1 Boring Old Man

It really does sort of look like a pipeline. It’s the SSRis, SNRIs, and Atypicals graphed by the  year of their FDA Approval. The first time I ever heard that term, pipeline, I thought it was a joke of some kind. But I found out it was in wide usage in the business and KOL worlds. I wonder if there was a similar chart for the First Generation Antipsychotics? for Tricyclic Antidepressants? or for the Benzodiazepines? some string of "me too" drugs that stretches all the way back to the 1950s?

I know that when I showed up for a psychiatric residency in 1974, I thought there was sure a lot of chatter about  only a few categories of drugs. In internal medicine, I can’t recall anything similar. Admittedly, I spent those medicine years in public facilities that had more limited formularies, but I doubt that there was anything like what I encountered coming to psychiatry. There was a difference back then. We talked about the differences among ourselves and picked the best choice for the situation. I for one didn’t even know which company made which drug or what was new and what was old. Now, the patients have often already tried many of them, and sometimes made a choice based on what they’ve heard about from somebody or seen on television before they show up ["ask your doctor if kerfunkeltine is right for you"]. In fact, that’s why they’ve come. Here are those drugs labeled:

I may have missed a few or added one or two that ought not be there, but I was aiming for a Gestalt, and I think it comes across. And alongside the flow of new drugs, there were lots of other things for Key Opinion Leaders [KOLs] to talk about: Sequencing; Combining; Augmenting; Indications; Statistics; XRs; StereoIsomers; Genetics; Receptors; Neurotransmitters; etc.

In my own mind, I saw classification like I later learned Karl Jaspers had: Brain Disease, the Major Syndromes [Psychotic Illness]; and Other. The Biological Psychiatrists were focusing on the Major Syndromes with treatment and etiologic research. And there were any number of disciplines and approaches in the fuzzy Other group, presumed to be psychological in origin and treatment. The DSM-III was an attempt to get the theories [specifically psychoanalytic theories] out of diagnosis, which made sense. But it also ablated the border between the Major Syndromes and the fuzzy Other group in the process.

Over time, there was a new boundary: Mainstream Psychiatrists treating with medications and researching the brain, and other disciplines focusing on psychotherapy and matters social. But for my purpose here, that pipeline now emptied onto the entire domain  of mental health treatment. PHARMA and Managed Care institutionalized this new way of looking at things. There were many who didn’t follow along, but were basically working off-the-grid. New Industries rose up [Contract Research Organizations, Medical Writers]. Old Institutions waned [mental hospitals, community mental health] or changed [jails-as-mental-hospitals]. And in the last decade the whole thing has turned into what could only be called one mell-of-a-hess.

I originally constructed that pipeline graph because in spite of all the hoopla about it drying up, it looked to me like it was still dripping. But I didn’t have much success in locating what else is under development [other than the Ketamine dreams]. And as I looked at it, I began to have another thought. It’s obvious that right now, we’re all in a period of paradigm exhaustion in this whole corner of the healthcare world. The focus is on what’s wrong with all the models instead of what each has to offer. The drugs are weak, over-used, more toxic than advertised. CBT’s effectiveness is waning, and no other specific psychotherapy fits the bill. Neuroscience, Genomics, and Technology have let even their biggest cheerleaders down  [Clinical Neuroscience? bah humbug!]. PHARMA is turning off CNS research. Guild Wars are reviving with an old familiar fire-in-the-belly and name calling. Even Managed Care is having trouble showing results.

As I mused about what paradigm is it that’s so exhausted?, I had the thought "you just drew it." I don’t mean the individual drugs, or even their classes. But the idea of a pipeline that would just keep on flowing and bringing the hope of something newer, something better. It was the pipeline that sustained KOL psychiatry. The other disciplines had gained access to third party coverage and practitioners worked to have a connection with a prescriber. Managed Care thrived on the existence of a pipeline of future hope and built a reimburement system around it. Researchers fought to do the Clinical Trials that sustained it. PHARMA milked it for all it was worth. Even the failings of the drugs kept people busy and things moving along. Nobody gave much thought about the fact that there were only two [maybe three] basic themes playing out in these drugs and that the main advantage was that they were better tolerated. The pipeline itself, or what it implied, is the paradigm that lasted for three decades – so long that for many, it’s all they’ve ever known. And when it started running dry, all hell broke loose. The rest of the universe may have already known that the pipeline is the paradigm, but I didn’t…

In surprise decision, FDA blocks crucial cognitive claim for Takeda’s Brintellix

FiercePharma

By Tracy Staton

March 29, 2016

The FDA doesn’t have to follow the advice of its expert review panels, but it usually does. That’s a standard line in stories about advisory committee votes. Unfortunately for Lundbeck and Takeda, their new Brintellix app is one of the unlucky ones. The agency issued a complete response letter on new labeling that might have given Brintellix a new edge in the crowded antidepressant field. The claim: Brintellix can give a brainpower boost to depressed patients, whose thinking abilities often suffer. Lundbeck and Takeda had scored study data showing that the novel med can help patients think, pay attention, and make decisions – something no other antidepressant had managed to pull off. And the trial didn’t test Brintellix against a placebo, but head-to-head with Eli Lilly’s rival drug Cymbalta.

When an FDA advisory panel met last month to review those data, they voted 8-2 for an approval. European regulators had already approved a new use for Brintellix, to improve cognitive function in depressed adults. The FDA didn’t agree, and that puts Lundbeck and Takeda’s long-term sales projection – $2 billion – in jeopardy. Lundbeck developed the med, and Takeda has U.S. marketing rights under a marketing deal with the Danish drugmaker…

In any case, the hoped-for cognitive claim will be delayed at best, and with just $94 million in 2015 sales, Brintellix hasn’t lived up to early launch expectations. It faces considerable competition in depression, particularly now that a raft of commonly used meds – including Pfizer’s Zoloft, Eli Lilly’s Prozac and GlaxoSmithKline’s Paxil – are now available in cheap generic versions. And with payers requiring patients to try older, less expensive meds before moving to brands, the marketing task for Brintellix has been heavy. After the panel vote last month, one investment firm pointed out that Brintellix would be "the only product on the market with a leaflet on cognitive effects," Alm. Brand wrote in a note to clients. Focusing label language on improvements in thinking, attention and decision-making "means doctors also will," the firm said…

Meanwhile, Lundbeck has been laying off workers and cutting other costs as part of a plan to save 3 billion kronor, or about $445 million, in annual costs by 2017. Most of the cuts were focused on the company’s HQ in Denmark and commercial operations, mainly in Europe.

^{Lundbeck stock from Feb 9 to March 30 [between the two FDA hearings]}

^{[click image for the .pdf]}

During the last month, I’ve talked to a couple of people who mentioned that they’d been started on Brintellix® [given samples]. They both said something like, "It’s a new one. It’s supposed to help you [focus or think] better." or something like that. These were not patients – but the daughter of a friend and a friend of my daughter. I didn’t really register much at the time, but thinking about it now, that had to come from somewhere to the prescribing primary care doctor. I would guess from a detail person [drug rep]. While my anectdote is hardly a scientific survey, it gives me a pause. Whether it’s on a package insert or "a leaflet" doesn’t matter if it’s in the dialog. It’s like the political "talking points" that spread from talk radio host into the general conversation. And the investor guy isn’t wrong when he says, "Focusing label language on improvements in thinking, attention and decision-making ‘means doctors also will,’ the firm said…."

A month ago I ran across a MEDPAGE TODAY article about Vortioxetine [Brintellix®] and a hearing at the FDA [see indications… and more vortioxetine story…]. Brintellix® had been approved by the FDA for use in Major Depressive Disorder in September of 2014. I  had previously run across it through a review article in the Journal of Clinical Psychiatry in December 2014 – a ghost-written garbled affair with multiple KOL guest authors [see the recommendation?…]. It seems that the manufacturers [Takeda and Lundbeck] had been planning for years to try to get it approved for treating the Cognitive Dysfuntion in Major Depressive Disorder. That would be a new category for FDA Approval and would’ve become a strong selling point for this late-coming antidepressant. I found a recent article by Lisa Cosgrove et al who had done a case study of this particular drug and its approval process [Under the Influence: the Interplay among Industry, Publishing, and Drug Regulation] that contained the results of both published and unpublished trials showing that in comparator studies, Brintellix® had uniformly come up short. And I later read a blog on George Dawson’s Real Psychiatry [Vortioxetine] about it.

• The NIMH presentation was thoughtful and concluded that the psychometrics being used were not a valid sole proxy for a specific Cognitive Dysfuntion designation.
• They had one positive study [FOCUS]. But the second study [CONNECT] didn’t replicate those results. It was reported as statistically significant, but in my opinion, the statistical analysis was flawed.
• There’s nothing in my clinical experience or reading that suggests that the affective and cognitive symptoms in depression can be cleanly parsed in this way. Frankly, this felt like a commercially driven ploy.

Takeda and Lundbeck Receive Complete Response Letter for Brintellix® [vortioxetine] sNDA

PRNewswire

from Takeda Pharmaceutical Company Limited; H. Lundbeck A/S

Mar 28, 2016, 20:02 ET

OSAKA, Japan and VALBY, Denmark, March 28, 2016 /PRNewswire/ — Takeda Pharmaceutical Company Limited [Takeda] and H. Lundbeck A/S [Lundbeck] today announced that the U.S. Food and Drug Administration [FDA] issued a complete response letter [CRL] for the supplemental new drug application [sNDA] to include new data in the clinical trials section of the U.S. label of Brintellix^® [vortioxetine] for treating certain aspects of cognitive dysfunction in adults with major depressive disorder [MDD]. The FDA approved Brintellix on September 30, 2013 for the treatment of MDD in adults. The CRL does not apply to the use of Brintellix in MDD.

Takeda and Lundbeck are disappointed with the response given that the U.S. FDA Psychopharmacologic Drugs Advisory Committee [PDAC] voted 8 to 2 that Takeda and Lundbeck presented substantial evidence to support a claim of effectiveness for Brintellix in treating certain aspects of cognitive dysfunction in adults with MDD. However, the companies were pleased that FDA recognized the importance of cognitive dysfunction in MDD and view it as a legitimate target for drug development…

I don’t nor will I ever know if my letter had anything to do with the FDA’s decision. Other than the average expectable "tree" narcissism ["if a tree falls in the forest and no one hears it, does it make a sound?], I’m not sure I care. I had already gotten my reward from hearing the echo. In another way, I’d actually feel even better if the decision came out this way totally based on the FDA’s own evaluation. Takeda and Lundbeck had gone all out and to a lot of expense trying for this indication [6 cognition-specific clinical trials, bringing a lot of big KOL guns to the IOM workshop and earlier hearing, etc]. I could only guess that the 8:2 vote for Approval was in response to their zeal and presentations. But it just wasn’t in the data, and that’s what the FDA is there to evaluate. So good on them. They did the right thing after all. As for my letter…

This last weekend, I finally saw the film, The Big Short, the Academy Award winning movie about the 2008 financial collapse. I’d spent more time than I’d like to admit looking into the ins and outs of what happened, and when I heard there was a movie, I wondered how they were going to present it. Would it be about Bob and Wendy Graham’s campaign to create the Derivative Market, abetted by Fed Chairman, Alan Greenspan? or about Brooksley Born’s valiant attempts to stop it? or the raters who overvalued the CDOs? or maybe about the visionary Yale economist, Robert Shiller, and his book, Irrational Exuberance that predicted the whole thing? or the simple fact that no market can ever keep growing forever? There were so many angles.

[spoiler alert!] But the way they did it was a surprise to me and just plain brilliant by my estimate. They told the story through the eyes of the few people on the edges of Wall Street who saw it clearly from the start, and when they hit parts where the movie-goer needed a few complicated things explained, they mimicked a technique from antiquity, the Greek Chorus, in the form of a blond in a bubble bath, a player at a roulette table, or an actor stepping out of character and talking directly to the audience – truthsayers on the sidelines. I thought it was one fine piece of film-making!

Back when the markets crashed [September 15, 2008], I hadn’t seen it coming. But thinking back on things, like a lot of people, I registered some of the warning signs without realizing what they were warning us about. Some years before, I had needed some money to pay for the last of our two girls’ college costs and had refinanced my house – standard operating procedure in those days. To my surprise, lenders were calling us at home vying to get our loan. It was actually kind of fun. I did a spreadsheet model of all the loan parameters, and my wife spent the days fielding the calls and using my model to compare the offers. But the significance eluded me. In 2004 when we sold our home to move out of the City, I was staggered [pleasantly staggered] by the selling price. But I just thought of it as our good fortune, saying, "Boy, this neighborhood has sure come up since we moved here twenty-five years ago." It never dawned on me that the banks were gathering mortgages not as investments, but to use as chips for playing in the huge casino called the Commodities Market [futures] – creating illusions, the inflated values that I had just taken advantage of.

I doubt that many among those of us who follow blogs like this didn’t find ourselves making analogies with the pharmaceutical industry and the Irrational Exuberance [and corruption] in psychopharmacology marketing that has plagued psychiatry  for the last quarter century. I won’t catalog all the obvious things that seemed parallel to me, but I want to mention one conceptual piece – futures. The traditional products traded on the Commodities Market are next season’s soy beans – growers selling their crops in advance to raise the money needed to plant and run their farms – buying and selling future value. The buyers take out insurance to cover their losses in case of a draught etc. With deregulation, that way of buying and selling future value was expanded to encompass almost anything and everything. And what better product than home mortgages – a guaranteed future value. For that matter, what better way to market tepid drugs to a hot market than to present them as on a continuum of future promise?

We’ve lived in a world where "new! improved!…" has been a permanent meme for our toothpaste and wash·day products. And it was easily transported to the psychopharmacology world of the 1980/1990s. The formula seemed to be keeping up an exuberant rhetoric of future-breakthroughs-just-around-the-corner, deceptive presentations maximizing efficacy and minimizing harms in scientific journals, expert testimonials and endorsements from all the right academic places, and questionable marketing techniques. The result has been a couple of decades when the psychiatric drugs have been consistently on top of the sales charts – an almost unimaginable outcome in a rational world. It happened with only two basic drug classes – the SSRIs and the Atypical Antipsychotics. And in spite of the pharmaceutical industry literally shutting down its CNS research several years ago, the so-called empty pipeline continues to produce "new! improved!…" versions of these drugs [see a future blog]. But unlike the mortgage futures market or something like the Madoff Ponzi scheme, it doesn’t seem that this version yet has any built-in ending. So long as the story line of future promise persists and new is still presumed to mean better, the drugs we call me too drugs keep on coming and remain successful.

One of the effective aspects of The Big Short was the subtle way it portrayed the real message of the story, how the Irrational Exuberance of the business end of the housing bubble either lost sight of or didn’t care about its impact on our everyday world [another analogy]. The graphic at the top was a scene of a visit to a defunct neighborhood of unoccupied new houses. And the six million who lost homes were represented by only one man [the insert picture above], but he got the message across in a only few brief appearances. The shots of traders being marched out of Lehman Brothers with boxes of personal items added to that side of the message – participant·victims, many of whom unlikely completely knew what they had been a part of until they entered the ranks of the disillusioned.

When March Madness time comes around, I always remember a time when it wasn’t about Basketball for me – during the decade when I was a Psychiatric Residency Training Director. That may sound like an honorific, but that’s not how it was. I was only a year beyond my own residency and wasn’t exactly recruited, I was conscripted amid a crisis when my predecessor abruptly quit. But "we need you to fill in" lasted for a long time. And during those years, March Madness referred to Match Week – the week in which we found out what residents were or were not coming for next year. A few years ago, I had a nostalgia attack and made a graph of the history of Match Week in psychiatry [fuzzy math…]. As you can see, 1978 wasn’t a time when psychiatry was high on the list – filling only about half the positions offered. So Match Week was a frantic period because there was much ado thereafter with the flow into psychiatry from outside the Match to negotiate.

Also for 1978, it was a circus. It was at the end if Deinstitutionalization, the end of the Community Mental Health Movement, just after the Viet Nam War, and a peak time for the ideological and guild battles in mental health. We often think of the modern era in psychiatry beginning in 1980 with the DSM-III’s publication, and in a way that’s true. But at the same time, it was the end of a whole lot of other things – very loud things. Actually, the graph accurately reflects how it felt through that first post-DSM-III decade. Things just seemed to calm down.

The dip from around 1988 until 2004 spans the period when I started a practice until I retired, so I was otherwise occupied, ergo I know nothing about the why? of the dip. Here are some selections and comparisons from the info about the 2016 match that came out yesterday [this was Match Week], and I added 2016 to the graph above:

The specialty choices of medical students is a broad topic, but it usually reflects something about the state of the specialty. The medical students are influenced a lot by their contact with attending physicians and residents they meet on their clinical rotations. And 2016 looks like business as usual [in fact, I’m a little surprised to see no effect from the turmoil one might’ve predicted from reading our various blogs].

Last summer, in announcing my discovery of a biomarker for suicidality, I failed to mention that it was unclear whether it was the Y chromosome itself or the absence of the second X chromosome that was the culprit. No progress has been made in answering this important question over the course of the last year.

Genomic Biomarker for Suicidality Found! Independent Georgia researcher, 1boringoldman, working closely with the CDCwebsite discovers clear evidence of…

In other news, our lab’s ongoing longitudinal analyses, now in the eighth year, is close to confirming a biomarker in a new psychiatric disorder – Seasonal Dementia – found only in predisposed individuals:

In Annie Proulx’s novel, The Shipping News, emotionally broken protagonist Quoyle and his young daughter move to his ancestral home in Newfoundland to reclaim his life. He goes to work for the local paper, The Gammy Bird, where reporter Billy tries to show him the ropes:

Billy: It’s finding the center of your story, the beating heart of it, that’s what makes a reporter. You have to start by making up some headlines. You know: short, punchy, dramatic headlines. Now, have a look, what do you see? [Points at dark clouds at the horizon]
Billy: Tell me the headline.
Quoyle: Horizon Fills With Dark Clouds?
Billy: Imminent Storm Threatens Village.
Quoyle: But what if no storm comes?
Billy: Village Spared From Deadly Storm.

Those are my favorite lines from a favorite book [and movie]. They come to mind whenever I watch the news in the evening. It’s a habit I’ve developed to remind me not to get too caught up in the dramatic rhetoric of journalism. And they came to mind reading this article in Mad in America:

Dr. Pies and Dr. Frances Make a Compelling Case that Their Profession is Doing Great Harm

Mad In America

by Robert Whitaker

March 17, 2016

• Psychiatry Through the Lens of Institutional Corruption [Whitaker]
  May 7, 2015
• Timberrr! Psychiatry’s Evidence Base For Antipsychotics Comes Crashing to the Ground [Whitaker]
  December 29, 2015
• Me, Allen Frances, and Climbing Out of a Pigeonhole [Whitaker]
  January 27, 2016
• Do Antipsychotics Help or Harm Psychotic Symptoms? [Frances]
  February 1, 2016
• Setting the Record Straight on Antipsychotics [Frances]
  February 16, 2016
• Long-term Antipsychotic Treatment: Effective and Often Necessary, with Caveats [Pies]
  February 22, 2016
• Psychiatry And Anti-Psychiatry [Frances]
  February 24, 2016

Robert Whitaker does the same thing most of the bloggers on his site do – he anthropomorphizes psychiatry as a unitary entity that is of a single mind. Psychiatry says… "one size fits all." Psychiatry says… "medications for life." Parenthetically, that notion of psychiatric one-mindedness has made my own discussions with people who are MIA followers quite difficult. And that problem continues here. When Drs. Pies and Frances clarify their positions, and they turn out to be fairly close to Whitaker’s, he sees them as going against this singular psychiatry he apparently thinks of as making universal recommendations.

As a consequence of positive results from numerous short-term [1–2 years] studies, prolonged use of antipsychotic medications over a long period has become the current standard of care in the field. Thus, antipsychotic medications are viewed as the cornerstone of treatment, in both the short-term and the long-term treatments of patients with schizophrenia.

American Psychiatric Association [APA] guidelines suggest clinicians to consider antipsychotic discontinuation for schizophrenia patients who have been symptom free for a year or more. Nevertheless, many clinicians keep schizophrenia patients on antipsychotics indefinitely assuming that the medication is essential for continued stability.

Antipsychotics are also viewed by some as leading, over a prolonged period, to eventual recovery for some patients with schizophrenia. A comprehensive review from the World Psychiatric Association section on Pharmacopsychiatry notes “Antipsychotic treatment has a significant impact on the long-term course of schizophrenic illness and can significantly facilitate recovery…”

Originally published in February 2004. This guideline is more than 5 years old and has not yet been updated to ensure that it reflects current knowledge and practice. In accordance with national standards, including those of the Agency for Healthcare Research and Quality’s National Guideline Clearinghouse, this guideline can no longer be assumed to be current.

But, as was seen above, psychiatry’s evidence base for antipsychotics, which states that the drugs are effective over the short term for curbing psychosis and effective for reducing the risk of relapse, does not promote such selective-use prescribing, and, indeed, any survey of 100 people diagnosed with a psychotic disorder in the past 25 years would find that most had been told they needed to take the drugs for life. Frances and Pies, in their blogs, were seeking to defend psychiatry’s prescribing practices and the long-term effectiveness of antipsychotics, but the caveat they expressed — that the drugs are effective for a certain subset of psychotic patients — naturally focuses attention on the drugs’ effects on those who don’t need them long-term, and that leads to a finding of great harm done.

And that finding, in turn, supports a demand, based on Frances and Pies own writings, for a radical rethinking of psychiatry’s use of antipsychotics.

In a follow-up blog, I will respond to their review of the “evidence” for the long-term effects of antipsychotics. That provides another an opportunity to watch their minds at work as they sift through the evidence. What studies do they dismiss? What studies do they embrace? This is a review that ultimately leads to this question: Do we see, in their assessment of the scientific literature, evidence of the critical thinking that we want to see present in a medical specialty that has such a large impact on our lives? And if not, what shall we do?

Psychiatry Through the Lens of Institutional Corruption

Mad in America

By Robert Whitaker

May 7, 2015

When you write a book, you usually do so in response to a prompt of some type, and in the process of researching and writing the book, you will come to see your subject in a new way. Psychiatry Under the Influence, a book I co-wrote with Lisa Cosgrove, provided that learning experience, and this is what I now know, with a much greater certainty than before: Our citizenry must develop a clear and cogent response to a medical specialty that, over the past 35 years, has displayed an “institutional corruption” that has done great injury to our society. In fact, I think this is one of the great political challenges of our times…

As I noted in the beginning of this post, co-writing this book led me to “see” this subject of psychiatry and its influence on our society in a new way. It puts the focus on society as the injured party, and it is easy to see that the social injury arising from this corruption is vast and profound.

The institution of psychiatry, with its disease model, has dramatically changed our society over the past 35 years. It has given us a new philosophy of being, and altered how we view children and teenagers, and their struggles. It has touched every corner of our society, and this societal change has arisen because of a story told to the public that has been shaped by guild and pharmaceutical influences, as opposed to a record of good science. That is the nature of the harm done: our society has organized itself around a “corrupt” narrative…

"Are you sure it’s not a chemical imbalance?"

He came to the clinic the last time I worked saying he’d had a show-stopping anxiety attack last Fall – one of those race-to-the-ER-I’m-dying anxiety attacks. Since then, he’s had several others and has had a background sense of doom. The story was in contrast to his appearance, a late twenties construction worker blessed with good looks. He wondered if it was a chemical imbalance, as both parents were nervous worried types. Nothing like this had ever happened. On those ER visits, he’d had EKGs, and had seen a Cardiologist with no findings of note. He was married and had a five year old. I probed around but couldn’t find anything that might explain his symptoms. He had some anti-anxiety medication which he rarely took. He went home with instructions to focus on what was going on before he felt anxious and have his wife check his pulse [?arrhythmia?]. I mention him here, because he was preoccupied with the chemical imbalance worry.

He returned with a page of normal pulse rates from when he was feeling anxious. He had thought hard about the period in the Fall when all of this started and came up with nothing much. "Are you sure it’s not a chemical imbalance?" He seemed really worried I was going to miss the diagnosis of chemical imbalance. With urging, there was something after all. Back in the Fall, he had been home for a couple of weeks between jobs, and he recalled feeling kind of "down – remorseful." He’d thought back to his high school years a lot and wished he spent more time thinking about his future instead of just having fun. He wished he’d finished college instead of just going to work in construction. That was the first I’d heard about college and I asked about that. He had gone to a small college in a nearby town but didn’t finish. "Are you sure it’s not a chemical imbalance?" he asked again.

So I told him what I was looking for, something that might have come up, something from before, something that might be haunting him. He said, "I feel haunted," and he became more engaged with my questions. When I asked why he didn’t finish college, he was quiet for a while and then told a story. When he’d moved to the town where he was going to be in college, he’d met a girl who was also starting school. They quickly became an item and it lasted for the next three years [both working their way through school, so it took longer]. They’d planned a move to another town with a full college, getting an apartment together, and finishing their education. They’d been accepted, and were working to save up for the move. One day on the job, he got a call from her dad. She’d just been killed in a head-on collision during a rainstorm. He’d talked to her on the phone 15 minutes before she died. That was in September, 10 years before the anxiety attack we were discussing – the one last September.

I won’t go on. You can figure out the rest, like why he stopped college. As best I could tell, one of the forces keeping him from connecting the dots between the past and present himself was that he didn’t want his wife to feel he was disappointed with her or their life. But that’s just a guess. I expect I’ll hear about that next time. Whatever comes, it was clear we were on the right track.

a follow-up

Back in September, I mentioned a case, a woman who had presented in a mentally obtunded state on an outrageous regimen of medications, prescribed by a telepsychiatrist at a contract mental health clinic [see blitzed…]. By October, we were making progress tapering her medications but it was becoming apparent that underneath it all, she had a movement disorder that looked for all the world like Tardive Dyskinesia [see some truths are self-evident…]. I mentioned her in December and the TD was full blown [a story: getting near the ending[s]…] and occupied the center stage.

Over the winter, the TD mercifully gradually lessened. She could voluntarily suppress the hand wringing, and "control" the jaw movements. I had a story from her reports and from her aunt and mother who had only come into her life recently. I knew snatches, but getting a clear timeline eluded me. And her mental state had cleared, but it became apparent that cleared wasn’t altogether clear. She still had a lot of signs of brain dysfunction. She tried to drive to appointments, but it took hours because she frequently got lost [a few miles with few turns]. She kept a spiral notebook and wrote everything down, "I’ll forget." She confabulated when she couldn’t recall things and perseverated on symptoms like depression, or confusion, or anxiety. Over the sessions, I was only able to piece together something of a timeline.

She had been married for twenty-three years, working as a dental hygienist and had three daughters. The marriage was difficult and she had divorced [been divorced?] eight years ago. About a year later, she was driving to see her kids for Christmas and had a head-on collision. She’d been unconscious. She was in the hospital for a while, having surgery on her neck [collar bone?]. A neurosurgeon had been involved and she had a scan [MRI? CAT?]. After a time, she went home, lived in an apartment, and worked in a hardware store. She had been in a relationship with a "military man" that ended very badly. She began to drink heavily. About two years ago, she fell on her patio and was unconscious "for seven hours" until being found by a neighbor. She was in a hospital for an unknown period of time. It was in the years since then when she seemed confused, couldn’t work, began to go to the mental health center, and got put on all that medication.

Looking at it in retrospect, I think the story is much different from the one I started with. I had presumed a personality diagnosis, mainly from family reports, and didn’t know about the head injuries. It’s now 6 months later, and I think the key point is that two years ago, she sustained a traumatic brain injury from that fall. The resulting confusion and emotional lability were interpreted as some kind of mental symptoms, and she was medicated [by someone who has since been fired] further complicating her cognitive impairment. The inappropriate overmedication with neuroleptics resulted in TD. We’ve figured out which hospitals she was in and records have been requested. We’ve set up a disability evaluation in a week, so hopefully she’ll have resources for the full neurocognitive work-up she needs. Surprising to me, benzodiazepines have helped her TD some and she can sleep [also my thanks to the blog follower who sent along a helpful article about TD Rx, and we’re pursuing it further].

I don’t know how to code that first case. He certainly feels ill in his mental, so I guess it’s a mental illness. And I don’t know how long I’ll need to see him. It depends on what comes next. I laughed out loud thinking about how we would fare in Collaborative Care where I would be talking to a Clinical Coordinator who would be talking to the Primary Care Physician who would be talking with him. I could and have coded the second case. There’s an ICD-10 code for Traumatic Brain Injury with residual Cognitive Impairment and one for Tardive Dyskinesia [though those codes don’t do this story justice]. In either case, I wonder how many sessions Managed Care might allow for each case if they were involved.

Our little [formerly] free charity clinic is growing. There’s a new clinic building next to the trailers we’ve operated out of [I stayed in the trailer]. We now take Medicare, Medicaid, ACA insurance from those who have it. It’s still free for those that don’t have resources or insurance. There are now "employees" working with the volunteers. Some of the doctors are "providers" and we charge the insured for their services. Some of us won’t sign up as "providers," so the clinic can’t be reimbursed for our services [nobody seems to mind]. There’s a new Electronic Health Record [EHR] system. That’s where my musings about coding come from.  I’m reluctantly using it for notes and prescriptions [most of the time], but it was designed by a fiend. I entertain my patients by talking to it when I use it, saying things like, "In medical school, I was taught to always maintain eye contact with patients, but now it’s ‘oh yeah, and do all this computer stuff on every patient’." My main beef is that I have to link to a diagnostic code for every prescription. I suspect there’s an epidemic of Major Depressive Disorder, Mild in the offing, treated with all kind of things, since this avenue is unavailable.

• Revisiting the Commercial–Academic Interface
  by Jeffrey M. Drazen, M.D.
  New England Journal of Medicine. 2015 372:1853-1854.
• Reconnecting the Dots — Reinterpreting Industry–Physician Relations
  by Lisa Rosenbaum, M.D.
  New England Journal of Medicine. 2015 372:1860-1864.
• Understanding Bias — The Case for Careful Study
  by Lisa Rosenbaum, M.D.
  New England Journal of Medicine. 2015; 372:1959-1963.
• Beyond Moral Outrage — Weighing the Trade-Offs of COI Regulation
  by Lisa Rosenbaum, M.D.
  New England Journal of Medicine. 2015; 372:2064-2068.

Data Sharing
by Dan L. Longo, and Jeffrey M. Drazen
New England Journal of Medicine. 2016  374:276-277.
[full text on-line]

• N-of-1 Policymaking — Tragedy, Trade-offs, and the Demise of Morcellation
  by Lisa Rosenbaum, M.D.
  New England Journal of Medicine. 2016 374:986-990.
  [full text on-line]

• Brigham Doc’s NEJM Paper Decries Morcellation’s Demise—Did She Get Confidential Patient Information?
  Cancer Letter
  By Matthew Bin Han Ong
  03/18/2016
• There They Go Again – the New England Medical Journal Publishes another Rant, this Time about Power Morcellation
  HealthCare Renewal
  by Roy Poses
  03/20/2016

A morcellator is a whirling machine [something like a roto-router]. It can be used to "chew up" uterine fibroids through a small incision under visualization, simplifying their removal:

Amy Reed, a 40-year-old anesthesiologist and mother of six, underwent a hysterectomy with intraoperative morcellation for presumptively benign uterine fibroids at Boston’s Brigham and Women’s Hospital… The masses turned out to contain foci of leiomyosarcoma, a rare, aggressive cancer that has a 5-year survival rate of 63% when diagnosed at stage I. Reed’s LMS was stage IV, so her likelihood of surviving 5 years was only about 14%.

Yet disproportionate focus on harms caused by use rather than nonuse is common. In 2004, for instance, the FDA placed a black-box warning on antidepressants for pediatric and adolescent use because of concern that they increased the risk of suicidality, although untreated depression probably poses equal or greater risk. Media stories about adolescents harmed by these medications had frightened parents and physicians. Since then, untreated depression has increased among both adolescents and adults, and some data suggest that adolescent suicide rates have also increased.

In this piece, Dr. Rosenbaum is essentially arguing, "Oh don’t get so emotional," and "Don’t blow a single case up into a campaign." She might as well say, "Stop being so hysterical!" Maybe she could make that argument fly a little higher if it weren’t for the obvious. All of her examples are in defense of lucrative industry positions and standing in opposition to the FDA‘s decisions. What was once our primo academic medical journal, The New England Journal of Medicine, is going out of its way to regularly become a mouthpiece for the pharmaceutical/medical device industries and their profit-driven motives.

The new medical-industrial complex.

by Relman AS.

New England Journal of Medicine. 1980  303[17]:963-70.

The most important health-care development of the day is the recent, relatively unheralded rise of a huge new industry that supplies health-care services for profit. Proprietary hospitals and nursing homes, diagnostic laboratories, home-care and emergency-room services, hemodialysis, and a wide variety of other services produced a gross income to this industry last year of about $35 billion to +40 billion. This new "medical-industrial complex" may be more efficient than its nonprofit competition, but it creates the problems of overuse and fragmentation of services, overemphasis on technology, and "cream-skimming," and it may also exercise undue influence on national health policy. In this medical market, physicians must act as discerning purchasing agents for their patients and therefore should have no conflicting financial interests. Closer attention from the public and the profession, and careful study, are necessary to ensure that the "medical-industrial complex" puts the interest of the public before those of its stockholders.

In my time in psychiatry, the specialty has often been shaped by its critics. When I arrived in 1974, Thomas Szasz was one of those major critics. While his principle focus was on civil liberties in his opposition to involuntary hospitalization and treatment, his argument was more fundamental – that the whole notion of mental illness was a myth as there was no evidence for biological causation. He went further, saying that the real motive for the whole complex of mental illness and psychiatry was to pathologize aberrant behavior in order to control it – short circuiting the due process of the law – that psychiatrists were the agents of a non-benevolent State. Though I came to psychiatry from the world of hard biological science, Szasz’s idea that Medicine and Illness are defined by abnormal biology was something I’d actually never heard anyone say before. I might have even thought something like that after medical school, an Internal Medicine Residency, and an NIH Fellowship in Immunology, I don’t recall. But it hadn’t taken very long as a practitioner to get over it. For one thing, three fourths of the people I saw in a referral only practice had sick-ness, ill-ness, dis–ease, sure enough – but without any abnormal biology. For another, for those with biologically based chronic illnesses, treating the biology part was relatively straightforward. It was the human experience of ill-ness that was the challenge. So I didn’t come to psychiatry to bring or find more biology. I had plenty enough already. I came to learn more about human experience.

Well that was the best decision I ever made … until it wasn’t. To my amazement, some ten years later, organized and academic psychiatry embraced Szasz’s definition that Medicine and Illness are defined by abnormal biology and drove head long into the world of biological causation. There were a gajillion other forces at work other than setting out to prove Szasz wrong. Who knows, maybe the new movers and shakers didn’t even think about Szasz, but that’s what they did nevertheless. So for me, another big change –  from a busy tenured academic position in a psychiatry department to a private office of my own down the road. From my perspective, that period didn’t feel like the swinging of a pendulum. It felt more like the Invasion of the Body Snatchers. I can say a lot about the why of that now, but then I was just at sea looking for dry land. As it played out, it was the second best decision I ever made, or had made for me, or both. I had been busting ass to hold our way-under-financed program in the road and hadn’t noticed the personal toll … until I didn’t have to do it any more. But what I’m getting at here is that for whatever myriad of reasons, mainstream organized and academic psychiatry embraced the biological definition with a passion, a definition popularized by their greatest critic. And it wasn’t the biological psychiatrists I knew or knew of from before leading the charge, it was a new breed. While some, like Tom Insel, were ideologues – many others were more in the entrepreneurial category, a group I now call the KOL Psychiatrists [borrowing the "Key Opinion Leader" term from PHARMA marketing lingo]. Only a few from that second group made it to Grassley’s List in the last post, but there are many more that should’ve been on it.

Psychiatry Now Admits It’s Been Wrong in Big Ways – But Can It Change?

Truthout

by Bruce Levine

March 5, 2014

Robert Whitaker’s Answer: I think we have to appreciate this fact: any medical specialty has guild interests, meaning that it needs to protect the market value of its treatments. If it is going to abandon one form of treatment, it needs to be able to replace it with another. It can’t change if there is no replacement in the offing. When the APA published DSM-III, it basically ceded talk therapy to psychologists, counselors, social workers and so forth…

Psychiatry’s three domains in the marketplace, were diagnostics, research, and the prescribing of drugs. Now, 34 years later, we see that its diagnostics are being dismissed as invalid; its research has failed to identify the biology of mental disorders; to validate its diagnostics; and its drug treatments are increasingly being seen as not very effective or even harmful. That is the story of a profession that has reason to feel insecure about its place in the marketplace…

So I don’t believe it will be possible for psychiatry to change unless it identifies a new function that would be marketable, so to speak. Psychiatry needs to identify a change that would be consistent with its interests as a guild. The one faint possibility I see – and this may seem counterintuitive – is for psychiatry to become the profession that provides a critical view of psychiatric drugs. Family doctors do most of the prescribing of psychiatric drugs today, without any real sense of their risks and benefits, and so psychiatrists could stake out a role as being the experts who know how to use the drugs in a very selective, cautious manner, and the experts who know how to incorporate such drug treatment into a holistic, integrated form of care. If the public sees the drugs as quite problematic, as medications that can serve a purpose – but only if prescribed in a very nuanced way – then it will want to turn to physicians who understand well the problems with the drugs and their limitations. That is what I think must happen for psychiatry to change. Psychiatry must see a financial benefit from a proposed change, one consistent with guild interests…

The split between therapists and psychiatrists [medication managers] that developed after the DSM-III came along is usually discussed in terms of ideology or guild membership, but it was largely the creation of the third party payers based on cost accounting. And some of the current plan to move the point of contact for mental health to primary care physicians with Collaborative Care feels like more of the same. So in a way, Robert Whitaker is completely right to discuss these matters in marketing terms, but his comments are based on a fiction that all psychiatrists are obligatory pan-diagnosis biomedical ideologues. Outside the class of the KOL Psychiatrists [who are themselves in a marketing frame of mind], the guild/ideology split is in part an artifact actively created and maintained by the Managed Care system. Far and away, the major source of referrals to the medication management psychiatrists are psychologists, counselors, social workers and so forth. And those who can’t find a psychiatrist to prescribe for them find someone in primary care who is willing. Likewise, there are many psychiatrists who practice outside this system altogether and are as put off by the antics of the the KOL Psychiatrist set as anyone else.

In meandering about…, I was musing about some [unscientifically derived] signs in the American Psychiatric Association Preliminary Scientific Program that psychiatry might be awakening from its long sleep during the era of the KOL Psychiatrists and Clinical Neuroscience. How much of that is fact and how much is wish is for others to judge. But that aside, there’s the obvious question whether psychiatry itself will be viable in the long term. The specialty is under active siege from Managed Care, the other mental health disciplines, and the those writing on Robert Whitaker’s Mad in America site [eg the end of psychiatry, BEHAVIORISM AND MENTAL HEALTH, etc]. Those outside forces have been both fueled and abetted by the academic/pharmaceutical alliance [a synonym for the KOL Psychiatrists] inside psychiatry and, to some extent, the NIMH of the last twenty years.