Wednesday, March 13, 2024

Two Million Reads - A Blogging Milestone of Sorts

 


Last night around midnight – I noticed that I had crossed the 2 million reads mark on this blog.  The Google Blogger interface that I use is not very granular so it is difficult to tell how many of those hits are actual reads as opposed to something else. By something else I mean hackers, bots, and people trying to use my blog for free advertising.  The products are typically illegal or barely legal drugs or psychiatric services outside of the US.  The increase in VPNs is also probably a factor.  Over the years the number of hits per page has flattened out while the overall number for the blog has increased. My assumption is that individual page reads with a VPN are not counted, but they are counted for the overall blog.

I am reassured and very grateful for the readers of this blog and have corresponded in detail with many of them.   They range from medical students considering a career in psychiatry to very senior medical scientists with hundreds of research publications.  In many cases they are advocating for a specific viewpoint.  In a few they want me to change a blog post in some way.  That rarely happens because of my level of experience and the degree of research I put into these posts.  Somewhere in the past I pointed out that one of my motivations for writing this blog came from colleagues who asked me what I read, where I found certain information, and how I came to know what I know. I hope I am successful at getting that information out there.

I am also very grateful to the academics out there who share their work and give me free advice.  One of the most striking examples was midnight correspondence with two philosophers who wrote a book about diagnostic decision making in the late 1980s. I used it to teach a course in not making diagnostic errors in medicine and psychiatry. Both professors were retired and I sent them emails in a later time zone at midnight. They gave me detailed responses within an hour. I don’t always get a response, but when I do it is exhilarating to be a part of academic discussions with some of the most accomplished people in the world.

It has not always been a walk in the park.  I was confused about gaslighting initially and tolerated too much of that activity before drawing a line.

I often wonder about why people read or do not read this blog.  The appearance is fairly basic compared with other sites that offer better graphics.  I think there is some reluctance or resentment based on the idea that I am profiting from this blog.  I can restate that this is completely non-commercial and not-for-profit.  I not only have not made a cent writing this blog but have had to pay licensing costs out-of-pocket for graphics and permissions.  A friend and colleague recently told me that he never thought about reading blogs.  The era seems to be one of podcasts and TikTok video clips. I have always found reading to be a lot faster.  And unlike TikTok I am intentionally not provocative.

One of the recurrent themes here on my blog is that there is no way to simplify psychiatry and do it well.  A psychiatrist considering themselves to be primarily a psychotherapist or primarily a psychopharmacologist is not considering large areas of the discipline.  The same is true of the psychiatrist who ignores medicine and neurology.  To paraphrase Euclid (325 BCE - 265 BCE)  “There is no royal road to psychiatry.”  You must know it all to do good work.  Complexity is good and necessary in human biology.

I currently have 123 folders in my References 2024 Folder and it’s only March.  I am working on a protocol that will allow me to submit research papers and blog them if they are rejected.  At the rate I am going I will write my own textbook in psychiatry in another 20 years.  Stay tuned!

 

And Thanks again!

 

George Dawson, MD, DFAPA

Tuesday, March 12, 2024

An Unpublished NEJM Letter

 



 I was notified this morning that a letter I sent in to the New England Journal of Medicine would not be published because they had limited space.  Anyone sending a letter is notified that if the letter does not respond to one of their articles you are limited to 400 words.  If your letter does respond to an article the word limit is 200 words.  I was responding to an essay by Lisa Rosenbaum, MD (1) and whether medicine is a calling or just a vocation and the implications that each of those categories have.   My first attempt at the 400-word mark (374 actual) is below:

 To The Editor:  The essay by Dr. Rosenbaum (1) highlights a critical issue in medical education, research, and practice.  Much of the analysis is dependent on the concept that medicine is either a job or a calling. The critical factor in all settings is the practice environment.  Over the past 30 years we have seen a severe deterioration in that environment and how it impacts physicians. 

Forty years ago – physicians were valued as knowledge workers.  Work quality was emphasized and teaching departments were run by senior physicians who emphasized teaching and research.  They were models for focused lifelong learning and were able to maintain interest and enthusiasm in their departments by balancing clinical demands and those learning tasks. Trainees in the department benefitted from identification with these physicians as well as learning clinical approaches in their specialty.  The department head often had a business administrator in the department, but there was no doubt that the focus was medicine first and business tasks were minimal.

Over the past several decades, business and political interests have changed the physician role to production workers. Physicians are now valued in corporations for productivity and all the administrative time that takes. Department heads are often more focused on business matters than teaching and research.  Meetings take on a business rather than academic orientation.  More time is spent learning about the business environment rather than learning medicine.  The administrative burden alone easily exceeds the time used in the past for teaching rounds and conferences.  This burden has also decreased physician efficiency and added hours per day producing documentation for billing purposes that is repetitive and excessive. It also detracts from the physician patient relationship that is further fragmented by physician extenders.

The modern practice environment is not conducive to producing and motivating physicians.  Rather than an environment where experts can have spirited exchanges about medical care – it is one where experts are second guessed by administrators with no medical training.  It is an environment that does not produce a calling.

Recognition of the severe deterioration in the practice environment is the first step in correcting the problem.  Steps need to be taken to restore practice environments to stimulating settings that can lead to a high level of expertise, quality, and humanistic care.    

 

George Dawson, MD, DFAPA

 

References:

1.  Rosenbaum L.  On calling – from privileged professionals to cogs of capitalism?  N Engl J Med 2024; 390: 471-5.

 

The final 200-word final submitted version is below:

 

Rosenbaum argues doctors' declining job satisfaction stems from corporatization, generational changes, and a shift to production-style management.1 Traditionally, senior physicians oversaw the practice, fostering a learning and research environment. Forty years later, business managers treat doctors as production workers2 in an increasingly inefficient environment. This clashes with physicians’ role as knowledge workers, requiring intellectual stimulation, collegiality, and patient-centered care.

That change is responsible for a marked deterioration in the training and practice environment.  Business practices have been emphasized to the point that there has been an adverse effect on physician time management for professional and personal activities. It is also a direct cause of burnout.3

Physicians function best as knowledge workers consistent with their training. Physicians have been forced into the role of production workers. The solution is not to develop a rhetorical response to being in that role. The solution is not an idealization of the “good old days” – but recreating and restoring the physician knowledge worker environment.  That is the first step toward making physician sacrifice meaningful again.

 

George Dawson, M.D.

 

1.  Rosenbaum L.  On calling – from privileged professionals to cogs of capitalism?  N Engl J Med 2024; 390: 471-5.

2.  Drucker PF. Knowledge worker productivity – the biggest challenge.  California Management Review 1999; 41: 71-94.

3.  Lacy BE, Chan JL. Physician burnout: the hidden health care crisis. Clinical gastroenterology and Hepatology. 2018;16(3):311-7.

 

It took me 5 rewrites to get to progressively less words.  When you tend to use as many words as I do that was a painful process.  If you are a blogger the pain is compounded by the fact that editorial control is lost and you cannot publish your comments anywhere else (including a blog) if you hope to get them published in a journal.  The NEJM has a 3-week deadline for letters based on their articles.  It took them 5 weeks to reject it. They obviously can publish whatever they want and provide whatever rationale that they want – but the space argument seems thin.

Let me suggest why I thought this letter – even pared down to 170 words was important enough for me to send.   A brief review of Dr. Rosenbaum’s essay is necessary and if you have access, I encourage you to read it.  The essay begins with standard blue-collar rhetoric rooted in reality – basically that the working man is subjected to the whims of corporations who rarely have their interests in mind.  A young physician from that family concludes that the idea of medicine as a calling is using that term “weaponized against trainees as a means of subjugation— a way to force them to accept poor working conditions.” 

The problem with that analysis is twofold.  First, trainees do not have a monopoly on subjugation by corporations or the government.  It has been a decades long process directed at practicing physicians.  Second, rhetorical “weaponization” of terms applied to the profession is unnecessary.  That battle has already been lost. The current work and training environment has been deliberately shaped by the managed care business and like-minded governments for the past 30 years. Businesses don’t have to use weaponized rhetoric.  All they have to do is replace physicians with non-physicians, tell them they can work somewhere else, or reduce their compensation or just not pay them if they don’t meet their productivity expectations. They can also use internal committees and business practices to scapegoat and gaslight physicians who they do not like.  There is essentially unlimited leverage to get what they want.  All those measures are far more powerful in getting physician compliance than suggesting they need to make sacrifices in the service of a calling.  Physicians today are expected to make significant sacrifices or else – all in the service of their business masters.  It is evident the young physician in the essay knows nothings about it. The only practice and training environment that he knows is the one that has been severely compromised.

From medicine-as-a-calling, Rosenbaum introduces us to workism.  This term was coined in an Atlantic magazine essay to suggest that somehow work is a central part of life, identity, and meaningfulness is life.  That author goes on to suggest that people born between 1981 and 1996 were encouraged in this attitude and found themselves instead in debt and with no meaningful life work.  That led to demoralization and nihilism about capitalism.  When I read these paragraphs, I had to wonder how naïve this generation could be?  How could they possibly think that American capitalism and the economy was good for anybody?  Don’t they read anything about the environment, pollution, climate change, environmental catastrophes, unnecessary wars, near economic catastrophes – all precipitated by American capitalism?  I don’t think the idealization of work or capitalism explains the lack of medicine-as-a-calling.

There is a glimpse of reality in the next section when we hear how of how a long-time residency director of internal medicine stepped down due to a misalignment of the missions of hospitals and training programs. That is really putting it mildly. In many cases that difference was all it took to destroy training programs.  It is common to hear how residents are just used as inexpensive labor – but that has always been the case. The real problem is that the quality of teaching is adversely affected when faculty are told that they must max out their productivity and at the same time – get no credit at all for teaching.  

Rosenbaum’s essay depends on generational stereotypes and barely touches the root of the problem.  I reference the work of Peter Drucker – widely considered a guru in business management.  He pointed out the differences between production workers and knowledge workers. Basically, knowledge workers are quality focused in areas that they have more expertise than the management does. They are generally felt to be critical to the business and the idea is to retain them and give them adequate resources. Establishing a culture of excellence in their knowledge base adds to the environment. Production workers are engaged in repetitive tasks.  Their supervisors generally have worked their way up from doing the same tasks and therefore know as much about their work.  Early experiments in mass production showed that analysis of the repetitive tasks by so-called efficiency experts could improve the overall production.

What has occurred in the past 30 years has been the mass conversion of physicians from knowledge workers to production workers. The associated practice and academic environments have suffered drastic changes. Academic physicians have found that a major part of their work – teaching and research has been devalued in many cases to nothing.  In the meantime, they are expected to see many more patients, often to the point that they find themselves in new clinics – just to increase the overall billing.  The electronic health record (EHR), billing, and coding, and maintenance of certification are all added time penalties with no associated productivity credit. They have little say about how they see patients or how many patients they see.

I will cite one of many examples to highlight these points.  Just 5 years ago,  an internist I know was audited by his managers who had him tracked from 8AM to 4PM by an efficiency expert. That time frame encompassed 90% of his patient contacts, but only 66% of his workload.  Every day when the efficiency expert left – he would ask: “Where are you going? I am here for another 4 hours.”  The managers wanted to use the efficiency expert report to suggest that he was not efficient enough in seeing patients – but the real problem was the lack of clerical support and the EHR. The exercise was enough for the internist to realize he was working in a hostile environment and he moved on.  A clear loss of a knowledge worker.  The corporate myth that everyone is replaceable missed again in this case. This internist had experience and skills that could not be duplicated by anyone else in that clinic. This cycle of corporate flexing repeats itself thousands of times per day.

There can be no calling to work in such an environment where your work is routinely denigrated and devalued.  It plays out as a personal attack. You will necessarily feel like a production worker and start to work on the goals of production workers like standardized working conditions, hours, and benefits.  When you come home at night – you will leave the job behind you and no longer think about the patients who have problems with no solutions or what you need to know to do a better job. There is no esprit de corps of cohesion, support, and invigoration necessary for a stimulating knowledge worker environment.

That is the recent attitude and it correlates directly with the business takeover of medicine – not the newest generations.  It also correlates with prominent editorials in the top journals of our field like the New England Journal of Medicine.  These editorials illustrate on almost a weekly basis that there is no end to the businessmen, politicians, and lawyers who want to run and ruin our profession.  To date – they have been tremendously successful.  There is also no lack of evidence that the medical profession has been completely inadequate advocating for a reasonable practice and training environment.

Medicine will never be a calling again until the work and practice environment has been repaired and removed from the complete control of businesses and governments.

And yes – it is that simple.

George Dawson, MD, DFAPA

 

References:

1:  Rosenbaum L.  On calling – from privileged professionals to cogs of capitalism?  N Engl J Med 2024; 390: 471-5.

2:  Drucker PF. Knowledge worker productivity – the biggest challenge.  California Management Review 1999; 41: 71-94.

Graphic Credit:

All details at this link.  Coming from 4 generations of railroad workers it was a natural choice:  
https://commons.wikimedia.org/wiki/File:Group_of_laborers_digging_through_dirt_pile_along_railway_bed_LCCN2016647134.jpg

Saturday, March 2, 2024

Kendler Keeping It Real…..

 



Kenneth Kendler, MD needs no introduction to anyone even vaguely familiar with the psychiatric literature.  If you need to do your own research his accomplishments and scientific papers are widely available on the Internet. This post is to focus on his recent commentary in JAMA psychiatry (1) over the issue of psychiatric diseases and whether or not they are brain diseases.  He starts out with a 1867 quote from Griesinger stating that the brain is the only logical origin for symptoms of insanity. His analysis is at the level of “pathological and physiological” factors.

He briefly reviews two common arguments about whether psychiatric disorders are brain diseases.  The first Cartesian dualism that a mind emerges from the brain and is not the same as a brain. Since a brain is necessary for all mental phenomenon there is no specific answer to the question about whether the phenomenon observed with psychiatric disorders are diseases.  The second common argument is that grossly detectable brain diseases (lesions at autopsy and sophisticated imaging)  eventually became the purview of neurology.  To complement Kendler’s commentary, I would add that this has never been strictly true since both overt lesions and physiological brain dysfunction has always been studied by psychiatrists.  It has been a common antipsychiatry argument advanced by Szasz and others based on 19th century concepts.  Ron Pies (2) has recently commented that it involved a misunderstanding of Virchow’s work on pathophysiology.   

An indirect way this problem has been handled is to suggest that it has to do with the vague definitions of disease (3).  Without a clear definition, anyone can use their own to declare that psychiatric disorders are not diseases. That has been a common tactic used to declare that not only that mental illnesses are not diseases – because of the lack of clear gross pathology they do not exist.  Dealing with the problem at this rhetorical level has not been very successful largely due to the lack of interest in rhetoric on the part of medical professionals and constant repetition by the rhetoricians.

More practical philosophical attempts at disease definition like loss of function models seem to not have much traction. Munson and Resnick (4) proposed one of these models and also suggested that the loss of function is related to programming errors in biological processes.    

Kendler suggests a clear path that has appeal to anyone who has studied pathophysiology and treated illnesses without clear lesions or with lesions that had to be the end product of some unknown pathophysiology.  That group of people would be anyone who has done an internship or residency in any medical field.  Anyone with that experience has seen a wide array of medical conditions that are polygenic in nature and have either an unknown or highly speculative pathophysiology.

The suggested path is genetics-> pathophysiology or more broadly “genetics -> brain -> schizophrenia.”  Rather than bemoaning all of the failed GWAS studies and Decade of the Brain, Kendler cites “the most robust empirical findings in all of psychiatry—that genetic risk factors impact causally and substantially on liability to all major psychiatric disorders.”  More specifically he cites a 2022 report that shows that gene expression (as mRNA levels) of risk variants for schizophrenia were noted in the brain and no other tissue.  That brings the brain expression in his causal link into clear focus. 

At that point he hedges and suggests that this may not be robust enough to suggest that a brain disease is occurring. For me it is plenty.  He goes on to suggest that there are 5 advantages of this approach including data driven rather than metaphysical, bypasses the 19th century need for gross lesions, fits with pluralism or multiple possible etiologies, can potentially provide information about other diseases affecting the brain, and avoids a hard line of demarcation between normal and disease at the physiological level.  The last point has been elaborated in the more recent past as quantitative versus qualitative diseases and the associated variants. 

On the limitation side – a genetics only approach is the main consideration.  The antipsychiatrists that he has alluded to may be realizing that they need to finally modify their 19th century rhetoric and I have seen the equally absurd claims that there are no genetic effects for psychiatric disorders.  The difference is that Kendler is an expert in the area – so only the most dedicated post modernists will claim that they did their own research and came to a different conclusion.  He does see the innovation of being able to detect tissue levels effects of genetic variants as a good starting point.  The goal is to elaborate the functional networks affected by these variants, describe mechanisms at the molecular level, and how those mechanisms are affected by variants (5).

This is really an inspiring commentary at a time when it is getting more fashionable to attack basic science research in psychiatry. I saw a comment just last week about how biological psychiatry was a drain on mental health research.  And there are frequent comments about how there should be more psychosocial research, even though there is no clear evidence that is necessary.

As a clinical psychiatrist and a physician first, my observations have been that most people go to medical school to gain knowledge about the human body and how to treat, prevent and where possible cure diseases. Speculative pathophysiology and mechanisms are all part of that starting in the first two years of basic science course and extending to clinical rounds at bedside during residency.  Philosophy and endless arguments about the nature of disease or psyche is not.  Psychiatry has lost its way many times due to an inability to recognize and respond to rhetoric. Kendler’s solution to the question of whether mental disorders are brain diseases is an elegant one and it is consistent with the way physicians are trained.  It also establishes a boundary that some questions in psychiatry are not answerable by philosophy.

Finally, what is still lacking?  I think that ultimately, we want medicine and psychiatry to be part of a comprehensive view of human biology. We need more comprehensive theories about human biology and how things really work at the physiological and molecular level.  That knowledge is currently spotty across all specialties. Biology theory rather than biological psychiatry is really the goal here and we can use more input from theoretical biologists of all specialties.

George Dawson, MD, DFAPA


References:

1:  Kendler KS. Are Psychiatric Disorders Brain Diseases?-A New Look at an Old Question. JAMA Psychiatry. 2024 Feb 28. doi: 10.1001/jamapsychiatry.2024.0036. Epub ahead of print.

2:  Pies R.  Did Szasz Misunderstand Virchow’s Concept of disease? Psychiatric Times. Feb 21, 2024.  https://www.psychiatrictimes.com/view/did-szasz-misunderstand-virchow-s-concept-of-disease

3:  Pies RW, Dawson G.  Epistemic Humility in Psychiatry: Why We Need More Montaigne and Less Savonarola.  Psychiatric Times.  Oct 19, 2023.  https://www.psychiatrictimes.com/view/epistemic-humility-in-psychiatry

4:  Albert DA, Munson R, Resnik MD.  Reasoning in Medicine: An Introduction to Clinical Inference.  Baltimore, Maryland: The Johns Hopkins University Press, 1988: 150-180.

5:  van Dongen J, Slagboom PE, Draisma HH, Martin NG, Boomsma DI. The continuing value of twin studies in the omics era. Nat Rev Genet. 2012 Sep;13(9):640-53. https://doi:10.1038/nrg3243

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Wednesday, February 28, 2024

A Trip To The Dermatologist

 


 

Pattern matching is an important skill for all physicians.  It is rarely discussed these days despite all the continuous hype about artificial intelligence replacing doctors by reading x-rays and other lab tests.  I taught a course in diagnostic reasoning for about 12 years and the examples of pattern matching I used were from dermatology and ophthalmology.   The dermatology experiment was a straightforward comparison of dermatologists to primary care physicians looking at the same slide set of rashes and skin lesions (1).  The dermatologists were correct more often, faster at diagnosing, and able to correctly diagnosis equivocal cases compared with the primary care physicians.

I want to be clear that does not mean that primary care doctors don’t do a good job.  Some are so good that dermatologists know that they need to attend to the diagnosis and treatment of some physicians who refer them significant numbers of patients with melanoma and other types of cancer.  All these factors were probably in my subconscious when I decide to call to see a dermatologist.

It was not easy.  The first appointment was a teleconference and I would call it a swing and a miss. I was given a very expensive prescription for ocular rosacea that did nothing. When I called again to be seen in person, I was given an elaborate algorithm based on how many problems I wanted to be seen about. The more problems – the longer the wait.  I decided to go outside of my usual healthcare providers to a private clinic closer to my home. 

I have noticed a gradual accumulation of dermatology problems with age. I have made every effort to avoid direct sunlight.  If I must be outside at any time when my shadow is shorter than my height, I am wearing a high SPF shirt and sunscreen, a baseball cap, and wrap around polarized sunglasses. I have probably been sunburned twice in my life and tanned once. About 2 years ago I noticed a ring-shaped red lesion on my right forearm.  Every now and then it seemed to burn but generally it was static.  I saw my primary care MD and he did a scraping and potassium hydroxide preparation to see if it was ringworm (tinea corporis). It was not, so he told me to apply the betamethasone ointment that I typically use for eczema to the area.  I did for a couple of weeks and there was no effect.

At about the same time, I happened to notice a blue spot on the lateral aspect of my left ankle.  That is a difficult area to see.  I went into see a primary care MD who used an ophthalmoscope for magnification and concluded it was a collection of pigmented cells that did not look like a melanoma.  She said she would describe it in my chart including recording the diameter so it could be followed along by primary care. 

I described all these problems to the Dermatologist's assistant before he walked in the room.  I had photos of all the dermatology products I had been using and what had been tried in the past.  Even though the pattern matching diagnosis in Dermatology is good, like other areas of medicine – the treatments seem to be hit or miss and even then the response seems to vary over time.  I made a note to myself that I should look for papers claiming that these are placebo treatments or it is just all regression to the mean.  But I doubt that there are any anti-Dermatologists out there complaining about that and too many diagnoses and too many medications.

The intake form that I completed was just 2 pages long and there was an occupation section probably to consider environmental exposures.  When the Dermatologist came in he was very cordial and talkative.  He established that we both went to the same medical school (27 years apart), lived in the same neighborhood while we attended, and knew some of the same professors.  He took the history and clarified the technical points to his assistant who had now become his scribe.  He used a dermatoscope to inspect the lesions and make rapid diagnoses on the right forearm (actinic keratosis), left ankle (fibroma secondary to trauma) and left malar area (actinic keratosis).  He recommended freezing the malar area and forearm with liquid nitrogen and said the fibroma was just a skin reaction to some trauma that did not require treatment. At that point we went into a more detailed discussion of the rosacea and ocular rosacea and failed treatments with doxycycline and tacrolimus.  He recommended a compounded product of azelaic acid, metronidazole, and ivermectin, advised me of the cost, and has his assistant set that up. It was a very efficient process – the diagnoses, freezing treatments, and discussion took about 20 minutes.  At the end all of the follow up, prescriptions, and documentation was done and he was moving on to the next person.

There are times when it pays to see an expert and this is an illustration of one of those times.  I had been looking at these lesions for 2 years and trying to take the next steps.  There are as many barriers to seeing a Dermatologist as there are to seeing a psychiatrist.  I knew enough to monitor these lesions and they did not seem to get worse, but they were also not improving. After 2 years I got the definitive diagnoses and treatment I had been looking for as well as reassurance that the ankle lesion was not a melanoma.

This is an impressive result compared with most physician visits.  Even considering that there were a couple of things that did not fit.  Sun exposure for one.  I am what is referred to as a white fish in upper Midwest vernacular.  That means apart from my blue veins and the redness of rosacea – my skin is generally as white as the background of this page.  I had some early exposure to people with skin cancer and have been very diligent about keeping my skin and retinal exposure to direct sunlight at a minimum.  I suppose there are other factors at play such as age and know there are senile keratoses – but this did not resemble typical lesions in my dermatology texts or online. The Dermatologist predicted that the freezing treatment would cause these lesions to slough off and be replaced by normal smooth skin.  I have a follow up in 3 months to see if that happens and if the compounded topical rosacea medication works.

I am currently studying high prevalence polygenic diseases and have included eczema on that list.  Some estimates say that 20% of the population may have it.  There is the association with asthma but in my case as my asthma improved with age, I developed eczema and then worsening eczema.   I expect there will be many parallels with psychiatric disorders and diseases when my comparison is done. 

In the meantime, a Dermatologist in the right setting is a good consultant to have in your corner.

 

George Dawson, MD, DFAPA

 

References:

1:  Norman, G.R., Brooks, L.R., Rosenthal, D., Allen, S.W., & Muzzin, L.J. (1989). The development of expertise in dermatology. Archives of Dermatology, 125, 1063–1068

 This is the original reference I used in my course on the diagnostic process and how not to make a mistakes.  The first author has written significant papers about this.  

Graphic:

I mapped the dermatology conditions onto the body outline. If someone has a better body outline or one that they use on a standardized form and you want to send it my way - please do.  I can make a much better graphic if the outline is a separate shape.  The actinic keratoses areas on the map are probably both only 2 cm in diameter.  The rosacea can happen anywhere on the face and most annoyingly on the eyelids.  The eczema is a whole body condition that started out subtly as intense pruritis on the extremities and eventually spread to the abdominal area, chest, and back.  Pruritis is the most significant symptom with occasional lesions that looks like abrasions.  It can be exacerbated by skin contact with allergens like ECG electrodes. 




Sunday, February 25, 2024

The Retired Consultant

 


I happened across this old post on approaching retirement today and reread it. Of course, I am biased but it holds up well.  It contains information about psychiatrists retiring that you will not see anywhere else – including why we are happy.  I currently spend much of my day doing the usual chores, exercising, and writing.  I have several writing projects going and am near completing one that is unique.

I don’t get out much and I like it that way. I am an introvert and have been subjected to the usual jokes about introversion.  The pandemic was a factor but not the only one.  I just got back from working out in a gym that has Cybex machines.  After that I went to Target to pick up a supply of blueberries and frozen burritos.   

On the way out – I stopped to get a mocha and 2 biscottis.  The barista was young and we talked about the closing time of the coffee shop relative to the store. I associated to what I was doing at that age.  I was a janitor in a dormitory. It was a thankless job.  Luckily with increasing college experience I was able to move on to more technical work as a lab and research assistant.  I wondered if she would reflect on her work as a barista when she got to be my age and I sincerely hoped she would get to my age and beyond.  I thought about writing a poem about that brief encounter, probably because I had just read two Emily Dickinson poems and have a history of writing free verse in the style of ee cummings.

On the drive home, public radio was playing election coverage from South Carolina.  It was the GOP primary and I shut it off. I always have public radio in the background – but listening to this is just too much.  I drove, drank my mocha and crunched on my biscotti in silence. I had some thoughts about biscotti.  A competitor has a much harder biscotti.  It is so hard the almonds are cut sharply with the slices.  The biscotti I was eating was not as hard but still had an almond and vanilla crunchy taste.

I started thinking about a paper I was writing. Even though it was about rhetoric, it seemed quite exciting.  I have not encountered any papers like it.  I thought about where it should be submitted and how I should modify the introduction. One of the most insightful and informative books I have read lately was about rhetoric. It tied together so many things.  The author was gracious enough to respond to two of my emails.  I need to incorporate more of his concepts into the paper – but his book is encyclopedic.

I thought about some advice I had given lately.  Even though I am retired and people know it – they still call me.  I tell them that technically I am not treating them or directly giving them medical advice because we do not have a physician patient relationship, I don’t have a working office setting or records, and I don’t have malpractice coverage.  They understand that and it doesn’t deter them.  I am licensed and recently contacted the Board of Medical Practice about continuing medical education (CME) credit reporting this summer. The pandemic created a lot of confusion about deferred CME reporting.  I need to report 75 credits and I currently have 74 with a 6 CME credit conference in March. I wonder how long I will keep that up in retirement.

On the home stretch, I think about the advice I have given people over the years.  The qualified advice on the system over the past 2 years tells me how bad things have gotten.  Parents calling me about their adult children who are not doing well.  Adult children calling me about parents who are not doing well.  The occasional email directly from a person who is dissatisfied with treatment. Many calls about what happens in emergency situations.  Many calls about what specific diagnoses, imaging findings, and labs really mean.  Was the emergency department trying to talk me out of being admitted? Why wasn’t I treated with anything?  It just seems like I sat there a long time, nothing happened, and they sent me home.  Are these side effects that I am getting from this medication and what can be done about it?  Are there any resources out there that can help me? I don’t seem to be getting any help?

I try to help people negotiate available systems and help them prioritize what should happen first.  There is a general reluctance to call their clinic or doctor and report that there are potential side effects. Overall, there is a lack of help for people with psychiatric disorders. I know that is not strictly true and that there are many large systems of psychiatric care nearby – but even when people get in - there is difficulty getting what they need. I shock them with basic information about when to call their doctor and what might be helpful to discuss.  I never second guess their doctor.  I am focused on how to help them get the answers they need.  It is not at all like practicing psychiatry.  The most valuable product of that work is a patient who feels understood at the end of the session. None of the people calling me feel understood at even a superficial level.

Just a few years ago, I was an insider working in an intense hospital environment. I was generally feeling the stress all day long. I had the physical manifestations of that stress that were measurable – but I pushed through every day and made it home to unwind.  In some cases I could not unwind and ended up calling my nursing staff at 2AM to make sure that things were going OK.  I think about that right after thinking that I should still be working – just based on all these systems problems that people are telling me about.

I come to the realization that I can’t do it anymore. Cognitively and technically it is certainly not a problem. I have no doubts that my diagnostic and treatment skills are still there. Physically it is an interesting story.  I just lifted plenty of weights and will lift more tomorrow.  My aerobic capacity is very good. I have posted some of my chronic health problems here on this blog to illustrate diagnostic, pathophysiology, and treatment concepts. So generally my health is pretty good.  That can always turn on a dime.  I can’t work anymore because of the stress response.  The mental and emotional demands of work become physical demands and that creates significant problems. Doctors reading this in those environments know what I am talking about and I wish them the best because I know nobody is trying to alleviate any of that pressure.  Nobody is trying to help them.

I finish off my mocha and biscotti as I am pulling into the driveway. It is 7PM and dark out here in Minnesota.  I had over 30 years of pulling in my driveway in the dark after work and still feeling tense and in some cases jumpy about what happened that day.  Things are different now.  I can decide how much pressure I am under and when I can unwind. I wish I could do more for all these people who need help – but I can’t. 

It is time to finally take care of myself.

 

George Dawson, MD, DFAPA


Supplementary:

@dahlle on Twitter read this post and posted the NASA Task Load Index - a workload measure that has been validated across a number of settings.  Just looking at the scales - it is easy to see how physicians can max out almost every scale except for the physical demands (at least for non-surgeons).  With enough stress - heart rate and blood pressure increase just like you are running.  

It is also an illustration of how things can get rapidly complicated when there are people actively standing in your way and other people demanding that you do more.  Work setting is critical here as well as adaptation to work.  I have talked with hospitalists who told me their cognitive performance dropped off steeply on day 6 (of 7).  On the other hand I have talked to physicians who were used to seeing 30 patients for a minute or two at a time in an afternoon who were not stressed at all. 


At least one study has established a dose response relationship between physician task load using this scale and burnout:

Harry E, Sinsky C, Dyrbye LN, Makowski MS, Trockel M, Tutty M, Carlasare LE, West CP, Shanafelt TD. Physician Task Load and the Risk of Burnout Among US Physicians in a National Survey. Jt Comm J Qual Patient Saf. 2021 Feb;47(2):76-85. doi: 10.1016/j.jcjq.2020.09.011. 


Graphics Credit:

Biscotti is via Wikimedia Commons.  https://commons.wikimedia.org/wiki/File:Biscotti_1.jpg

Mokkie, CC BY-SA 4.0 <https://creativecommons.org/licenses/by-sa/4.0>, via Wikimedia Commons



Thursday, February 8, 2024

Blame Gun Extremists – Not Parents

 

   


 The Crumbley verdict is in and in the usual manner – the media is either celebrating it or bothered by it.  The bothered response is more muted this time – probably because Americans have been conditioned to see national court cases as vindication or rejection of whatever moral position they seem to have on the issue. Without reading the court transcript – media reports suggest that the prosecution in the case portrayed Jennifer Crumbley as a distracted mother who did not pay adequate attention to her son – 15-year-old Ethan Crumbley’s mental status.  If she had - he would not have had access to the 9mm semiautomatic handgun that he used in the Oxford school shootings.  On November 30, 2021 – he shot and killed 4 students and wounded 7.  The jury agreed with the prosecution despite Ms. Crumbley’s statement: "You never would think you'd have to protect your child from harming somebody else. That’s what blew my mind. That was the hardest I had to stomach is that my child harmed and killed other people."  She was found guilty of 4 counts of involuntary manslaughter and the sentence is pending. 

Jennifer Crumbley is of course right.  Professionals charged with assessing the potential for harming others cannot accomplish this task with any degree of certainty.  Should untrained parents be held to that standard, especially when they are emotionally involved with the children they are supposed to assess?  A summary of her court testimony is available from several sites at this point. It focuses on testimony and texts that suggest her son was having difficulty at school and that other people noticed he was moody and depressed. The parents were called in by school officials because they had noticed violent content in his drawings, but after a meeting they did not insist that he be removed from school.  I do not know the school professionals involved – but if there was that level of concern – why not insist that the parents take their son home and give them a clear plan of care?

With any criminal proceeding there are always a lot of discrepancies.  Jennifer Crumbley denied that her son was symptomatic (hearing voices and depressed).  She denied knowing anything about his preoccupation with violent thoughts.  Ethan Crumbley apparently intentionally injured birds and enjoyed doing that.  I do not know if the parents were aware of this or not. There was some debate about the family’s health insurance situation.  Coverage for Ethan lapsed when his father lost his job and his mother was trying to enroll him during the next enrollment period in her plan.  There is also the question of what is generally available for emergency psychiatric care for a 15 yr old.  I don't know if that was bought up during the hearings or not.  I can't speak to what is available in that specific area, but I can say that it is generally non-existent throughout much of the country.    

There is some opinion in the media right now that this trial is precedent setting in that it may translate to parents being held responsible for the crimes of their children. Although I am not a lawyer – to me the precedent seems to already have been set – parents are not responsible for the crimes of their children.  There have been other parents convicted in cases where their children were involved in school shootings.  In one case the mother of a 6-year-old who shot his teacher was sentenced to 21 months, but that was for illegally obtaining a firearm by denying a that she had a drug problem.  In the other case, a father of a shooter who killed 7 people was eventually charged with 7 counts of reckless conduct for assisting his son in obtaining a firearm license even when he had expressed thoughts about killing himself and others.

The critical events in the Crumbley case seem to be the parent purchasing the handgun for their son as a way to lift his spirits, not securing the gun when he was not under their direct supervision, and the two meetings at school on the day before and the day of the shooting. On the first of those days there was concern that he was researching ammunition on his phone during class.  He explained that he went shooting with his mother and that was a hobby.  The counselor called his mother who communicated by text and joked that he had to learn to not get caught.  On the day of the shooting, his parents were called in after he was seen watching a violent video in class, drawing guns and a bleeding body on a math worksheet and writing several nihilistic statements. The counselor was concerned that he might be suicidal. During the meeting the Dean of Students brought in Ethan’s back pack but nobody searched it.  The handgun was in the backpack.  He returned to school from that meeting with his backpack and started the shooting (2).  

In a related matter – there is a civil suit but the trail of that paperwork is difficult to follow.  The original suit against the school and staff was dropped but a subsequent suit against the counselor and Dean of Students was allowed to proceed. There was also a lawsuit against the Michigan State police.

From what I know about this case so far, it appears that Jennifer Crumbley’s trial was primarily an attack on her character. Combined with hindsight that is a powerful approach to find someone guilty of a crime.  I looked up the definition of involuntary manslaughter in the state of Michigan according to this reference it requires proving one of 2 theories:

1:  That the deaths were caused by grossly negligent actions of the defendant

2:  That the defendant neglected her duty as a parent to “exercise reasonable care to control their minor child so as to prevent the minor child from intentionally harming others or prevent the minor child from conducting themselves in a way that creates an unreasonable risk of bodily harm to others.”

There is a lot of room between "gross negligence" and "reasonable care." In this case the parents were responsive to school authorities and those responses at the time satisfied those authorities to the point that they allowed Ethan to return to school.  

Applicable laws in the State of Michigan state that handgun purchasers must be 18 years of age to purchase from a private seller and 21 years of age to purchase from a federal licensed firearms dealer (FFL).  The handgun purchase in this case occurred when Ethan Crumbley was 15 years of age.  Michigan will not have a safe storage law for firearms until February 13, 2024.  The law mandates that unattended firearms must be locked and unloaded and it defines crimes and penalties for problems that occur as a result of violations defined as behavior ranging from threats to deaths resulting from unauthorized access to that firearm.  Since the Oxford school shootings occurred in November 2021 – that law does not apply. 

The medical literature has a few studies that appear to address the issue of age-related firearm purchases and homicide and suicide.  The authors of one study (6) found no correlation between higher age requirements and homicide rates of 18-20 year olds; but discuss the reasons why that was the case.  Most of those reasons come back to the firearm density in the United States and how easy it is to access firearms through back channels.  Any casual inspection of those firearm density figures in the United States – shows an incredible number of firearms even relative to war zones across the globe. The United States ranks 9th in gun homicides.  The 8 countries ranking higher all have significant amounts of gang and cartel related violence, some to the point that it is driving the current immigrant crisis at the southern border.  Five of those 8 countries have the highest crime index.  Four have the highest homicide rates.  The US has the gun homicide rate of lawless low and middle income (LMIC) countries.  

The cultural effects of gun extremism are never discussed as being a cause of gun violence in the United States.  Over the past 50 years, gun extremists have pushed for increasing accessibility to firearms by shall issue laws, stand your ground laws, fewer restrictions, and loopholes that allow back door access to firearms. In the process, common sense gun laws that were developed in the 19th century, like city ordinances that forbade carrying guns in town have fallen by the wayside.  Some gun extremists are pushing to eliminate domestic violence charges as a disqualifier for gun possession. In that landscape there is a subcultural effect that (for some) guns are a legitimate way to express anger or dissatisfaction in school or the workplace. Nobody is standing up against that myth.  If anything, the gun extremists are rationalizing it as mental illness or not enough guns (arm the teachers) rather than far, far too many guns.

That is what I think about when I think about the Jennifer Crumbley verdict. In many ways she was set up to take a fall for 50 years of gun extremism. Certainly, her son should have never had a handgun.  But do other parents buy firearms for their children?  They certainly pose them with guns on Christmas cards. When I was a kid 50 years ago – no kid had one and it was the law. There was a good reason for it and that reason was not discovered until the 21st century.  Teenagers may look like adults but they do not have the brain development or judgment of adults. Combining that with a general culture of gun extremism and a subculture of mass shootings is a recipe for disaster. Until we recognize the cultural effects and how guns became part of the culture wars – we will not be able to stop this violence and loss of life.  

Parents may have become the next casualty.

 

George Dawson, MD, DFAPA


Photo Credit to my colleague Eduardo A. Colon, MD


References:

1:  El-Bawab N.  Jennifer Crumbley says she wishes son had 'killed us instead' as she took stand in manslaughter trial.  February 1, 2024.  https://abcnews.go.com/US/jennifer-crumbley-takes-stand-manslaughter-trial-tied-sons/story

2:  Snell R.  Oxford school shooting victim's family sues Michigan State Police in latest legal challenge.  October 5, 2023  https://www.detroitnews.com/story/news/local/michigan/2023/10/05/oxford-school-shooting-victims-family-sues-michigan-state-police/71074873007/

3:  Stack MK.  What Is This Mother Really Guilty Of?  New York Times.  Febnruary 1, 2024. https://www.nytimes.com/2024/02/01/opinion/mother-homicide-court-crumbley.html

4:  Strom S. Michigan Involuntary Manslaughter Law.  FindLaw.  February 7, 2024. https://www.findlaw.com/state/michigan-law/michigan-involuntary-manslaughter-law.html

5:  Associated Press.  Timeline: Key moments surrounding the 2021 Michigan high school shooting as mother of shooter is found guilty.  https://www.nbcchicago.com/news/local/timeline-key-moments-surrounding-the-2021-michigan-high-school-shooting-as-mother-of-shooter-is-found-guilty/3348384/

6:  Moe CA, Haviland MJ, Bowen AG, Rowhani-Rahbar A, Rivara FP. Association of Minimum Age Laws for Handgun Purchase and Possession With Homicides Perpetrated by Young Adults Aged 18 to 20 Years. JAMA Pediatr. 2020 Nov 1;174(11):1056-1062. doi: 10.1001/jamapediatrics.2020.3182. Erratum in: JAMA Pediatr. 2020 Nov 1;174(11):1119. PMID: 32870238; PMCID: PMC7489426.







Sunday, February 4, 2024

Drugs from Gas Stations and Other Notes from the Field...

 


The Food and Drug Administration has not approved tianeptine for use in the United States; however, it is readily purchased in elixir formulations online or at gas stations informally referred to as “gas station heroin”  - from reference 1

 I shot the photo at the top of this post at my local gas station.  A couple of months ago they installed this neon sign advertising Kratom for sale and another selling Delta-10 THC.  Both compounds are intoxicants and are a part of the multigenerational drug epidemic that the United States finds itself in.   Depending on how you are reading about it that epidemic may seem restricted to fentanyl or in some cases amphetamines – but make no mistake about it there is a general trend in making all intoxicants more easily accessible and even making it seem like they are a legitimate business. Even the fentanyl story is only partially told.  The backdrop of excessive prescription opioid prescribing is rarely told – apart from a dramatized version.  The only good that has come of this is that all the hype about medicinal cannabis seems to be rapidly dwindling along with the lack of medical evidence that it has any such properties.

That brings me to the latest gas station intoxicant – tianeptine. It was originally intended to be an antidepressant based on a very general tricyclic structure.  I made the graphic below for a rapid structural comparison with standard tricyclic antidepressants (nortriptyline) and selective serotonin reuptake inhibitors (escitalopram). It is obviously not structurally like either class of compounds and has a unique moiety – the 5,5 dioxo structure on the central cycloheptane ring.


In terms of receptor affinities, the first property that jumped out at me was that tianeptine had none of the usual receptor or transporter affinities expected of typical antidepressants in the PDSP database.  The only affinity in that data set was for the mu opioid receptor (MOR). 

 

 

NET

SERT

DAT

5-HT2A

5-HT1A

MOR

tianeptine

-

>10,000

>10,000

>10,000

>10,000

383 nM

nortriptyline

1.8 nM

15 nM

1,140 nM

294 nM

5 nM

 

escitalopram

6,514 nM

1.1 nM

>10,000

>10,000

>10,000

 

A recent CDC report (1) describes a spike in tianeptine ingestions and complications due to contamination from synthetic cannabinoid receptor agonists (SCRAs) between June and November 2023.  Fourteen of the 17 exposure calls involved patients drinking an elixir called Neptune’s Fix – a mixture of tianeptine and kavain or Piper methysticum root.  Six of the patients ingested other compounds including benzodiazepines, Kratom, trazodone, tramadol, and gabapentin.  Nine had previously used tianeptine. Thirteen of the 17 patients were admitted to intensive care units (ICU) and 7 required intubation and ventilatory support.  There were cardiovascular complications including conduction abnormalities, hypotension, tachycardia, and a cardiac arrest. All the patients had altered mental status.

Six samples of the Neptune’s Fix preparation from 2 of the patients were analyzed by gas chromatography-(GS-MS) and compared with a standard database of compounds of interest.  All of the bottles were labelled tianeptine and kavain. Two of the samples contained THC and CBD.  Two of the samples contained the SCRAs ADB-4en-PINACA and MDMB-4en-PINACA. 

The overall message of the report is that tianeptine preparations available as unregulated preparations can potentially be addictive and may contain adulterants that can produce severe adverse effects requiring resuscitation or ICU admission.  This has been noted in previous literature about SCRAs including severe psychiatric effects.  There have been 144 synthetic cannabinoids identified since 2014.  In some circles these compounds are referred to as JWH compounds after the organic chemist who first synthesized and researched them.

The way that tianeptine is described in the literature seems to parallel the interests of the authors.  The FDA references are uniformly negative because they are focused on severe side effects including death and addiction. Authors who are interested in the opioidergic system in depression will describe how it is a legal antidepressant in several countries and minimize both potential addiction and severe side effects. Either way it maps well onto the current American pro-drug culture. The sheer number of new intoxicants and widespread access to these intoxicants is staggering. Hundreds of new compounds in the past ten years.  Addictive compounds readily available at gas stations?  Those compounds laced with additional problematic intoxicants?  The so-called War on Drugs is obviously non-existent at this time. 

One of the questions I always get from people in response to posts about contaminated, adulterated, and counterfeit intoxicants is why?  Why would drug dealers or semi-legitimate businesses want to kill off or injure their customers?  What is their motivation? The most obvious one is that they don’t care.  There always seems to be a significant number of people out there interested in a new or higher high so demand is never a problem.  The second is marketing.  In a previous post I described a case where fentanyl was being pressed into tablets that looked like Xanax bars and the purchasers were not only aware of that but preferred to purchase those tablets even after directly observing them being made. A third possibility is ignorance. People looking to find intoxicants and sell them on the street are not medicinal chemists – even though they may talk like it. Some of these compounds vary in potency by a factor of a hundred or a thousand.  The fourth is a lack of accountability.  Even the most cynical conceptualization of the pharmaceutical industry recognizes the fact that the products are approved, manufactured, and monitored according to standards. Manufacturers are subject to regulatory bodies, criminal and civil liability, and accountability at the business level from a board of directors and at the shareholder level. It is fairly easy to find that the industry has paid tens of billions of dollars in civil and criminal penalties over the past 30 years. None of these incentives applies at the level of small companies marketing unapproved but unregulated drugs or street sales of illicit drugs. For that matter it probably also does not apply at the level of legal cannabis dispensaries. Even though legally prescribed and regulated medications have risks – unregulated and street drug risk is much higher.  As demonstrated in this post that risk starts with what is really in the bottle complicated by even higher risk adulterants. 

I always think of the former President of Mexico Vincente Fox in these situations.  When asked about the American drug problem and the involvement of Mexico he characterized the problem as “America’s insatiable appetite for drugs.”  When I think about people going into a gas station and buying Neptune’s Fix or Kratom or Delta-10 THC and not really knowing what they are getting in the bottle – he can’t be wrong.

George Dawson, MD, DFAPA



Supplementary:  On not caring that I mentioned in the above post.  I think there is a case to be made that the same attitude can fuel legitimate retail sales of drugs that reinforce their own used including alcohol, cannabis, and tobacco. Increasing liquor stores will increase alcohol consumption by increasing access.  That increased access comes with smaller distances to liquor stores, home delivery, placing liquor stores in proximity to other retail stores and supermarkets, and the commoditization of alcohol – you will always be able to find a cheaper drink. Since a significant portion of any population are problematic drinkers all this increased access directly impacts them. The people that create all this access, typically argue that the intoxicants are legal, they run a legitimate business, and not creating all this access puts them at a disadvantage compared to other sellers.  That argument leaves out the significant morbidity and mortality associated with alcohol and ironically that argument is typically used when advocates are trying to legalize another intoxicant as in:  “Our new intoxicant is not as dangerous or lethal as alcohol.”

 

References:

1:  Counts CJ, Spadaro AV, Cerbini TA, et al. Notes from the Field: Cluster of Severe Illness from Neptune’s Fix Tianeptine Linked to Synthetic Cannabinoids — New Jersey, June–November 2023. MMWR Morb Mortal Wkly Rep 2024;73:89–90. DOI: http://dx.doi.org/10.15585/mmwr.mm7304a5.

2:  El Zahran T, Schier J, Glidden E, et al. Characteristics of Tianeptine Exposures Reported to the National Poison Data System — United States, 2000–2017. MMWR Morb Mortal Wkly Rep 2018;67:815–818. DOI: http://dx.doi.org/10.15585/mmwr.mm6730a2

3:  Samuels BA, Nautiyal KM, Kruegel AC, Levinstein MR, Magalong VM, Gassaway MM, Grinnell SG, Han J, Ansonoff MA, Pintar JE, Javitch JA, Sames D, Hen R. The Behavioral Effects of the Antidepressant Tianeptine Require the Mu-Opioid Receptor. Neuropsychopharmacology. 2017 Sep;42(10):2052-2063. doi: 10.1038/npp.2017.60. Epub 2017 Mar 17. PMID: 28303899; PMCID: PMC5561344.

4:  Nobile B, Ramoz N, Jaussent I, Gorwood P, Olié E, Castroman JL, Guillaume S, Courtet P. Polymorphism A118G of opioid receptor mu 1 (OPRM1) is associated with emergence of suicidal ideation at antidepressant onset in a large naturalistic cohort of depressed outpatients. Sci Rep. 2019 Feb 22;9(1):2569. doi: 10.1038/s41598-019-39622-3. PMID: 30796320; PMCID: PMC6385304.

5: Wikipedia contributors. Nortriptyline. Wikipedia, The Free Encyclopedia. December 20, 2023, 17:01 UTC. Available at: https://en.wikipedia.org/w/index.php?title=Nortriptyline&oldid=1190922632

Accessed February 4, 2024.  Wikipedia table was used for nortriptyline because the PDSP database was no longer working.

6:  Jelen LA, Stone JM, Young AH, Mehta MA. The opioid system in depression. Neurosci Biobehav Rev. 2022 Sep;140:104800. doi: 10.1016/j.neubiorev.2022.104800. Epub 2022 Jul 30. PMID: 35914624; PMCID: PMC10166717.

7:  FDA.  Tianeptine Products Linked to Serious Harm, Overdoses, Death.  https://www.fda.gov/consumers/consumer-updates/tianeptine-products-linked-serious-harm-overdoses-death

8:  FDA.  Tianeptine in Dietary Supplements.  https://www.fda.gov/food/dietary-supplement-ingredient-directory/tianeptine-dietary-supplements

9:  FDA.  FDA warns consumers not to purchase or use Neptune’s Fix or any tianeptine product due to serious risks.  https://www.fda.gov/drugs/drug-safety-and-availability/fda-warns-consumers-not-purchase-or-use-neptunes-fix-or-any-tianeptine-product-due-serious-risks