Happy Labor Day 2023!

 

Over the years of writing this blog I have put out a Labor Day message to describe any progress in the physician workspace in the past year.  The practice environment for physicians has deteriorated significantly over the past 3 decades and those changes are generally locked in by the healthcare business managers backed by both Congress and state governments. I have used the following graphic several times on this blog to illustrate what happened over specific time frames and it is probably time to add some additional details.

The impact of managed care on medical practice has been clear for the past 30 years.  In many cases that model is being adopted by physicians in private practice settings. For example, it is common now to see a specialist initially but in follow up see one of the physician extenders working with them. That can make health care a lot less personal and it leads me to think about the reason why physicians are trained to provide continuity of care in the first place.

But even more than that issue is the explosion of online services provided for flat rates that focus on seemingly basic problems in exchange for payment. On my streaming services that typically involves a company that offers prescriptions for depression, anxiety, hair loss, and erectile dysfunction.  A second company offers beta blockers for performance anxiety.  Given the side effect potential for these medications – I am curious about how comprehensive the initial evaluations are and the follow up visits.

I was recently hospitalized and had a first hand look at what the modern hospital workplace looks like.  When I was in training there were discrete teams by specialty and they consisted of physicians at all levels of training.  A typical team might have 1-2 med students, 1-2 interns, a resident, a senior resident or fellow, and the attending. The work load would depend on whether your service admitted people to the hospital (typically internal medicine, surgery, neurology, renal medicine, cardiology, psychiatry) or consulted to those teams (infectious disease, endocrinology, pulmonology, rheumatology, cardiology, psychiatry).  The admitting services were the most intense because of irregular admissions and complicated unstable patients. Teams generally had places to meet, where patients were presented to the attending and there were formal didactics. Bedside teaching occurred on rounds.

During my hospitalization, I was not seen by a single physician in my room. When I went out into the hallway, both sides of the hall were lined by people facing computer screens. There was one consulting team standing outside a patient door – visible only because it was obvious the fellow and attending were discussing cases. The level of crowding was striking and it left me with the impression that all these people could not possibly be physicians.  Managed care shaped the form of these teams and who was in that hallway. First, they eliminated the usual admitting services and replaced them all with hospitalists. Then they replaced at least some physicians on those teams with non-physicians. Those moves benefit business decisions but I have not seen a single adequate study on the impact it has on medical care.

Training physicians in hospitals has typically involved hands on learning, consultation from senior and expert physicians, and active learning environment, and in many cases the opportunity for research.  All these areas need to be preserved in the practice environment in order to stimulate practicing physicians to maintain high standards. An environment that leads to burnout, sleep deprivation, and moral injury is not adequate to the task. The question always has been whether physicians have any kind of leverage that could lead to appropriate modifications. That question has never been put to the test and in fact, healthcare organizations in the United States generally flaunt their power over physicians rather than attempting to negotiate with them.

Will a union make a difference? My experience with unions started out in my family of origin.  My father was a member of the Brotherhood of Locomotive Firemen and Engineers (BLFE). He worked as a locomotive fireman and then an engineer.  He had to be a union member in order to work.  He generally was not very happy about it. The railroad industry was run on a seniority system and as railroad utilization decreased – younger workers like my father had a difficult time finding job assignments. Even though they were technically employed by a railroad and reimbursement for the work was good, it seemed like only the most senior engineers benefitted to the point that they could make a good living.  As a result, the contracts negotiated by the unions did not mean that much to my father. He also tended to see the union as corrupt because, the union officials clearly made far more than he was making trying to work in their system.  Railroads unions were also compartmentalized - so a strike against one railroad did not mean a strike against all.  As a result, workers from the railroad that was the object of the strike could work for competing railroads during the strike. If similar rules apply to physicians a uniform practice environment is no guarantee, but the onerous aspects might be eliminated.   

Unions for physicians and residents are becoming increasingly popular but they have more restrictions that in a blue-collar environment. The National Labor relations Board (NLRB) enforces the National Labor Relations Act (NLRA) and decides what public sector employees can form unions (1). Independent contractors, supervisors, and managers are excluded because the focus of the act was on laborers. The general categories are loosely defined so it takes an NLRB investigation to determine who can be in the union. Tenure and tenure track employees were eliminated by a Supreme Court ruling. Only salaried employees who do not do a significant amount of supervision are allowed to be union members. If a union is allowed, the goals in terms of collective bargaining, representation, and impact on hospital policies need to be determined.  Although the momentum for unions is building, there is a considerable amount of inertia from the managed care era. During that time, we had many physicians who were eager to escape a deteriorating practice environment to become administrators and basically enforce business policies. It remains to be seen if unions can have a favorable impact on local health care policy and practices – but just establishing more is a step in the right direction.    

More resistance to Maintenance of Certification by various boards and the American Board of Medical Specialties is also growing. I went to the alternate system National Board of Physicians and Surgeons (NBPAS) certification in 2018 and have not looked back. At the same time, I realize that I was outside of any system demanding that I recertify through an ABMS board and as a result – in a unique situation relative to younger colleagues. A petition was started in July to end ABMS MOC and so far there are 20,000 + signatures. There was an initiative in the APA to stop MOC about 10 years ago, but the administrative process prevented it from being put on a ballot. The basic problems with MOC is that there is no evidence it is necessary for quality care, in fact most health care organizations have abandoned true quality programs. Second, it is not reflective of clinical practice. Most physicians – even generalists end up in a niche and focus their educational efforts and mastery in that area. It makes no sense to keep taking examinations outside of that area. Third, it is a substantial time and financial commitment and it clearly generates a lot of revenue for ABMS specialty boards. Fourth, there is some suggestion that MOC should be tied to state licensing (Maintenance of Licensure or MOL). This would allow states and health care organizations even more power in controlling physicians – even during their private times when they would need to spend time studying for barely relevant examinations. Elimination of MOC is another positive step in the direction of restoring a more reasonable practice environment.

Beyond a better practice environment and what it takes to make that politically – the profession of medicine is at stake.  I have written about a lot of the technicalities – but this is deeply personal. Going to medical school and studying medicine was the best thing I could have done with my life. By identifying with the practicing physicians in my various training programs I learned how to live and breathe medicine and psychiatry 24 hours a day. Always thinking about it, never far from a journal article that I wanted to read, and always focused on how that translated to clinical practice – usually a very hard problem I was seeing in practice. From the very first patient contact, the importance of communicating with people in an empathic, unhurried and comprehensive way was obvious.  We cannot afford to lose that transformative effect that medicine has on people.  We cannot dumb things down for the business world and make human biology less complex. I know there are many docs out there that think like me.  Whether we can unionize or cancel MOC – we can never lose sight of the fact that we need to preserve a transformative profession for the sake of future generations of physicians and their patients.

 

 

George Dawson, MD, DFAPA

 

References:

1:  Bowling D 3rd, Richman BD, Schulman KA. The Rise and Potential of Physician Unions. JAMA. 2022 Aug 16;328(7):617-618. doi: 10.1001/jama.2022.12835. PMID: 35900755. 

The True Big Pharma Backers Show Themselves

 

Here is a hint – they are not psychiatrists or even physicians.  They are Republicans.  That may come as a shock to those of you who have absorbed all of the pharma conflict of interest stories about physicians over the past 20 years. Psychiatry in general was selected for much of that criticism. The average physician in the US had no significant conflict of interest even when trivial compensation like meals during continuing medical education (CME) courses were tallied. Some members of Congress even went so far to investigate some psychiatrist’s personal employment arrangements to point out any potential conflicts of interest when it came to pharmaceutical manufacturers.

Today we finally have some clarification on who really backs Big Pharma and wants to assure their large profits.  It should come as no surprise that it is Congress – specifically members of the pro-business GOP.  For years, Congressional conflict-of-interest has been sanitized by their disclosures as if that somehow prevented them from passing pro-Pharma legislation and regulations. For the record the amount of lobby money to the major parties varies from year to year.  For 2022 a total of $26,297,445 was donated from the pharmaceutical industry with $15,175,518 to the Democrats and $10,994,723 to the Republicans. That is an average donation of $29,159 to $105,910.  By contrast the Open Payments site recording payments to health care professionals claims that drug and medical device companies gave physicians $12.59 billion in 2022, but they are counting funds used to pay for research as well as profits from ownership of patents and medical devices (a total of $8.87 billion).  Looking at general payments alone, the physicians receiving any type of reimbursement averaged about $441. The current reporting rule is that any amount exceeding $10 or an aggregate of $100 in the case of meals must be reported.

I previously asked the question whether a slice of pizza given to a doctor at grand rounds was more likely to get results for the pharmaceutical industry than the average donation to Congress ($46,579 at the time).  I made the point that despite the continuous criticism of psychiatrists, they happen to be way down on the list of physicians getting these donations with about 37% receiving general payments and 3.6% receiving payments totaling more than $10,000.

But all the corruption by trivial payments discussion was based on shaky research. It is quite easy to demonstrate that physicians want to try new drugs as they come into the marketplace and show that marketing efforts correlate with prescriptions. We had a No Free Lunch movement to prevent corruption by pizza slices. We had a great deal of agitation about ghost writers, pharmaceutical companies not publishing negative studies, faulty research, side effect reporting, etc. Almost all of that involved psychiatry and often several self-appointed critics from the field.  There are undoubtedly problems with clinical trials in all specialties, but during that 20-year span from about 1998-2018 it seemed as if there was an active conspiracy to sell psychiatric medications.  To some extent that continues but it has less legitimacy in the field particularly since drug detailing and sales have been eliminated from most clinics and hospitals.

All of that commotion was probably good cover for Congress who was actually receiving payments that could make a difference.  And during that time pharmaceutical companies recorded record profits.

What is different now?  The Biden administration has decided that it wants to negotiate prices for Medicare Part D prescriptions. They are on solid ground. The Veterans Administration (VA) negotiates drug prices and has 399 drugs on their formulary.  A GAO study showed that they paid 54% less per unit than Medicare. HHS has already selected the drugs that will be negotiated in the initial round and as expected most of them are the high expenditure drugs in the plan.

The Republicans claim that these negotiations will decrease access to care and raise drug prices although there is no evidence that the VA negotiations have done that. They also claim that there will be reduced innovation, research and development, and job losses. They seem to have missed the overall picture that pharmaceutical companies in other countries succeed – even when there are negotiated prices with the health plan in those countries. Of the top 15 pharmaceutical companies in the world 8 are in the United States and the remainder in Switzerland, UK, France, Denmark, and Japan. The numbers given for fewer new drugs, fewer new indications, and drop in R&D spending seem highly speculative to me.  For example, the drop of $663B in R&D spending is the equivalent of about half of the total revenue for the top 15 companies.   I seriously doubt they are spending that much on R&D. During the 20 year period that I am referring to companies left entire therapeutic areas and it was common knowledge that marketing was going to drive pharmaceutical sales. There is an entire section about decreased jobs.  Are the Republicans really suggesting that Americans should pay (by far) the highest amounts for prescription drugs in order to fund a jobs program? And finally, the suggestion that the plan is “legally dubious”.  Apparently Congress is set up to help industries optimize profits rather than protect people who can’t pay a thousand dollars or more for a Medicare Part D copay.         

This post also has implications of pharmacy benefit managers or PBMs.  You remember them?  They are the business entities charged with “managing” your pharmacy benefits allegedly to make medications most “cost effective”.  PBMs make about $315 B annually for doing nothing more than managing prescription drug programs for employers and other large entities with health insurance programs. In practice they are a price multiplier rather than a price reducer.  PBMs control the spread or difference between what the insurance pays for a medication and what they reimburse pharmacies. In some cases, their reimbursement for pharmacies is lower than the actual cost of the medication. Since they are leveraging large number of patients, local pharmacies typically do not have much of a choice if they expect to do business – even though an affiliation with a PBM is draining. PBMs can own their own pharmacies and reimburse those pharmacies more than community pharmacies.   For a physician the most onerous aspect of PBMs occurs with prices for drugs and their positions on formularies for hospitals and clinics.  A formulary is a restricted list of medications available for physicians in that health plan to prescribe for their patients.  That can mean a patient has to change their prescription for it to be covered or some newer medication may not be covered at all.  During negotiations with manufacturers, PBMs can get a rebate from the manufacturer if they get their product exclusively in the formulary. That rebate is kept by the PBM rather than shared with the people paying for the drug.  

The pharmaceutical landscape is a minefield that is set up to optimize corporate profits. Pharmaceutical companies are essentially guaranteed high margins based on patent exclusivity and high prices.  PBMs generate a lot of revenue, add no value, and many pharmacists would add are a drain on their businesses. Let's face it - these businesses like most of healthcare in the US were essentially invented in Congress.  If they are not a recipe for making money - I don't know what is.  The Medicare Part D price negotiations through the Inflation Reduction Act is the first bright spot I have seen in a long time.  Republicans clearly want to maintain the status quo and that means extremely expensive medications and copays for anyone who is in the Medicare Part D coverage gap. If you were ever surprised by one of these copays like I was recently – support the Biden Administration’s attempt to control high drug prices.

George Dawson, MD, DFAPA

Supplementary 1:  An obvious point that I forgot in the original post in terms of backing Big Pharma is the idea that any physician would back limited access to a needed medication because of financial (rationing) restrictions.  Toward the latter half of my career, if anything physicians have made extraordinary efforts to get medications for their patients including having to manage large collections of samples and try to supply some patients from those samples.  Incredibly - some critics saw that as another perk from pharmaceutical companies that was corrupting physicians.  Some politicians on the other hand who are getting very large donations from pharmaceutical companies have no hesitation in suggesting that American patients should continue to pay exorbitant costs for pharmaceuticals - even if it means not being able to afford medication and compromised health.   

Supplementary 2:  Must watch video on regulatory capture or how Congress profits from disrupting free markets and establishing monopolies. Pharma and electronic health record (EHR) companies are cited examples, but there are additional examples including broadband and AI:

 https://www.youtube.com/watch?v=F9cO3-MLHOM

  

The Donut Hole Gets Real

 

Like most people my age I am taking some medications regularly and got the text message today from my pharmacy that I could pick up one of those prescriptions. The medication is a commonly prescribed medication from a group of medicine called  Non-Vitamin K antagonist oral anticoagulants or NOACs.  The medication is apixaban or Eliquis. People commonly take it to prevent blood clots or emboli and the complication including stroke, thrombosis, and pulmonary emboli. I have been taking it for about 2 years.

I usually get a prescription for 180 – 5 mg tabs and the last time I picked it up was on May 25, 2023.  At that time there was a copay of $94.  I am on Medicare A and B and a Medicare Supplemental Policy.

This time as I drove through the line the pharmacist told me the copay was $500. I asked him to clarify what had happened, but he had no idea.  Even though I had all of my previous refills at this pharmacy he had no idea what had happened and advised me to call the insurance company. When I got home that is exactly what I did. They advised me that this was the standard coverage gap for prescription drugs also known as the donut hole.  The insurance company pays for $4660 worth of medication (in my case almost all apixaban) and at that point copays stop and the patient is responsible for a flat 25% of the total cost of the medication or the $500).  When the patient incurs a total of $7,400 in pharmaceutical costs the number falls to 5% of the total, but by then it is probably a new year and the running tally resets. The customer service rep told me that I might be able to apply for assistance through company or state program, but they all had low-income requirements.

The donut hole started in 2006 as a result of the Medicare Prescription Drug, Improvement, and Modernization Act of 2003. All Medicare Part D plans have it. It initially required patients to pay 100% of the drug cost during the coverage gap.  That was reduced to the current 25% by the Affordable Care Act (ACA) passed in 2010. By 2025 there will be a cap of $2,000 for costs incurred in the coverage gap. 

It turns out that apixaban is number 10 on the list of 17 most expensive drugs purchased through Medicare programs.  In 2019, the average person taking it spent $7,234 for 12 refills per year and $2,172 in out-of-pocket costs.  A reform of this pricing has been suggested but obviously has not been done since I am paying about the 2019 list price.   The top drugs on this list are easily not affordable for many people. The cost of the top 5 agents are $16,348 to $182,162 per year with out-of-pocket costs ranging from $3,242 to $11,532 due to the coverage gap (1).  Apixaban in the single largest Medicare Part D expenditure at $12.5 billion per year (last filed in 2021).

Flashbacks of my work in acute care. For 22 years, I treated low to no income people in acute care settings. I was lucky to work with excellent social workers who would exhaust every available resource to help them with funding for medical care and housing.  Getting their medications funded was a chronic problem.  People on Social Security Disability do not get a lot of money each month.  At one point the state instituted a spenddown.  That meant if you were hypothetically making $1,000/month in disability payments, the state could demand that you spend a significant portion of your disability on medications before they would add any additional money for that purpose.  It is not possible to live very well – if at all under those financial constraints.

One of our attempts to adapt was to use the company scholarship programs to get them assistance from pharmaceutical companies. With many patients that took a great deal of coordination and filling out forms.  It also required nursing time for both the paperwork and an additional effort to manage free samples of medication. We were often scrambling to find medications in urgent situations or because one of the authorizations had lapsed.  All the samples also had to be catalogued by lot number in case there was a recall of that medication. I did not look forward to dealing with the forms or samples but realized we had to do it or some people would not get the medication they needed.

Today the tables were turned and I was looking at an arbitrary payment or I would not get the medication.  I have also heard this story many times. People unable to pick up a needed medication because of the copay – leading to an abrupt discontinuation or attempting to stretch out an existing medication until the first of the year. You really cannot stretch out an apixaban prescription.  I have read many news stories about people trying to stretch out their expensive forms of insulin resulting in medical compromise and death. I was lucky enough to have savings to cover the $500.

What are the problems with the donut hole?  I can think of at least 4:

1: It kicks the can down the road (also known as cost shifting). When confronted with these large payments, I can imagine a lot of people tell the pharmacist to forget about it and drive away. In the case of this medication that can lead to strokes, pulmonary emboli, thrombosis of large blood vessels, and/or death.  Treatment typically involves hospitalization and possible nursing home placement.  Worst case scenario might involve death, prolonged rehabilitation and the hospital or nursing home eventually seeks all of a patient’s assets to cover the accumulating bills.  All of those events could have been prevented with the prescribed medication.

2:  The structure of this billing is an incentive for pharmaceutical companies to increase prices since that will cause benefits to hit the wall earlier and cause the patient to enter the coverage gap and to pay more cash.  In fact, it is an obvious way to extract the maximum payment from both the insurance company and the patient. 

3:  It is another classic example of how politicians work to subsidize businesses in a non-transparent way.  I know more about medical billing than most people but I had no idea I was turning over $500 today until I was advised by the pharmacist.  

4:  This is a clear example of why the Republican and Libertarian ideas about "free market" healthcare are false.  In other words, we would choose to pay for what we really wanted in a free market and pay those market prices.  Obviously, anyone would pay $500 (or more) to prevent a stroke - but not if it means not eating.  The politicians involved will say: “well yes – but there is no free market.”  Of course, there is no free market. The market is actively manipulated to optimize profits for health care companies and minimize guidance from physicians.  That is the political system in the US. No doctor that I know of wants to prescribe a medication and hear at some point that the patient could not afford to take it. Sometime that news is very slow and the prescribing doctor does not find out until they see the patient back in a couple of months.

Don't ever think that American "free market" capitalism is a big deal in health care.  It is a big deal when politicians work with businesses to give them access to your assets and allows other businesses with more focal products like pharmaceuticals to charge whatever they want. There is no better example than the donut hole.  The cost savings that these companies promised is not from cost containment, but from rationing and that is a big difference. 

 

George Dawson, MD, DFAPA

 

References:

Dusetzina SB. Relief in Sight - Estimated Savings under Medicare Part D Redesign. N Engl J Med. 2021 Dec 23;385(26):e93. doi: 10.1056/NEJMp2116586. Epub 2021 Nov 10. PMID: 34758246.

Supplementary 1:

I downloaded this list of medication arranged by total Medicare Part D expenditure from the CMS web site on 8/26/2023.  The most recent data they have is for 2021.  Medications for psychiatric indications do not appear until # 24 Invega Sustenna and #31 Latuda.  More than a little interesting because psychiatrists have endured medication based attacks for over 20 years - primarily on grossly inflated conflict of interest concerns, pharmaceutical company profits concerns, and drug safety.  Many of those attacks continue today even though most of these medications are inexpensive generics and much of the rhetoric has lost its punch.  These same critics apparently have no similar concerns about significantly more profitable and higher risk medications.  That adds to my commentary in this post. 

Supplementary 2:  The Medicare Part Drugs selected for HHS negotiations with manufacturers include the following.    There is some overlap with the most expensive medication listed above but Farxiga, Entresto, Enbrel, and the list of diabetes mellitus medication are not on that list. For more information on the list click on the link at the bottom of the table. 

Medicare Drugs Selected by HHS for Price Negotiations

Eliquis

Jardiance

Xarelto

Januvia

Farxiga

Entresto

Enbrel

Imbruvica

Stelara

Fiasp; Fiasp FlexTouch; Fiasp PenFill; NovoLog; NovoLog FlexPen; NovoLog PenFill

https://www.hhs.gov/about/news/2023/08/29/hhs-selects-the-first-drugs-for-medicare-drug-price-negotiation.html

 

 

Graphic Credit:

Evan-Amos, Glazed Donut Public domain, via Wikimedia Commons"

Link:

https://commons.wikimedia.org/wiki/File:Glazed-Donut.jpgalt="Glazed-Donut

File:

https://upload.wikimedia.org/wikipedia/commons/thumb/a/a5/Glazed-Donut.jpg/512px-Glazed-Donut.jpg

 

 

 

 

 

 

 

 

The Whale

I finally saw this movie as it hit my subscription networks. It is an interesting story from many perspectives that is expertly told and acted. It raises several perspectives relevant to psychiatry but thankfully that explicit connection was left out of the production.  As the final credits rolled – I noticed that it was adapted from a play.  This is the closest I would come to seeing a play.  I do not think that I am constitutionally able to watch plays. They all seem contrived, overacted, and at times require a level of immediate and shared imagination that I do not possess.  I prefer solid ground as a jumping off point – even if things go awry from there.

The stark reality of this film is the home of Charlie (played by Brendan Fraser).  We meet him as he is teaching an online course in creative writing and see a typical Zoom interface. Charlie is the only one without a visual display.  He explains that his camera is broken. The scene cuts to his home. It is a dismal setting.  We see that Charlie is massively obese, barely able to ambulate and then with great effort, and in very poor health. At one point his nurse and friend Liz (played by Hong Chau) enters and tells him that he has hypertension and congestive heart failure to the point he needs to be seen emergently or he will be dead in a few days.  His poor health is displayed many times as he starts laughing but that rapidly turns into a cough and then chest pain. Over the course of the story, we learn that Charlie was not always like this but after losing his lover Alan to suicide he began overeating and gained a massive amount of weight. We see him binge eating at several points in the film – in one case biting off a fourth of a large meatball and cheese sub sandwich and obstructing his own airway to the point that Liz had to jump on his back to dislodge the food. After chastising him she picks the remaining sandwich off the floor and hands it to him.

The food theme is prominent over the several days duration of the film. Charlie gets a pizza delivered every day and he leaves the money in the mailbox.  The delivery driver talks with him through the door and eventually they address each other by their first names. At the last delivery the driver asks Charlies repeatedly if he is OK and appears to walk away.  As Charlie opens the door, he notices the driver is off to his left looking at him and appearing mildly shocked. Neither of them speaks but Charlie goes back in the house obviously upset and binge eats the pizza along with several additional items he adds from his refrigerator.

Charlie’s self-destructive eating and the associated self-loathing is a prominent theme throughout along with the expression of disgust.  He actively seeks confirmation that he is disgusting on a physical basis but only gets it spontaneously from his daughter Ellie (played by Sadie Sink).  Ellie is an angry teenager, performing suboptimally in school and she directs much anger at Charlie for abandoning her at 8 years of age when he left for the relationship with Alan.   Charlie actively seeks a relationship with her and at one point promises her a large sum of money just to spend more time with him, even though the time he has left is measured in days. He repeatedly apologized for his “bad decisions” in the past and emphasizes that he wants to try to make things right.  He would go as far as helping her write essays that might allow her to pass to the next grade in high school.

Two other characters are introduced over the course of the film.  Thomas (played by Ty Simpkins) shows up at Charlie’s door one day as a Christian missionary. He presents himself as a person intent on saving Charlie through God and Christianity.  He comes into dialogues with both Liz and Ellie.  Liz pointedly tells him to stay away from Charlie - that there are people who do not need to be saved.  She also points out the significant flaws in the local church that Thomas is affiliated with. Her father is the pastor of that church and Alan was her brother. Her father tried to arrange a marriage for Alan and described his suicide as a tragic accident. In his conversation with Ellie, Thomas discloses enough details of his life and why he might be estranged from his parents that Ellie is able to track them down. That eventually leads to reconciliation.

Charlie’s ex-wife Mary (played by Samantha Morton) appears toward the end of the film. There is a detailed discussion of the mistakes that were made and Mary’s chance meeting of Alan in a WalMart parking lot.  Even though there is a lot of tension, there is still an obvious level of caring between Charlie and Mary. Mary discusses Charlie’s unflagging optimism as one of his attributes that she misses. At some point it becomes obvious that the large sum of money that Charlie intends to give to Ellie may have come at a cost to his own health.  He has no health insurance and Liz points out what additional services he could have received.  Charlie refuses medical care and emergency services based on the cost, although that refusal is also consistent with his self-destructive path. He hears Liz describe the stress that he is putting her through but is unfazed.

Throughout the film, an essay about Moby Dick is referred to. The basic message of the essay is that the author can deny aspects of his own life and introspection about it – by focusing on killing whales. We eventually learn that this essay was written by Ellie when she was in the 5^th grade.  Charlie asks people to read him the essay when he is in a medical crisis with chest pain, shortness of breath, and diaphoresis.  He finds it comforting.  He also retypes the essay and gives it to her for school and she becomes enraged when she finds out. Charlie emphasizes that he only meant to show her that he appreciated her intelligence and creativity.

At a psychological level, Charlie is dependent and self-effacing. His motivation appears to be trying to correct past mistakes, especially abandoning Ellie, even though that was a complicated process that he was only partially responsible for. His reaction in these problematic scenarios is to accept the blame and go far beyond that to see himself as a disgusting person and ultimately a physically disgusting person (his characterization) that he produced by excessive eating.   

Several reviewers commented on the empathy in the film, but I really did not see any. Nobody seems interested in what happened to Charlie and how he got into this predicament – only that he is in it. They are attached to Charlie for various reasons but also out of their own self-interest.  As in real life, a lot of emotion happens in those settings as people are frustrated with Charlie when he does not accept their advice.

A relevant psychiatric dimension is the issue of involuntary treatment. In these last days of his life we see that Charlie has very high blood pressure, congestive heart failure, and possible angina that necessitate emergency care. Liz confirms that she has discussed his situation with an emergency medicine physician who concurs with her opinion.  Charlie even Googles his numerical blood pressure to confirm that it is an emergency. And through the film, he says he will not be treated and Liz agrees that she will not force the issue. But suppose that she wanted to.  What might happen in this situation?  Charlie could be transported to the ED, treated, and agree with admission for stabilization. He has no apparent psychiatric diagnosis, but it does not take too much imagination to see how any extended dialogue would get into the area of self-care and self-destruction to the point that the attending physician would consider an emergency hold. It is not uncommon to see people who have secluded themselves and not taken care of themselves admitted to inpatient psychiatric units with as many medical problems as Charlie. Suicide by food or lack of self-care is less dramatic than other methods but it can produce the same result.

Would Charlie be seen as depressed?  Probably – but is that the real problem? Moral injury seems to be a more proximate cause superimposed on a man who accepts all of the bad things happening in his life as his fault and reacts according. It allows him a veneer of optimism, while never having to confront the realty that human relationships are more complicated than that.  

Psychiatric speculation aside, this is a complex film that you must see.  The writing and acting is excellent.  The interpersonal drama has unique dynamics and is first rate.  I hope to see all these actors in other projects. It is a well thought out story line – right down to Charlie’s Zoom exit from his creative writing class. And importantly there is a clear message that there are all kinds of people out there struggling through life as best as they can every day. Those struggles may prove resistant to the insights and best advice from others.   

 

George Dawson, MD, DFAPA

I Have Hit A Wall

 I am currently working on two complex posts that will require a lot of research and graphics work but hopefully will be worth it at the end. I thought I would include a few comments about this here basically to document the progress and to see if anyone has already done the more detailed neuroscience post.  I also plan on taking a break by posting on a topic that I can more easily cover about – subclinical hypothyroidism.  That will hopefully appear in the next few days. There is a long history of endocrinology interfacing with psychiatry and as a research fellow in that field I am very aware of the associated concepts.

The complex posts are the neuroscience of a central autonomic network (CAN) and the borderline personality disorder concept. I am very interested in the CAN because of the issue of cardiac anxiety. In other words – can the heart itself be a source of anxiety and if that is the case should it be addressed differently?  And what are the implications for nosology?  The current DSM approach is agnostic when it comes to potential mechanisms of anxiety, but should it be? Considering the wide variety of medical approaches for anxiety including a few that are cardioselective – it would be useful to know if the anxiety originates in the brain or somewhere else and if that implies a different type of treatment.

The borderline personality disorder concept has always been controversial – but various psychiatrists and researchers also have a history of addressing the controversies and providing solutions for patients.  Most importantly those techniques have demonstrated efficacy for reducing suicidal ideation and self-injurious behaviors. Despite those advances an editorial in a recent British journal called for the abandonment of that diagnostic class and substituting an older diagnosis. Much of the justification for replacing the diagnosis seems to suggest that it is a pejorative label.  Having worked in a multitude of medical settings I can attest to the fact that pejoratives exist everywhere in medicine and it has very little to do with diagnostic criteria. It is largely related to countertransference issues by health care workers who are unaware of that concept and who are psychologically unable to maintain a neutral stance in emotionally taxing situations with patients. Changing a diagnosis is unlikely to change that predicament. I could generate a long list of what I have heard patients referred to – but is counterproductive and does not address the issue. I am not suggesting that every health care worker needs training in countertransference management.  Maintaining a professional stance can occur with appropriate coaching, education, and supervision.  As an example, I was asked to consult during a grand rounds on this topic presented by Emergency Medicine and comment on physician reactions in common situations.    

The basic problem with the CAN concept is not the basic structures involved but the initial signals and connectivity.  As an example, I am looking at my diagram of the subfornical organ and note there are 10 major efferent connections and 6 major afferent connections with some overlap.  The subfornical organ is one very small component of the CAN.  Not sure about my ability to diagram that complexity but I am going to give it a try.

I am also hoping this comment about hitting this wall provides me with some insights on how to approach this work. My only full-time job these days is blogging. After doing several presentations in the past year – I know I am much more enthusiastic about what I am researching and presenting than anybody who attends those presentations. I am also aware of the biases in society against old people and retired people. But I can’t let any of that get to me. I will stop when it is obvious that I have nothing left to contribute or I am stopped by a health problem.   

When you are a blogger – it seems like it is always feast or famine.  I have been very productive and posted what I think are excellent posts that nobody reads.  At other times and seemingly out of the blue there are bursts of reader activity that are hard to decipher with the available tools on blogger.  A friend of mine read through a few of my posts and said: “That is a lot of work.”  I appreciated that comment because it captured the reality of many posts and the implicit “for nothing.”  I still think there is an undercurrent of thinking that all bloggers or influencers get paid for what they post.  I have never been reimbursed for what you see written here and all the permissions that I have acquired over the years specifies the non-profit aspect. 

Finally – if you do read what I post here I appreciate it. Take the time to let me know if you want to see any psychiatry or medicine specific topic and I will do my best to write about it. If you look back over the years of posts – several firsts have been posted here that are not seen anywhere else – both in psychiatry and medicine in general. I see that as validation of some of my approaches.

In the meantime – stay tuned!

 

George Dawson, MD, DFAPA

 

 

Graphics Credit:

Atrribution:

I, Xauxa, CC BY-SA 3.0 <http://creativecommons.org/licenses/by-sa/3.0/>, via Wikimedia Commons

Page URL:

https://commons.wikimedia.org/wiki/File:Solna_Karolinska_institutet_Brick_wall02.jpg

File URL:

https://upload.wikimedia.org/wikipedia/commons/8/88/Solna_Karolinska_institutet_Brick_wall02.jpg

 

Is This An Episode of the X-Files?

I am a life long science fiction fan and that includes the X-Files, Fringe, and Millennium.  I consider these shows to be high quality sci-fi but at the same time don’t believe that any of this stuff happens in real life. Recent events suggest that we seem to be in the midst of some kind of mass belief system that we have not only been visited by aliens but we also possess their aircraft and have been attempting to reverse engineer it.  If that is not enough, we have biological specimens from these extraterrestrial beings and confirmation that they are not human. Further that there has been a conspiracy to cover up these events that has resulted in homicide(s) and that the motivation is the power source technology in these aircraft could destroy the fossil fuel business – hence the conspiracy.  X-Files creator Chris Carter could not have come up with a better storyline.  The only thing we are missing - agents Fox Mulder and Dana Scully.  

This story rapidly unfolded as a result of Congressional testimony by Maj. David Grusch (retired) who is described as an intelligence officer.  In the introduction he described learning about the acquisition of unidentified aerial phenomena (UAP) aircraft and a reverse engineering program operating at levels of secrecy above the level of the government.  Cmdr. David Fravor described his encounter with a high-speed large Tic Tac shaped UAP object.  It was the only UAP incident that he encountered as a pilot.  The other aviator to testify was Ryan Graves described as a former F-18 pilot.  His statement emphasizes that aviators are trained observers and that there have been no credible UAP explanations to account for the perceived technology.  The message from all three witnesses endorses the need for transparency, protection for witnesses who are generally military and commercial pilots that may be stigmatized by these reports, and the need for a systematic reporting system that is transparent (to a point), and allows for adequate investigation of these phenomenon since they may represent a risk to flight safety and national security.

The follow up on the evening news was a report on TMZ that consisted a segment entitled UFO Whistleblower Makes Bombshell Claims. TMZ leader Harvey Levin is an attorney and journalist by training and generally takes an affiliative approach to people he interviews.  The TMZ web site has a section devoted to the UAP/UFO issue. On the July 27 program (10:36 mark) he interviewed Congressman Tim Burchett (R-TN) about the testimony specifically about whether murders had been committed to cover up the whereabouts of alien spacecraft.  Harvey Levin’s  specific questions: “Do you have evidence of somebody or people being murdered who were potential whistleblowers?” and “That intelligence officer was telling you guys I want to lead you to the right authorities – is Congress pursuing that?”   

Congressman Burchett said that in order to get the classified testimony the panel needs to go to the skiff  or a highly secure area to hear it and that he has requested that access. The Congressman makes it seem like there is an orchestrated attempt to prevent that from happening: “It’s like whack-a-mole man – you hit that thing and another one pops up.”  Given the tenor of Grusch’s testimony and the fact that he is no longer an intelligence officer and probably does not have security clearance it seemed like standard protocol rather than whack-a-mole to me.  The Congressman goes on to say that “he knows where the bodies and the craft are.”  He continues to say that he has seen things that “you would not believe” and agreed with a colleague that these objects were nothing that the US or it’s adversaries have so “it had to be something from out of that realm.”  He alludes to a conspiracy against UAP/UFO investigations: “We’re getting close to the target that’s why they are firing at us.  They put up every obstacle imaginable.”  When Harvey Levin asks about the motivation for this conspiracy Burchett replies: “Because it’s an energy source that would put a lot of billionaires out of work.,,, it’s about power, it’s about money it’s about deceit and that’s what defines Washington DC – both parties.”

To recap – we have testimony of aviators, an intelligence officer, and these statements by a US Congressman outlining a conspiracy to conceal alien spacecraft and life forms from the people and the Congressman was good enough to provide a rationale. But are there any inconsistencies in that story? It turns out there is.  Only 1 of the 3 witnesses testifies that people have been harmed and possibly murdered as part of the coverup. In fact, one witness explicitly said that he and several other pilots reporting the UAP phenomenon had never heard of such a thing. Then there are the suggested remedies for the current problem including a systematized reporting system, guarantees of no repercussions for the reporting pilots, and concerns about the security of the US air space.  If these were really EAP/UFOs would any of that be necessary? The testimony included speculation that the technology of the observed vehicles greatly exceeded anything available here on earth.  That implies that if these really are extraterrestrials – they can do whatever they want. I can extrapolate to say that if enemies of the US had that level of technology, they could easily do the same. There was also the theme of underreporting due to stigma.  The USA already has by far the most UFO sightings of any country – ten times more than the next country and more than the next 5 countries on the list at 105,000 incidents. Are we hoping to generate even more?  The statements by Congressman Burchett also seem problematic – not just from the conspiracy angle but also the motivation for the conspiracy to conceal the evidence. Suddenly we have a Republican Congressman backing inexpensive and clean energy and peace for the common man in the form of no more unnecessary wars for petroleum?  And all it took was discovering an alien energy source transported hundreds of light years across the galaxy?  All these inconsistencies cause me to hit the pause button.

An even more striking counter point was provided in the morning by astronomer Saavik Ford, PhD (8).  Qualifying her remarks by saying that there is nothing more astronomers would like than to discover alien life, that many astronomers became interested in the field by exposure to science fiction, that she was named after a Star Trek character, and the statistical argument that given the number of stars in the galaxy the odds are high that there are habitable planets that would support life out there – she proceeds to provide clear and convincing counterarguments to why there is no evidence of alien life forms on Earth.  She states: “There has never been any evidence of alien craft or alien people or creatures that are coming to visit us.”  When asked specifically about the testimony she points out that astronomers have been scanning the skies every night for decades and have seen no evidence, especially the amount of material suggested. She points out that the Voyager probes will takes 80,000 years to reach the nearest star – therefore aliens visiting Earth would need unimaginable technology to cover that distance in a reasonable amount of time.  She also debunks the idea that discovering “amazing technology” would lead to cover-ups but rather proliferation to the point that it would be apparent in other aspects of life.  She described the “leap from 'unidentified' to 'it must be aliens'” as a “bizarre psychological phenomenon” that is unique to the US.  At that point she describes the concentration of UFO sightings in the US and asks why aliens would travel hundreds of light years for long periods of time just to visit the United States?  She ends by reiterating that astronomers would not only like to discover life forms in space but also would like the proof so that they could use it as leverage against NASA and NSF budget cuts.

If you have read to this point and looked at the evidence, think about your conclusions so far. Think about the emotion elicited by the Congressional hearing and the way it was portrayed in the popular press and tabloid news. I can qualify my opinion in a similar way to Dr. Ford.  I read nothing but sci-fi in middle school and watched all the science fiction that I could on TV and in movies. X-Files, Fringe, and Millennium were some of my favorite shows. I am not sure about the positive effects of discovering alien life forms but I am certain that has probably not happened.  

My money is on Dr. Ford.

George Dawson, MD, DFAPA

Request for Information:  I am interested in acquiring a copy of a photo of the Tic Tac shaped UFO/UAP described in the above post.  I saw the original in a network television video and it looked exactly like a very large white Tic Tac (about 40 feet long).  I can't find it anywhere and the only declassified UAP video and photos that I can find are the usual grainy black and white photos.  The photo of the Tic Tac object was much higher in resolution.  If you know where I can find these images please post the link to me here.  Thanks.

References:

1:  U.S. recovered non-human 'biologics' from UFO crash sites, former intel official says.  MPR July 27,2023  Link

2:  Subcommittee on National Security, the Border, and Foreign Affairs Hearing.  Accessed on July 27, 2023  https://www.youtube.com/watch?v=KQ7Dw-739VY&t=2550s

3:  Subcommittee on National Security, the Border, and Foreign Affairs.  https://oversightdemocrats.house.gov/subcommittees/subcommittee-on-national-security-the-border-and-foreign-affairs

4:  Cmdr David Fravor (retired).  July 27, 2023. Statement for the House Oversight Committee.  https://oversight.house.gov/wp-content/uploads/2023/07/David-Fravor-Statement-for-House-Oversight-Committee.pdf

Statement on encounter with high-speed Tic-Tac UAP in 2004

5:  Ryan Graves. Statement for House Oversight Committee.  July 27, 2023.  https://oversight.house.gov/wp-content/uploads/2023/07/Ryan-HOC-Testimony.pdf

6:  David Grusch.  Statement for House Oversight Committee.  July 27, 2023.  https://oversight.house.gov/wp-content/uploads/2023/07/Dave_G_HOC_Speech_FINAL_For_Trans.pdf

7:  TMZ show of July 27, 2023 – links in the above text.

8:  Top Story with Tom Llamas - July 26 | NBC News NOW  accessed on 7/16/2023.  Dr. Ford’s interview begins at the 40-minute mark:  https://www.youtube.com/watch?v=vPNBWTS7WuM

9:  UFO Optical Illusions - Astronaut Kelly says it's hard to ID strange objects in flight.   https://www.youtube.com/watch?v=p_O7B6Ld4Zs

Supplementary 1:

This Twitter video is an excellent example of how easy it is to make a perceptual error and misidentify an object that appears in the perceptual field:  https://twitter.com/i/status/1685679542927847424

Graphics Credit:

maxime raynal from France, CC BY 2.0 https://creativecommons.org/licenses/by/2.0, via Wikimedia Commons.  The file is not altered in any way.

Page URL:  https://commons.wikimedia.org/wiki/File:Ufo_-_Flickr_-_Amanclos.jpg

File URL:  https://upload.wikimedia.org/wikipedia/commons/5/5d/Ufo_-_Flickr_-_Amanclos.jpg

Post SSRI Sexual Dysfunction (PSSD) - Current Status

 

Post Selective Serotonin Reuptake Inhibitor Sexual Dysfunction (PSSD) is a proposed disorder of sexual dysfunction that continues after antidepressant medication has been discontinued.  The symptoms include (2) prior treatment with an SSRI, a change in genital sensation after the SSRI has been stopped, decreased libido, anorgasmia, erectile dysfunction, and a duration of symptoms for 3 months following the cessation of the SSRI.  It is also a diagnosis of exclusion since pre-SSRI sexual dysfunction and other medications or medical conditions that could account for the symptoms need to be ruled out. It is a controversial diagnosis at this point because the true prevalence of the condition is unknown and the studies of the condition are generally low quality.

The diagnostic criteria for PSSD and PGAD are listed in the graphic above. It is not clear at this point what the diagnostic standard is for these disorders and heterogeneity is clearly an issue. For example, do a certain number or pattern of symptoms need to be present or could a single symptom be present with SSRI exposure and qualify for the diagnosis.

The controversy about PSSD reached its zenith with a recent article suggesting that antidepressants caused “chemical castration.”  When I first heard about this issue a few years ago it reminded me of the decades old problem of priapism (persistent painful erections) associated with trazodone use.  At the time (now about 27 years ago) I did a literature search on the incidence of spontaneous priapism in adult males and found that it matched the frequency suggested with trazodone use - but there were problems with determination of the true prevalence in both cases.

Prevalence estimates in the literature are approximate because they depend either on voluntary reporting (since there is no formal pharmacovigilance system in the United States) or available survey samples that typically have some obvious bias. In the 27 years since, I have warned every male patient I prescribed trazodone to and what to do about the problem. None of those patients developed priapism.  Two noticed they had AM erections that seemed unusual but did not develop priapism.  They ignored the erections, did not call me, and noticed that everything went back to normal.  In my experience, that is how most people manage side effects – even when you tell them they are potentially severe and may require medical or surgical intervention.

My experience with sexual side effects of antidepressants is similar. Since these side effects are common with antidepressants – it is one of many that I verbally advised patients about. My protocol was to provide people with the MedlinePlus handouts, advise them how to access the package insert for all of the detailed information, but then discuss the side effects they are most likely to encounter including antidepressant withdrawal, rare side effects that can be very serious like serotonin syndrome and drug induced liver disease, and a general advisory to call me with any questions about what might be a drug side effect: "If you feel ill assume it may be the medication and call me."  On the latter, I emphasize the call to me should been as soon as the problem develops and that I never expect that a person will “get used to” medication side effects.

The literature suggests that direct discussion of sexual side effects is more likely to result in patient reports if those side effects occur. In my experience it generally requires an explanation of what to look for in terms of libido and actual sexual functioning. Assessment is complicated by the high prevalence of these symptoms in depression and the fact that some people prefer the antidepressant effect over any lack of effect or deleterious effects on sexual functioning.

A logical place to start considering PSSD is to look at prevalence estimates from available studies.  A 19-year retrospective observational analysis of 12,302 men in an HMO setting (1) estimated the prevalence of PSSD to be 1 in 216 patients (0.46%) treated with SSRIs. The prevalence of PSSD was 4.3 per 100,000.  Cases were identified by exposure to SSRI and treatment of (erectile dysfunction) ED with PDE-5 inhibitors.  Other conditions were ruled out on an administrative basis based on BMI and medications that that potentially cause ED.  The authors point out that the design had limitations in that the trade-off of medical treatment as a proxy for ED diagnoses may underestimate the prevalence of ED/PSSD. 

In a second systematic review (2) – look at PSSD and Persistent Genital Arousal Disorder (PGAD).  PGAD can occur in the context of no treatment with an SSRI but it has also been reported after SSRI treatment.  The main differentiating point is that is has sensations of persistent genital arousal or genital dysesthesias. It may also be associated with uncontrolled orgasms.  Time criteria suggested is greater than 3 months.

These authors reference the European Medicines Agency (EMA) recognizing the PSSD diagnosis in 2019 (3).  Unfortunately, the EMA web site is only slightly more user friendly that the FDA website.  I have linked to the referenced document and included the relevant text at the top of this post.  I could find no more detailed information about the rationale for inclusion.  The suggested links just brought me back to the original document. References or even regulatory documents would be useful in this case to determine the EMA rationale for this position. It appears to have been based on a pharmacovigilance signal and that could be generated from registries in Europe, but at this point I cannot confirm the information.

The available literature on PSSD consists primarily of case reports, speculation about the biological plausibility of the disorder, and in the discussions calls for more studies of the true prevalence of the disorder.   19 studies were included in the review. Incidence or prevalence of PGAD could not be determined.

Physical causes of some of these symptoms are obviously important.  Herpes zoster or shingles infections cause about 100,000 cases of genital dysesthesias per year. There have been reports of Herpes simplex genital viral infections (HSV-1, HSV-2) causing similar symptoms. HSV-1 and HSV-2 cause significant neuropathic symptoms during acute recurrences, but that has been thought to resolve with each recurrence. Local and systemic neurological conditions affecting pelvic nerves and the autonomic nervous system are also potential causes.  There are many complicating factors when considering sexual dysfunction in the population as a whole, in untreated depression and in treated depression.

1:  Baseline rate/causes of sexual dysfunction:

In the largest post Kinsey study (7,8) , a national probability sample in the US looked at 7 indicators of sexual dysfunction including decreased desire for sex, arousal difficulties, inability to achieve climax, anxiety about sexual performance, climaxing or ejaculating too soon, physical pain during intercourse, and not finding sexual intercourse pleasurable. Only sexually active respondents were analyzed. 43% of women and 31% of men reported a problem.  Psychosocial and medical factors were also investigated and found to be relevant.  The authors conclude that sexual dysfunction is a significant public health problem.  The codebook for the original study was downloaded and medication history was not included.

2:  Baseline rate of sexual dysfunction due to depression:

Rates of sexual dysfunction in both sexes due to depression are similarly high. A comprehensive review of that literature by Gonçalves, et al (9) showed high rates of dysfunction in women than men.  Their data is summarized in the far right column in the table below.  These researchers also pointed out an important methodological problem with studies that depend on standard rating scales - some do not ask if the respondent considers the symptom to significantly affect their level of functioning. It is possible to do a rating scale experiment that show impairment when the respondent does not believe they are impaired.

3:  Antidepressant sexual side effects:

Sexual side effects are a well-known side effect of modern antidepressants.  Various strategies have been suggested over the years to reduce or eliminate these side effects.  The only strategy I found effective was to change to a different antidepressant.  Prevalence rates of these side effects were initially available from package inserts and comparisons with placebo in drug trials.  The last summary information I have looking at those numbers is from the 2012 Drug Facts and Comparisons.  In a comparison of all of the available SSRIs at the time the following rates were suggested: decreased libido 1-12%, paresthesia (non-specific) 1-4%, abnormal ejaculation 6-27%, female genital disorders 2-10%, male genital disorders 4-10%, sexual dysfunction/impotence/anorgasmia 1-13%.   Comparisons across antidepressant classes is difficult because of changing categories. For example, SNRIs (venlafaxine, desvenlafaxine, duloxetine, milnacipran) generally have lower sexual dysfunction figures.  By the time duloxetine was marketed the package insert contained ratings from the Arizona Sexual Experiences Scale (ASEX) and comparisons with placebo.

 Conclusions:

 There are several problems with the current conceptualization of PSSD including:

1:  The evidence basis is largely anecdotal case reports, case series and abundant speculation based on those case reports.  There are no controlled studies so the prevalence of PSSD in populations untreated with antidepressants is unknown. Experts in the PSSD field also suggest this is due to changing diagnostic criteria (Goldstein).

2:  Both untreated depression and treated depression have significant symptom overlap with the suggested diagnosis of PSSD

3:  The incidence of sexual dysfunction in the general population without depression who have never been treated with antidepressant medication is high and varies as expected with comorbidities, age and other medical treatments. (Laumann). 

4:  There are no validated instruments or protocols to identify cases of PSSD. Multiple authors suggest determining the prevalence of the problem more accurately but that study would have to be carefully designed.

5:  Opinions in the popular press can bias prevalence studies at this point.  In the past, survey studies have proven that they can elicit any predetermined opinions and should be avoided.  How to eliminate this factor introduced by the press and anti-antidepressant advocates is not clear.  

6:  The determination of the pharmacovigilance signal by the EMA should be clarified.  It is possible that I did not find it.  In that case, I would appreciate being directed to that source. I emailed the European Medicines Agency asking for clarification on July 10 and am still waiting for a response. The process also has lessons for the United States.  I have long been an advocate for a more formal pharmacovigilance system in the US.  The next step would be a system like the Netherlands where any person could call in a suspected adverse event and there would be a connection to formal regulation as wording in package inserts.

7:  For psychiatrists in the US, I would see the current situation as comparable to the FDA warnings on suicidal behavior and suicidality on SSRIs and treat it the same way.  Even though pharmacovigilance in the US is basically post marketing surveillance, it makes sense to add PSSD/PGD to the informed consent discussion with patients as a potential risk of antidepressant treatment. It can be mentioned in the same discussion as sexual side effects from these medications. I would also describe these diagnoses as a work in progress at this point due to the limiting factors.

8:  The impact of the current level of discussion in the press and the effect it may have on patients taking antidepressants has not been determined at this point. In my practice in the past, most people make their own determinization of whether these warnings apply to them and may discuss it in the office, but it is reasonable to ask if they have any concerns while discussing side effects.

9: Ideological bias – there is clearly a faction of criticism that conflates pharmaceutical interests with psychiatry and makes it seem like there is a psychiatric agenda to overprescribe medications and cover-up side effects.  This same faction has a very limited to non-existent scientific basis and an equally robust clinical approach to psychiatric problems. More importantly they appear to not treat serious problems and at times have criticized people who find both psychiatric diagnosis and treatment helpful. An awareness of this bias is necessary when evaluating literature focused on the characterization and prevalence of PSSD. 

10:  Ratings from existing trials: The current controversy is reminiscent of the emotional blunting controversy (10) and the suggestion that antidepressants work by blunting emotions. Ron Pies and I reviewed studies that used the Montgomery–Åsberg Depression Rating Scale (MADRS) to show that decreased feeling was correlated with depression and that emotional blunting improved with treatment.  Existing rating scales for antidepressant trials have only 1 item that rates sexual functioning and that it the Hamilton Depression Rating Scale (HAMD). There is limited opportunity to do retrospective studies on existing clinical trials on that basis.

11:  The nocebo effect: The nocebo effect is essentially a negative expectation or expectancy that affects both the potential efficacy and side effect profile of a medication.  The effect is significant for all medication including antidepressants.  In antidepressant trials an analysis of the placebo exposed group showed that 63.9% reported treatment emergent adverse events, 11.2% experienced worsening depression, and 4.7% discontinued the trial due to an adverse event – all while taking placebo. In a recent review Colloca and Barsky discuss the importance of the media, press, and direct exposure to people with adverse events “all foster nocebo responses.” They give an example of how negative press coverage led to a 2,000 fold increase in adverse event reporting when a new medication covered by the national health plan came out. 

 If you have followed my various lines of reasoning so far it is probably apparent that I take any pharmacovigilance signal seriously. You must when you are a clinician who warns people about side effects that occur in the 1 in 10,000 to 1 in 50,000 range.  I consider the best prevalence estimate in this case to be less than 1 in 1,000, but all the experts clearly acknowledge problems with the diagnostic criteria and changing criteria.  In order to take the PSSD problem seriously it must be considered a multidisciplinary problem. Psychiatrists, neurologists, OBGYN specialists, urologists, psychologists, and physical therapists have all written about the problem and in many cases documented successful treatments. In some of those papers, multiple individual or combined treatments were highly successful. From a psychiatric standpoint, SSRIs have been resumed and treatment like adding bupropion or vortioxetine have seen successful – but the evidence basis is very limited. If this condition came to my attention in a patient, I was treating my preferred approach would be to discontinue the SSRI or SNRI if possible and develop a referral source where I could refer the patient for the necessary evaluation looking for neuropathic causes and documenting the level of sexual dysfunction. In my region that would probably involve referrals of men and women to a well-known Urology clinic that has sub-specialists in this area. The ultimate plan would also depend on patient preference, individual history of treated depression, and where the research in this disorder was at the time. Every individual needs a unique plan and looking at the heterogeneity of findings in this research – unique plans will be the rule and not the exception.

Currently, prevalence studies as well as studies that look at the issue of how these symptoms vary as people transition during episodes of treatment for depression and/or anxiety are required.  That will be a significant undertaking.  Observational studies based on active treatment may be a suitable substitute but safeguards need to be taken to assure adequate documentation of baseline sexual dysfunction, a clearly defined diagnosis and diagnostic thresholds, correlation with antidepressant treatment, and hopefully resolution both with or without treatment.

Lastly, if you are a person with any of the sexual problems described in this post – antidepressant related or not the best potential solution is a direct discussion with your personal physician or psychiatrist. If necessary, send them a link to this post and suggest they read the last two paragraphs. As always my posts are intended to be educational informed by clinical practice and not suggest that I know more than anyone else.

 

George Dawson, MD, DFAPA

 

 

References:

1:  Ben-Sheetrit J, Hermon Y, Birkenfeld S, Gutman Y, Csoka AB, Toren P. Estimating the risk of irreversible post-SSRI sexual dysfunction (PSSD) due to serotonergic antidepressants. Ann Gen Psychiatry. 2023 Apr 21;22(1):15. doi: 10.1186/s12991-023-00447-0. PMID: 37085865; PMCID: PMC10122283.

2:  Tarchi L, Merola GP, Baccaredda-Boy O, Arganini F, Cassioli E, Rossi E, Maggi M, Baldwin DS, Ricca V, Castellini G. Selective serotonin reuptake inhibitors, post-treatment sexual dysfunction and persistent genital arousal disorder: A systematic review. Pharmacoepidemiol Drug Saf. 2023 Jun 9. doi: 10.1002/pds.5653. Epub ahead of print. PMID: 37294623.

3:  European Medicines Agency. Pharmacovigilance Risk Assessment Committee recommendations on safety signals. 11 June 20191 EMA/PRAC/265221/2019 Pharmacovigilance Risk Assessment Committee (PRAC).  https://www.ema.europa.eu/en/documents/other/new-product-information-wording-extracts-prac-recommendations-signals-adopted-13-16-may-2019-prac_en.pdf

4:  Healy D, Bahrick A, Bak M, Barbato A, Calabrò RS, et al. Diagnostic criteria for enduring sexual dysfunction after treatment with antidepressants, finasteride and isotretinoin. Int J Risk Saf Med. 2022;33(1):65-76. doi: 10.3233/JRS-210023. PMID: 34719438; PMCID: PMC8925105.

5:  Lewer, D., O'Reilly, C., Mojtabai, R., & Evans-Lacko, S. (2015). Antidepressant use in 27 European countries: Associations with sociodemographic, cultural and economic factors. The British Journal of Psychiatry, 207(3), 221-226. doi:10.1192/bjp.bp.114.156786

6:  Goldstein I, Komisaruk BR, Pukall CF, et al. International Society for the Study of Women's Sexual Health (ISSWSH) Review of Epidemiology and Pathophysiology, and a Consensus Nomenclature and Process of Care for the Management of Persistent Genital Arousal Disorder/Genito-Pelvic Dysesthesia (PGAD/GPD). J Sex Med. 2021 Apr;18(4):665-697. doi: 10.1016/j.jsxm.2021.01.172. Epub 2021 Feb 19. PMID: 33612417.

7:  Laumann EO, Paik A, Rosen RC. Sexual dysfunction in the United States: prevalence and predictors. JAMA. 1999 Feb 10;281(6):537-44. doi: 10.1001/jama.281.6.537. Erratum in: JAMA 1999 Apr 7;281(13):1174. PMID: 10022110.

8:  Laumann, Edward O., Gagnon, John H., Michael, Robert T., and Michaels, Stuart. National Health and Social Life Survey, 1992: [United States]. Inter-university Consortium for Political and Social Research [distributor], 2008-04-17. https://doi.org/10.3886/ICPSR06647.v2 

9:  Gonçalves WS, Gherman BR, Abdo CHN, Coutinho ESF, Nardi AE, Appolinario JC. Prevalence of sexual dysfunction in depressive and persistent depressive disorders: a systematic review and meta-analysis. Int J Impot Res. 2023 Jun;35(4):340-349. doi: 10.1038/s41443-022-00539-7. Epub 2022 Feb 21. PMID: 35194149

10:  Dawson G, Pies RW.  Antidepressants do not work by numbing emotions. Psychiatric Times. Sept 26, 2022:  https://www.psychiatrictimes.com/view/antidepressants-do-not-work-by-numbing-emotions

11:  LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Adverse Drug Reaction Probability Scale (Naranjo) in Drug Induced Liver Injury. [Updated 2019 May 4]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK548069/

12:  Colloca L, Barsky AJ. Placebo and Nocebo Effects. N Engl J Med. 2020 Feb 6;382(6):554-561. doi: 10.1056/NEJMra1907805. PMID: 32023375.

13:  Haanpää M, Paavonen J. Transient urinary retention and chronic neuropathic pain associated with genital herpes simplex virus infection. Acta Obstet Gynecol Scand. 2004 Oct;83(10):946-9. doi: 10.1111/j.0001-6349.2004.00500.x. PMID: 15453891.

14:  Ooi C, Zawar V. Hyperaesthesia following genital herpes: a case report. Dermatol Res Pract. 2011;2011:903595. doi: 10.1155/2011/903595. Epub 2011 Apr 18. PMID: 21747842; PMCID: PMC3130996.

15:  Whalen AM, Mateo CM, Growdon AS, Miller AF. Sacral Myeloradiculitis: An Uncommon Complication of Genital Herpes Infection. Pediatrics. 2019 Jul;144(1):e20182631. doi: 10.1542/peds.2018-2631. PMID: 31217310.

16:  Reisman Y. Sexual Consequences of Post-SSRI Syndrome. Sex Med Rev. 2017 Oct;5(4):429-433. doi: 10.1016/j.sxmr.2017.05.002. Epub 2017 Jun 20. PMID: 28642048.

 

 

Case Reports (not exhaustive – truncated at 10 – I think these references capture the largest numbers):

1:  Ekhart GC, van Puijenbroek EP. Blijvende seksuele functiestoornissen na staken van een SSRI? [Does sexual dysfunction persist upon discontinuation of selective serotonin reuptake inhibitors?]. Tijdschr Psychiatr. 2014;56(5):336-40. Dutch. PMID: 24838589.

From 2002 to 2012, 19 cases reported to Netherlands Pharmacovigilance Centre, Lareb occurring after patients has stopped the medications for 2 months to 3 years. Approximately 1 million people per year are prescribed antidepressants in the Netherlands.  See: https://www.statista.com/statistics/718241/usage-of-dispensed-antidepressants-in-the-netherlands/

2:  Patacchini A, Cosci F. A Paradigmatic Case of Postselective Serotonin Reuptake Inhibitors Sexual Dysfunction or Withdrawal After Discontinuation of Selective Serotonin Reuptake Inhibitors? J Clin Psychopharmacol. 2020 Jan/Feb;40(1):93-95. doi: 10.1097/JCP.0000000000001154. PMID: 31834096.

3:  Bolton JM, Sareen J, Reiss JP. Genital anaesthesia persisting six years after sertraline discontinuation. J Sex Marital Ther. 2006 Jul-Sep;32(4):327-30. doi: 10.1080/00926230600666410. PMID: 16709553.

Single case of a 26-year-old man.

4:  Waldinger MD, van Coevorden RS, Schweitzer DH, Georgiadis J. Penile anesthesia in Post SSRI Sexual Dysfunction (PSSD) responds to low-power laser irradiation: a case study and hypothesis about the role of transient receptor potential (TRP) ion channels. Eur J Pharmacol. 2015 Apr 15;753:263-8. doi: 10.1016/j.ejphar.2014.11.031. Epub 2014 Dec 4. PMID: 25483212.

43 yr old man with loss of smell, taste, and skin sensation shortly after he started to take paroxetine for depression.  He has associated problems with sexual functioning and sensation for 2 years after the paroxetine was discontinued.  Full Text

5:  De Luca R, Bonanno M, Manuli A, Calabrò RS. Cutting the First Turf to Heal Post-SSRI Sexual Dysfunction: A Male Retrospective Cohort Study. Medicines (Basel). 2022 Sep 1;9(9):45. doi: 10.3390/medicines9090045. PMID: 36135826; PMCID: PMC9503765.

13 male patients referred for treatment.  PSSD sx onset 2-4 weeks after discontinuation of SSRI.  Retrospective, uncontrolled treatment study. Most patients were significantly improved at 12 month follow up after treatment with vortioxetine, bupropion, or mechanical stimulation on a standard scale.

6:  Reisman Y, Jannini TB, Jannini EA. Post-selective serotonin reuptake inhibitor sexual dysfunctions (PSSD): clinical experience with a multimodal approach. Journal of Men's Health. 2022 Aug 1;18(8):165.

12 male patients with a “high probability” of PSSD 9-26 months post treatment with an SSRI (one patient was treated with amitriptyline). Retrospective, uncontrolled treatment study with all patients improving at 12 months.

7:  Chinchilla Alfaro K, van Hunsel F, Ekhart C. Persistent sexual dysfunction after SSRI withdrawal: a scoping review and presentation of 86 cases from the Netherlands. Expert Opin Drug Saf. 2022 Apr;21(4):553-561. doi: 10.1080/14740338.2022.2007883. Epub 2021 Nov 27. PMID: 34791958.

86 cases reported to the Netherlands Pharmacovigilance Center of Lareb from 1992 to 2021.  Longest duration was 23 years.  Common symptoms were loss of libido, erectile dysfunction, and anorgasmia.

8:  Dannon PN, Iancu I, Cohen A, Lowengrub K, Grunhaus L, Kotler M. Three year naturalistic outcome study of panic disorder patients treated with paroxetine. BMC Psychiatry. 2004 Jun 11;4:16. doi: 10.1186/1471-244X-4-16. PMID: 15191617; PMCID: PMC441384.

143 patients with panic disorders treated with paroxetine were followed for one an acute treatment phase followed by either 12 month or 24-month paroxetine maintenance.  Relapse rates in both groups were similar. Sexual side effects were determined clinically rather than a structured interview asking about sexual desire and sexual function. Prevalence of sexual side effects was 30% in both groups and the presence of agoraphobia potentiated these side effects – consistent with some psychological theories.  Not clear about the status of sexual side effects during the discontinuation phase.

9:  Healy D, Le Noury J, Mangin D. Enduring sexual dysfunction after treatment with antidepressants, 5α-reductase inhibitors and isotretinoin: 300 cases. Int J Risk Saf Med. 2018;29(3-4):125-134. doi: 10.3233/JRS-180744. PMID: 29733030; PMCID: PMC6004900.

300 cases (221 on antidepressants) solicited through a web site established by the authors. They acknowledge the design of the likely encouraged reporting. The authors calculate a causality score based on the Naranjo algorithm that is described as the “probability of an adverse drug reaction.”  This paper has a unique take on the effects of antidepressants that are not seen in any other references. It is available online and I encourage anyone who is interested to access it and read it.  One example that is incredible and seems uncomplicated by clinical experience: “The ability of serotonin reuptake inhibitors to reduce genital sensation is well known. Almost everyone who takes one will experience some degree of genital numbing, often within 30 minutes of taking the first dose.”

10.  Csoka AB, Bahrick A, Mehtonen OP. Persistent sexual dysfunction after discontinuation of selective serotonin reuptake inhibitors. J Sex Med. 2008 Jan;5(1):227-33. doi: 10.1111/j.1743-6109.2007.00630.x. Erratum in: J Sex Med. 2008 Dec;5(12):2977.. Csoka, A [corrected to Csoka, AB]. PMID: 18173768.

3 cases of persistent sexual dysfunction 3 of 1300 subjects from an Internet group that were assessed as credible were interviewed.  No medical causes for the sexual dysfunction were determined. 

Supplementary 1:

I received a reply today from the European Medicines Agency on my request for information on their regulatory decision to include language on sexual dysfunction from SSRIs.  The entire response is given below.  

 

Dear Dr Dawson,

Thank you for your request for access to documents.

We are writing to inform you that the Agency is not in a position to process your request.

Transparency is an important feature of the European Medicines Agency's operations.  As for any public authority, the Agency strives to be as open as possible about how it works and how it comes to its decisions.

However, due to the increasingly high volume of access to documents requests resulting in an excessive workload, and in order to avoid the core business tasks of the Agency and its performance being jeopardised by the administrative workload related to activities within Regulation (EC) 1049/2001 regarding public access to European Parliament, Council and Commission documents (the Regulation), the Agency has taken the decision to process only access to documents requests submitted by citizens of the European Union and natural or legal persons residing or having their registered office in a EU Member State.  This approach reflects Article 2(1) of Regulation (EC) No 1049/2001 and was agreed by the EMA Executive Board on 15 June 2018.

This is also clearly outlined on the Agency’s website at https://www.ema.europa.eu/en/about-us/how-we-work/access-documents under the heading “Who can request access to documents”.

If you have a European affiliate, please submit a new access to documents request indicating the relevant location from EMA’s online webform https://www.ema.europa.eu/en/about-us/contact/send-question-european-medicines-agency.

Thank you for your understanding.

Kind regards,

European Medicines Agency Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands Telephone: +31 (0)88 781 6000 Supplementary 2: The graphic below is the reference I could find on their current site that led me to request additional information: