UpToDate and the Rx Transitions in Mental Health

 

For the nonphysicians reading this UpToDate is a comprehensive online resource for physicians that has essentially replaced internal medicine texts. Before it existed, most physicians who practiced adult clinical medicine could purchase a new internal medicine text every 4 or 5 years for $200-300. UpToDate (UTD) requires an annual subscription that is roughly double that cost. Many large groups of physicians provide access to their medical staff free of charge. In my last years of practice, I had an out-of-pocket subscription but I let it lapse 2 years ago. I renewed it just last week.

My rationale for the subscription comes down to several factors.  First, I need access to the best current information on complex diseases and their treatment.  The counterargument is that you can access it online – but that information is often not balanced or realistic.  UTD is carefully edited by experts in the field who often comment on what they do in their clinics.  There are several levels of editing.  Second, continuing medical education credit is available just from studying what you are interested in.  I can do a deep dive into a subject on UTD and end up with several hours of CME credit that is necessary for licensing.  The free CME credit I can access is often low in quality and requires too much time – like needing to watch an hour-long video to get 1 hour of CME credit. I really have a hard time understanding why anyone would watch or listen to a program when reading is much faster.  The only useful exception is listening while driving.  Third, there is a drug interaction program.  After extensively researching hundreds of polypharmacy combinations – I still like running those analyses.  Fourth, researching my own medical problems.  A colleague pointed out that was one of the main reasons he subscribes.  In today’s world of brief medical appointments, it is good to have some expert backup.  And if any medication is suggested I always do my own drug interaction checks and do not assume the prescribing physician or pharmacists has.  I have suggested modifications of prescriptions to my physicians on that basis.  Fifth, as a reference for my blog.  UTD references are in many of my posts.

When I renewed this time there was an option for Rx Transitions in Mental Health.  I have positively mentioned UTD in the past as a source for physicians on antidepressant tapering and transitions.  Any experienced psychiatrist has done hundreds of these transitions or tapers.  The original UTD chapters were written by senior psychopharmacology experts and they were approaches I had used many times in the past.  It was also a reminder that contrary to some recent discussions about antidepressant withdrawal – psychiatrists have been aware of these issues and have addressed them for decades.

The Rx Transitions interface is sparse. It is explicit about the intent: “to provide clinicians with information about switching antidepressant medications”.   There is a column on the left of antidepressant to be stopped SSRIs (citalopram, escitalopram, fluoxetine, sertraline), SNRIs (duloxetine venlafaxine ER) and DNRIs (bupropion ER).  After selecting the drug and the dose – a drop-down menu appears with a brief list of important information including a link to the drug interaction program.  A more expanded list of antidepressants being started pops up that includes paroxetine, milnacipran and levomilnacipran, mirtazapine, vortioxetine, and vilazodone.  Once that is checked three different schedules are provided for an immediate, rapid or standard switch.  That roughly translates to switches on day 1, week 1 or week 2 respectively.  Several paragraphs of additional information are shown and the entire summary can be printed.

I have included a graphic at the top of this post to illustrate the possible transitions. The possibilities are illustrated for the starting prescription of citalopram and ending the transition with any of the 12 antidepressants on the right side of the diagram.  That is 12 possible transitions x 3 starting doses or 36 possible transitions. If we made similar connections for all the drug and dosages on the left side of the diagram there would be a total of 346.  All would ask about immediate, rapid, or standard switches and all would show additional information about the switch is subsequent windows.

The question is whether this add on would be useful for you in your clinical practice. The first consideration is that UTD has had sections about how to do this in the main resource for years.  They are written by expert psychopharmacologists.  When I have looked at them as a reference, they back up what experienced psychiatrists do in practice.  Secondly, do you treat much depression and should you?  There has been movement in the past 20 years to suggest that antidepressant prescribing should be a function in primary care.  Both the America College of Physicians (ACP) and the American Academy of Family Physicians (AAFP) have guidelines about this.  Collaborative care models have been suggested but many if not most primary care MDs have inadequate psychiatric back up. Context is very important since I doubt that getting a prescription in a primary care clinic is the same as seeing a psychiatrist. As an example – if I am discussing an antidepressant transition, I have asked that patient if they have ever stopped the medication and if they have ever had withdrawal symptoms. Some primary care physicians tell me they see minimal withdrawal symptoms because people tend to just stop the medication if they get side effects.  In that case starting a new medication is starting from scratch.

In psychiatric practice it is common to see people on the max doses of antidepressant monotherapy or polypharmacy.  In those cases, I would typically see people much more often until I was sure they had made the transition without side effects or withdrawal.  That might include initial tapering and close monitoring of depressive symptoms.  A final variable is whether the person can be counted upon to self-monitor.  I always told my patients to call me at the earliest sign of a side effect and further that I did not ever expect they would get used to side effects.  That did not prevent many from not reporting side effects until they came in for the follow up visit.  That is another reason for scheduling close follow up during these transitions.

Rx Transitions in Mental Health may be useful for physicians who have not had a lot of experience making these transitions.  It is an outline for what is possible in both the time domain and end results based on the list of medications that are used.  I think the choices could be further simplified.  For example, I do not see the utility for transitioning to paroxetine – an antidepressant with the highest withdrawal and drug interaction risk from any other medication in the diagram.  Similarly, I do not see the utility in including both citalopram and escitalopram as antidepressants to transition to, especially now that they are both generic drugs. Escitalopram is preferred because it has a lower effective dosage and better side effect profile. Using this program assumes a knowledge of antidepressants in general.  There are still many prescribed for other indications like sleep, headaches, and chronic pain.  Depression specialty clinics still prescribe tricyclic antidepressants and monoamine oxidase inhibitors that require special considerations.  There are also augmenting therapies (aripiprazole brexpiprazole, buspirone) that factor into the transitions. For the basic cases listed and with all the qualifications posted in the software – many will find the suggestions useful.

An easy thought experiment is possible to assist in the decision to get Rx Transitions.  Just look at the above diagram and think about each transition listed.  If you have done it many times before without any complications and are aware of all the considerations and precautions - you probably don't need it.  

The written chapter in UpToDate (2) is more comprehensive than the antidepressant switching tool.  It discusses concepts like antidepressant equivalent doses, pharmacokinetics, antidepressant withdrawal/discontinuation, and has links to specific classes of antidepressants, general approaches to treating depression, and treatment resistant depression.   Even at that level – psychiatric training should provide the clinical psychiatrist with what they need.  If you are a psychiatrist, I would encourage you to read this chapter first if you are considering subscribing to UTD for the psychiatric content only.  I hope that you know all this information cold including how to set up the medication transitions and monitor them.  As previously stated, there are many other reasons for psychiatrists to subscribe to UTD.

Primary care physicians will probably find this chapter to be very useful – especially if you have been nominated in your group to treat anxiety and depression.  I would recommend reading the chapter (2) first.  If your group provides access, they might also consider the switching tool but I would not consider it a necessity. If you have been using UTD for years you are probably aware of this chapter.     

 

George Dawson, MD, DFAPA      

 

Supplementary:

I have had UpToDate staff comment on this blog before.  If you are an UTD staff member please post a reference to the very first chapter on antidepressants transitions in UTD.  I think the original chapter was written by Ross J. Baldessarini, MD.  I would appreciate knowing how long that content has been in UTD.  

References:

1:  Rx Transitions for Mental Health: Antidepressant switching tool. In: UpToDate, Connor RF (Ed), Wolters Kluwer. (Accessed on October 2, 2025.)

2:  Hirsch N, Birnbaum RJ.  Switching antidepressant medications in adults.  In: UpToDate, Connor RF (Ed), Wolters Kluwer. (Accessed on October 2, 2025.)

Why Equal Opportunity for Women Is Not “Woke”

 

I encountered two media events in the last couple of days that I thought I would respond to.  The first was an interview of Dana White talking about why there is no such thing as toxic masculinity and that you can’t be too masculine.  The second was the Trump-Hegseth lecture to the commanders of the armed forces and how there would now be male performance standards and grooming standards for members of the armed forces that were consistent with the new warrior ethos. President Trump also made an irresponsible comment about nuclear weapons that I will only say was not strategic or realistic.  He seemed to imply that because we have more of these weapons and they are more modern we could intimidate other nuclear powers and win a war.  I hope that I have been clear on this blog that in even a limited nuclear war whether you are close to the explosions and fallout or not – all of humanity loses.  By loses I mean up to and including extinction of all humans.

As I was watching the Dana White clip my first thought was: “Toxic masculinity is watching two guys inflict brain damage on one another.”  I remember watching him comment early in his career about how people never get injured badly in these fights despite being knocked out by punches, kicks, and chokes. Fighters have died in boxing matches and mixed martial arts competition (MMA) but apparently not in White’s ultimate fighting championship (UFC) competitions.  Despite that distinction it is just not realistic to think there are not injuries from these sudden accelerations and decelerations to the brain in any combat sports.  All it takes is repetitive nonconcussive impacts (1).

Like most of these complex subjects – masculinity and femininity all depend on your definitions.  And in academics the definitions may come down to your field.  My initial attempt at trying to research it yielded a steady stream of papers from the fields of post modern philosophy and literature, gender studies, and English literature.  A Medline search was more productive but still vague. I narrowed it down from 19,266 references (masculinity) to 333 (masculinity AND definition) to 93 (masculinity AND definition AND review). Even then the results are sparse since they include many references to medical disorders that may be masculinizing or feminizing. 

The overall process or how we arrived at stereotype of masculine or feminine is rarely discussed.  It is usually just assumed that the universe of human traits, attributes, and behaviors segregate neatly into two categories based on biological sex. These stereotypes come into play in some assessments like the Minnesota Multiphasic Personality Inventory (MMPI).  Scale 5 on that assessment is the Masculinity-Femininity scale.  It contains subscales Mf2 Stereotypic Feminine Interests and MF3 Denial of Stereotypic Masculine Interests.  High scores on the MF2 scale indicate and interest in stereotypical occupational and pastime interests.  High score on the Mf3 scale indicate a denial of stereotypical masculine occupations and interests.  Examples of masculine occupations include a forest ranger or a building contractor). The examples of feminine occupations include librarian or nurse.  Some sources state this scale is not usually interpreted in current use and it was originally intended for use with occupational interest. From the examples given – many of us know men and women working in occupations in opposition to what used to be considered stereotypically masculine or feminine (eg. women park rangers and men nurses).

A relevant dimension that I have not seen investigated in any systematic way is how societal conventions have affected masculinity and femininity stereotypes.  In a patriarchal society, where women have less access to jobs that are dominated by men – it will appear that they chose work based on their preferences. The change in the distribution of men and women in the work environment has changed dramatically in the past 40 years. When I started in medical school there were specialties where women were actively discriminated against and their numbers were naturally low. In psychiatry – I have never worked in a department where there were fewer women than men.  That includes jobs where heavy physical work predominates. All things equal – women have demonstrated that they can perform as well in jobs that men do.  That includes professional sports.  In this previous post – I pointed out the landmark district court ruling that expanded women’s access to high school sports with the result being highly skilled professional sports teams.

This wholescale integration of women into all aspects of society has been overwhelmingly positive.  The obvious rational argument is that no society can afford to eliminate the intellectual, creative, and physical resource of half of their population without suffering.  The proof of that is in what has happened so far. More high caliber workers and researchers and overall a much more productive society.  If there has been a downside – I have missed it.  Feel free to let me know about it in the comments below.

There has been a predictable political reaction to the integration of women in the workplace. Forty years ago, the family model was the husband was the breadwinner and the wife was expected to be the homemaker.  If a woman dared to get hired into a predominately male workplace – they were criticized for taking a job from a man. Their choice was to brave that criticism or take a traditionally female job where compensation was less. There are social and political forces out there today that think that 40-year-old model was the best one.  They do not see women in the workplace as a tremendous asset, only a detriment.  That often extends to women not being seen as physical or intellectual equals or having the same basic problem as men needing to generate income for families.  The end result of that bias is a male-centric society operating on male gender stereotypes.    

Dated masculine-feminine stereotyping also works against men.  Here is an example.  Sam wants to bring one of his college professors home for a visit.  He lives in a scenic part of the state and his professor said he would like to see it.  He is concerned about how his professor will be perceived by his largely blue-collar family and friends.  He confides in another friend at college: “I am worried that my professor’s vocabulary, style, and articulation will not be accepted.  I am really worried they will think he is gay and he is not.”  This brief example points to common stereotypes used by subcultures and some of the associated problems.  In this case, the subculture demands that men exercise a very limited male stereotype and if they move too far outside of that they will be criticized or not tolerated.

Common criticism of the concept of toxic masculinity is that it is not well defined, it can be stigmatizing, and the outcomes of people who have it are not well studied.  Considering all the possible traits, attributes, and vocations it is easy to imagine that a sample of men with relatively homogeneous toxic masculinity might be difficult to find.

Some authors have attempted a definition.  Sanders, et al (3) use a dimensional approach across 5 categories: masculine superiority, domination and desire, gender rigidity, emotional restriction, and repressed suffering. The researchers came up with a 35-item scale consisting of statements that subjects disagreed or agreed with on a 5-point scale.  The entire scale is available at reference 2.  A few examples of the test statements:

6. People are attracted to men who dominate others

7. Muscles are indicators of masculinity

10. Men are superior to women

11. Gender and sex are the same thing

15. Men cheating on their partner is natural

 The only aggression noted in the scale is sexual aggression in the statement: “Men can’t rape women because consent isn’t a real thing.”  There are no statements about verbal or physical aggression. The authors conclude the scale has adequate psychometric properties but it appears form the references that it was not widely adopted. 

Rather than define toxic masculinity in terms of what it is – a better approach may be to define it in terms of what it is not. I suggest the following:

1:  Acceptance of women as equals in every possible way – entitled to the same rights, independence, and privileges as men in society.  I am sure that most people agree with this on paper – but in many applications this statement is still difficult to implement.

2:  Refusal to accept the stereotype that women and the physical appearance of woman are primarily for the sexual interest and satisfaction of men.  This is commonly referred to as objectifying women, and despite an equality revolution in the 1970s it still permeates most aspects of American society. As far as I can tell there has been no initiative to educate boys at an early age about this bias and how it can affect their sexual behavior. We are counting on men to become self-enlightened at some point in their lives.

3:  Aggression against women as either physical or verbal forms of aggression is never acceptable. Aggression in general and the potential for aggression including the use of firearms is identified by some as a masculine trait. Aggression against women is a complex construct because in many cases it involves seeing a woman as the exclusive property of a man.   

4:  All people must be accepted and not discriminated against based on masculine or feminine stereotypes.  This is more complicated than it seems. My example of the professor in a blue-collar world is one – but there are many more. It includes the idea that gender is not necessarily equivalent to biological sex.

Coming around to the introductory paragraph.  Dana White’s comment about how “you can’t be too masculine” requires context and definition.  He provided neither. If he includes encouraging people to beat people up – even if they are consenting adults and doing it as a job then I would disagree.  I notice his standard argument is that he has improved the medical and safety standards of the UFC so that nobody has died (there have been fatalities in both mixed martial arts (MMA) and professional boxing). I would not agree. Most men are not UFC fighters and don’t get into physical altercations at all.  Prevalence surveys suggest that 30-40% of adolescent males get into fights (versus 20% of females), 1/3 of adult males get into fights, 1/3 may be at risk for intimate partner violence, and about 10% of male homicides are preceded by a fight.  Substance use and intoxication are frequent correlates.  I am personally aware of 5 cases where bar fights resulted in death.  In all cases the victim was struck just once.  All these prevalence studies also investigate aggression from women and the numbers are lower but substantial.

It may be easier for some people to see aggression as a male trait pushing into a zone of toxic masculinity.  There are too many complicating factors to make that statement.  I would suggest that an attitude of needing to settle disputes no matter how trivial with physical violence or using physical violence to intimidate people or take advantage of them crosses that line.  In that case – aggression is overvalued beyond any societal norm.     

In terms of classification – masculinity stereotypes are qualitative rather than quantitative categories.  Nobody is measuring them in terms of quantity and the same thing applies at the biological level.  Testosterone levels have a cutoff between normal and deficient and is age adjusted. Having more testosterone does not make you more masculine but it may cause side effects. The same might be said of any psychological construct of toxic masculinity.

There has been a good response to the awkward Hegseth lecture from retired Generals and women who served as officers, pilots, and in special forces. The consensus of that sample at this point is that the lecture was an insult to women in the military (as well as the assembled officers) because they perform as well as the men and did not get any special considerations for promotion or placement in combat ready positions.  There has been a pattern of regulations that prevented women from serving in combat or special forces that seems to be implemented on an arbitrary basis. The women who qualified and served are proof that they can do that work like they have done every other kind of work in modern society.  There was also a suggestion that without women, enlistment quotas would not be met.  Beyond these comments there are many references on women in the military and in combat positions by country and policy.  It is not like this is a novel consideration.

These same generals pointed out why the officers in the room at that lecture would not be saying anything.  Military protocol is that they must defer to civilian authority and cannot question it.  They also pointed out the exception that they cannot follow illegal orders.  The retired generals all said this is why Trump’s comments about deploying the military in cities and using the military against civilians was wrong. 

What is the real difference between men and women fighter pilots and combat veterans? Just a Y chromosome. That’s it and there is nothing "woke" about it.

 

George Dawson, MD, DFAPA

Supplementary 1:  What about Fuck Around and Find Out (FAFO) messaging? 

This blurb from Hegseth:

“That's why pacifism is so naive and dangerous. It ignores human nature and it ignores human history. Either you protect your people and your sovereignty or you will be subservient to something or someone. It's a truth as old as time.

And since waging war is so costly in blood and treasure, we owe our republic a military that will win any war we choose or any war that is thrust upon us. Should our enemies choose foolishly to challenge us, they will be crushed by the violence, precision and ferocity of the War Department. In other words, to our enemies, FAFO.”

If you are naïve to hep Internet slang (like I am) – you might have had to look up FAFO (like I did).  As noted in the above sentence – it is aggressive language.  The type of language you can see expressed in the road rage incidents of any real crime TV show. It is not the longstanding peace through strength position that the US has taken with previous administrations.  When you spend more on your military than the next 10 countries in the world and have a large standing military it could be construed as the language of a bully trying to provoke someone into unwise action. I am sure that I could provide some quotes from Sun Tzu that would make more strategic sense.  I am also sure that is why his line fell flat with military officers who are scholars in this area.

It is not the first time the FAFO rhetoric has been used by the Trump administration. Eight months ago Trump posted a photo of himself dressed like a gangster in front of an FAFO sign on his social media.  It was a message to Columbia after they refused to receive 2 airplanes carrying deported immigrants. Trump apparently threatened tariffs and visa bans. 

In keeping with the one of the overall themes of this post – is this form of symbolism and verbal aggression toxic masculinity?  If you consider gangsters and verbal aggression to be a masculine trait – then yes, it is.  

Supplementary 2:

Commentary from retired Generals on the Hegseth speech.  All links are to transcripts or videos.

Retired Brigadier General Ty Seidule:  Retired Army brigadier calls Hegseth and Trump's military meeting 'an insult'. Link

Retired Lt. Gen. Mark Hertling:  A Retired General Blasted Trump And Pete Hegseth For Their "Insulting" And "Offensive" Remarks To Military Leaders.  Link and Link

Retired Major General Randy Manner:  Major General Takes on Trumps “Enemy Within” Comment Link

Retired Army Gen. Barry McCaffrey: Comments on Trump Hegseth  Link

Retired U.S. Army Major General Mark MacCarley: Link

Retired Lt. Gen. Russel Honoré:  Retired general criticizes Trump and Hegseth’s new military standards.  Link

Retired Lt. Gen. Ben Hodges: Link

Ret. General Wesley Clark: “A lot of the rhetoric that came out struck me as culture wars stuff.”  Link

Former Army Vice Chief of Staff Gen.  Peter Chiarelli (Ret) on This Week:  Link

CHIARELLI: "No, there's nothing unlawful about what he said. Nothing whatsoever. I'm concerned about what I considered an attack on women, and the fact that -- that there are -- there are people who say that women have been let into different combat fields and cannot meet the standards. I just don't believe that's true. I know when the Army opened up the Ranger program, the standards did not change at all. Not at all. And the fact of the matter is on today's battlefield, everybody's in combat. Everybody's in combat. We found that out in Iraq. The minute you set foot from Kuwait into Iraq, you went into harm's way. And we needed medics. And many of our women -- many of our women were assigned to medical units. So, we had to pull them out and send them up with convoys. And they did amazing."

Retired Lt. General Ben Hodges:  Face the Nation  Link

MARGARET BRENNAN: I want to pick – pick up where we left off with Senator Duckworth, who is a Purple Heart recipient for her time serving this country in combat.  Men and women have different basic fitness standards. The secretary, in his remarks at Quantico, said women – or he suggested women were being given a pass or were held to lower standards for fitness requirements. Do you think his change to the, quote/unquote, "male standard" is necessary?

LIEUTENANT GENERAL BEN HODGES: I think this is completely unnecessary. I have 38 years in the Army, and we've served with women in all sorts of different environments and deployments. And I never had a case where a female soldier was not able to do what she had to do. So, this is a – seems to me an unnecessary, almost a medieval approach that doesn't reflect the requirements that we have for women and men who are intelligent, able to operate in a modern battlefield environment.

Ret. Colonel Don Christensen:  “His speech directly attacked the values of many of the senior officers and enlisted members in the audience, and I would expect many of them to demonstrate their disgust by retiring,” Don Christensen, a retired Air Force colonel and former military lawyer who watched the speech, said of Hegseth.  Link

References:

1:  Daneshvar DH, Nair ES, Baucom ZH, et al. Leveraging football accelerometer data to quantify associations between repetitive head impacts and chronic traumatic encephalopathy in males. Nat Commun. 2023 Jun 20;14(1):3470. doi: 10.1038/s41467-023-39183-0. PMID: 37340004; PMCID: PMC10281995.

2:  Graham JR. The MMPI – a Practical Guide. 2^nd ed.  Oxford, England: Oxford University Press, 1987:  136-139.

3:  Sanders SM, Garcia-Aguilera C, Borgogna NC, Sy JR, Comoglio G, Schultz OA, Goldman J. The Toxic Masculinity Scale: Development and Initial Validation. Behavioral Sciences. 2024 Nov 14;14(11):1096.

 

Graphics Credit:

Wikimedia Commons:  English: Corporal Brandy Bates, a team member with Female Engagement Team 8 and native of Ann Arbor, Mich., walks around the corner of a mud wall while supporting soldiers from the Afghan National Army’s 215th Corps and U.S. Marines with Lima Company, 3rd Battalion, 7th Marine Regiment, during a recent foot patrol through the village of Tughay, Sangin district, Helmand province. The FET supports 3/7 by bridging the cultural gap and interacting with the local Afghan women.

This image was released by the United States Marine Corps with the ID 111206-M-GF563-025 posted on December 15, 2011.

https://commons.wikimedia.org/wiki/File:Female_Engagement_Team_builds_trust,_rapport_with_women_in_Sangin_111206-M-GF563-025.jpg

 

 

How People Think About Escalator Malfunctions

 

What would you do if you were in your favorite shopping mall and the escalator was not working?  Would you consider it an act of sabotage and demand an investigation?  Most people would just walk up the frozen staircase and not give it a second thought. You don’t have to take my word for it.  Just go out in the wild, find a frozen escalator and see what happens. The escalator in the mall I go to is usually not working.  There is no outrage or complaints to the manager. People just walk up and down it using the stair function.  That is what most people know about escalators from personal experience.  This post will examine how you could think about that problem.  But first – a few facts about escalators.

There are about 35,000 escalators in the US. Escalator density varies widely from state-to-state from much higher number in large metropolitan areas to only 2 escalators in the state of Wyoming.  Performance metrics are available for systems where they are used extensively like transit systems. Systems are rated on availability and how long they operate before failing.  The engineering metric is Mean Time Before Failure (MTBF).  An example from one metro transit system of 588 escalators measured availability at about 92% and MTBF of 153 hours (6.4 days). The average time to repair those escalators was 14 hours.  Of all the maintenance work done only 32% was scheduled.  The remainder was due to service calls, safety repairs, and customer incidents.  Interestingly service calls included escalators that turned off unexpectedly. All this data indicates that escalators are high maintenance devices compared with other commonly used devices like your automobile.

There are an estimated 10,000-17,000 escalator related injures per year.  75% of those injuries are from falls and slips (1).  Risk factors include advanced age and alcohol use. Many of those injuries are severe enough to require admission to a trauma center and in rare cases can result in death.

If you encounter a frozen escalator or one working erratically you could tell yourself: “Well I know from my personal experience that escalators will not be working from time to time. This is a little annoying but I can walk up the escalator or find an elevator like everyone else. I assume the next time I am here it will be repaired.”  If you know more about escalators you might think: “I know escalators have a high failure rate and about one in ten may not be available on any given day – this is to be expected.  I will just work around it”  After all the escalator was put there for the convenience of customers and the public.

These lines of thought are the collective reality that we experience. In considering a probability model of thought our collective experience creates a high probability that when we encounter a broken escalator, we will consider it a routine occurrence and quickly move to a work around.  A thought experiment illustrates this fact.  If I poll 100 people on how they handle a broken escalator – most of them will give the expected responses.  The outliers may be people who know about escalator maintenance or how these situations need to be handled.

But there are outliers.  Outliers could have phobias about escalators.  Escalators have well known safety hazards of falling and slipping. They have an awkward motion for many people and a person with vertigo or other balance problems may find it difficult to use them.  These people may have had a mishap on an escalator and sustained an injury.  There is a term for escalator phobia that I will not use here because I don’t think it adds much. People who are phobic of escalators may tend to avoid them.  That is easier to do in shopping malls than transit systems.  Not having worked in escalator dense areas I have never encountered a person with that phobia but have seen many people with phobias about crossing bridges and railroad tracks. 

Are there other ways to think about a broken escalator than just inconvenience.  As I was writing this, I thought of Jason Bourne one of my favorite fictional movie characters.  In the famous escape from Waterloo Station the scene begins and ends with escalators.  Fortunately for Bourne they were working in both cases.  But if they were not working, we can speculate he would probably be seeing the problem though his usual combination of situational awareness that would include alternate routes and what could be used to his strategic advantage.  The bottleneck created is an example of potential strategic use.

There are outliers beyond the outliers.  Folks with unique interpretations of everyday situations at a frequency of one person in a thousand to ten thousand.  They may have never seen an escalator or how it works.  But if they were born and raised in a modern society that is not very likely.  One recent interpretation was that the escalator was not working because it was sabotaged.  Where does sabotage fit in to a probabilistic model of everyday thought?  Sabotage is an unlikely explanation of everyday events.  People who I have professionally encountered over the years have told me about how the electricity in their home, their health, their food, their pets, their automobile, their work, their spouse, their legal status, and their finances were sabotaged by several methods.  Some of the methods were incredible like beams from satellites or delivery vans parked outside on the street using some kind of electronic device.  Others seemed more possible like “they came in the middle of the night and replaced my wife while we were sleeping.  She looks sounds, and acts the same but I know she is not real.”

Note the operative term they in the above scenarios.  They are a possible or imagined enemy causing the real or imagined problems. They can easily be a scapegoat.  Rod Serling was an expert in looking at how this dynamic plays out in society.  Slightly after the McCarthy era – he wrote an episode of the Twilight Zone called The Monsters are Due on Maple Street.  The entire plot focuses on what happens when there is a power outage on a residential street and people start looking for a scapegoat.  The final narrative is a comment on human nature and how we can be counted upon as a group to get the probabilities wrong.

What happens if the sabotage explanation persists and cannot be explained by groupthink, spycraft or reality?  Fixed false explanations and beliefs about action or delusions come to the attention of psychiatrists as paranoia on an individual level.  There are various disorders and those diagnoses depend on other features but one of the central features is the delusion.  There are also many people living in the community who are hypervigilant and suspicious without false beliefs who function normally.  Paranoia can be a personality feature or a delusion.

The ability to modify delusional beliefs by psychotherapy has been suggested since 1952.  Aaron Beck – one of the founders of cognitive behavior therapy published a case report (1) on the successful treatment of delusional thinking is a patient with schizophrenia.  Since then, techniques have been discussed in many supportive psychotherapy texts (2-5).  The common elements of psychotherapy including the therapeutic relationship, therapeutic alliance, and specific interventions necessary to discuss delusions are all covered in detail.  A detailed phenomenological interview and discussion are necessary focused on the onset of the thought.  This is necessary to explore emotional elements and how they potentially lead to a delusion.  Anxiety is a common initial state with many delusions being an explanation for the anxiety.

In the case of escalators – it is easy to imagine a person anxious and rushing to an appointment or trying to complete their shopping and they discover the escalator they use for that purpose is broken.  They may express frustration: “Why today?”, Why me?”, “Today of all days!”, etc.  But it is unlikely that they would think the escalator is sabotaged to prevent them from completing their task. Having an established set of delusions prior to the incident would increase the probability of thinking about sabotage.     

If I was seeing a patient with escalator paranoia telling me about how the escalators he was using were sabotaged – I would proceed with preparation for the therapy with the basic steps outlined above.  At some point we would need to discuss alternate explanations for the escalator malfunction.  That list may look like this and this list is not exhaustive:

1:  Need for service or maintenance/mechanical failure

2:  Power outage and other random events

3:  Imagined sabotage by a real or imagined enemy

4:  Control by a government agency

5:  A sign from a deity – a curse or a message

6:  Telekinesis – the person observing the malfunction believes he is causing it telepathically.

That discussion would examine whatever theories a person has with the goal of moving toward numbers 1 and 2 on the list.  That conversation as psychotherapy may take several months before there is any significant progress. It could involve gathering much evidence for and against the hypotheses and beliefs.  The contrast with politics and the Twilight Zone episode is interesting because it potentially works in the opposite direction. Direct evidence against the hypothesis is never considered since it is based on a political theory of persecution.  The message is reinforced by loyal followers and affiliated media.  These days that involves significant amplification through social media. The press in general does a very poor job of fact checking and refuting the process that Rod Serling correctly characterized in 1960 (6).  That group dynamic is difficult to stop and we currently watching that unfold.    

 

George Dawson, MD, DFAPA

 

References:

1:  Schminke LH, Jeger V, Evangelopoulos DS, Zimmerman H, Exadaktylos AK. Riding the Escalator: How Dangerous is it Really? West J Emerg Med. 2013 Mar;14(2):141-5. doi: 10.5811/westjem.2012.12.13346. PMID: 23599850; PMCID: PMC3628462.

2:  Beck AT. Successful outpatient psychotherapy of a chronic schizophrenic with a delusion based on borrowed guilt. Psychiatry. 1952 Aug;15(3):305-12. doi: 10.1080/00332747.1952.11022883. PMID: 12983446.

3:  Perris C.  Cognitive therapy with schizophrenic patients.  New York. The Guilford Press, 1989: 160-186.

4:  Wright JH, Turkington D, Kingdon DG, Basco MR.  Cognitive-behavioral therapy for severe mental illness – an illustrated guide.  Arlington, VA.  American Psychiatric Publishing, Inc., 2009:  99-123.

5:  Garrett M.  Psychotherapy for psychosis – integrating cognitive behavioral and psychodynamic treatment.  New York.  The Guilford Press, 2019: 194-197.

6:  Novalis PN, Rojcewicz SJ, Peele R.  Clinical manual of supportive psychotherapy.  Washington, DC. American Psychiatric Press, 1993: 138-146.

7:  Serling R.  The monsters are due on Maple Street.  Twilight Zone.  Season 1, Episode 22 originally aired on March 4, 1960. YouTube clip.

 

Graphics Credit:

Sascha Kohlmann, CC BY-SA 3.0 <https://creativecommons.org/licenses/by-sa/3.0>, via Wikimedia Commons 

The FDA and the Trump Formulary or What Separates Physicians from Politicians

 

 The difference between politicians and physicians was on full display at President Trump and HHS Secretary Robert Kennedy press conference several days ago.   It was hyped as an important announcement about autism for a month. They announced that Tylenol (acetaminophen or APAP hereafter) was a cause of autism.  In the associated hyperbole – Trump shouted not to take Tylenol and suggested that pregnant women should "tough it out".  That even though fever alone is a risk factor for complications of pregnancy and there are no safer analgesics.  Kennedy suggested that this was somehow “transparency” about science at the FDA, CDC, and HHS, praised their cooperation and suggested that past research was somehow flawed because of a focus on genetics.

The news media had a field day with the press conference.  Twenty-four-hour news channels were playing it every half hour. Controversy rather than accuracy is how they get views. What better way to describe science as pushback on the Trump Kennedy statements.  Real science is now pushing back against political rhetoric that claims to have essentially replaced the scientific method.  It is a case study in political black and white thinking versus the probabilistic thinking of medicine and science.

The purpose of this post is to look at the science and the rhetoric around this conference. Acetaminophen (APAP) has been FDA approved since 1951.  The first Tylenol product was an elixir for children marketed in 1955.   It was approved as an over-the-counter medication in 1960 using an FDA monograph procedure that allowed drugs to be grandfathered in if they were in general use prior to the stricter regulations that began in the 1970s. These monographs are updated with new information including risks in pregnancy. 

The Trump-Kennedy Autism Press Conference (TKAC) suggests that physicians may not be aware of APAP toxicity as much as they should be.  The reality is that physicians are highly aware of that problem. As interns, most physicians are involved in treating APAP overdoses and preventing severe hepatotoxicity and death. APAP toxicity is the second leading cause of liver transplantation worldwide. Only half of the overdoses are intentional with the remainder either accidental (due to mixing APAP containing products or not following the directions) or taking APAP with alcohol use, alcoholic liver disease, liver disease, nutritional compromise, or herbal supplements. It is critical that APAP toxicity is recognized as soon as possible to prevent irreversible liver damage and death.  It is the reason why OTC bottles of APAP have the following warnings:

On the warning for pregnant or breast-feeding women, the FDA has risk categories in the approved labelling.  APAP is listed as a Category C drug defined as shown in the slide below.  In 2015 the FDA stopped using the category system and started using the Pregnancy and Lactation Labeling Rule (PLLR) – a more detailed narrative form. Despite a letter to physicians from the FDA on the APAP in pregnancy issue and the standard advice physicians have used for years I can find no new FDA package insert and no detailed PLLR language from that agency. 

This post will discuss these issues is to look at the history, rhetoric, and epidemiology in this post and then depending on how much information I think is relevant to post on the genetics, pathophysiology, and toxicology of autism in subsequent posts.  I will touch on a few of those points here to address the rhetoric.

The TKAC conference characterized autism as a “crisis” and cited an unexplained increase in the prevalence of autism over the past 20 years.  By unexplained I mean they were taking it at face value as a real increase rather than reading the research and what those authors had to say about the reasons. The reality of the prevalence numbers and the design of these studies need to be examined. I have previously posted that variation in prevalence estimates for psychiatric disorders depends a lot on methodology.  That includes the study design, how the subjects are recruited, the assessments used to make the diagnoses, and the data analysis.  There are also cultural effects over time on the same culture and in comparisons of different international cultures.

In the United States there has been a marked increase in awareness of autism.  That awareness has increased significantly with the advent of the DSM 5 autism spectrum disorder diagnosis.  It is common to hear people declare that they think that either they or someone they know “is on the spectrum.”  That includes celebrities.  Increased awareness can increase early identification programs that can increase the prevalence.  The expansion in prevalence also reflects the inclusion of people with less severe symptoms.  An example comes from the ADDM CDC study that looks at autism prevalence between selected states.  Cases are identified through educational and medical records.  California had the highest 4- and 8-year-old autism rates of any state and it was thought to be due to a program that trained hundreds of pediatricians to identify cases early and refer them to local centers for intervention.    

The diagnostic criteria for autism have also evolved as shown in the diagram below.  From very few criteria applied to more disabled populations (Kanner, Rutter) to more elaborate criteria that went from a syndrome (DSM-IV) to a spectrum (DSM 5) encompassing milder forms of the disorder (7,8). That expectedly increases the prevalence of the disorder.  The smaller graphic illustrates that 3 DSM-IV syndromes were collapsed into a DSM 5 autism spectrum disorder.  I am on record that the term spectrum makes no biological sense to me.  It is merely a convenient way that humans have to deal with very complicated biological processes.  In this case nosological convenience has blurred the boundary between people with mild forms of the disorder and no disorder.  The DSM deals with that like it does with all disorders by including a necessary significant impairment in functioning term.

Very few prevalence studies look at cross sections of all the patients with that diagnosis in the community (12). In acute care psychiatry it is common to see 50- to 70-year-old adults in crisis situations because the parents they were living with have been hospitalized or died. These same people will not be in a medical or educational database with the studied diagnoses and will not be counted in those prevalence estimates.  I have been able to locate only one study (12) showing that using the same criteria at the same point in time - the prevalence of autism in the older population is the same as it is in the younger population.

Another consideration of prevalence is that is the diagnosis of autism is not an easy one.  It assumes the clinician has expertise in making the diagnosis and has adequate time to gather and consider all the necessary information. A paper by Fusar-Poli et al (13) highlights typical errors of misdiagnosis, the lag between first presentation and the accurate diagnosis, and reasons behind those misdiagnoses in a large sample of people presenting to specialty clinics for a diagnosis of autism spectrum disorder (ASD). That same paper begins with a vignette of a middle-aged man living in the community with some assistance to illustrate how autism can present in the older undiagnosed population.    

An interesting footnote about criteria. Like all psychiatric disorders at one point in time only psychological causes were considered as etiologies for the disease.  In the case of autism it was the refrigerator mother hypothesis.  Cold, distant mothers were considered the cause of autism.  Folstein and Rutter’s 1977 genetic study of autism helped to reverse that line of thinking and bring the likely cause back to genetics and biology.  

That biological cause was a focus of criticism in the TKAC conference.  Secretary Kennedy went on record stating that genetic research is unproductive and produces no “actionable” information.  Throughout most of my career the same was said about Huntington’s Disease.  When the genetic tests for Huntington’s came on the scene, we used them like everyone else but there was still not much optimism about an effective treatment that addressed the pathophysiology of the disorder. All of that may have changed a few days ago when a report about a therapy for Huntington’s (10) that may slow progression was made public. (9) There are currently several papers about the potential for using gene therapy for autism and other developmental disorders(11).

With all the criticism of current research at this news conference a couple of major actionable research discoveries were not covered.  The first are studies that show paternal and maternal age are risk factors for autism in offspring (14-21).  Increasing age of the father and mother are both risk factors for offspring with autism.  Paternal age greater than 50 years old doubles the risk of a child with autism compared with 20-29 yr old fathers. (20).  Spontaneous mutations in DNA are a likely mechanism but several others are hypothesized.

DNA effects would also suggest that environmental factors leading to mutations may be important.  The work done at the NIH (22-25) on this issue was not mentioned at all. One of the researchers in this area announced that her lab was terminated by the Trump administration.  She was working on the effect of environmental toxins on parental DNA and her research showed an effect for maternal solvent exposure, pesticide exposure and low fatty acid intake, and occupational exposures to phenols, ethylene oxide and pharmaceuticals.  All these exposures are actionable by a government interested in protecting people from environmental and occupational toxic exposures.

Coming back to the rhetoric of the TKAC conference the overall goals seem clear – to persuade the American people that there is a crisis, that politicians rather than scientists are best equipped to solve that crisis, and that politicians can give you medical advice but at the same time you should consult with your physician.  This is typical authoritarian rhetoric and if you really believe it – there is no longer any need for science or medicine. The “crisis” in terms of increased prevalence is explainable by broadened diagnostic criteria, inclusion of less severely disabled individuals, and increased awareness. The statement about the toxicity of acetaminophen is also exaggerated since in the end – despite the President declaring that nobody should use acetaminophen – both he and the HHS Secretary walked those statements back to the current recommendations to “consult your physician.”  The criticism about the lack of actionable research suggests a lack of awareness of what has been done – including work by government scientists who were fired by this administration.  I have illustrated this with a small fraction of the autism research that is currently out there.

As a final preliminary comment – politics and rhetoric occur both inside and outside of medicine.  I have seen similar statements made by researchers over the years that in the end did not pan out.  They did not pan out because those hypotheses were exhaustively investigated and disproven by other researchers attempting to replicate that research.  There is no similar political process. In medicine especially in some epidemiological research - a clear answer at the margins is often not possible. That is why medical treatment does not guarantee a result and involves a detailed informed consent discussion of potential risks and benefits.  In politics - all it takes for a new hypothesis is somebody winning an election.  And when that happens it is more likely to be a declaration than a hypothesis.

Do the American people really want to make health care decisions based on who won an election?    

 

George Dawson, MD, DFAPA

Supplementary:  An interview with the study author was released today and it can be accessed on the JAMA web site:  https://jamanetwork.com/journals/jama/fullarticle/2839562

The reference is:  Schweitzer K. Acetaminophen Use in Pregnancy—Study Author Explains the Data. JAMA. Published online September 29, 2025. doi:10.1001/jama.2025.19345

 

References:

1: Rosen NE, Lord C, Volkmar FR. The Diagnosis of Autism: From Kanner to DSM-III to DSM-5 and Beyond. J Autism Dev Disord. 2021 Dec;51(12):4253-4270. doi: 10.1007/s10803-021-04904-1. Epub 2021 Feb 24. PMID: 33624215; PMCID: PMC8531066.

2: Brugha TS, McManus S, Bankart J, Scott F, Purdon S, Smith J, Bebbington P, Jenkins R, Meltzer H. Epidemiology of autism spectrum disorders in adults in the community in England. Arch Gen Psychiatry. 2011 May;68(5):459-65. doi: 10.1001/archgenpsychiatry.2011.38. PMID: 21536975.

3: Kanner L. Autistic disturbances of affective contact. Nervous child. 1943 Apr;2(3):217-50.

4: Folstein S, Rutter M. Infantile autism: a genetic study of 21 twin pairs. J Child Psychol Psychiatry. 1977 Sep;18(4):297-321. doi: 10.1111/j.1469-7610.1977.tb00443.x. PMID: 562353.

5: Murphy D, Glaser K, Hayward H, et al. Crossing the divide: a longitudinal study of effective treatments for people with autism and attention deficit hyperactivity disorder across the lifespan. Southampton (UK): NIHR Journals Library; 2018 Jun. (Programme Grants for Applied Research, No. 6.2.) Chapter 17, Improving outcomes through better diagnosis: the effects of changes in DSM-V on clinical diagnosis. Available from: https://www.ncbi.nlm.nih.gov/books/NBK518676/

6: Shaw KA, Williams S, Patrick ME, et al. Prevalence and Early Identification of Autism Spectrum Disorder Among Children Aged 4 and 8 Years — Autism and Developmental Disabilities Monitoring Network, 16 Sites, United States, 2022. MMWR Surveill Summ 2025;74(No. SS-2):1–22. DOI: http://dx.doi.org/10.15585/mmwr.ss7402a1.

7: Arvidsson O, Gillberg C, Lichtenstein P, Lundström S. Secular changes in the symptom level of clinically diagnosed autism. J Child Psychol Psychiatry. 2018 Jul;59(7):744-751. doi: 10.1111/jcpp.12864. Epub 2018 Jan 29. PMID: 29377119.

8: Avlund SH, Thomsen PH, Schendel D, Jørgensen M, Clausen L. Time Trends in Diagnostics and Clinical Features of Young Children Referred on Suspicion of Autism: A Population-Based Clinical Cohort Study, 2000-2010. J Autism Dev Disord. 2021 Feb;51(2):444-458. doi: 10.1007/s10803-020-04555-8. PMID: 32474837.

9: Tabrizi SJ, Flower MD, Ross CA, Wild EJ. Huntington disease: new insights into molecular pathogenesis and therapeutic opportunities. Nature Reviews Neurology. 2020 Oct;16(10):529-46.

10: Kaiser J.  In a first, a gene therapy seems to slow Huntington disease.  Science, September 24,2025.  doi:10.1126/science.zbkgxvm

11: Sahin M, Sur M. Genes, circuits, and precision therapies for autism and related neurodevelopmental disorders. Science. 2015 Nov 20;350(6263):10.1126/science.aab3897 aab3897. doi: 10.1126/science.aab3897. Epub 2015 Oct 15. PMID: 26472761; PMCID: PMC4739545.

12:  Brugha TS, McManus S, Bankart J, Scott F, Purdon S, Smith J, Bebbington P, Jenkins R, Meltzer H. Epidemiology of autism spectrum disorders in adults in the community in England. Arch Gen Psychiatry. 2011 May;68(5):459-65. doi: 10.1001/archgenpsychiatry.2011.38. PMID: 21536975.

13:  Fusar-Poli L, Brondino N, Politi P, Aguglia E. Missed diagnoses and misdiagnoses of adults with autism spectrum disorder. Eur Arch Psychiatry Clin Neurosci. 2022 Mar;272(2):187-198. doi: 10.1007/s00406-020-01189-w. Epub 2020 Sep 6. PMID: 32892291; PMCID: PMC8866369.

14: Hultman, C. M., Sandin, S., Levine, S. Z., Lichtenstein, P., & Reichenberg, A. (2011). Advancing paternal age and risk of autism: New evidence from a population-based study and a meta-analysis of epidemiological studies. Molecular Psychiatry, 16(12), 1203–1212. https://doi.org/10.1038/mp.2010.121

15: S. E. W. Sandin et al., "Autism risk associated with parental age and with increasing parental age difference in a population-based cohort of 5,766,794 children," Molecular Psychiatry, 2015

16: Wu, S., Wu, F., Ding, Y., Hou, J., Bi, J., & Zhang, Z. (2017). Advanced parental age and autism risk in children: A systematic review and meta-analysis. Acta Psychiatrica Scandinavica, 135(1), 29–41. https://doi.org/10.1111/acps.12666

17: Reichenberg, A., Gross, R., Weiser, M., Bresnahan, M., Silverman, J., Harlap, S., Rabinowitz, J., Shulman, C., Malaspina, D., Lubin, G., Knobler, H. Y., Davidson, M., & Susser, E. (2006). Advancing paternal age and autism. Archives of General Psychiatry, 63(9), 1026–1032. https://doi.org/10.1001/archpsyc.63.9.1026

18: Wood, K. A., & Goriely, A. (2022). The impact of paternal age on new mutations and disease in the next generation. Fertility and Sterility, 118(6), 1001–1012. https://doi.org/10.1016/j.fertnstert.2022.

19: McGrath, J. J., Petersen, L., Agerbo, E., Mors, O., Mortensen, P. B., & Pedersen, C. B. (2014). A comprehensive assessment of parental age and psychiatric disorders. JAMA Psychiatry, 71(3), 301–309. https://doi.org/10.1001/jamapsychiatry.20

20: Sandin, S., Hultman, C. M., Kolevzon, A., Gross, R., MacCabe, J. H., & Reichenberg, A. (2012). Advancing maternal age is associated with increasing risk for autism: A review and meta-analysis. Journal of the American Academy of Child and Adolescent Psychiatry, 51(5), 477–486.e1. https://doi.org/10.1016/j.jaac.2012.02.018

21: Ye Q, Apsley AT, Hastings WJ, Etzel L, Newschaffer C, Shalev I. Parental age at birth, telomere length, and autism spectrum disorders in the UK Biobank cohort. Autism Res. 2024 Nov;17(11):2223-2231. doi: 10.1002/aur.3258. Epub 2024 Oct 30. PMID: 39474987.

22: McCanlies EC, Gu JK, Ma CC, Sanderson WT, Ludeña-Rodriguez YJ, Hertz-Picciotto I. The effects of parental occupational exposures on autism spectrum disorder severity and skills in cognitive and adaptive domains in children with autism spectrum disorder. Int J Hyg Environ Health. 2025 Jul;268:114613. doi: 10.1016/j.ijheh.2025.114613. Epub 2025 Jun 28. PMID: 40582232; PMCID: PMC12415903.

23: McCanlies EC, Gu JK, Kashon M, Yucesoy B, Ma CC, Sanderson WT, Kim K, Ludeña-Rodriguez YJ, Hertz-Picciotto I. Parental occupational exposure to solvents and autism spectrum disorder: An exploratory look at gene-environment interactions. Environ Res. 2023 Jul 1;228:115769. doi: 10.1016/j.envres.2023.115769. Epub 2023 Mar 31. PMID: 37004853; PMCID: PMC10273405.

24: McCanlies EC, Ma CC, Gu JK, Fekedulegn D, Sanderson WT, Ludeña-Rodriguez YJ, Hertz-Picciotto I. The CHARGE study: an assessment of parental occupational exposures and autism spectrum disorder. Occup Environ Med. 2019 Sep;76(9):644-651. doi: 10.1136/oemed-2018-105395. Epub 2019 Jun 27. PMID: 31248991.

25: Schmidt RJ, Kogan V, Shelton JF, Delwiche L, Hansen RL, Ozonoff S, Ma CC, McCanlies EC, Bennett DH, Hertz-Picciotto I, Tancredi DJ, Volk HE. Combined Prenatal Pesticide Exposure and Folic Acid Intake in Relation to Autism Spectrum Disorder. Environ Health Perspect. 2017 Sep 8;125(9):097007. doi: 10.1289/EHP604. PMID: 28934093; PMCID: PMC5915192.

26: Pernia S, DeMaagd G. The New Pregnancy and Lactation Labeling Rule. P T. 2016 Nov;41(11):713-715. PMID: 27904304; PMCID: PMC5083079.

Reference Credit:

h/t to Tyler Black, MD @tylerblack32 for reference 12.

Graphics Credit

1:  DSM-IV and DSM 5 graphics are from the respective DSMs copyrighted by the American Psychiatric Association and reproduced here only for educational purposes.  

2:  FDA package insert information is reproduced here and considered in the public domain.

3:  The detailed ADDM graphic of ASD prevalence by state is form the Mortality and Morbidity Weekly Report (MMWR) (see reference 6 and is in the public domain).

4:  Lipak GS.  The epidemiology of autism.  In:  Textbook of Psychiatric Epidemiology. 3rd ed.  Tsuang MT, Tohen M, Jones PB (eds).  Wiley-Blackwell. Oxford, UK.  2011, p. 475.  

Reference for lead graphic - licensed from publisher.  

Commentary on the Trump Kennedy Press Conference Commentaries with time points in the transcript: 

1:  Trump at 4:43

“Which is basically commonly known as Tylenol during pregnancy and can be associated with a very increased risk of autism. So taking Tylenol is not good. All right, I'll say it; it's not good. For this reason they are strongly recommending that women limit Tylenol use during pregnancy unless medically necessary. That's, for instance, in cases of extremely high fever that you feel you can't tough it out; you can't do it. I guess there's that. It's a small number of cases, I think. But if you can't tough it out, if you can't do it, that's what you're going to have to do. You'll take a Tylenol, but it'll be very sparingly. It can be something that's very dangerous to the woman's health. In other words, a fever that's very, very dangerous and ideally a doctor's decision because I think you shouldn't take it, and you”

Trump simultaneously skirts the issue of the potential dangers of acetaminophen in pregnancy while walking back that recommendation to the current package insert statement (see graphic above). 

2:  Trump at 36:59

“I understand it's maybe 10% of the women that are pregnant would perhaps be forced to use it, and that would mean you just can't tough it out. No matter what you do, you can't tough it out. So that's up to you and your doctor.”

Trump seems to confuse the analgesic effect of acetaminophen with the antipyretic effects important to prevent complications of pregnancy.  

3:  Trump at 40:12

“Don't take Tylenol. Don't give Tylenol to the baby after the baby's born. Every time the baby gets a shot, the baby goes, gets a shot, they say, "Here, take a couple of Tylenol." I've heard that for years. Take Tylenol. Don't take Tylenol, don't have your baby take Tylenol. Now, Tylenol is fine for people that aren't pregnant, that aren't in the situation that we're talking about one very specific situation. If you're pregnant, don't take Tylenol. When you have your baby, don't give your baby Tylenol at all unless it's absolutely necessary. Don't do it.”

Trump clearly states not to take acetaminophen if you are pregnant - with no package insert qualifier. He also suggests that it is dangerous for infants. 

4:  Trump at 44:03

“And the other things I told you about, just… The word, tough it out. It's easy for me to say tough it out. But sometimes in life with a lot of other things, you have to tough it out also. Don't take Tylenol. Don't give Tylenol to the baby. When the baby's born, they throw it at you, "Here, give them a couple of Tylenol." They give them a shot. They give them a vaccine. And every time they give them a vaccine, they throw in Tylenol. And some of these babies they're long born, and all of a sudden they're gone. And it doesn't hurt not to do it. It doesn't hurt. There's no downside. There's no downside at all.”

Trump persists with his "tough it out" message missing the point of acetaminophen use in pregnancy.  He also suggests that vaccinations lead to more acetaminophen use in infants. 

5:  Kennedy at 14:10

“NIH research teams are currently testing multiple hypotheses with no area off-limits. We promise transparency as we uncover the potential causes and treatments, and we will notify the public regularly of our progress. Today we are announcing two important findings from our autism work that are vital for parents to know as they make these decisions. First, HHS will act on acetaminophen. The FDA is responding to clinical and laboratory studies that suggest a potential association between acetaminophen used during pregnancy and adverse neurodevelopmental outcomes, including later diagnosis for ADHD and autism. Scientists have proposed biological mechanisms linking prenatal acetaminophen exposure to altered brain development. We have also evaluated the contrary studies that show no association. Today, the FDA will issue a physician's notice about the risk of acetaminophen during pregnancy and begin the process to initiate a safety label change. HHS will launch a nationwide public service campaign to inform families and protect public health.”

No mention of the research program cancelled by the Trump administration as noted above. Not clear who he means when he talks about "we" evaluating studies.  Does he mean him and Trump?  Is there anybody left at NIH, CDC, HHS who can do those evaluations?

6:  Kennedy at 15:28

“The FDA also recognized that acetaminophen is often the only tool for fevers and pain in pregnancy, as other alternatives have well-documented adverse effects. HHS wants, therefore, to encourage clinicians to exercise their best judgment and use of acetaminophen for fevers and pain in pregnancy by prescribing the lowest effective dose for the shortest necessary duration and only when treatment is required. Furthermore, thanks also to the politicization of science. The safety of acetaminophen against the risk of neurodevelopmental disorders in young children has never been validated.”

Kennedy takes credit for the longstanding advice on the package insert of acetaminophen - namely discuss with your physician. 

7:  Kennedy at 52:13

"But also it's just common sense, because you're only seeing this in people who are under 50 years of age. If it were better recognition or diagnosis, you'd see it in 70-year-old men. I've never seen this happening in people my age. I've never seen a case of full-blown autism, and that means profound autism, I want to be very careful, head banging, stimming, toe walking, nonverbal, non-toilet trained. I've never in my life seen a 70-year-old man who looks like that. You're only seeing it in kids. It's an epidemic"

Kennedy simultaneously displays his lack of knowledge about the historical development of the autism diagnosis (DSM-IV restricted age of onset to 3 years) and perpetuates a stereotype of a person with severe developmental disabilities who would typically require institutional care.  There are many older individuals with ASD living in the community - some may be your neighbors. And as noted in the above post - the expansion in prevalence has occurred primarily due to milder cases that were included in new diagnostic criteria.

How To Fail A Sleep Test...

 

“Xi – Kah – Vah” 

“Xi – Kah – Vah” 

“Xi – Kah – Vah”  ….

I kept repeating this mentally hoping my old Transcendental Meditation mantra would send me off to sleep. That was after I had repeated the US Army relaxation technique that was guaranteed to bring on sleep.  It was 3AM and I was still wide awake.  Still worse – I was in a sleep lab trying to find out why my AHI has been pegged for the past 3 months.  AHI is the Apnea-Hypopnea Index and according to the manufacturer of my CPAP machine is measure the number of apneic episodes per hour that last longer than 10 seconds.  For the 20 years I have been on CPAP – the number has been 1-3, but 3 months ago it started going up to 10+ with no good explanation - other than possible central sleep apnea in addition to obstructive sleep apnea.  

My body weight and general life style have not changed at all.  I continue to get good overall scores on my CPAP machine despite the AHI.  I consulted my sleep medicine doc and he decided to increase the pressure and see if that worked.  It did not - so we decided to do another sleep lab test or polysomnography. It is a big deal since you are observed and filmed, connected to electrodes (EEG, ECG, OCG, laryngeal vibration, chest and abdominal respirations, legs (for RLS), and masseters for bruxism.  You are also sleeping in a strange place.

An unsettling factor in the mix is that according to polygenic risk analysis – I am loaded for Amyotrophic Lateral Sclerosis (ALS) genes.  And by loaded, I mean I am in the 100^th percentile for risk.  I am not aware of central sleep apnea being the initial sign of ALS and neither was my sleep medicine doc – but I do not want to be the first case report.  So, I am hoping those genes remain quiescent and do not express themselves. 

I showed up at the lab at 8PM.  A technician explained their protocol and that after I was connected, I needed to contact her via the intercom if I needed to get up at night.  Under no circumstances was I supposed to get up by myself because it would endanger all the electrode connections.  I told her I was ready and she came back in and hooked me up over a period of about 20 minutes and then tested the connections. She also explained that I was not going to be started on CPAP - it would be added later in the night only if I needed it and then BiPAP would be added on top of that if I needed it.  Since I already had a diagnosis of obstructive sleep apnea (OSA) – that did not make a lot of sense to me.  But I was not upset and wanted to proceed with the ordered protocol.  I watched TV for about 20 minutes and it was lights out by 10PM.   

It did not take long to realize that I was just laying there thinking.  I recalled my first polysomnography in a sleep lab that was built in the Neurology Clinic of the hospital where I worked.  I had the feeling at that time that I did not sleep a wink but the tech said – “Oh no you slept all right and you have severe sleep apnea.” (AHI>50).  Since that time, I have been 100% compliant with CPAP.  I use it every night – no matter where I am. 

I checked my watch and it was 1AM.  Three hours of laying there thinking and no sleep in sight.  Time to try my sleep reverie trick.  Sleep reverie is a reliable sign of sleep onset being very close and, in my case, it takes the form of vivid and often nonsensical mental images.  For example – the image of a man walking down metal stairs from a loading dock.  A man working on an outboard motor.  A futuristic gray pickup truck driving down the road.  A 500 ml beaker in front of a small flat screen TV.  These images flash for a few seconds and I am asleep.  Some time ago, I thought I could speed sleep onset by recalling the early states of sleep reverie.  What did it feel like in the body and brain just before the images started?  I tried reproducing those sensations several times and almost had it.  I generated a brief flash of sleep reveries and it was gone – I was still wide awake.

I checked my watch and it was 3AM.  Still wide awake.  Flash on my mantra, muscle relaxation, breathing exercises, mindfulness exercises – all the tricks of the trade and I got nothing. My mind is wandering to far away places.  I am back in Africa in 1974 traveling up into the Aberdare Mountains to visit friends.  I am 25 years old and traveling with a young woman who is 23.  We are travelling in a high-speed taxi called a matatu.  They come in various forms but this one is a small Toyota pick up truck with a metal enclosure over the back.  My travelling companion and I are crammed into that enclosure with a dozen villagers trying to get up into the mountains.  Every time I got out of one of these things - I kissed the ground.  Many people were killed in matatus every year. I remember how we both looked.  We did not say much.  We knew we had to get to that school before dark and were focused on making good time.  I see us walking the final 1/2 mile along a dirt road like it is a movie.  I flash ahead to hiking in the bamboo forest with her future husband and a mutual friend.  I flash ahead to getting overrun by soldier ants at his house up in the mountains and wondering if we were going to survive that night.  In the end we were saved by a paraffin refrigerator -  ants do not cross a line of kerosene.  I think about a good friend who lived on my school compound and what it would have been like to talk regularly with him over the past 50 years - like we talked back then.

I checked my watch again and it was 5AM.  The technician’s voice came over the intercom: 

“You are not sleeping.”

“I know – I came close a few times – but never fell asleep.” (referring to the aborted sleep reveries).

“Do you want to just get up and leave?”

“I suppose”.

The technician came in and took about 10 minutes to disconnect all the electrodes.  I had 6 piles of salt and electrode paste on my scalp. 

“It should come off with just shampoo. Your doctor will look at the study.  He may decide to have you come back and give you a sleeping pill.”  

I thought about what happened on the way home calling on my years of studying sleep. I have had insomnia since I was a little kid with night terrors – but I only stayed awake all night long when it was necessary for my role as a physician. The first time was covering the coronary care unit as an intern and believing that another intern and I were responsible for a person on a balloon pump who was actively bleeding. Even as a psychiatrist there were the occasional all-nighters – typically catatonic patients who had questionable intake or agitation and aggression that did not respond to the usual measures.  And of course, complicated medical problems that always seemed to end up on my unit.  It got worse with the electronic health record because I could see almost everything from home.  But none of that is a problem in retirement.  My sleep is generally normal and I have no problem getting at least 6-7 hours per night.

The behavioral aspect of sleep provides some clues.  We all learn to fall asleep in a certain environment.  The environment I am used to is hooked up to a CPAP machine.  It has a certain sensation and noises.  The air splint from the pressure creates a certain internal sensation. Even though I was not bothered by trying to sleep without it – the lack of those sensations may have been the reason I could not sleep at all. 

A second issue was the bed.  I was handed a remote control and advised I could adjust the firmness of the mattress with the remote.  I did it at every time check dropping it by 30 percent each time.  By 5AM I was down to 30 (where 100 is the firmest).  I recently changed my home mattress and it required a trial before I could find an exact replacement.  There is a literature on mattress qualities and sleep that looks at firmness, temperature, and materials.  Most of the studies are interested in sleep but some look at spinal alignment and pain.  The results are generally mixed probably due to patient characteristics.  For example, although one review (1) finds that a medium firm mattress may work for most people – there are still are those at both ends of the spectrum that sleep better with very firm or soft mattresses.  I purchased my last mattress based on a study that I think was in the British Journal of Medicine (BMJ) suggesting that pillow top mattresses may work the best. With the replacement I tried a firm orthopedic mattress that resulted in back pain every day.  A new pillow top worked very well.  The sleep lab bed did not seem to change at all with the remote control and that may also have been a factor.  

So how do you fail a sleep study?  The short answer is by not sleeping but there are complicating factors.  I am waiting to find out if there will be a modified protocol and watching my AHI.

George Dawson, MD, DFAPA

 

1:  Caggiari G, Talesa GR, Toro G, Jannelli E, Monteleone G, Puddu L. What type of mattress should be chosen to avoid back pain and improve sleep quality? Review of the literature. J Orthop Traumatol. 2021 Dec 8;22(1):51. doi: 10.1186/s10195-021-00616-5. PMID: 34878594; PMCID: PMC8655046.