1 Boring Old Man

Will $650 Million Solve the Mystery of Mental Illness?

Chasing the genetics holy grail neglects current patient need

Psychology Today

by Allen J. Frances, M.D.

July 24, 2014

I am a great supporter of mental health research, but worry that it has lost its sense of proportion and is chasing the wrong priorities. The really glamorous stuff consumes almost all of the enormous NIMH budget and now has behind it the huge addition of a $650 million dollar private donation aimed at solving the genetics of mental illness. Neuroscience is an extremely easy sell to Congress and rich philanthropists because it promises so much – that we are on the brink of achieving fundamental breakthroughs in understanding how our genes and brains work [and sometimes don’t work]. But such overpromising ignores the painful lessons of history. The neuroscience and genetic revolutions have been astounding in their technical virtuosity and fascinating in their findings- but to date have not helped a single patient. We have learned a great deal in basic science, but nothing at all that translates to better clinical care.

 

But there is a cruel paradox when it comes to mental disorders. While we chase the receding holy grail of future basic science breakthrough, we are shamefully neglecting the needs of patients who are suffering right now. It is probably on average worse being a patient with severe mental illness in the US now than it was 150 years ago. It is certainly much worse being a patient with severe mental illness in the US as compared to most European countries. Access to community care and decent housing is deteriorating; hundreds of thousands of psychiatric patients are homeless or in prison; there is little system in the mental health system; and almost all research is strictly biological.

I think the welcome infusion of $650 million dollars would have been much better spent to achieve current tangible results [by funding research and model programs to improve the dreary lives of our patients], rather than betting everything on the future long shot that big bucks can dramatically speed up what will doubtless be decades of painstaking and frustrating genetics research. The neglect of the severely mentally ill is a blight on our society that genetics research will not solve. Its OK to shoot for the stars, but not when we are failing in our day to day responsibility. Less glamour, more compassion.

more compassion.

When I read about the $ 650 M commitment to the Stanley Center [$650M gift to Broad seeks to propel psychiatric research], my reaction mirrored Dr. Frances’. I think he’s even more honest than I might have been when he says, "The neuroscience and genetic revolutions have been astounding in their technical virtuosity and fascinating in their findings- but to date have not helped a single patient. We have learned a great deal in basic science, but nothing at all that translates to better clinical care." I might have been too timid to put it quite that strongly, but I sure thought it as soon as I read it. It’s Mr. Stanley’s money and he can choose to do with it whatever he wants to do. He didn’t ask me or Dr. Frances. But if he had…

I guess people think that neuroscience research is like the Manhattan Project, or NASA, or DARPA. If we just throw money and talent at it, it will yield up its secrets. Those were projects where we knew where we were going and a lot about how to get there. The infusions of brainpower and treasure insured that the details would be ironed out and we sped towards the goal. Neuroscience research, particularly genetic neuroscience research, is a horse of a different color. It’s exploratory, a trip into the unknown. We don’t really even know the questions to ask or what we’d do with the answers if we had them. And with much mental illness, we don’t even know if the problems have anything to do with neuroscience, in spite of hearing little else for decades. With Steve Hyman in charge of the Stanley Center and Tom Insel in charge of the NIMH, regrettably, that’s not likely to change.

Back in February when I first read about Pradaxa® [how many examples?…, foot-in-mouth disease…], I couldn’t help but comment even though it had nothing to do with psychiatry. Without even reading the articles, just the basic premise was suspicious – that Boehringer Ingelheim had introduced a "blood thinner" [anticoagulant] that didn’t have to be monitored with blood tests. After a medical lifetime of monitering people on Warfarin with monthly clotting tests, I couldn’t figure how one could achieve the same results with a medication that didn’t have to be monitored. And when I actually read the articles, I still couldn’t. To me, Pradaxa® is a nightmare. It is an anticoagulant that, unlike Warfarin, can’t be reversed if a person has a bleeding episode. Having spent plenty of nights in a former career pumping patients full of Vitamin K to reverse dangerous bleeding, I wondered what one was to do when a person on Pradaxa® slarted bleeding. I had a vision of the little Dutch Boy trying to stop leaks in the Dyke and running out of fingers.

Dabigatran: how the drug company withheld important analyses.

by Cohen D.

British Medical Journal. 2014; 349:g4670.

[full text on-line]

Concerns over data in key dabigatran trial.

by Cohen D.

British Medical Journal. 2014; 349:g4747.

[full text on-line]

The trouble with dabigatran.

by Charlton B and Redberg R.

British Medical Journal. 2014; 349:g4681.

[full text on-line]

Dabigatran, bleeding, and the regulators.

by Moore TJ, Cohen MR, and Mattison DR.

British Medical Journal. 2014; 349:g4517.

[full text on-line]

This weeks BMJ hit the ground running on the Pradaxa® story, and good for them. It’s is full of detailed articles documenting the whole mess. There’s plenty of blame to go around: NICE, the FDA, Boehringer Ingelheim, and all physicians involved – including the one that recommended it for my friend, a Habitat for Humanity crew chief who jumps in to do the jobs other volunteers don’t know how to do. I can just hear the phone call that he fell from a ladder [again]. Around that same time he was started on Pradaxa®, a cardiologist from the same practice frowned with disapproval when I declined his recommendation that I take a Statin for my until-recently-normal LDL [although I did get a laugh when I added "I don’t need a Mammogram either"].

“He who knows syphilis knows medicine”
Sir William Osler, the Father of Modern Medicine

Some years back, I saw a play, Miss Evers’ Boys, about the Tuskegee syphilis study. In 1932. 600 black men were recruited into a Public Healtrh Service study that went on for forty years. In return for participating, they were given free medical care and burial insurance. The back story was that this was a study about the natural course of syphilis and 399 of these men had the disease, but weren’t told. They were only told they had the bad blood [a colloquialism with many meanings]. When penicillin came along in the 1940s, the definitive treatment for the disease, it was neither used nor discussed. The play centered on the study nurse, the Miss Evers of the play, who "saw after" the participants all those years knowing they weren’t being treated. The study was finally leaked in 1972, and the aftermath brought many changes in the safeguards for human experimentation [see Wikipedia’s Tuskegee syphilis experiment]. By the end of the study in 1972, only 74 of the test subjects were alive. Of the original 399 men, 28 had died of syphilis, 100 were dead of related complications, 40 of their wives had been infected and 19 of their children were born with congenital syphilis. It’s a story of epidemiology; of racism; and of the origin of Informed Consent and Institutional Review Boards. The entire 1997 HBO Movie of Miss Evers’ Boys is available on-line [1:57:59]…

[1964] I paid my room and board in early medical school by being the house manager for a medical fraternity house. That essentially entailed keeping up with the elderly black man who had actually run the place since the dawn of time. One day I returned from a lecture where I’d heard for the first time about Tabes Dorsalis [tertiary syphilis of the spine], and I noticed that his walk looked a lot like the film I’d seen in class that day. I asked him about it and he said he was just "getting old." I engaged an upper classman who went to the hospital and got his chart. Sure enough, he’d been treated with heavy metal injections as a young man [for bad blood], but nothing since. We escorted him to the neurology clinic where he was treated with Penicillin [and became a Grand Rounds case].

[1967] The first patient I had as an Intern was an elderly man admitted after abruptly losing his voice. The next day, we got an emergency page and found him in extremis coughing up blood and he quickly arrested and died. That afternoon, his VDRL [lab test for syphilis] came back positive. At autopsy, he had a syphilitic aortic aneurism that had ruptured into his trachea. The hoarseness was from the compromised recurrent laryngeal nerve [that wraps under the aorta on its way to the vocal cord].

[1973] When I was an Air Force Doctor overseas, an older civilian administrator was admitted with jaundice and delirium from liver failure. He had the physical findings of chronic cirrhosis though he was not a drinker. But he also had fever and signs of some acute process. He had a history of hepatitis in the South Pacific in World War II and we speculated he had Chronic Active Hepatitis. But then on the second hospital day, he developed a generalized rash, present on his hands and feet [a characteristic sign of secondary syphilis]. Scrapings of the rash revealed those little corkscrew Treponema pallidum organisms bending in the middle that I’d only seen in pictures [the organisms that cause Syphilis]. In spite of our starting him on a very low dose of penicillin, he had a Jarisch–Herxheimer reaction [toxicity from the sudden death of the organisms] requiring high doses of steroids. He had been infected by a dalliance with the wife of a ranking officer at a base in another European country [a delicate and touchy point]. He recovered nicely, but unfortunately we were right the first time. On a subsequent liver biopsy, he also had Chronic Active Hepatitis that had been complicated by the Syphilis infection.

William Osler was "the Father of Modern Medicine" in part because he exemplified the era of the grand clinician – physicians who spent their lives carefully mapping the signs and symptoms, the clinical course, the family and environmental histories of diseases. They collected detailed case histories extracting patterns that became syndromes, many of which still carry their names. Their treatment options were limited, but hard won advances informed by their clinical precision. As monstrous as it was to withhold the diagnosis in the Tuskegee Study early on, and even worse, to withhold treatment when it became available, the idea of gathering precise epidemiological data was consistent with the way medicine operated in the latter nineteenth and early twentieth century.

In our current era, there is a race to treatment based on small differences and speculation, both measured and hypothesized. Each evening, we expect our evening news to be accompanied by an announcement of some medical advance or breakthrough, punctuated by direct to consumer ads with their mumbled warnings. We’ve become used to questionnaires, rating scales, laboratory examinations, and loud whirring machines replacing the classic history and physical examinations of the past. My point here is not simply nostalgia for former days, it’s about the hurried pace with which we race into action, to treatment. The current Tamiflu debacle is an exempler. Billions have been spent on a medication to stave off a hypothesized global epidemic. Now it appears that that medication, while not inert, is hardly suited to the task. We’ve defined Mild Neurocognitive Disorder and the Attenuated Psychosis Syndrome without having a solid anchor that tells us that they are, indeed, the precursors we seek. We are subjected to recurrent studies that try to convince us to use SSRIs in teens with little evidence that they even treat adolescent depression itself, much less prevent anything, and with that come accusations of withholding treatment.

^{Emil Kraepelin           Alois Alzheimer          Auguste Deter}

In 1907, Alois Alzheimer working in the lab of Emil Kraepelin, presented the brain findings on his patient, Auguste Deter, a woman who had died after developing dementia at age 51. Besides general brain shrinkage, there were characteristic microscopic findings: plagues in the extracellular spaces and neurons with neuro·fibrillary tangles in the cytoplasm.

Plaques were known from cases of senile dementia, but the tangles were felt to be a unique finding in pre·senile dementia. Kraepelin immortalized his colleague after Alzheimer’s untimely death by using his name in his classification. When I was a medical student, I was taught that the term Alzheimer’s Disease was reserved for the pre·senile cases, but in recent times, that distinction has fallen by the wayside – so Alzheimer’s Disease is a progressive dementia with characteristic brain findings.

There are a number of neurodegenerative diseases with distinguishing features listed in the DSM-5: Alzheimer’s disease, Frontotemporal lobar degeneration, Lewy body disease, Vascular disease, Traumatic brain injury, Substance/medication use, HIV infection, Prion disease, Parkinson’s disease, Huntington’s disease, Another medical condition, Multiple etiologies, Unspecified. In the case of Alzheimer’s, the diagnostic feature has formerly only be seen at autopsy, though there are apparently scans and other tests becoming available for antemortem diagnosis. There is a rare form that runs in families with a genetic marker and the findings are seen in the dementia that can develop with Down’s Syndrome. Since there’s no sure diagnosis in life, the DSM-5 provides probable and possible variants.

Major Neurocognitive Disorder, probable Alzheimer’s Disease
Major Neurocognitive Disorder, possible Alzheimer’s Disease
Mild Neurocognitive Disorder, probable Alzheimer’s Disease
Mild Neurocognitive Disorder, possible Alzheimer’s Disease

DSM 5 Is Guide Not Bible—Ignore Its Ten Worst Changes

APA approval of DSM-5 is a sad day for psychiatry.

Psychology Today: DSM5 in Distress

by Allen Frances MD

December 2, 2012

This is the saddest moment in my 45 year career of studying, practicing, and teaching psychiatry. The Board of Trustees of the American Psychiatric Association has given its final approval to a deeply flawed DSM 5 containing many changes that seem clearly unsafe and scientifically unsound. My best advice to clinicians, to the press, and to the general public – be skeptical and don’t follow DSM 5 blindly down a road likely to lead to massive over-diagnosis and harmful over-medication. Just ignore the ten changes that make no sense…

The motives of the people working on DSM 5 have often been questioned. They have been accused of having a financial conflict of interest because some have [minimal] drug company ties and also because so many of the DSM 5 changes will enhance Pharma profits by adding to our already existing societal overdose of carelessly prescribed psychiatric medicine. But I know the people working on DSM 5 and know this charge to be both unfair and untrue. Indeed, they have made some very bad decisions, but they did so with pure hearts and not because they wanted to help the drug companies. Their’s is an intellectual, not financial, conflict of interest that results from the natural tendency of highly specialized experts to over value their pet ideas, to want to expand their own areas of research interest, and to be oblivious to the distortions that occur in translating DSM 5 to real life clinical practice…

[3] The everyday forgetting characteristic of old age will now be misdiagnosed as Minor Neurocognitive Disorder, creating a huge false positive population of people who are not at special risk for dementia. Since there is no effective treatment for this ‘condition’ [or for dementia], the label provides absolutely no benefit [while creating great anxiety] even for those at true risk for later developing dementia. It is a dead loss for the many who will be mislabeled.

A Comparison of DSM-IV and DSM-5 Panel Members’ Financial Associations with Industry: A Pernicious Problem Persists

PLoS Medicine

by Lisa Cosgrove and Sheldon Krimsky

March 13, 2012

[full text on-line]

At NewYork-Presbyterian Hospital, Its Ex-C.E.O. Finds Lucrative Work

New York Times

By ANEMONA HARTOCOLLIS

July 15, 2014

[full article available online]

For Hospital CEOs, Retirement May Mean Never Having to Lose Your Paycheck

Healthcare Renewal

by Roy Poses

July 17, 2014

[full article available online]

Dr Herbert Pardes was once one of the best paid CEOs of a US non-profit hospital system. A new New York Times article reported that the hospital system continued to pay him millions after his retirement… In 2009, we first discussed the compensation given to Dr Herbert Pardes, the CEO of New York – Presbyterian Healthcare System, which appeared to make him one of the best paid, if not the best paid non-profit hospital system CEO in the US. His total compensation for 2008 was $9.8 million, according to the NY Post. While his compensation was lower in 2007, approximately $5.1 million, 9 other executives made over $1 million, and the 10 together made over $26 million. This amount was approximately 20% of the system’s total surplus, and 1% of its total budget. The Times reported that since then, Dr Padres continued to do very well financially,

Dr. Pardes’s compensation has consistently been among the highest of any New York hospital C.E.O. His compensation in 2011, his last year as chief executive, was $4.1 million, including base pay of $1.7 million and a bonus of $1.8 million.

According to the Times, after Dr Pardes retired in 2011,

The next year, Dr. Pardes earned $5.6 million, which included $1 million in base salary, a $1.8 million bonus for his final year as chief executive and more than $2 million in deferred compensation, according to hospital tax records. That exceeded the amount earned by Dr. Pardes’s successor, Dr. Steven Corwin, who made $3.6 million that year. Three years after retirement, Dr. Pardes is still employed by the hospital as the executive vice chairman of its board of trustees, a position that compensation experts say is rare in the nonprofit world,…

So the year after Dr Pardes retired, he made as much from what most people might have thought was his former employer as he did in 2007 as CEO, when he was one of the best paid non-profit CEOs in the country, and more than he made in 2011, the year of his retirement…

Herb Pardes From Wikipedia

Herbert Pardes [born c. 1932] is an American physician, psychiatrist, and the Executive Vice Chairman of NewYork–Presbyterian Hospital. He was previously president of Presbyterian Hospital; a few years after its merger with New York Hospital he became CEO of the combined entity, which was named NewYork–Presbyterian Hospital. He is a national figure in psychiatry and academic medicine. Prior to his retirement at New York Presbyterian, Pardes in 2008 was receiving compensation in excess of nine million dollars annually while CEO at the hospital along with other benefits.

Education and career

Dr. Pardes received his Bachelor of Science degree summa cum laude from Rutgers University in 1956 and his medical degree from the State University of New York-Downstate Medical Center in Brooklyn in 1960. From 1978 to 1984, he was director of the National Institute of Mental Health [NIMH], where he strengthened the Institute’s research program and emphasized the need to increase research support for psychiatry. From 1989 he was president of American Psychiatric Association [APA]. He is a former Dean of the Columbia University College of Physicians and Surgeons. Before becoming dean, Pardes was chair of Columbia’s Department of Psychiatry, where he remains a professor…

In his commentary about the New York Times article, Dr. Poses goes through the various rationalizations for Pardes being paid that obscene amount of money. They’re in his blog post. I want to skip all of that. That money has to come from somewhere and the only possibility is the pockets of the patients or their insurance carriers. Oh by the way, NewYork–Presbyterian is a not-for-profit hospital system. By accepting that salary, he’s making the statement that medicine is a business first and foremost, part of the system we now have that contributes to the wealth inequity in our country, that contributes to the ridiculous rising cost of healthcare, that contributes to the feeding frenzy of the hospital corporations, the pharmaceutical and medical equipment industries, and the insurance/managed care goliaths.

I honestly don’t believe that the black box warnings lead to an increase in either suicides or suicide attempts based on scientific grounds, some of which are shown here. But that’s not what fuels my writing about this. What keeps me writing is what I do believe, not what I don’t believe. I’ve seen two completed suicides from SSRIs that I’m sure about. Thankfully, neither was a patient of mine, but I was privy to enough information to be unquestioning about what happened. I may fill this blog with graphs and population statistics, but as a clinician, I’m a one-person-at-a-time doctor. And people like me are at a loss because I can’t or won’t report why I can say that with such conviction. I also believe in Akathisia of the kind that’s described in patient reports, books, on RxISK, in blogs etc. I believe it because I’ve seen it personally in its very loud forms. I can’t or won’t report the stories that lead to that conviction either, so I can only say that I have no doubts. I think the black box warning is correct – the truth:

In the first decade of this century, there was a preoccupation with the idea that more efficacy could be extracted from these antidepressants. By the end of the decade, sequencing, augmenting, and combining had each failed to produce the dreamed of enhancement, and so for a time, researchers had a love affair with "personalized medicine" – coming up with some test that would predict response to one or the other antidepressants. It would seem like sequencing and combining would’ve answered that question, but apparently not. At the time, it was thought that genotyping would be the key [but anything would’ve done]. The Australian Brain Trainer, Evian Gordon, gathered one group of KOLs and began the iSPOT study. And Dr. Trevidi was funded for an NIMH study, EMBARC, to look for biomarkers that predicted drug response. His study started with Placebo, Citalopram [Celexa®], and Bupropion XL [Welbutrin XL®], but the Citalopram was replaced for unknown reasons with Sertraline [Zoloft®] not long after the study began. It was funded from September 30, 2010 through June 30, 2014. The NIMH web site has the following data available for funds allotted:

That comes to $9,199,613 so far. The overall cost to the NIMH for the four funded studies in the figure above [STAR*D, IMPACTS, CO-MED, and EMBARC] exceeds $50 M. Some time back, I had added a note to my calendar that EMBARC ended on June 30, 2014. My prediction was that it would not be completed – based on Dr. Trivedi’s poor track record and my own conviction that it wouldn’t show anything of any value just based on reading the protocol. While that cynical prediction remains an open question, the study should now be completed and yet it is still listed as "recruiting."

I doubt seriously that there’s anyone on the planet waiting to have a biomarker test to decide between Zoloft® and Welbutrin XL® for a depressed patient, particularly with a ~$10 M price-tag. TMAP was a scam; STAR*D was a bust; IMPACTS never even got off the ground. CO-MED flat-lined. Can EMBARC live up to that record? [I warned you I couldn’t contain the sarcasm]. It’s stories like this that account for my negativity about Dr. Insel’s NIMH. These people have been funded for a series of ill-conceived, badly designed, and poorly executed studies one after another for a decade and a half to the tune of $50 M. There’s just no need for that. STAR*D produced hundreds of forgettable papers, but never even really reported on what the study proposed to find out. Insel’s NIMH famously selects the directions for research rather than selecting from among the creativity of researchers own proposals. They chase things like personalized medicine, algorithmic medicine, measurement based medicine, translational medicine, RDoC, etc. – fads that come and go – and genomics, proteonomics, neuroimaging, connectomics – shiny objects that have appeared in view. And the same people get funded over and over, like the examples mentioned above, independent of their track records.

I woke up Thursday morning to an email alerting me to the fact that my blog had disappeared. I tried it and saw:

Was it something I said? The nice technician in Utah [who knew it was in Utah?] said not-to-worry. It had been moved to a new server [?] and the domain pointer hadn’t been ‘hooked up.’ The department that looks into such matters didn’t open until 10:00 AM EST. Oh by the way, after it’s hooked up. it’ll take several days "for global DNS propagation."

I had an uncanny and uncomfortable feeling that the blog was gone for good in spite of the technician’s reassurances, and I thought through its ten year history as I rocked on the porch waiting for the sun to come up. It didn’t take me very long in that mode to understand the why of my "uncanny" feeling. My daughter had set up the blog as 3oldmen.com when I retired in 2003. The other two "old men" were lifelong friends who had retired to the same place I did. They didn’t write much on it. So when my own posts turned serious, she joked sarcastically, "I should change the name to 1boringoldman.com!" I actually liked the sound of that, so we did change it. Those two friends both died within a week of each other at the end of April [in memory…]. So my "uncanny" feeling when the blog disappeared this morning wasn’t so hard to figure out after all – just another example of the realization of finality that grief brings [displaced onto a bunch of magnetic ones and zeros somewhere in Utah].

I actually should’ve realized that almost immediately. There have been so many reminders of them in the recent weeks. The original bond among the three of us was as veterans of the Civil Rights years in the South, the two of them more than I [see, for example Look out Lord, here comes Al Clayton]. This week, PBS’ The American Experience had two pieces on the year 1964, 50 years later. That was "Mississippi Freedom Summer," my first year in medical school in Memphis. Watching the documentary brought floods of my own memories from those days, and with them came the memories of the two of them. I actually met them ten years later in Atlanta – 1974. They had weathered the 1960s in Nashville in the thick of things. So we all had plenty of stories to tell, and became fast friends in the telling.

It hadn’t fully occurred to me that my zeal in writing about what happened in psychiatry had something to do with the Civil Rights days. But sitting on my porch with a wandering mind that morning brought the parallels immediately to the front burner. I had grown up in what might be called an enlightened Southern household. Racism wasn’t tolerated, but quietly not tolerated. All of that changed for me on September 16, 1963, a few days before I was to leave for medical school in Memphis. I read in the paper about a church bombing in Birmingham the day before that killed four little girls. I guess in today’s parlance, I was ‘radicalized’ at that moment. Then I didn’t know what was happening, and it was only in retrospect that I realized how much that article changed the trajectory of my life, who my friends were, and how I saw the world. The same thing happened in October 2008 when I read about Senator Grassley’s investigation of Dr. Charles Nemeroff, chairman of the department of psychiatry at Emory University where I was on the clinical faculty. I had left an academic career there some twenty-five years before when psychiatry changed so dramatically after the coming of the DSM-III and the neoKraepelinians. Wherever things were going back then wasn’t where I was headed, and I exited stage left [by mutual agreement]. By 2008, I was five years retired from a private practice in Atlanta to these mountains near where I grew up to think about other things. But reading about Nemeroff’s misadventures with industry had the same impact that the bombing had back when I was young. In both cases, there was something I knew on the edge of my mind, but I didn’t quite know I knew. But it didn’t take too much of a pin prick to know it all over the place. I had ignored Nemeroff as a self promoter, but hadn’t keyed in to his industry connections, his challenged morality, or his power [or how many others there were around like him].

About that same time, I started working some in a little clinic and realized what seemingly outrageous medication regimens were being prescribed. I had no idea that polypharmacy had become the name of the game. I had been a psychotherapist using not very much medication. It seemed that everyone was Bipolar and had a chemical imbalance. In rural Appalachia? Chemical Imbalance? Bipolar? I bought some contemporary psychopharmacology books and couldn’t even finish reading them – gibberish. I’d practiced in a cocoon and missed a revolution it seems, and the more I saw of it the gladder I was to have missed it. That reminded me of those days in the sixties when I woke up and saw the world I’d grown up in a very different, much darker way. I felt guilty back then for what I hadn’t really seen clearly. I also feel guilty about what happened in psychiatry in the twenty-five years between 1983 when I left academia and 2008 when Senator Grassley blew his whistle – the years when I was in a self-styled exile. I guess you can feel as guilty for not looking as you can for seeing but not doing anything.

But the point of this post came after all those thoughts. By this time, the sun was up and my dogs were clammoring for breakfast. I had figured out in the recent days after my friends died that they had given me back something I’d lost in those Memphis years [along with being great friends]. Memphis was a hard place to be of the Civil Rights persuasion in the 1960s. There weren’t so many of us that were white. The garbage strike, the King assassination, a less well known hospital strike that shut down my training program, tanks and soldiers in the streets, sniper shots in the night. There was a racial divide in those days as wide as the Mississippi that runs through the town. When we left for Europe in 1971 [drafted into the Air Force], I wouldn’t have bet on our returning to the South. But three years later, I picked Atlanta for a psychiatry residency from among many other [actually better] choices. It felt like something I was supposed to do, but the remnants of those darker days were still hanging like storm clouds. Almost immediately, I met Al and Andy, like-minded Southerners who introduced me to many more. They’d made their peace with all that had happened and literally gave me back the South. I didn’t feel like a stranger in my own land anymore [because I wasn’t]. And the parallel to the present is very clear to me now. Through this blog, I’ve connected with any number of new friends that I may never meet in person, but that doesn’t too much matter. They’ve helped me reconnect with a psychiatry that I understand, even though we come from diverse ideological backgrounds, places, and even countries. I just don’t feel like an exile anymore [because I’m not]. I guess it felt like I’d lost that connection too when I saw that message up there.

Re: Changes in antidepressant use by young people and suicidal behavior after FDA warnings and media coverage: quasi-experimental study

by Catherine W Barber, Matthew Miller, and Deborah Azrael

British Medical Journal 2014 348:g359.

In the spirit of Lu et al’s [1] warning not to sound alarms about antidepressant use prematurely, we used readily available national data to investigate whether youth suicide attempts in the U.S. increased after 2003 and 2004—the years in which the FDA issued warnings about antidepressant safety. Attempts did not increase. Lu et al’s opposite finding probably has more to do with the unusual proxy they used [one they said was validated by a paper that two of us — MM and CB — co-authored] [see a madness to our method – a new introduction…] than with an actual change in suicidal behavior among youth. We briefly summarize here five readily available, online data sources that provide more direct and valid measures of youth suicidal behavior, and we discuss problems with the proxy that Lu’s study used.

The CDC’s Youth Risk Behavior Survey [YRBS] is a pencil-and-paper questionnaire filled out by high school students [3]. There was no increase in self-reported suicide attempts from 2003 to 2005 according to the YRBS [see Figure 1]; in fact, there was a decline in suicidal thoughts, plans, and medically-treated attempts from the late ‘90s through 2009 [with some increases in more recent years]. Two databases that estimate national hospital visit rates based on a sample of hospitals also saw no increase in youth self-harm following 2004. The first is the Health Care Utilization Project’s [HCUP] online database [4], which shows no increase in inpatient discharges for intentional self-harm diagnoses [E950-E959] among those ages 17 and under. The CDC’s WISQARS-Nonfatal database [5] also shows no increase in emergency department care for self-harm in this age group [although numbers jump around from year to year]. Both HCUP and WISQARS-Nonfatal are estimates based on a national sample of hospitals and thus subject to sampling error. California’s EPIC website, on the other hand, presents a census of inpatient discharges for the entire state [6]. There, too, no increases in self-harm hospitalization rates among children, adolescents, and young adults were observed following the FDA warnings. Finally, and most consequently, according to official mortality data available on the CDC WISQARS-Fatal website [5], the suicide rate among youth was largely flat 2000-2010, with an increase in 2011.

Lu’s study findings are roundly unsupported by national data. While the national and California data sources have limitations, each is a more direct indicator of intentional self-harm than the data Lu et al used. Lu et al used poisonings by psychotropics [ICD-9 code 969] as a proxy for suicide attempts in claims data from 11 health plans, in spite of the fact that the code covers both intentional and unintentional poisonings. Our paper, which is the sole reference to their claim that code 969 is a “validated” proxy for suicide attempts, in fact shows that in the U.S. National Inpatient Sample the code has a sensitivity of just 40% [i.e., it misses 60% of discharges coded to intentional self-harm] and a positive predictive value of 67% [i.e., a third of the discharges it captures are not intentional self-harm].

On balance, the evidence shows no increase in suicidal behavior among young people following the drop in antidepressant prescribing. It is important that we get this right because the safety of young people is at stake. Lu et al’s paper sounding the alarm that attempts increased was extensively covered in the media. Their advice that the media should be more circumspect when covering dire warnings about antidepressant prescribing applies as well to their own paper.

1. a madness to our method…
2. are you listening?…
3. another campaign?…
4. read me him…
5. a madness to our method – a new introduction…
6. return to a madness in our method…
7. all databases are not created equal…

Our paper, which is the sole reference to their claim that code 969 is a “validated” proxy for suicide attempts, in fact shows that in the U.S. National Inpatient Sample the code has a sensitivity of just 40% [i.e., it misses 60% of discharges coded to intentional self-harm] and a positive predictive value of 67% [i.e., a third of the discharges it captures are not intentional self-harm].