Why “Reading” and “Doing Your Own Research” are not nearly enough….

 

 

Medical training is an exercise in repeatedly meeting people who know a lot more about the field than you do and hoping to learn something in the process.  It happens regularly – often several times a day.  It is a common occurrence to meet people with encyclopedic knowledge – not just of textbooks and papers but disease patterns and presentations as well as the best treatment approaches.  The knowledge can be obtained through straight didactics, informal seminars, bedside interactions, and direct observation.  It can be affiliative or adversarial. In other words, you might get the attending physician who asks you a series of questions until you run your knowledge base dry or you might get the attending who realizes that your life is difficult and details the pathophysiology while pointing you to the latest review to read.

All that dynamic learning happens in a certain time frame where everyone must focus on the problems of the day.  The recent COVID-19 epidemic is a striking case in point. During the years of my training and practice the pandemic of interest was the human immunodeficiency virus (HIV-1, HIV-2). I started to see those patients in residency training – typically for the neuropsychiatric manifestations. At the time there were full isolation precautions and we had to wear surgical gowns, caps, and masks to see the patients. There was also the concern about needlestick injuries and injuries sustained by during surgery on HIV positive patients – that was subsequently shown to be a rare occurrence.  

All primary care and specialty physicians need to have a knowledge of HIV/AIDS – because of the potential protean manifestations, the need to maintain medications, and for infection control purposes.  It is also useful to recall epidemiological and infectious disease concepts – the most relevant being that for a while the infectious agent of the disease was not known.  Early in the course it was characterized by epidemiological features. When the virus was eventually isolated – steady progress was made in the development of antivirals to the point where the virus can be suppressed and is no longer detectable.

Over the course of learning about the illness and its treatment – I observed a heavy toll on treatment providers. There were no effective treatments early on.  I had lunch every day with an infectious disease team who ran one of the early HIV/AIDS clinics. Providing care in that setting took an emotional toll on them.

Against that 40 year backdrop – Aaron Rodgers recent press conference stands in tragic contrast.  For a time, Rodgers assumed the role of inscrutable new age guru.  He refused to state his COVID vaccine status but talked in detail about the rejuvenative properties of ayahuasca.  But I want to focus on his 208-word commentary on HIV, COVID, and Dr. Fauci. The full video is linked above for viewing.  I will address his commentary on a subject-by-subject basis.

1:  There was a “game plan” in the 1980s to create a pandemic with a “virus that’s going wild.”

Multiple lines of evidence show that HIV resulted from cross species transmission of Simian Immunodeficiency Virus (SIV) existing in African primate species. The transmission occurred through infected blood or bodily fluid exposure from hunting (1).  The key concept is that many human pandemics originate from cross species transmission.  Further – there is ample evidence that the cross over to humans occurred decades before the first AIDS fatality occurred in the US in the 1980s.  The only "game plan" in place was evolution in nature - over millions of years.

2:  Dr. Fauci was given $350 million dollars to research this:

Dr. Fauci was appointed head of the National Institute of Allergy and Infectious Diseases (NIAID) in 1982. NIAID is one of 27 institutes and centers of the National Institute of Health (NIH).  The funding for AIDS research is available on several sites. In this paper Tables 4.2 and 4.3 give the research dollars as well as the distribution by institute. In 1982 for example – there was $3.6M in AIDS funding.  Looking at the 1990-1991 allocation NIAID got 53.1% of the research allocation. The detailed allocation of that grant money consists of intramural and extramural research funding as well as funding clinical centers of research with adequate patient numbers to advance the field. From that paper:

“The need for more—and more appropriate—facilities specifically for AIDS work was acutely apparent in early 1988 when NIH director James Wyngaarden and NIH AIDS coordinator Anthony Fauci testified before several congressional committees (U.S. Congress, 1988a:259, 1988c:331). Their concerns were echoed in the June 1988 report of the Presidential Commission on the HIV Epidemic. The commission noted that plans for AIDS office and lab space were seriously delayed, and recommended that intramural construction and instrumentation needs be assessed and made a high priority in future budget requests…”

When Dr. Fauci assumed control of NIAID, the total budget of that agency was $350M.  He described it as a relatively secondary institution, that he built up to a $6.3B agency over the next 38 years (3). 

3:  The only drug they came up with was AZT:

 Azidothymidine (AZT) was developed in 1964 by the National Cancer Institute (NCI) as a potential anti-cancer therapy.  It was ineffective but was included in screening as an HIV treatment where it stopped viral replication without damaging normal cells.  It was the first FDA approved drug to treat AIDS in 1987. Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections (ACTG) was founded at that time along with other networks though NIAID to conduct clinical trials in therapeutics for AIDS. Subsequent trials established more safe and effective doses as well as demonstrating a delayed onset of AIDS in HIV infected persons with AZT making it the first effective HIV treatment.

NIAID funded research for combination therapy, triple drug therapy and novel agents to the point where there are now 30 anti-retroviral drugs and new classes of therapeutic agents.  During Dr. Fauci’s tenure at NIAID, research has gone from antiretroviral treatment (ART) based remission to clinical trials looking at strategies for potential ART-free remission of HIV or cure (4).  That goal has not been realized but there is no question that the research work on HIV has been productive resulting in reduced transmission and mortality.

 4:  An “environment” was created where only one drug worked

The environment was a research environment looking for treatments at a time where there were so many AIDS related deaths that it led to public outcry and activism. AZT was discovered as effective in a standard screening protocol, but additional clinical trials were necessary to establish doses, safety, and efficacy for FDA approval.

5:  Just like HIV – only remdesivir worked for COVID until there was a vaccine

Just like HIV – additional therapies became available for COVID (SARS-CoV-2) including nirmatrelvir-ritonavir (Paxlovid), simnotrelvir-ritonavir, and high titer convalescent plasma.  A recent review of the issue of vaccine versus pills for COVID concludes that it is a false dilemma and that they may have complementary roles (5). There is active research continuing in SARS-CoV-2 antivirals and no reason to expect that there will not be many additional medications.

6:  Dr. Fauci had a conflict of interest because of a “stake in the Moderna vaccine.”

Dr. Fauci has no stock in Pharma companies. The “stake” in vaccines are royalty payments that researchers are obligated to take, the majority occurring before the COVID pandemic. That standard and the average payments have been documented in the medical literature where Dr. Fauci is on record as having donated payments to charity (6).  Without having a detailed list of royalty payments, what they were for, and the outcomes it is difficult to make any additional comments except to say that there was no violation of NIH policy – in fact not accepting the payments was a violation. Royalties are based on discoveries and not getting products to market, FDA approval, or sales.  My further speculation is that the royalties are a small fraction of actual sales and company profits and the original NIH policy was probably designed to retain talented researchers who would otherwise be lost to private industry. Major universities and research institutes generally allow their faculty to accept consulting and royalty fees. I have worked in several settings where those arrangements were spelled out in the initial employment contract, including intellectual property ownership.

7:  Pfizer is also “criminally corrupt” based on a fine that was paid.

Large fines against pharmaceutical companies are the rule rather than the exception.  In looking at this list of the largest settlements most of the fines are based on regulatory laws having to do with off label promotion of drugs beyond what is indicated in the FDA package insert. Practically all of the penalties have to do with marketing rather than research or production. It has been well known for decades that Pharma companies aggressively market their products to physicians, hospitals, clinics, and now direct-to-consumer advertising to potential patients. You could look at a list like this and decide against using a company’s product – but it might mean not taking a potentially safe and effective drug.  The same type of enforcement actions are taken against companies in other fields such as information technology.

8:  People who can “do their own research” and “read” are commonly vilified for that if they question authority

There is a basic difference between authority and expertise. The only vilification that I have noticed is of experts. Dr. Fauci is an extreme example but during COVID it extended to many local public health officials. It was a direct product of the minimization of COVID by President Trump and many of his officials as well as the MAGA movement.  Further it has led to political violence that includes threats of physical harm to Dr. Fauci and many other public health officials.  These threats are unprecedented and have been attributed to right wing political rhetoric.

9:  Why should science be trusted if it can’t be questioned.

Science is continuously questioned and this is probably the most significant public misunderstanding.  Science is a process where results are continuously challenged and updated. The politization of the COVID pandemic illustrates what happens when people who are not trained in the scientific method get involved. Suddenly each scientific modification means that somebody was wrong or lying. Scientists are treated like politicians and the politicians feel free to say anything that is not grounded in science. 

That is not how science works. It takes actual observations over time to test hypotheses.  As one example – I have collected about 200 hypotheses on the pathophysiology of depression over the past 40 years and to date – there are not sufficient observations to prove or disprove them and get to the level of a theory of depression. An equivalent scenario is the endless speculation of the lab leak hypotheses versus the cross-species transmission hypothesis of COVID origins.  Although the probability lies in the direction of cross species transmission – there are insufficient direct observations to prove one versus the other and ample discussions of the lab leak hypothesis by people with a complete lack of expertise.

Finally, with the errors in Rodger’s statement – I would be remiss if I did not mention Brandolini’s Law. Simply stated:

“The amount of energy needed to refute bullshit is an order of magnitude bigger than to produce it.”

This is true – especially when the false argument does not have to be based on facts, process, or rigorous standards. The politization of COVID and many other health issues by the extreme right wing should be a lesson that is not forgotten.  This video clip is a case in point.

 

George Dawson, MD, DFAPA

Supplementary 1:  The NIH policy on royalty payments to inventors can be viewed at this link.  The abbreviation IC stands for the Institutes and Centers of the NIH.  More detailed information can be found at this link.  The NIH also has conflict of interest policy (see conflict of interest in Appendix 1).

 Supplementary 2:  A few relevant titles from my library - note dates. 

 

References:

1:  Sharp PM, Hahn BH. Origins of HIV and the AIDS pandemic. Cold Spring Harb Perspect Med. 2011 Sep;1(1):a006841. doi: 10.1101/cshperspect.a006841. PMID: 22229120; PMCID: PMC3234451.

2:  Institute of Medicine (US) Committee to Study the AIDS Research Program of the National Institutes of Health. The AIDS Research Program of the National Institutes of Health. Washington (DC): National Academies Press (US); 1991. 4, Supporting the NIH AIDS Research Program. Available from: https://www.ncbi.nlm.nih.gov/books/NBK234085/

3:  Anthony Fauci: a scientific adviser's role from HIV to COVID-19. Bull World Health Organ. 2023 Jan 1;101(1):8-9. doi: 10.2471/BLT.23.030123. PMID: 36593776; PMCID: PMC9795384.

4:  Schou MD, Søgaard OS, Rasmussen TA. Clinical trials aimed at HIV cure or remission: new pathways and lessons learned. Expert Rev Anti Infect Ther. 2023 Jul-Dec;21(11):1227-1243. doi: 10.1080/14787210.2023.2273919. Epub 2023 Nov 8. PMID: 37856845.

5:  Papadakos SP, Mazonakis N, Papadakis M, Tsioutis C, Spernovasilis N. Pill versus vaccine for COVID-19: Is there a genuine dilemma? Ethics Med Public Health. 2022 Apr;21:100741. doi: 10.1016/j.jemep.2021.100741. Epub 2021 Nov 23. PMID: 34841029; PMCID: PMC8608621.

6:  Tanne JH. Royalty payments to staff researchers cause new NIH troubles. BMJ. 2005 Jan 22;330(7484):162. doi: 10.1136/bmj.330.7484.162-a. PMID: 15661767; PMCID: PMC545012.

7:  Mehellou Y, De Clercq E. Twenty-six years of anti-HIV drug discovery: where do we stand and where do we go? J Med Chem. 2010 Jan 28;53(2):521-38. doi: 10.1021/jm900492g. PMID: 19785437.

8:  Burke RV, Distler AS, McCall TC, Hunter E, Dhapodkar S, Chiari-Keith L, Alford AA. A qualitative analysis of public health officials' experience in California during COVID-19: priorities and recommendations. Front Public Health. 2023 Sep 13;11:1175661. doi: 10.3389/fpubh.2023.1175661. PMID: 37771831; PMCID: PMC10525347.

9:  Ward JA, Stone EM, Mui P, Resnick B. Pandemic-Related Workplace Violence and Its Impact on Public Health Officials, March 2020‒January 2021. Am J Public Health. 2022 May;112(5):736-746. doi: 10.2105/AJPH.2021.306649. Epub 2022 Mar 17. PMID: 35298237; PMCID: PMC9010912.

 10:  Royster J, Meyer JA, Cunningham MC, Hall K, Patel K, McCall TC, Alford AA. Local public health under threat: Harassment faced by local health department leaders during the COVID-19 pandemic. Public Health Pract (Oxf). 2024 Jan 24;7:100468. doi: 10.1016/j.puhip.2024.100468. PMID: 38328527; PMCID: PMC10847788.

 

The Consolations of the Forest – Alone In A Cabin on the Siberian Taiga

 

I thought I would review a book sent to me by a friend who I emailed about the concept of suffering. At issue was whether suffering was useful or not. That issue was used as a social media cudgel against psychiatrists – specifically that psychiatrists are trained to alleviate suffering but if they did not people would benefit from it instead. That is obviously an overly simplistic argument by a person who does not know very much about psychiatric practice.  I don’t want to get too far afield from the actual book.

The author is Sylvain Tesson who is generally described as a world adventurer who writes about those adventures. He wrote this book over the course of 6 months living in relative isolation on the shores of Lake Baikal in Siberia when he was 39 years old.  He is currently 51.

Lake Baikal is in the Southern region of Siberia and it is the world’s oldest and deepest freshwater lake. Irkutsk – the 25^th largest city in Russia in on the main outflow river from the lake – the Angara River about 45 miles from the lake. Irkutsk has a population of about 600,000 people and is probably best known to people of my generation from the board game Risk where it is a separate region rather than a city.  After reading the book I did research Tesson’s academic background and he has a degree in geopolitics. He is obviously well read and provides many of those references in the text.

Tesson’s previous exposure to Lake Baikal led to his interest in a more prolonged stay at a rough time of the year.  He documents what occurred along with his associations in diary form beginning on February 14 when he arrives on the lakeshore and ending on July 28 as a boat sent to pick him up is coming in from the horizon. He describes his motivation for this adventure in the introductory chapter. The climate in that area is temperate and comparable to Canada and the upper Midwestern states in the US.  He stayed during winter and spring and temperature ranges from -20 F to above freezing. He did this with the intention that living as a hermit would lead to desired changes – while documenting the day-to-day effects of the climate, changes in the ecosystem, occasional social contacts, his hiking and outdoor adventures, and the necessary work to maintain himself. It is presented mostly as a document of what he experienced and the associations (both autobiographical and literary) that he has with those experiences. At no point was this an argument that we can all be saved by living the life of a hermit.  It is more of a document about a part of that experience and what others have said about it.

He was well supplied for this adventure including 6 months of food and solar panels for recharging batteries and a satellite phone. Despite the relative isolation he describes plenty of traffic on both the frozen and thawed lake providing visitors and, in some cases, additional supplies. There was abundant wild life but he did not have a firearm apart from a flare gun for scaring off bears. His main protein source was fish from the lake.  He did not hunt any mammals or birds.  He had 67 books that were compromised mainly of humanities titles, but also some fiction and descriptions of surviving winter in Siberia. 

He described high levels of activity across terrain elevations and temperature ranges.  Much of the terrain was difficult to navigate because of the presence of underbrush, deep snow, and dwarf pines.  Tesson was undeterred by temperatures in the – 27F range.  He makes detailed observations and descriptions of the nature and scenery.  On some days he is trekking 10 miles to get to a fishing site, on others he is going 80 miles on a 6-day round trip.  He acknowledges that his levels of physical exertion and the resulting pain and exhaustion are high at times.     

What is it about hermitism that is life changing?  Tesson believes it is silence against a background of the splendor of nature existing forever in an idyllic setting. One of his last observations:

“It is good to know that out there in a forest in the world there is a cabin where something is possible, something fairly close to the sheer happiness of being alive.” (p. 232).

It seems apparent that he knew this all along and had to prove it to himself.  Full circle back to the theme of suffering.  Tesson suffered but that he tolerated it to attain a goal. At any point he could have called the nearest neighbor, called it off, and gone home.  The suffering is over at that point.  That is no equivalent to the suffering that accompanies medical problems that can seem random and senseless.  In many cases – people are expected to expend energy and tolerate suffering not toward any higher goal or advantage but because there are no effective treatments or they can’t access them.  It is also not the same as acute and unpredictable stress like an accident or natural catastrophe.

Despite seeing his hermitage as transformative he is circumspect about the experience.  He quotes Aldo Leopold that “hermitism is elitism”.  It is not a solution to the ecological problems of modern-day life because any mass exodus to the wild would destroy the forests. In fact he talks about how some of that had been done.

There is no description of the potential limitations of hermit life.  As a physician – medical emergencies and access to care is at the top of that list. To an extent that is age dependent but even a healthy 30-year-old can come down with acute appendicitis or break a bone.  He is very conscious about dying of exposure and guards against that.

In writing about the advantages – he does not consider alternatives.  For example, I was born and raised on the shore of one of the largest freshwater lakes in the world and could experience much of what Tesson experiences by walking 6 blocks to the lake.  There were no bears but plenty of fishing, ice transitions, and winter sports every year.  And all of that occurred in a town of 8,000 people and homes full of modern conveniences.  The largest close city was Duluth about 70 miles away with a population of 100,000.

A secondary observation is that the hermit in the woods is a more honorable position to be in because there is a smaller carbon footprint.  The hermit only uses the resources they need and does not squander energy or material goods.

One of the thought experiments prompted by Tesson’s hermetism is the characteristics of a transformative environment.  Each of us can probably think back to several of the environments in our life and not have to think too much about the impact it had on us.  Taking the histories of thousands of people illustrates how varied those environments are and how varied the responses can be to environments that are qualitatively similar. I spent a week hiking through Glacier National Park with a friend of mine when I was in my 20s. The scenery was magnificent and it was rigorous hiking at altitude (5393 ft). It was also populated by grizzly bears and you could always see them at a distance. There were bear warnings every day and we took them seriously. My friend thought I was too serious about it until we encountered a ranger in a fern filled valley loudly banging a shovel and his hard hat together to “warn the bears”. The effect it had on me was “great place to visit but I don’t want to live there.”

As a physician – the training and work environments are striking. Medical school was probably the most.  Going from the lecture hall to seeing people dying in front of you to being responsible for preventing those deaths probably had the most impact on me than anything. That is probably the closest I can come to an environment that Tesson describes as “changed myself completely.”  It was my equivalent of the Russian taiga.

It also raises the question of what is suffering and these days – what is trauma? There are a lot of variables. One of the critical dimensions seems to be voluntariness – whether people choose to suffer or not.  If they do – is there enough information ahead of time for true consent?  In this context – there is knowledge about what to expect and probably some experience in tolerating the environment. The example I am most familiar with is athletes where painful effort is required and career ending injuries are always possible. Tesson’s hermetism seems to fit this model compared with unexpected serious illness or injury.  The latter can also be life changing in unpredictable ways but it is not possible to predict whether the individual would consider the event a net positive or negative.

A second consideration is what increases our tolerance or in the more popular vernacular - resilience to the stress. In Tesson’s case he seems to attribute much to solace, silence, freedom, and the beauty of nature as a counterpoint to the noise, artificiality, regimentation, and excesses of modern life.  There are Darwinian considerations that he does not cover – primarily that many people in populations everywhere could not survive in such an environment.

Thirdly, people often view trying times much more positively in retrospect. I think back to another experience in my 20s – climbing Mt. Kenya with a coworker and friend. We were both habituated to 5,000 feet and ran regularly at that altitude. I have a single grainy photo of me climbing the scree at about 12,000 feet. We were poorly prepared and knew very little about mountaineering. The first night we stayed in a hut at about 10,000 feet and I had altitude sickness. That night hyraxes – small rodent like mammals weighing 4-10 pounds scurried about the hut running over us as we tried to sleep. I was able to recover the next day and continue the ascent but at the time it was a miserable experience and I could not wait to get off that mountain.  I recalled a quote from Pirsig that Zen happens in the valleys and not on the mountaintops.  In retrospect – I really like that old picture.  But at the time I was not sure I was going to make it.

Tesson’s literary and social observations are as interesting as his social and ecological ones.  I was interested in his take on DH Lawrence’ Lady Chatterley’s Lover. I have not read the book since college. It was widely considered to be an advance in explicit sexuality and was high controversial in the early 20^th century.  It was banned as obscenity in several countries including the US. Some opinions focused more on sexual life as being part of the larger life picture.  Tesson describes it more of a “requiem for wounded nature.”  He focuses on the effect of mining and the industrial revolution on the landscape and how the main protagonist describes the adverse effects on the environment and the human spirit. (p.89).

Boredom was always an interesting topic to me as a psychiatrist. No matter where I am it seems to be a completely alien feeling. I can’t recall ever being bored. Tesson comments that he was warned that boredom might not only get the best of him in solitude but that boredom can kill. (p. 79).  He did not take the warning seriously.  He discusses why the solitary man must be a virtuous man.  He describes a “double penance”  that can occur and quotes Rosseau: “The civil man desires the approval of others, the solitary man must of necessity be content with himself, or his life is unbearable. And so, the latter is forced to be virtuous.”  The double penance occurs at both levels.  Contemporary theory just focusing on the cognitive aspects of boredom suggest that spontaneous thought is a factor and, in that department, Tesson never seem to be lacking.

Should you read this book?  If you have read any of my past book reviews, I try to make things as conditional as possible. I recently read a paper on how many people read books after they graduate from high school or college.  It is a surprisingly low percentage and the same survey looked at how many people read assigned texts in college and that percentage was far below expected. This book is logistically straightforward to read. It is arranged in diary form. Some days are described in a paragraph and the more detailed days takes several pages. It can be read by dates or months. It is a unique book that ties in life in the wilderness with literary references.  Some of the books referenced you may have read.  The others are interesting enough to investigate. Following Tesson’s lead – I like the idea that there are people living successfully in the Russian taiga and that he wrote about his adventure and philosophy.  It is good to know how one man experienced personal growth and the sheer happiness of being alive in such a setting.

George Dawson, MD, DFAPA

 

Supplemental:  I also want to credit the translator of this book from French – Linda Coverdale, PhD. There is a 7-page addendum - Translators Notes – that adds significant details about geology and the history of the area as well as literary references.

 

Reference:

1:  Tesson S.  The Consolations of the Forest – Alone In A Cabin on the Siberian Taiga.  Rizzoli International Publications, Inc. New York; 2014.

The Joy of Basketball – And What Is Humanly Possible…..

 

In addition to the clinical work – psychiatrists need to have their finger on the pulse of popular culture.  Not just the content – but the process of it all.  How else can you talk with a young patient who is describing their experience of a rock and roll lyric and what it means for their life?  Or patients who are caught up in the latest cultural movements – whether they are useful or not.  Sports of course are a big part of the culture and in the last few months there has been no bigger sports phenomenon than Caitlin Clark of the Iowa Hawkeyes basketball team.  As I type this – she and her teammates are scheduled to appear in the NCAA Women’s Basketball Championship tomorrow afternoon. 

If you are just catching up that is a small part of the story. The statistics leading up to this game are readily available elsewhere and I will just mention a few highpoints without specific numbers.  Clark is the all-time leading scorer for men and women who have played NCAA basketball. The Iowa team has set both live attendance records and records for television viewers - as the most watched basketball game in the history of ESPN and the second most watched non-football event on that network. With that demand the tickets prices for games have also increased greatly sparking new enthusiasm for the viability of women’s sports at all levels. 

What is it about this player and her team that have cause all this excitement? I preface this by saying that I am not a big basketball fan.  I played it in intramural sports and for two years I was one of the statisticians for my high school team.  I have never followed any team consistently but have usually seen the US Olympic teams and a lot of clips of the great players from the NBA. NBA players clearly have a high degree of athleticism and much greater than usual height and physical stature. I recently learned that if you are over 7 feet tall - one person in 6 plays in the NBA.  My maximum height as an adult was 5’10”.  At that height only 0.117% of men play in the NBA.  Currently only 2 of 560 total players in the NBA are 5’9” or less.

The average height in NCAA women’s basketball is quoted between 5’8” and 6’1” by various sources although there are some very tall players ranging from 6’5” to 6’7”.  Caitlin Clark is 6’0” and the team range in height is 5’9” to 6’2”.  Watching Iowa and their closely matched competitors play – physical size fades into the background.  They obviously have the form and the skillset of accomplished basketball players.  I watched NBA star Steph Curry comment on Clark that she is more than just a shooter – she has an excellent ground game.  Seeing clips from her high school games – she had it back then.

There will be the invariable comparisons between men and women.  About how Clark could “never play in the NBA.”  That misses a huge point – there are highly accomplished woman athletes that are every bit as skilled as men.  As an observer of mostly individual sports – it doesn’t take much critical ability to realize that you will never be able to skate like Bonnie Blair, or ski like Lindsey Vonn, or play tennis like Serena Williams, or swim as fast as Katie Ledecky.  More than that you can learn something from watching them.  As a speedskater – I read everything I could find that was written by Bonnie Blair on training. I had the same thoughts about Caitlin Clark describing her jump shot and the left hand component consisting of a thumb flick maneuver.  If you watch her videos, it is so fast it is barely noticeable.  Even as an old man I want to try it. I can imagine that there are boys out there thinking the same thing and wanting to learn how to handle the ball like her.  Like everything else in the world – whether academics or sports – women add greatly to it and that recognition needs to be automatic rather than qualified. People should not give it a second thought.  It is not a “battle of the sexes” and it never has been.

The greats in any field are more than just technically competent.  They set a bar that encourages everyone else.  People start thinking: "That is not something I can do – but I am going to try it." Clark, her coach, and her teammates all consistently say this in post-game press conferences.  There is the realization that an inspirational teammate makes everybody better and that the team is more than just one person no matter how good they are.

What about the average person who has no sporting aspirations? There is a team loyalty factor.  But beyond that – it is inspirational from the standpoint of being a member of the human race. To watch someone accomplish something that nobody has done or done as well before.  Back in the early days of this blog – I posted a link to a video clip that I thought was a good explanation. It involves seeing someone perform so well that it feels uplifting. I get that feeling watching Caitlin Clark ball handling and shooting from well outside of the 3 point line.

The current state of women’s collegiate basketball as well as the abundance of great women athletes is also a reminder that 40 to 50 years ago things were not this good. They were not even close.  I was a high school athlete at that time. Most women’s basketball teams were intramural. Almost all of the high school resources were focused on boy’s football, hockey, basketball, wrestling, and baseball.  In 1972, two female high school athletes who were highly competitive in tennis, running, and cross-country skiing sued to be able to compete in those programs at their high schools. Since there were no programs available for girls – they sued to participate in the boys’ program.  Judge Miles Lord in a landmark ruling (1) concluded that they should be allowed to compete in those programs and compete with boys because discrimination in sports programs solely based on sex was a violation of the 14^th Amendment. He was backed up in appeal by the Eighth Circuit Court of Appeals (2). This ruling led to the development of far more resources for girls’ and women’s’ athletic programs than were previously possible. This ruling illustrates that when given the resources it leads to the development of the expected high caliber of competition and athletes. 

Are there any downsides to these developments?  I do not see any.  As a physician I have seen women athletes with significant and disabling injuries from both contact and non-contact sports.  Anyone watching the current basketball competition realizes that contact and injury can occur even during a game that is considered a non-contact sport. Judge Lord initially emphasized the availability of non-contact sports but today the question comes down to whether girls and women should be able to choose to risk injury by participating in the same way that boys and men do.  I cannot think of a reason why they should not have that freedom of choice. 

There has been criticism for trash talking, posturing on the court, and the usual differences of opinion about what players say in post-game press conferences. I have not seen any behavior to the level of what men's teams have been doing for decades.

I wish Caitlin Clark and all her teammates a great game tomorrow. I have the same wish for their opponents.  If I tune in and sit back to watch great basketball – I will be thinking:  “This is what happens when women have the chance to develop and compete in any field.” 

I am glad I lived to see it….

 

George Dawson, MD, DFAPA

NCAA Woman’s Basketball Postscript -

I watched the last half of the game yesterday. I am not a basketball analyst so I will not give my impressions of what happened.  It is likely if you are reading this that you have heard numerous opinions about this from friends, family, and coworkers. I first noted detailed post-game analyses at the hospital where I used to work. Every day after rounds I would take a break and walk down to the coffee shop for my usual tea or mocha. If it was a Monday – it was a safe bet that I would hear a detailed analysis of the Sunday football game by staff members of multiple disciplines. In some cases, it would involve criticism of the coaching staff, suggestions about who should be drafted, and of course criticism of players.

The post-game comments of the coaches and players of the South Carolina-Iowa game had none of that.  In fact, some of the commentary was the most enlightened commentary about organized team sports that I have seen anywhere. And it was all presented matter-of-fact – no gnashing of teeth or excessive self-criticism and sadness.  Several themes were apparent.

First, the importance of the coaches both on and off the court. Both sets of players emphasized good relationships with the coaches.  They were described as maternal figures and women who had done a lot for the game of basketball.  Both coaches in their Q&A emphasized their interest in growing the game and making sure their players got a lot of out the game besides winning. They emphasized developing a culture where the players know what to say to players, where everyone feels supported and in the case of Coach Staley – where there is extended family involvement. She emphasized recruiting players who had respect for their parents, how those parents had access to the coaching staff, and how both were focused on players succeeding.

Second, confidence at the player level was an important point. The coaches and players talked about it  - how it is instilled and how it develops. It was described as a significant factor is being able to compete irrespective of statistics and related concerns.  Coach Bluder pointed out how Clark came in to their program confident that they could get into the Final Four and despite the naysayers was able to convince everyone that she was correct. 

Third, respect was a frequently used word.  Respect for coaches, teammates, opponents, and fans was an important part of the equation. Numerous examples were given at all levels including previous players who advanced women’s basketball.

Finally, there was an overall plan and formula. This was probably best elaborated by coach Staley who emphasized that the staff who worked with her in implementing these plans were extremely important in the overall success of the team.   

 All things considered NCAA woman’s basketball is an impressive sport no matter what way you analyze it.  Women clearly know how to play basketball.  They know how to win and they know how to lose.  They know exactly where basketball is in the scheme of things.

We can all learn a valuable lesson from that…

 

George Dawson, MD, DFAPA 

 

References:

South Carolina National Championship Postgame Press Conference - 2024 NCAA Tournament  https://www.youtube.com/watch?v=tULkNrlqkI8

Iowa National Championship Postgame Press Conference - 2024 NCAA Tournament  https://www.youtube.com/watch?v=NE6rI8Dkcvw

 

References:

 1:  Judge Lord ordering a school district to allow high school girls to compete on boys' sports teams: Brenden v. Ind. School Dist. 742, 342 F.Supp 1224 (D. Minn. 1972).

The District Court,

“Miles W. Lord, J., held that where plaintiff high school girls wished to take part in interscholastic boys' athletics in tennis in one instance and in cross country and cross-country skiing in second instance and it was shown that plaintiffs could compete effectively on those teams and there were no alternative competitive programs sponsored by their schools which would provide an equal opportunity for competition for female plaintiffs, application of rule prohibiting girls from participating in boys' interscholastic athletic program as to plaintiffs was arbitrary and unreasonable, in violation of the equal protection clause of the Fourteenth Amendment, and application of rules as to plaintiffs could not stand.”

https://www.upress.umn.edu/book-division/images/other-images/equality-for-women-in-high-school-sports_1

 

2:  Eighth Circuit affirming Judge Lord: Brenden v. Ind. School Dist. 742, 477 F.2d 1292 (8th Cir. 1973).

“The Court of Appeals,· Heaney, Circuit · Judge, held that where · high schools attended by plaintiffs, two female students, provided teams for males in noncontact sports - of tennis. – and cross country skiing and running but did not provide such teams for females and where . plaintiffs were - qualified to compete with· boys in such sports, application  of rule -prohibiting females from participating in the boys' interscholastic athletic program as to plaintiffs was arbitrary and unreasonable and in violation of equal protection clause of Fourteenth Amendment. · Affirmed.”

https://www.upress.umn.edu/book-division/images/other-images/equality-for-women-in-high-school-sports_2

Graphics Credit:  Click directly on the photo for the Wikimedia Commons page.  Details from that page include:

John Mac, CC BY-SA 2.0 Caitlin Clark three-pointer (cropped).

Book Reviews on this Blog…..

 

 

Receiving a novel to review this morning reminded me that I should probably comment on that process.  I am very grateful to any authors, editors, or publishers who send papers, books, and book chapters my way.  I have a rigorous reading schedule – especially post-retirement.  Scientific papers are my top priority and I generally read 4 or 5 a day.  That number can go way up if I am working on a specific blog post that requires it.

I rarely read fiction but it all depends on what I am focused on.  For example, the question of suffering came up and I am fortunate to have brilliant friends who are not averse to considering these questions.  One of them sent me Sylvain Tesson’s The Consolations of the Forest – Alone In A Cabin on the Siberian Taiga.  I am halfway through that at this point. I have also read technical texts on rhetoric, philosophy, pollical science, anthropology, and history all in support of the blog.  I consider basic science texts like the medical school courses to all be relevant and will even reach back to my undergrad biology and chemistry majors for reading material. 

My preferred reading is what I consider to be detailed and hopefully innovative work in psychiatry.  To that end I would really like to see the following:

1:  A detailed text on the history of psychiatry.  Every current text that I have seen has major deficiencies.

2:  A detailed text on the evolution of psychiatric hypotheses about mental illnesses and why they never seem to be resolved.  The closest I have come to some answer to that question is from the work of theoretical physicist Sabine Hossenfelder and the idea that there are many mathematical hypotheses about the creation of the universe that seem sound but there are no observations available that can prove or disprove them.  She used the term borrowed from a colleague – ascientific to describe that phenomenon.  I think it is a much more accurate term than unscientific. 

3:  A detailed text on the information exchange between psychiatrists and patients. We talk and teach a lot about interviewing techniques but never address the details like: Is there an absolute minimum or maximum? And how can it be determined?

4:  A detailed text on biological complexity in medicine and psychiatry. Our literature is full of references to heterogeneity and suggestions about how to deal with it.  There is very little commentary about how this originates in the biological complexity of living organisms.  We study it from the basic science side but there is no consolidation with what we observe clinically.  At that point it becomes more of a political argument with suggestions that it needs to be controlled in some way or that there are better measures for it.

5:  A definitive text on clinical trials in psychiatry.  If you pick up texts on clinical trials in medicine you will rarely see a reference to psychiatry. I can read any number of clinical trials in the field and show how deficiencies or practicalities may have affected the results.  Psychiatry probably has more meta-analysis of clinical trials than any other specialty and yet the data has more deficiencies.

6:  The only philosophy that really interests me is Van Fraassen's work on empirically adequate models and how that applies to medicine and psychiatry.  It seems fairly clear to me that this is the way we are taught in college, medical school, and residency and yet there is surprisingly little commentary about it. Instead we see elaborate philosophical theories about psychiatry that typically illustrate that the author(s) either knows very little about psychiatrists or how they are trained or they have an entirely different agenda and need to attack the field to advance it.  

7:  Clinical trials with small effects do not interest me.  The same is true for meta-analyses of those trials and pilot studies.  I am much more interested in innovative analyses of that data or innovative designs.  I am interested in the gamut of diagnostic and therapeutic modalities as well as preclinical and basic science studies.  We are in need of better clinical trials technology and have been for at least 20 years. 

These are just a few of the priorities that I think about daily.  And I would happily read those texts or book chapters and review them.  In fact, if anyone at the American Psychiatric Press or Mayo Clinic reads this blog, I am looking forward to Keith Rasmussen’s Ketamine – The Story of Modern Psychiatry’s Most Fascinating Molecule especially the chapter Recreational Use of Ketamine: The World Discovers the K-Hole. Send me a copy and I will read and review it.

A few considerations for anyone interested.  My writing style is too dense at times and people editing my writing often suggest fewer words.  I must admit editing helps greatly. Unfortunately, I don’t have an editor apart from what happens in the word processor.  So you might have to deal with that in the final product. My preferred format is PDF, largely because I have no space left for books.  The picture above is a random half shelf sample from my library.  I have 36 full shelves and 16 half shelves in the room where I am typing this as well as an additional storage room in my basement full of books.  I can guarantee that no one else will see any PDF sent my way and have successfully restricted access to thousands of papers and drafts sent to me over the years.   

The content of this blog is open access and reusable.  According to the CC licensing it just requires crediting and referencing me. I do not make any money on this blog and there are never any charges. Any book or chapter review done could be copied and pasted to any online site and I would be happy to post it on Amazon myself.

I am currently the co-editor of a small newsletter and do not want any additional editorial work.  I also do not seek any peer review positions for journals largely because that experience for me has not been a good one.

Consider this post a hopeful clarification. If you are thinking about sending me the final version of a book, book chapter, or paper and need additional information – feel free to email me with questions before sending anything.

 

George Dawson, MD, DFAPA

Free Associating in the MRI Scanner…

 

I finished my second MRI scan this year earlier this afternoon. So far lifetime – I have had 5 and will have 6 by the end of next month.  I am sure that many people reading this have had the experience and I would not rate it as pleasant at all.  Just the obsessive checklist that must be completed prior to the scan is enough to raise the anxiety level. Is my body free of implanted or tattooed or accidentally placed metals?  When they were scanning my pancreas – my first thought was: “What about that laparoscopic cholecystectomy I had done in 2019?”  I had read the operative report and it described two permanent clips being placed on the cystic duct prior to dividing it and removing the gallbladder.  I contacted the surgeon about that and he was certain the clips were not ferromagnetic.

One of the last questions is: “Are you claustrophobic?”  And if you are is your primary care doctor prescribing a sedative and if you take that sedative is there somebody here who can drive you home?” I would be hard pressed to think of many people who would not be claustrophobic in an MRI tube.  After all you are in a tight space with very loud noises for a prolonged period. As the radio frequency waves are generated the tube heats up.  It is better than hurtling through space in a larger tube during air travel – and I smiled to myself as I thought of the comparison.

In all cases I have been given a headset and asked about musical preferences and volume.  So far, the headsets don’t block the sound of the machine and obviously are not noise cancellation devices. It did lead me to think about designing headsets without ferromagnetic materials and what that might involve. The only designs I have seen so far use air conduction through tubes rather than electrical connections.

Music selection is as much of a problem as the low-fi headset.  I forgot to ask if I could use my own playlist – but it was safely locked up far away from the 1.5T magnet. I tried to be more specific this time: “Have you got any Canned Heat?”  My most recent play list starts with 3 Canned Heat songs from 1967 – but looking at the tech I estimated he was born in 1980 and the other in the 1990s.  When they rolled me out of the tube one had been replaced by a woman with brightly colored hair who may have been born in the 21^st century.  I changed my answer to “Classic rock.”  That can be a disappointing genre because too much of it is bubble gum music.  Over the 30 minutes in the tube, the heaviest it got was AC/DC Highway to Hell and James Gang Funk 49.  I did enjoy Steve Perry (Journey)  and was tempted to sing along like I do in the car.  But I am sure that would have not been a good idea and may have resulted in additional imaging time and I can no longer hit the high notes.

My mind wandered to fMRI research. How in the world can research subjects be expected to produce real world results from inside the catastrophic MRI world?  I decided not to include my real catastrophic thinking in this post because it is idiosyncratic and I don't want to affect anyone else's decision to get an MRI scan.  And today I just had one or two brief thoughts. I spend most of the time in the tube actively distracting myself and doing sigh breathing exercises to control my heart rate.  Today I opened my eyes in the tube – briefly for the first time.  All I could see was an expanse of whiteness in front of my face with a row of fasteners bisecting the field.  I was pleasantly surprised to find it was about 6 inches away – farther than I had imagined it.  

While I was thinking about research, I also thought about all of the MRI scans I had ordered on my patients.  Going through the procedure yourself leads to questions about the how it is presented to patients for informed consent. I was careful to describe the issues with confined space and noise as well as the advantage of no radiation and better resolution.  Being hospital based, I had the advantage of an anesthesia team being available to sedate and monitor patients who were unable to tolerate it. As I was showing one person their results by holding the film against a window in their room they fainted and I was able to catch them on the way down.  The realistic appearance of the brain in that scan led to that reaction.

Forty years ago, I was an intern in this hospital. My very first rotation was Internal Medicine.  Back in those days it was a county hospital.  Today it is a massive flagship hospital of one of the largest health care organizations in Minnesota. That included a building program to the tune of hundreds of millions of dollars. The original hospital remains at the center, but it is obscured by new wings and buildings. The parking lot I parked in did not exist at the time.  There was a lot out front that you accessed with a magnetic card.  One night I was working late and a guy approached me for money as I entered that lot. I handed him $20 to avoid what I thought might be coming. It was a tough neighborhood.

Once you enter the building – you can step back in time where old meets new.  One of those places is medical imaging. During internship and in the 22 years I worked there radiology (as we used to call it) was one of my favorite haunts. I knew the radiologists and knew I could ask them questions about films.  Surprisingly many of them had questions about psychiatry. Before the electronic health record, I would make a drawing of the positive findings from CT and MRI scans and redraw it in the patient’s chart.  As radiology became digitized it was easier to cut and past images.  I could still discuss images with the neuroradiologist.  I missed all of that when I left that practice.

The MRI tech comes over the headphones:  “OK we are going to come in and inject the contrast.”  They know I had a mild reaction to CT scan contrast but the MRI contrast is gadolinium based and I have had it before.  The last time they checked my pre and post creatinine levels, but at this facility that is replaced by questions about renal insufficiency and dialysis.  That seems like a low bar.  He checks in again in 5 minutes to make sure that I am not having a reaction.

Another sequence of radiofrequency waves starts and there is a pulsating beat that reminds me of a rock and roll song.  I try to recall the song just based on the beat.  I check my muscle tension and realize my shoulders are rolled forward – so I force myself to relax, move my neck, and do some patterned breathing. I would really like to hear some Nirvana at this point.

The tech is on the headphones again.  “OK you are doing great – 5 minutes left.”  That reminded me of a previous scan when I got a similar message and remembered all of the songs that played afterwards.  This time ZZ Top LaGrange comes on. It is a 4 minute song.  At the end – they roll me out of the tube and tell me I have done a great job.

Last night I was wondering whether I was getting progressively more anxious about MRI scans or whether this was a form of exposure therapy. I was surprisingly calm during this one and more confident that I will live to MRI another day.

 

George Dawson, MD, DFAPA

Supplementary:  I have received some early feedback on why I am getting these MRI scans. First and foremost - I am interested in addressing serious problems and preventing disability. I personally know many people who were disabled as the result of spinal injuries that occurred from seemingly trivial events like turning to see someone walking through the door or turning over in bed. I am also aware of age related injuries that occur in active people. Falling off your bike at age 70 is not the same as falling off your bike at age 30 or 40.  All of these scenarios suggest to me that numerous age-related changes in the spine in the absence of any course of effective strengthening can lead to catastrophic problems.   

In addition to the symptoms, I would like to get an opinion of whether it is safe to do aspects of my exercise routine.  I would really like to get back out on the ice speedskating - but I am not going to if it means I will get progressively disabled from spinal problems.  I saw Lindsey Vonn speak to this recently.  I am certainly not comparing myself directly to one of the greatest skiers of all time - but I could relate to why she finally decided to quit.  

“My body is broken beyond repair and it isn’t letting me have the final season I dreamed of,” Vonn said. “My body is screaming at me to STOP and it’s time for me to listen.”   

A lot of aging athletes like myself have the thought that as long as we exercise and stay very active - we will be able to continue in sports as long as we want.  In retrospect, I think I have shown that you can certainly push it much farther than expected and much farther than average - but like the best there is a breaking point. 

Without yet knowing the result of this scan - the possibilities are significant. In the ideal world, it will show age related changes and that would just indicate continuing the physical therapy that I have been doing for 20 years.  If a potential surgical problem shows up that is more complicated.  I do know skaters who have had back surgery and most back surgery has highly variable results. I have also observed and assisted on many back surgeries in medical school where neurosurgery was my preferred surgical rotation - but I assume surgical technique has improved greatly since then.  Would I get back surgery if there was a high likelihood of symptomatic relief and I could return to skating?  Would I get back surgery without that guarantee?  All of that is up in the air at this point. 

Image Credit:  Image credit and Creative Commons licensing can be obtained by clicking directly on the image at the top of this post.

Are Medication Trials For Depression Too Long In Duration?

Depression is a significant cause of disability in the world.  That is complicated by the fact that there are not enough resources to treat people with depression, access is rationed in many areas including the United States, there is a high rate of attrition during treatment, and depression is often associated with significant medical and neurological disability further restricting access to adequate care. 

Over the past 30 years, strategies for treating depression have increased considerably since antidepressants medications are not uniformly effective and they have side effects that may not be well tolerated.  Antidepressants have evolved over the years from monoamine oxidase inhibitors to tricyclic antidepressants to selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) and norepinephrine dopamine reuptake inhibitors (NDRI).  The suggested pharmacology of more modern antidepressants is even more complex and the initial classifications may mean a lot less than what was initially hypothesized.

Although antidepressant monotherapy is the preferred treatment path – failure of one or two rounds of antidepressants can result in combinations of augmenting agents designed to improve treatment response.  Early augmenting agents included triiodothyronine, thyroxine, and lithium.  More recent augmenting therapies include additional antidepressants (typically bupropion), aripiprazole or brexpiprazole, or buspirone.  There are several additional agents that are used in lower frequencies.  Context is important in considering the origins of the augmenting therapies. When thyroid hormones were added, there was an active research focus on neuroendocrinology including the impact of physical illnesses on thyroid function. Later focus on treatment resistant depression assumed that all depression was treatable - it was just a question of finding the correct treatment. Both hypotheses have had low yields. 

The relative advantage of these approaches is that they are potentially cost effective (most antidepressant medications are generic and prescribed by non-psychiatrists), they are readily available, and they are more culturally accepted than they used to be.  The disadvantages include side effects most commonly nausea, vomiting, diarrhea, sexual side effects, and dry mouth. Patients need close monitoring initially to prevent side effects and assure that the medication is working. The physicians doing that monitoring also have to be aware of rare serious side effects that require emergency treatment – like serotonin syndrome, neuroleptic malignant syndrome, and acute neurological side effects.  A good knowledge of general medicine is also required to avoid treating people with chronic illnesses where there are contraindications. 

Another disadvantage is treatment non-response.  What happens if two different prescriptions are tried for adequate amounts of time and there is no response. Where does the treating physician go from there?  Seeing thousands of patients well into a course of treatment for depression and/or anxiety this is a very common problem – often complicated by additional problems including insomnia and substance use disorder.

Before anyone suggests addition exercise or psychotherapy at that point – practically all patients seeing psychiatrists have already done that.  Most of the people I treated had seen more than one therapist and these days they are branded therapists (CBT, DBT, IPT, etc).  The only non-pharmacological modality that was rarely used was bright light therapy and I typically discussed that as an add on to antidepressants. That therapy requires purchasing a device and using it for set periods of time each day. 

For the people with severe treatment resistant depression, more complicated interventions including electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), and ketamine (intranasal, IV, IM) are on the horizon but difficult to find in one place.  As an acute care psychiatrist, I had very easy access to ECT.  As an outpatient psychiatrist there was essentially no access, even when I called the facility where I previously worked. Because of the current systems problems, my patients needing ECT had better access if they presented to emergency departments where they knew ECT was an option and got admitted to that hospital. The same barriers seemed to preclude any contact with me as an outpatient psychiatrist.  No calls for a collegial discussion and in many cases no discharge records from the treating facility.  Siloed care these days is a major impediment to care.

Last weekend, I was exposed to a modern approach that concentrated all the advanced treatment modalities in the same clinic that happened to be staffed by researchers interested in treatment resistant depression. Before I get to their approach – I designed the slide at the top of this post to illustrate the standard approach to moderate to severe depression over the course of my career starting in 1984.  I remind readers that psychiatrists are seeing a highly selected group of patients who have probably already failed several antidepressants and psychotherapies.  As time goes by and the number of non-psychiatric prescribers continues to increase greatly – that selection process will greatly intensify.

Looking at the general scheme of antidepressant approaches to only depressive disorders (DSM major depression and persistent depressive disorder) – there has been a clear progression of newer medications designated by older class names like tricyclic antidepressants (TCA), selective serotonin reuptake inhibitors (SSRI), serotonin norepinephrine reuptake inhibitors (SNRI), and monoamine oxidase inhibitors (MAOI). These general class names have significant limitations – not the least of which being reuptake blockade by of specific transporters is probably only part of the mechanism of action and some class designations depend more on chemical structure than physiology. If anyone would like a second explanatory slide with all of the current FDA approved antidepressants and more modern nomenclatures – let me know and I will make the slide.

In treating significant depressions – psychiatry added adequate dosing and duration and therapeutic drug monitoring (TDM) to determine adequate trials of antidepressants therapy.  There were active debates and research suggesting 6 weeks might be adequate on the lower end and 16 weeks as adequate duration on the high end. Pharmacokinetic factors came into play with some antidepressants with longer or shorter half-lives. If an adequate trial of medication was completed there was the question of “What’s next?”  The next issue was either changing the antidepressant or adding an augmenting therapy (adjunctive therapy per the FDA).   As noted in the graphic thyroid hormones (Triiodothyronine or T3 and tetraiodothyronine or T4/thyroxine) were both used early on in doses that were typically much lower than physiological doses (25 – 50 mcg) as well as stimulant medications (amphetamines). As time went by additional adjunctive strategies were added.  The first study of adding lithium to tricyclic antidepressants occurred in 1981 (1).  Adjunctive medications started to take off in the early part of the century with pharmaceutical companies getting that indication for newer antipsychotic medications that also had bipolar disorder indications (see specific dates of approval).   

The upside to these strategies was that antidepressant effects could be improved often to the point that depression remitted. The potential downsides were twofold – the burden of taking a second medication that could introduce new side effects or synergistic side effects with the current therapy and the prospect of endless medication trials.  Now there was the additional time of seeing whether any of several adjunctive therapies worked in addition to the antidepressant monotherapy trials. Although I did not indicate it on the diagram – several antidepressant combinations were also suggested and some patients were taking 3 or 4 antidepressants at once.  That was a significant departure from quality metrics used in the late 20^th century where antidepressant monotherapy was the rule.

The concept of treatment resistant depression – generally defined as a failure of a specified course of pharmacotherapy was often stimulus for these trials. The application in clinical practice was not as clearcut because of the number of choices and how individual patient factors affected those choices. Acuity, disability, and access were the usual limiting factors leading to cessation of pharmacotherapy trials and a trial of neurostimulation like electroconvulsive therapy (ECT).

Last week, I saw a unique solution to this bottleneck problem presented by C. Sophia Albott, MD, MA entitled  “Next Generation Treatments for Resistant Depression: The UMN Interventional Psychiatry Approach.”  She described a well-staffed clinic with a stimulating practice environment that offered ECT, transcranial magnetic stimulation (TMS), ketamine (intranasal, IM, and IV), Vagal Nerve Stimulation (VNS), and Behavioral Activation Therapy provided to all the patients in their clinic.  Their general hierarchy was to start with TMS and if that was not effective to branch out into other specific therapies. The overall description of the clinic and some of their early successes suggests to me that this is potentially a good approach.  The idea of these therapies all being concentrated in one place, taking over treatment of the patient until they are in remission, and additional support is what is lacking in most systems of care.

I am sure that some would wax philosophical about similar clinics being the future of the field – but there still needs to be psychiatrists out in the community providing acute care and consultation to primary care physicians. A subspeciality clinic could function well as back-up those psychiatrists who often lack a referral resource for neuromodulation and other advanced techniques.  The largest potential benefit would be to patients who are being maintained in long term medication trials longer than they should be. This approach may be the best way to shorten the period of disability and suffering from difficult to treat depression as well as the adverse effects of polypharmacy.

George Dawson, MD, DFAPA

 

References:

1:  Dé Montigny C, Grunberg F, Mayer A, Deschenes JP. Lithium induces rapid relief of depression in tricyclic antidepressant drug non-responders. Br J Psychiatry. 1981 Mar;138:252-6. doi: 10.1192/bjp.138.3.252. PMID: 7272619.

2:  Trivedi MH, Rush AJ, Crismon ML, et al. Clinical Results for Patients With Major Depressive Disorder in the Texas Medication Algorithm Project. Arch Gen Psychiatry. 2004;61(7):669–680. doi:10.1001/archpsyc.61.7.669

3:  Sonmez AI, Wilson S, Olsen S, Sullivan C, Herman A, Widge A, Nahas Z, Albott CS. Outcomes from University of Minnesota Clinical rTMS Clinic for resistant depression: naturalistic data on suicidal ideation. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation. 2021 Nov 1;14(6):1652.

4:  Papakostas, G.I., Trivedi, M.H., Shelton, R.C. et al. Comparative effectiveness research trial for antidepressant incomplete and non-responders with treatment resistant depression (ASCERTAIN-TRD) a randomized clinical trial. Mol Psychiatry (2024). https://doi.org/10.1038/s41380-024-02468-x

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