "insane" are subjected to the coercive controls of the state because persons more powerful than they have labeled them as "psychotic" "criminals" are subjected to such controls because they have violated legal rules applicable equally to all…

The fundamental parallel between master and slave on the one hand, and institutional psychiatrist and involuntarily hospitalized patient on the other, lies in this: in each instance, the former member of the pair defines the social role of the latter, and casts him in that role by force…

In this therapeutic-meliorist view of society, the ill form a special class of ”victims” who must, both for their own good and for the interests of the community, be "helped"  — coercively and against their will, if necessary — by the healthy, and especially by physicians who are "scientifically" qualified to be their masters. This perspective developed first and has advanced farthest in psychiatry, where the oppression of "insane patients" by "sane physicians" is by now a social custom hallowed by medical and legal tradition. At present, the medical profession as a whole seems to be emulating this model. In the Therapeutic State toward which we appear to be moving, the principal requirement for the position of Big Brother may be an M.D. degree.
I want to say "ditto" to my last post. Dr. Binder seems to be a decent person, and I expect her concern for the jailed psychotic people is genuine. But she isn’t talking like she knows what awaits her up ahead. The collective other have decided that the problem isn’t mental illness but something else. She should probably go to the Mad in America site and read a few blogs, then read the British Psychological Society’s report, then think about this era of KOLs we’ve just been though, before proceeding as if good intentions will carry the day. She doesn’t seem to grasp that she’s now representing an organization that many see as the problem rather than part of the solution.

Right now, there’s an enormous and somewhat understandable back lash to the recent era of psychopharmacological/neuroscientific goings on, and pressing ahead without addressing all the conflicts in the air is likely to be a lesson in futility. The sentiment expressed above by Robert Whitaker and in the British Psychological Society’s Report suggests that psychotic conditions aren’t, in fact, mental illness at all, but rather some barometer of social ills and imbalances, or even a sign of psychiatrists not listening.

If Dr. Binder is serious about approaching this problem, she’s going to have to address all of the views. The official mouthpieces in psychiatry right now seem to think that they can just ignore what’s happened in these last 20 or 30 years if they start behaving in more rational ways now. They think that they can avoid acknowledging the sins of the fathers. That is unlikely to help anyone at this point.  All they’re going to hear about is forced drugging, imprisonment, overmedication, "bio-bio-bio," medical models, the DSM-whatever, pharma this and pharma that.

Dr. Lieberman had a shot at attacking and discounting the critics which was decidedly ill-conceived. Dr. Summergrad was more balanced, but didn’t address or acknowledge the conflicts in the air. Dr. Binder has the opportunity to take a different and more realistic tack, but I’m afraid that the course she’s setting here could use a bit more thought because it raises specters she’s failing to mention. For the moment, it would be a much better idea to look into problems like this one, and get input from as many players as she can find. "We must reduce the use of our jails and prisons as warehouses for Americans with mental illness" is totally correct. But for the moment, she needs to listen to some time honored advice, "Don’t take sides." At least not yet…
Mickey @ 3:25 PM

the center stage…

Posted on Wednesday 12 August 2015

I’ve been preoccupied with other matters for a month or so, and looking at my posts – I’m afraid they’re kind of just newsy as a result. I’m free of those distractions at last, and find some things that deserve thinking about rather than just reporting. One such thing is the post I’d like to go back to by James Coyne on the PLoS blog Mind the Brain called Barney Carroll on domesticating psychosis. It’s a short post that’s long on substance and freely available on the Internet, so I’ll skip the summary. It’s about Dr. Coyne’s recent presentation BPS’s Understanding psychosis and schizophrenia – a skeptic’s perspective as a visiting lecturer at the Royal Edinburgh Infirmary, University of Edinburgh. It’s obviously about the British Psychological Society’s Report, Understanding psychosis and schizophrenia. It’s a testimony to a frequent commenter here, Dr. Bernard Carroll, his keen eye and skillful and sometimes piercing writing style. And it’s about both Dr. Coyne’s and Dr. Carroll’s thoughts about the BPS Report. All of that is sitting right there for the reading. I wouldn’t miss it.

I’ve had a lot to say about that Report along the way myself, the views of the retired old psychiatrist I see in the mirror. But Dr. Coyne used a YouTube video of Kris Kristofferson singing The Silver Tongued Devil and I to illustrate Dr. Carroll’s wordsmithery – and posted Janis Joplin’s Me and Bobby McGhee [a Kristofferson classic] below it. Those videos reminded me of an earlier and much different time. Kristofferson himself embodied the contrasts of those years – a Rhodes Scholar, Air Force Captain, Ranger, and helicopter pilot who turned down an English Instructorship at West Point to become a songwriter in Nashville. Those were interesting times.

In 1974, I was a fully trained Internist fresh out of the Air Force myself, and my 1960s mindset was solidly in place. I showed up in a psychiatry residency, drawn by an interest in the psychology of my medical patients. I had rarely encountered psychosis, but I found myself working in a charity hospital emergency receiving unit during the maximally chaotic days of deinstitutionalization – days when psychosis was everywhere, or so it seemed from my new vantage. The simple sentiments of the Beatles’ sixties, "all you need is love" and "give peace a chance," came face to face with the stark terror that psychosis can be. In Dr. Carroll’s words:
…the clinical reality of decompensating psychotic patients smashing furniture to stop the voices, smearing faeces, living in filth, going to the streets, eating out of dumpsters…"
and more. In those days, I assured my internal medicine friends who teased me for changing to "the easy life of psychiatry" that my second residency was definitely more challenging than my first – knowing full well that they couldn’t possibly know what I was talking about. It wasn’t the hallucinations or the paranoid delusions ["secondary" symptoms] that made Acute Schizophrenia so paralyzing, it was the gross breakdown in the basic elements of mental life – emotional signaling, logical and abstract thinking, a capacity for pleasure, a solid identity sense, etc [the "primary" symptoms]. That first year of residency was spent learning about a version of human experience that I hadn’t previously even imagined.

I had already thought about the 1960s mentality reading the BPS Report. The anti-establishment tone, the discounting of the dire changes in mental functioning, the simple solutions to complex phenomena were all familiar from those salad days in my own past. But Dr. Coyne’s musical interlude helped me remember the time when my own sixties naiveté first met the stark reality of psychosis, and I understand more fully what bothers about that BPS [British Psychological Society] Report. It’s as reductionistic as that of the other pole of the antipodes, those psychiatrists who talk as if antipsychotic medication compliance is all there is to treating people with psychotic illness. Dr. Carroll’s term is dead center – "Domesticating Psychosis" – as are Dr. Pies’ “Trivializing the Suffering of Psychosis… and Dr. Pierre’s “Romanticizing psychosis”.

Much of the BPS Report was about empathy and collaboration, about kindness and respect, about the humanistic values that are an integral part of any interaction with the people who come looking for help – essential ingredients of medical care from long before science caught up. These are hardly new discoveries or unique to the profession of psychology. They are the bedrock of the values I’ve known for my fifty years in medicine, psychiatry included.

So the notion that there’s some concrete impersonal ‘disease model‘ as it’s presented in this Report or in the anti-psychiatry blogs can’t help but grate. I have to actively remind myself that it’s true that there are psychiatrists [that I sarcastically refer to as the KOLs] who do naively speak as if brain science is all there is; who have abetted an epidemic of inappropriate overmedication [that I’m as pissed off about as any psychologist]; who, by the way, are the negative stimulus for this blog in the first place; and who discredit the legitimate biological psychiatrists that have contributed so much to our knowledge and patient care. So I’m mad too. With that reminder, I can usually back off from reacting.

But this BPS report has obviously gotten to me, gotten to a lot of us. I said my emotional response was complicated. Even now, I can still feel those 60s feelings that were perhaps appropriate for things like Segregation, the Cold War, or our misbegotten war in Southeast Asia. But they don’t come close to encompassing the magnitude that is psychotic illnesses – back then or now. This Report was too much the polemic, too "sixties", too politically correct, and too simplifying. It attempted to "make nice" with one of the more painful and devastating afflictions that can befall a human being, particularly the young. And while we can all be excited with the cases that recover, there are many who have a very different trajectory.

This post sat in my draft folder for two or three weeks because I didn’t want to sound like an "anti-psychologist." I’m not such a critter. Many of my favorite teachers, students, and colleagues are psychologists [and social workers]. My reaction wasn’t because of the discipline difference and I’ve certainly qualified as being sympathetic to over-medication issues. But I am surprised at this report overall. It feels like the same kind of thing that happened in psychiatry – a group with a strong ideological bias grabbed the reigns and taken the center stage…
Mickey @ 10:00 AM

therapeutic trials…

Posted on Saturday 8 August 2015

My first real medical specialty was Rheumatology. I trained at a place that had a strong section, and they spent a lot of time with the trainees – high standards all around. Rheumatology was [and is] an unusual medical specialty. There are more than the usual number of diseases of unknown etiology; fewer cases with classic presentations [a lot of overlap among syndromes]; a lot of mystery about etiology and pathophysiology [mechanisms]; and biological markers with only statistical specificity [not sure things]. I suppose if I’d thought about it, it wouldn’t have been a half-bad prequel to psychiatry, where all of those things are even more true [like I said in the last post, I must be drawn to mystery and ambiguity].

That same fuzziness surrounded treatments. There was almost no disease specificity, some situation where this diagnosis leads to this drug. In a patient with Rheumatoid Arthritis, developing a "hot joint" might be a call for an anti-inflammatory agent, or physical therapy, or even putting on a plaster cast. "It depends…" introduced the answers to most questions in the Rheumatology Clinic. The attendings made up for the lack of precision by being very careful – taking careful histories, doing careful exams, making careful treatment choices – and the best lesson of all, carefully following up their interventions. Every treatment was considered to be a therapeutic trial.

I’ve tried to follow that lead in psychiatry, making every prescription a clinical trial. It was easy in private practice. I saw people for a long time by usual standards, and there weren’t that many who were on medication. I used to joke that I wrote more prescriptions for antihistamines than psychiatric drugs [you’d have to live in Atlanta to understand why]. But in my stint as a volunteer in a charity clinic, I worried that I wouldn’t be able to do that. I was pleasantly surprised to find that it wasn’t true. I work infrequently, so it’s easy to remember patients visit to visit. And I’m surprised how easy it is to develop a therapeutic alliance even in that setting. When I first started, I was horrified at the polypharmacy and drug regimens the patients were on, and wanted to slash and burn. I quickly learned the error of my ways and backed off. These patients lead hard lives, and they become attached to their medications.

What I found was that down the road, it was much easier to get  people off of unnecessary medications once we got to know each other. I’ve been there for six or seven years now, and there’s no-one in the clinic on antipsychotics anymore who doesn’t carry a bonafide psychotic diagnosis.  I’m kind of proud of that. When I started, almost everyone was taking some flavor of Atypical Antipsychotic – sometimes two. But there’s actually something specific that has me on this airy topic.

There are a reasonable number of patients who have a Generalized Anxiety Disorder. In practice, I never saw them. I just wasn’t the person you would refer such patients to. So it was a new experience for me. They’re a very similar lot. They don’t have "fixed" anxiety – meaning anxiety in certain situations or settings. They’re always anxious. You can see it as they walk into the room, trying to not let it show, eyes darting, jumpy. If you’re a me, you start looking for triggers, or conflicts. What you find is nada, just a lifetime of anxiety as far back as they can remember. Often, they say something like "my Mom had it too." There are invariably somatic complaints and fears of imminent catastrophe, with a history of frequent trips to the ER for suspected heart attacks and the like.

I found that if I tried a medication, they rarely took it for much past the first pill. Feeling any medication effect scared them, and they stopped – even with the minor tranquillizers. I read that SSRIs were supposed to help. But one is rarely helped by a medication you won’t take. I began to start them on homeopathic doses, thinking I could sneak my way up after a time of acclimation. So I would start with 5 mg of Citalopam for example. To my surprise, they returned, saying it helped. In cases where I added a Benzo as a prn for anxious situations, the same thing happened. So I prescribed half of an 0.25mg Aprazolam, and heard the same report. 5mg Citalopam? 0.125mg Aprazolam? Who’d have thought? Over the years, I’ve seen enough of these patients, and written enough of these mini-dose prescriptions, to see that as the way to treat such cases straight away. I still do my "therapeutic trial" thing, but in these patients, it always seems to come out the same. I have no clue about the why? of it.

What brought it to mind was seeing a patient in the clinic who I now only see every three months for refills. She was one of the first I tried on these baby doses. She is now working part time and proudly announced that she hadn’t been to the Emergency Room for over a year. Both things are major accomplishments. She was downright effusive about how much better her life is. I rarely have very much good to say about our medications, so I made a mental note to write about it – I guess to prove I’m no therapeutic nihilist.
Mickey @ 8:11 PM

we’re really going to miss this guy…

Posted on Saturday 8 August 2015

my daughter’s chance meeting on the streets of Boston…

Mickey @ 3:15 PM


Posted on Wednesday 5 August 2015

I’ve always liked a good mystery. Nancy Drew was my favorite book·mobile selection, until I discovered The Complete Sherlock Holmes [my parents finally bought it for me because I would”t return it to the library]. Math problems were like mysteries to me – looking for the hidden answer. Little wonder I was a medical researcher who ended up a psychoanalyst. My own analyst had a field day with all of this – what secrets was I in search of? I learned some interesting things about that, but there was no cure. I still scroll the Netflix roster periodically for some new British Mystery series [before re·watching either the British or Swedish Wallander]. And it’s little wonder I ended up in medical research, then migrated to psychoanalysis.

In former times, Internists were called Diagnosticians, unraveling those who·dun·it cases that make it to the T.V. shows like House. But by the time I came along, those cases went to specialists, and office practice began to focus on health care management and preventive medicine, sending the mysteries on to the higher ups. And even the specialists see the same mysteries repeatedly. I still spend a week every summer with a group of doctors I worked with as an Internist forty years ago. In an oft-told story, one night, one of the guys [Gastroenterologist] and I were reminiscing, and he said, "You know, nowadays when I see a new case, I know in minutes what they’ve got and what’s going to happen. I still ask all the questions, do all the tests, but I’m rarely wrong." His music was mastery. I said, "I never know for a very long time." My music was mystery.

So there was one part of the evolved role of the General Internist I was assigned to be in a three year tour in the Air Force that I didn’t much like – the focus of health maintenance and preventive medicine. It’s not that I didn’t think it was a good idea for doctors to talk about smoking, obesity, even the perils of being a couch potato. It’s not even that I found it boring, which it was. It was something where I felt like I was treating "proxies" or "surrogates" that I couldn’t really evaluate myself. What I’m talking about are things like how tightly to regulate glucose control in Diabetes; what level of Blood Pressure elevation constituted Hypertension requiring treatment; what was a High Cholesterol level in need of dietary adjustment or medication; when is alcohol consumption something to talk about; and so on and so on. Those may have been mysteries, but I couldn’t solve them. The literature was long on conclusions and short on solid data. A lot of it felt like the opinions of armchair scientists, and didn’t give me much conviction in my dealings with patients – particularly treating hypertension. I just didn’t like treating lab values and physical findings like Blood Pressure. I felt more at home with whole diseases.

Flash forward: In the waning days of my academic career, our new chairman, a disciple of the neoKraepelinian changes in psychiatry, and I had a recurrent discussion. He was a devotee of evidence-based medicine in psychiatry, the beginning search for biomarkers, and the brain science approach that has flowered since those salad days. I claimed that psychiatry was the repository of ambiguity in medicine, each case being its own unique mystery, and things that got "cleared up" would leave psychiatry and become part of general medicine like Syphilis when Penicillin arrived. These were good·hearted discussions, though they became the substrate for my ultimate exodus to the world of practice. And because I had left Internal Medicine, I never made my peace with my questions about treating these surrogates·of·future·health. So some of what goes on in modern medicine brings up those old questions about preventive treatment.

In the 70s, the congenital hyperlipidemias had just become characterized, and there was no question that they needed treating. These patients had heart attacks and strokes starting in their thirties unless you did something. But what about mild elevations of serum lipids without those underlying diseases? Nowadays, it’s an obsession. I live in an elderly community where everyone is on a Statin, and can wax eloquent on their lab values. I declined the offer when my perfectly normal values exceeded the newer recommendations. So I guess I’m not a believer after all. I wonder what I would do if I had an asymptomatic positive Hepatitis C lab test in my hand. Would I spring for a $90,000 Solvadi® treatment, or leave that money in the bank for my kids’ futures? And I thought about that reading Roy Poses’ really interesting post on Healthcare Renewal about the new "breakthrough" cholesterol lowering treatment, Praluent®, that costs over $1000/month [see Praluent, the Next Expensive "Game Changer," Blockbuster," "New Hope," – But Not Yet Shown to Benefit Patients]. After a detailed vetting of the Clinical Trials, Dr. Poses concludes with:
All the enthusiasm about this drug may be premature, and does not appear to be evidence-based.  That clinical research sponsored by organizations that sell health care goods and services may be manipulated to make the sponsors’ products look better than they really are is now an old story.  We have seen multiple instances in which drugs and devices turned out to be less efficacious and/or more dangerous than originally advertised.  Excess enthusiasm about such new innovations may drive up costs, and worse, hurt patients.  Physicians, other health care professionals, and those concerned about health policy ought to be much more skeptical about every new instance of a purportedly wondrous innovation. 

Evidence-based medicine rigorously applied suggests that individual health care and health policy decisions should be driven by the best available evidence, mostly from clinical research, about the benefits and harms of tests, treatments, programs, and so on, in the context of what outcomes matter to patients.  The skepticism EBM should engender could lead to health care that is more about patients and their outcomes, and less about ideology, hype, and hucksterism.

How high must our health care costs go, and how many unproven treatments must eventually be exposed as such before we learn that lesson?

Sounds good to me. In the face of many medical mysteries, premature closure is the greatest danger of all. We even have a name for it. We call it Watchful Waiting. Hercule Poirot is at his best when he remains vexed and doesn’t jump to conclusions…
Mickey @ 10:29 PM

our decision…

Posted on Wednesday 5 August 2015

While it’s tempting to just mount a counter·argument to this article as I and others have done so many times in the past, I’m going to forgo doing only that. If you’re reading this, you probably have your own views and arguments on this topic, and hearing mine wouldn’t add much. Dr. Friedman concludes that the Black Box Warning on antidepressants should be rescinded altogether. I’d prefer to also comment on certain other aspects of his argument, or more accurately, the logic of his argument [also, I’ll mention as an aside that I thought the article linked as toxic social pressure below [Suicide on Campus and the Pressure of Perfection] was interesting and worth a look]:
New York Times
by Richard A. Friedman
AUGUST 3, 2015

Is our culture of relentless achievement and success driving our young people to suicide? You would certainly think so, given the prevailing narrative in the media about the recent spate of suicides on college campuses: one high-achieving student after another succumbing to the toxic social pressure for perfection. It’s a plausible but incomplete explanation. No doubt the intense social pressure on young people, especially girls and young women, is daunting, but stress is only part of the story: We should also focus on adolescent mental illness and its treatment.

At least 90 percent of people who commit suicide have a diagnosable and potentially treatable mental illness like depression, or alcohol or other drug abuse problems, often in combination. Suicide is the third leading cause of death among young people and has been rising since 2007. The unidentified killer in this story is untreated psychiatric illness. In 2013, for example, 8.7 percent of people between the ages of 18 and 25 experienced a major depression episode in the previous year, but only half of them received any psychiatric treatment, according to the National Survey on Drug Use and Health. And in 57 percent of these episodes, patients were seen by a general practitioner or family doctor — neither of whom is typically an expert in the treatment of mental illness.

Worse, antidepressants, which can be lifesaving, are probably being underused in young people. Their use fell significantly after the Food and Drug Administration issued its so-called black-box warning in 2004, stating that all antidepressants were associated with a risk of increased suicidal feeling, thinking and behavior in adolescents. That warning was later extended to young adults. One very large study, including 1.1 million adolescents and 1.4 million young adults, examined data for automated health care claims for 2000 to 2010 from 11 health plans in the United States Mental Health Research Network. Disturbingly, the study found that antidepressant use plunged 31 percent among adolescents and 24 percent among young adults within two years after the F.D.A. advisory was issued…

Since there is no evidence that the F.D.A. black-box warning has been helpful, and there is a very reasonable possibility that it has discouraged patients from taking antidepressants and physicians from prescribing these medications, the government should rescind the black-box warning on antidepressants altogether. Parents and teenagers, and their doctors, too, should not be afraid of antidepressants and should know that they can be very helpful. Indeed, with careful use and monitoring, they can be lifesaving. The only thing we should all fear is depression, a natural killer that we can effectively treat.
He begins with a sociocultural phenomenon and its impact on the psychology of many college students – "the intense social pressure on young people, especially girls and young women" – as a potential cause of teen suicides – stress. But then says that there’s more – something called adolescent mental illness. That transition, from a sociocultural problem of modern life to a disease [biological?] is frequent and unexplained. He implies that it’s not stress, but something else. Is it in the genes? the water? the air? It’s never explained. Is it increasing in frequency? Apparently, otherwise he wouldn’t be talking about it in an article about "the prevailing narrative in the media about the recent spate of suicides on college campuses." So the problem isn’t toxic social pressure, or any of the other issues that we traditionally discuss about the difficulties of adolescence development, at least in Friedman’s mind. It’s adolescent mental illness.
The unidentified killer in this story is untreated psychiatric illness. In 2013, for example, 8.7 percent of people between the ages of 18 and 25 experienced a major depression episode in the previous year, but only half of them received any psychiatric treatment, according to the National Survey on Drug Use and Health.
There’a an illogic in this line of thinking that just slides right on by, often ignored. In logical terms, it’s a tautology. Increased suicide rate, ergo increased adolescent mental illness, ergo medicine required, ergo … And so he quotes Lu et al, one of the all time bad population studies in that it used an invalid proxy for suicidality [see all databases are not created equal…] on his way to his next piece of illogic. Parenthetically, that study didn’t show much of a "fall off." It rather showed that things leveled out instead of accelerating like a runaway train [see end of story…boxes black are back I…, boxes black are back I…, and unsupportable and totally irrational…].
But this NYT piece is just a rewrite of Dr. Friedman’s NEJM article from last year [Antidepressants’ Black-Box Warning: 10 Years Later] – I guess for public consumption. Before moving on to the final piece of logic, we should mention the Cochrane Collaboration meta-analysis of Antidepressants in Adolescence:
Cochrane Systematic Reviews
by Sarah E Hetrick, Joanne E McKenzie, Georgina R Cox, Magenta B Simmons, and Sally N Merry
14 NOV 2012

… Based on 14 of the trials [2490 participants in total], there was evidence that those treated with an antidepressant had lower depression severity scores than those on placebo, however, the size of this difference was small. Based on 17 trials [3229 participants in total], there was evidence of an increased risk [64%] of suicide-related outcomes for those on antidepressants compared with those given placebo…

The conclusion to these articles is always the same. Repeal the Black Box Warning.
The logic? We want people to save lives by prescribing more antidepressants to kids. The ones lost to this idiosyncratic and rare suicidality thing will be made up for in lives saved by giving the drug. The argument that is being offered is fine to say. But the mandate of the FDA is to tell me about the possible adverse effects of the drug so I can weigh the risk benefit ratio with every drug in every case. To suggest that the FDA should con me into a false sense of security by not telling me a potential danger is illogical to a fault. He can preach his gospel wherever he wants to, but don’t withhold the truth in the process. I’ve seen this suicidal reaction with my own eyes, by my own prescription. I’ve seen completed suicides, thankfully not in cases where I prescribed. And I’ve prescribed SSRIs to a few adolescents but watched them like a hawk. The drugs actually weren’t much help after all. Dr. Friedman says:
Since there is no evidence that the F.D.A. black-box warning has been helpful, and there is a very reasonable possibility that it has discouraged patients from taking antidepressants and physicians from prescribing these medications, the government should rescind the black-box warning on antidepressants altogether.
It is not the FDA’s job to be helpful in that way. They’re supposed to provide me with accurate information to pass on to my patients, and in this case, their parents. It’s our decision what to do with that information. Not the FDA’s and certainly not Dr. Friedman’s.
Mickey @ 1:33 AM

not really given the chance…

Posted on Monday 3 August 2015

by S. Charles Schulz M.D. and Donald W. Black, M.D.
American Journal of Psychiatry. 2015 172[8]:793.

To the Editor: There are currently no standard treatments for borderline personality disorder. Several psychotherapies have been developed, and a few are now considered evidence-based. Medications have also been explored, yet randomized controlled trials are few in number, leading to a lack of consensus regarding the best approach…

To address the potential benefit of quetiapine [approved by the FDA for schizophrenia and bipolar disorder], we conducted a double-blind, placebo-controlled study, which was investigator initiated and sponsored by AstraZeneca. The results showed positive effects of the lower dose tested [150 mg/day], with more than half responding as defined by a 50% decrease in symptom ratings. There were fewer such effects at the higher dose, and there were more side effects and patient attrition. The report was accompanied by an editorial appropriately noting the strengths and limitations of the study, including its 8-week duration for an illness that often lasts many years.

Two subjects initially enrolled at the University of Minnesota site were immediately dropped from the study when their misuse of the study medication was discovered. The University Internal Review Board reviewed what occurred and concluded that we had acted appropriately. Nonetheless, a member of the Ethics Center alleged to the New York Times that the investigators had acted irresponsibly. The newspaper reported this allegation in a recent issue and did not include a statement to the newspaper from the University of Minnesota that no investigator misconduct had occurred.

Many large clinical trials have had issues with behavioral problems and protocol violations by some subjects, and for these reasons all such studies have procedures to dismiss subjects. Such problems are part of both clinical and research care with seriously ill patients. Despite this subject misconduct, the results of the study provide clinicians and patients with new evidence-based guidance on dose, effectiveness, and side effects of quetiapine in borderline personality disorder. The next step is to examine the effect of quetiapine in borderline personality disorder patients in combination with an evidence-based psychotherapy. Our patients deserve no less than the continued investigation of our options for their treatment.
Here’s a less sanitized version of the story:
Fear and Loathing in Bioethics
by Carl Elliot
August 1, 2015

If you recall, in April the Times reported yet another mismanaged clinical trial in the U’s Department of Psychiatry. Two sex offenders were recruited into a clinical trial of Seroquel for Borderline Personality Disorder, despite the fact that they did not actually have the disorder. Then one of them slipped his study medication into the oatmeal at the facility where he was housed. According a report from Alpha House, the sex offender facility:
    Some residents noticed pink particles in the oatmeal. After eating breakfast the residents and staff reported feeling sedated and some were "knocked out’ for the remainder of the day. Staff asked X if he had put the study medication into the oatmeal and he denied it. After failing a polygraph test X was re-imprisoned…

    Under guidelines governing federally funded clinical trials, the men would have been considered prisoners and their participation given special scrutiny, several outside ethics experts said. Although the trial was not federally funded, many universities follow similar rules for research involving human subjects. [The university asserts the men were not prisoners.]

    Other concerns about the study were raised even before the oatmeal drugging. The study’s safety officer, Dr. Scott Crow, noted in a memo that not a single patient had failed the screening process for enrollment in the study, even though outside experts said it was unlikely that everyone who applied would meet the criteria. Dr. Schulz said the failures were not recorded because the patients were formally screened only after undergoing initial telephone interviews that eliminated unlikely candidates.

    “What a sloppy trial,” said Nancy Dubler, a bioethicist who served for years on the Institutional Review Board, or I.R.B., at Montefiore Medical Center in the Bronx. She is an expert on the inclusion of prisoners in clinical trials and said closer attention should have been paid to the events at Alpha…
I felt kind of sad reading Dr. Schulz’s letter in the AJP. Whether or not the NYT published some statement from the University of Minnesota giving him a clean bill of health is such a non-issue after the years of the UMn saying everything is just fine. That’s the only kind of letter they write until getting hit in the head with a 2×4.  But the sad feeling was also about the naiveté of the letter and his whole enterprise of serial drug studies in patients with the Borderline Personality Disorder. I usually shy away from talking about psychodynamic formulations here. Such things are out of vogue, and have little to do with my usual topics of the Academic·Industrial·Complex or Data Transparency, but this may be a time for an exception.

Borderline patients come in many sizes and shapes. They are united as a group by certain shared phenomena with varying intensity. They are intolerant of being alone. They tend to simplify other people [good/bad] and any given person can jump from one to the other designation in a heartbeat. They are needy, but confused about what they need, so they end up coercing others into doing things that are ultimately to their own detriment. Rather than having periodic life crises, they often live crisis lives in a pattern where the solution to the last problem/crisis sets the stage for the next problem/crisis. The term "borderline" stuck because they confound every treatment. The basic difficulty is an infantile need for attachment combined with an equally infantile inability to maintain a consistent view of another. As I said in an anachronism… and Academic·Industrial·Complex II…, the notion that any drug will have a lasting benefit is unlikely. They go through drugs just as they go through people [and therapists]. So the clinical trials are more for the sponsors than the afflicted. They are treatable with modified therapies – psychodynamic or behavioral [dialectic behavior therapy] – but in either case, it is "heroic" psychotherapy and success is hardly guaranteed. Antics like the ones reported here [the Seroquel in the oatmeal] or sexual acting out [polymorphous sexual perversion] are not uncommon. While I’ve focused here on the difficulty these patients pose for others, they live difficult and painful lives and successful treatment is well worth the effort if it can be mustered.

So back to my response of sadness to the letter. I don’t get the sense that Dr. Schulz really understands the Borderline patients and where they hurt. He sure didn’t understand Katie Thomas’ article in the NYT [A Drug Trial’s Frayed Promise], what Carl Elliot was getting at, and why some statement from UMn was immaterial. I had the same feeling when I read that oral history interview [Interview with S. Charles Schulz, M.D.]. He was troubled by Carl Elliot’s campaign about Dan Markingson, but seemed clueless about why Carl was so upset and persistent. The place where I felt it most strongly was in his response to a letter from Mary Weiss back in the day, worrying about her son – Dan Markingson’s psychotic state. Instead of going to see Dan to see what she was talking about, he conclaved with co-investigator Dr. Stephen Olson to frame a response letter saying that they were doing nothing wrong.

Patients with First Episode Schizophrenia or Borderline Personality Disorder are in intense emotional tangles. They aren’t orderly. They don’t fit into routines. They’re too busy inside their minds and need a lot of attending to. Even the "sex offender" who flavored the oatmeal with his Seroquel was probably actually "Borderline" and needed to be seen rather than just removed for bad subject behavior. Dan Markingson was definitely in need of being seen at the time his mother wrote her frantic plea, not dealt with by a falsely reassuring letter. Carl Elliot and Leigh Turner of the University’s Bioethics Department deserved to be seen and engaged rather than discounted from afar – treated as nuisances. Reading of Dr. Schulz’s plans to make the UMn a Research Center for Psychiatry when he came to Minnesota and his pride in building his program in the Interview with S. Charles Schulz, M.D. added to the sad feeling, because he didn’t seem to grasp that his remoteness, lack of active engagement, and defensiveness was much of the reason things finally went so badly for him, for Dan, for his program.

But mostly, I felt sad for Dan and his Mom all over again. Success in a case like Dan’s is never assured, but most of us feel that he was not really given the chance to make it out of that dark and crazy place…
Mickey @ 1:14 PM

biggest indictment…

Posted on Saturday 1 August 2015

Well, I didn’t plan it, but this post actually turns out to be a sequel [maybe prequel] to another post from two weeks ago [probably approximates zero…]. There, I was reporting on an analysis that showed that the major use of antipsychotics in children is not to treat psychosis, but rather to control disruptive impulsiveness in developmentally challenged children – aka behavior control. Remember that the first Atypical Antipsychotic, Risperdal®, came out of the gate looking for an FDA Approval for that very indication with a study by Janssen’s Risperidone Disruptive Behavior Study Group [Double-Blind, Placebo-Controlled Study of Risperidone for the Treatment of Disruptive Behaviors in Children With Subaverage Intelligence 2002] and were turned down. That study was later repurposed, ghost written, and republished under Dr. Joseph Biederman’s name to support a claim of efficacy in his proposed Bipolar Child diagnosis [Risperidone for the treatment of affective symptoms in children with disruptive behavior disorder: a post hoc analysis of data from a 6-week, multicenter, randomized, double-blind, parallel-arm study 2006]. Many of us believe that the Bipolar Child designation was more a rationalization to use Antipsychotics in children for behavior control than a valid psychiatric condition.

So this story is back on the front burner because of suits against Janssen by boys who developed gynecomastia [breast enlargement] while on Risperdal®. Back in the early days, the drug had been associated with elevated Prolactin levels – a sticking point brought up repeatedly by Janssen’s competitors. In 2003, Janssen published a study refuting the charge that their drug caused gynecomastia. Now one of the authors, Toronto Pediatric Endocrinologist Dr. Denis Daneman, is claiming that Janssen misled him when he was involved with that 2003 study:
Toronto Star
By David Bruser and Jesse McLean
July 31, 2015

A medical journal article co-authored by SickKids hospital’s top pediatrician was manipulated by a drug company and understated the risks of a powerful antipsychotic used to treat kids with behavioural problems, the former head of the U.S. drug regulator alleges. The 2003 article concluded there was no correlation between long-term use of Risperdal and an increased risk of certain side-effects, including the growth of breasts in boys. The listed authors included respected experts in the pediatric field — Toronto’s Dr. Denis Daneman and two U.S. doctors — and three employees from Janssen, which makes Risperdal.

The medical article was singled out in recent U.S. lawsuits against Janssen as an alleged example of drug company influence on doctors and published research. A court exhibit shows a draft of the study describing an association with certain side-effects — a finding that a Janssen employee internally flagged as “significant.” This information is not in the published version of the article.

“My name is on an article in which there is some data that has been left out. That, to me, crosses a line,” Daneman, pediatrician-in-chief at the Hospital for Sick Children, told the Star…

This is a story about the role of a drug company in the production of a scientific journal article. The alleged manipulation of the medical article is outlined in a report by expert witness Dr. David Kessler, former head of the U.S. Food and Drug Administration and a pediatrician by training. The report, filed in U.S. court, said Janssen “controlled and influenced” more than 40 manuscripts, including the one co-authored by Daneman. Kessler called the company’s alleged promotion of the drug for unapproved use in vulnerable children “deeply troubling”…

An independent biostatistician is now reanalyzing the 2003 study’s data to determine whether the original results stand or if they need to be corrected on the public record, Daneman said. “If, indeed, these allegations are true, then I would feel used,” he said, adding that his contributions to the paper “were made in good faith and based on the assumption that my colleagues and I had access to all the relevant data.” He said he was not included in internal Janssen discussions about certain revisions to the article. “There is this deception there that is intolerable,” he said…

In a 2012 deposition where he was questioned by a U.S. plaintiff’s lawyer, Daneman, a pediatric endocrinologist, agreed the study he participated in had data calculation errors that had the effect of understating the frequency of side-effects. In an interview with the Star, Daneman said there was no intent on his part to exclude significant results…

The 2003 study analyzed results from five Janssen clinical trials to investigate prolactin levels in children and teens taking Risperdal, and “explore any relationship with side-effects hypothetically attributable to prolactin.” Daneman said his role in the study was commenting on parts of the article and suggesting changes and that somebody else wrote it. He told the Star he was paid about $1,000 by Janssen for his participation. “I gave the money to charity because of the concerns that had been raised about potential conflicts of interest,” he said…
Let me say up front that I’m suspicious that this is an example of a "best defense  is a good offense" trick, but I wanted to look at the original study Dr. Daneman signed on to. Notice that Drs. Robert Findling and Goedele De Smedt are also authors on the original 2002 study mentioned above:
by Findling, Kusumakar, Daneman, Moshang, De Smedt, and Binder.
Journal of Clinical Psychiatry. 2003 64[11]:1362-1369.

BACKGROUND: This analysis was designed to investigate prolactin levels in children and adolescents on long-term risperidone treatment and explore any relationship with side effects hypothetically attributable to prolactin [SHAP].
METHOD: Data from 5 clinical trials [total N = 700] were pooled for this post hoc analysis. Children and adolescents aged 5 to 15 years with subaverage intelligence quotients and conduct or other disruptive behavior disorders received risperidone treatment [0.02-0.06 mg/kg/day] for up to 55 weeks. Outcome measures analyzed included serum prolactin levels, reported adverse events, and the conduct problem subscore of the Nisonger Child Behavior Rating Form.
RESULTS: Mean prolactin levels rose from 7.8 ng/mL at baseline to a peak of 29.4 ng/mL at weeks 4 to 7 of active treatment, then progressively decreased to 16.1 ng/mL at weeks 40 to 48 [N = 358] and 13.0 ng/mL at weeks 52 to 55 [N = 42]. There was no relationship between pro-lactin levels and age. Females returned to a mean value within the normal range [</= 30 ng/mL] by weeks 8 to 12, and males were close to normal values [</= 18 ng/mL] by weeks 16 to 24. At least 1 SHAP was reported by 13 [2.2%] of 592 children. There was no direct correlation between prolactin elevation and SHAP.
CONCLUSION: With long-term risperidone treatment in children and adolescents, serum prolactin levels tended to rise and peak within the first 1 to 2 months and then steadily decline to values within or very close to the normal range by 3 to 5 months.

Side Effects Hypothetically Attributable to Prolactin [SHAP] is a mouthful. This from the Outcome measures section of the paper:
    Patients with SHAP were classified according to 2 sets of criteria, SHAP[A] and SHAP[B]. The criteria used to define the SHAP[A] population were breast enlargement [gynecomastia], amenorrhea, menorrhagia, lactation nonpuerperal, menstrual disorder, and vaginal hemorrhage. An alternate definition of SHAP was used for the SHAP[B] population. SHAP[B] excluded males 10 years or older with gynecomastia, females with less than 31 days of breast enlargement [gynecomastia], and females with amenorrhea < 1 week. It is considered normal for males to have gynecomastia at some point in the evolution of puberty, with the frequency estimated as high as 50%. Adolescent gynecomastia may be unilateral or bilateral, occurs most frequently during stages 3 and 4 of puberty, and lasts a few months to 2 years [in one series, 27% of cases lasted 1 year and 7% lasted 2 years]. Females during puberty tend to experience breast enlargement and irregular menstrual cycles, and therefore these symptoms were not classified as SHAP.
The only two mentions of Denis Daneman ["D.D."] in the paper were with Thomas Moshang ["T.M."], a full time Janssen employee…
    There are no data in children as to the degree of prolactin elevation that warrants concern in relationship to potential inhibition of growth or sexual development or potential side effects, such as gynecomastia or galactorrhea. It is the experience of the authors [pediatric endocrinologists T.M. and D.D.] that prolactin levels above 18 ng/mL but below 30 ng/mL are rarely, if ever, associated with clinical manifestation or alterations of the hypothalamic-pituitary-gonadal axis. Prolonged elevations of prolactin approaching serum concentrations of 100 ng/mL warrant careful clinical investigation.
    The first analysis, SHAP[A], used a more inclusive definition of SHAP, and the second analysis, SHAP[B], excluded additional symptoms that the pediatric endocrinologist authors [T.M. and D.D.] attributed to puberty. SHAP[A] included gynecomastia irrespective of age, amenorrhea, menorrhagia, breast enlargement, lactation nonpuerperal, menstrual disorder, and vaginal hemorrhage. Dysmenorrhea during puberty was excluded.

Notice the absence of references. Dr. Daneman’s opinion in concert with that of an industry doctor basically threw out the symptom that mattered.

My point in this post isn’t just about Dr. Daneman’s culpability in this obviously wrongly interpreted study twelve years ago. He was a key link in Janssen’s campaign to maximize its Risperdal® profits by developing an off-label pediatric market. I admit that this is a particular sticking point for me. I sat through the TMAP trial in 2012 and listened to drug reps and marketing managers describe campaigns targeting child psychiatrists and pediatricians to use Risperdal® off label – campaigns based on outright lies [see on every call…]. But my main point is Dr. Daneman’s argument that Janssen with-held evidence from him. It wasn’t his fault, he didn’t write that paper. He just commented on it. He even gave away the money he received.

If what he says is true, he is guilty of two sins instead of just one. His name was on that author line, and his excuse is that he didn’t bother to look into the  anything substantive about the paper? an industry funded study? with his industry paid colleague? for which he was being paid outright?
Daneman said his role in the study was commenting on parts of the article and suggesting changes and that somebody else wrote it.
That’s no excuse at all, and speaks to the essence of the meaning of the word author:
    au·thor []
          One that creates, founds, or originates:

That’s what happened in all these despicable articles that we talk about here and elsewhere. The authors weren’t authors. They signed on to professionally written industry jury-rigged papers without really involving themselves with their creation, or their veracity. Dr. Daneman didn’t embrace his authorship on this paper. It was used by Janssen to keep their campaign alive to sell Risperdal® off label for managing retarded kids behavior, now apparently the main pediatric use for the drugs [probably approximates zero…]. He was used as a ticket into a journal with an unsubstantiated opinion disembodied from the study itself –  and the ripples are still being felt years later, billions of dollars later, a group of boys with female breasts later. His excuse is his biggest indictment…
Mickey @ 9:28 PM


Posted on Saturday 1 August 2015

Continuing from the why of it…, there’s something backwards about Randomized Clinical Trials [probably best called randomized, double blinded, placebo controlled, clinical trials]. If you don’t know the story of how they came to be, these resources on the history of Louis Lasagna ought to help: David Healy’s blog, The Tragedy of Lou Lasagna and Don Klein’s interview with Louis Lasagna. Lasagna was quite a figure – originating the study of the placebo effect, rewriting the Hippocratic Oath, and as Senator Kefauver’s science guy in the legislation that brought the efficacy requirement and Clinical Trials into the FDA Mandate in 1962. Prior to 1962, the FDA’s job was to make sure drugs were safe. After 1962, they were required to also certify that they did what the drug maker said they did [efficacy] – at  least sort of. The bar was set low – two positive adequate and well controlled studies carried out by experts with scientific training" [out of as many trials as you care to run]. It makes sense. How else can you measure efficacy other than trying the drug out in the target population?
  • placebo controlled: The subjects on the drug and the controls get identical pills…
  • randomized: subjects are assigned to groups by a random number generator…
  • double blind: Neither the subjects nor staff know who’s on what until it’s over…
  • protocol: Analytic methods and outcome parameters are defined before the trial begins…
These trials are limited, artificial, usually short term, and analyzed primarily by statistical rather than clinical effects. So what a positive trial usually says about a treatment is that it’s not inert,  not that it’s clinically effective – and that it’s not toxic, at least short-term.

And so to, "there’s something backwards about Randomized Clinical Trials"

This was a low standard. Approval was never intended to tell doctors what to do with the drugs. The RTCs required for approval weren’t the end of anything. They were only a rough beginning – where things started. It was assumed that Medicine itself would take over after approval and figure out how to use the drugs in practice through its collective clinical experience. That’s why my introduction to the last post [the why of it…] was so awkward. I didn’t know how to say where I learn about new drugs, because it is from everywhere – bedside, clinic, colleagues, mentors, conferences, case reports, reps, the PDR, meetings, textbooks, journals, CME, my patients, your patients, even RCTs, etc., and it never really stops. It’s just part of the ongoing stuff of doctoring.

But then along came Evidence Based Medicine [wince]. At first glance, that term ought to be sacrosanct. Who wants a doctor who shoots from the hip? makes wild guesses? Of course, a doctor should base decisions on evidence. But that’s not what Evidence Based Medicine has come to mean. It now seems to mean «backed up by a positive clinical trial». And that’s what I mean by "there’s something backwards about Randomized Clinical Trials." The weakest link, the one most vulnerable to manipulation and distortion, has been elevated to the position of being the gold standard. How that happened is a long story that I don’t know as well as I’d like. But the why and the consequences are painfully obvious.

Since the pharmaceutical and device industries pay for and essentially write-up the RCTs, it gives them an enormous control over what physicians do. Their jury-rigged articles are further distorted in the direct-to-consumer and other advertisements. And even a trial that is honestly analyzed and published is only a crude approximation of the clinical reality of widespread usage. This kind of Evidence Based Medicine based on RCTs gives Managed Care a tool to deny medications or other treatments [and lots of other things]. It reduces the needs of an individual patient to membership of a proxy grouping. It implies a precision and generalizability to medical science never realized [or realizable]. It trivializes and marginalizes the other very important resources that we physicians traditionally use to learn about and prescribe drugs ourselves. And it takes the responsibility away from a doctor to assess in an ongoing and diligent process all the evidence in his/her clinical decision making.

So that’s what’s backwards about Randomized Clinical Trials"

The relationship of a model airplane to a Jumbo Jet comes to mind…
Mickey @ 4:57 PM

the why of it…

Posted on Friday 31 July 2015

For as much time as I’ve spent thinking about Randomized Clinical Trials in my retirement years, I never gave them a moment’s thought in two different medical careers. I didn’t really have much of an idea how drugs became approved, or how drug patents worked. As odd as that may sound, I expect that was true for the overwhelming majority of my contemporaries. In Internal Medicine, I learned about medications from textbooks rather than journal articles. In psychiatry, a person like me practicing psychotherapy doesn’t write many prescriptions, and I still relied on textbooks or review articles rather than looking at Randomized Clinical Trials. With rare exceptions, I rode on the "trailing edge" of medications, waiting until drugs were in widespread use before learning about them or prescribing them. The concept of a "pipeline" delivering a stream of new medications wasn’t even in my consciousness. I guess I thought that new medications came along when and if they were discovered. Writing this makes me feel incredibly naive – but I think that’s just the way it was. The only class of drugs I can recall actively keeping up with were the antibiotics – and that was because of those microbes’ incredible ability to become resistant.

So, in my oft told story, five years after retiring I had started volunteering some and was completely horrified at the drug cocktails the patients were taking. Then one morning, I read this over a cup of coffee:
New York Times
October 3, 2008

One of the nation’s most influential psychiatrists earned more than $2.8 million in consulting arrangements with drug makers from 2000 to 2007, failed to report at least $1.2 million of that income to his university and violated federal research rules, according to documents provided to Congressional investigators. The psychiatrist, Dr. Charles B. Nemeroff of Emory University, is the most prominent figure to date in a series of disclosures that is shaking the world of academic medicine and seems likely to force broad changes in the relationships between doctors and drug makers…
The chairman of the department I’d been a part of for then thirty-four years? arrangements with drug makers? a crook!? So that’s when I started to learn about Randomized Clinical Trials, and drug approval processes, and PHARMA, and more corruption than I would have thought possible.

Flash forward to the present. Over the intervening seven years, I’ve learned a lot about RCTs. About halfway back, I realized that the pharmaceutical companies being able to keep the raw data secret, or being able to simply not publish results they didn’t like, were an essential ingredients in the problem and I’ve spent a lot of my time involved in the fight for Data Transparency. There’s a lot more wrong – things like the alliance between academic medicine and industry, guest authors and ghost authors, the intrusions of third party carriers into medical care, etc. But frankly, I’ve spent so much time learning the ropes [with the help of some really good teachers], that it has been hard to get far enough away from the details to have an overall perspective on the big picture.

When I first read David Healy’s book, Pharmageddon [2012], I was still learning about Randomized Clinical Trials [RCTs], and I had looked at a number of them in as much depth as I could given the inaccessibility of the actual trial data. I could see how much subtle distortion there had been in the analyses and presentations in journal articles. The book added the history of RCTs and gave me a valuable perspective on how this tangled system had come into being  over the years. But there was one point that I didn’t intuitively grasp at the time. He seemed to be saying that there was a basic flaw in the RCT system over and above the distortions. At the time, It seemed to me that if the RCTs were properly conducted, properly analyzed, and properly reported that everything would be fine. I could tell he thought otherwise, but I just didn’t get the why of it on first reading. 

And I might as well add Evidence-Based Medicine and Measurement-Based Medicine in here along with RCTs. On the one hand, what is the alternative to evidence-based medicine? Wild guesses? And yet, every time I hear Evidence-Based Medicine [EBM], I wince involuntarily. The one that gets the biggest wince is Evidence-Based Psychotherapy [which means Cognitive Behavior Therapy (CBT)]. Well, I get it now – what’s wrong with RCTs – what Healy was saying. Rather than talk about the the why of it, I’ll refer you to the horse’s mouth, because Dr. Healy is in the middle of talking about it again on his blog:
If I had thought about my own experience as a physician [that introductory italicized paragraph that I started with], I might have gotten the why of it sooner. There’s a lot to say about this point, but I’m going think about it for a bit. In the meantime, you might take a look at Dr. Healy’s blogs, or even order the book if you don’t intuitively get it [like I didn’t]…
Mickey @ 4:36 PM