The Era of Blockbuster Drugs In Psychiatry Is Almost Over

Four years ago, I commented on a prediction that the era of “blockbuster drugs” in psychiatry would soon be over. That designation is used for medications that generate $1 billion in sales per year. Even at the time of my original comment, most of the drugs prescribed by psychiatrists were generic drugs that were often very inexpensive. The example that I frequently refer to is the antidepressant citalopram that was available for four dollars per month.

Last week PharmaCompass, a drug industry analytic and service company came out with a list of the top 100 drugs by sales in that industry. They listed the top 30 drugs by sales and their website lists the top 500 drugs with additional metrics such as whether or not sales are increasing or decreasing and by the percentage. There were no psychiatric drugs in the top 30. Lyrica or pregabalin, a drug used primarily for neuropathic pain and fibromyalgia came in at number 16 and generated $4.6 billion in sales. Some consider it to have a tertiary indication for anxiety but I would not consider it to be a drug primarily for psychiatric applications.

Sales Position	Company / Companies	Product Name	Active Ingredient	Main Therapeutic Indication	2018 Revenue in US$ billion
1	AbbVie Inc., Eisai	Humira®	Adalimumab	Autoimmune Disorder	20.47
2	Bristol Myers Squibb, Pfizer	Eliquis	Apixaban	Cardiovascular Diseases	9.87
3	Celgene	Revlimid	Lenalidomide	Oncology	9.69
4	Bristol Myers Squibb, Ono Pharmaceuticals	Opdivo	Nivolumab	Oncology	7.57
5	Amgen, Pfizer, Takeda	Enbrel	Etanercept	Immunology	7.45
6	Merck & Co.	Keytruda	Pembrolizumab	Oncology	7.17
7	Roche	Herceptin	Trastuzumab	Oncology	7.05
8	Roche	Avastin	Bevacizumab	Oncology	6.92
9	Roche	Mabthera/ Rituxan	Rituximab	Oncology, Immunology	6.82
10	Bayer, Johnson & Johnson	Xarelto	Rivaroxaban	Cardiovascular Diseases	6.58
11	Bayer, Regeneron	Eylea	Aflibercept	Ophthalmology	6.55
12	Johnson & Johnson, Merck & Co., Mitsubishi Tanabe	Remicade	Infliximab	Autoimmune Disorders	6.44
13	AbbVie, Johnson & Johnson	Imbruvica	Ibrutinib	Oncology	6.21
14	Pfizer	Prevnar 13/ Prevenar 13	Pneumococcal 7-Valent Conjugate	Vaccine	5.80
15	Johnson & Johnson, Mitsubishi Tanabe	Stelara	Ustekinumab	Immunology, Dermatology	5.25

Medications for neurological and mental disorders had a total market share of $55.8 billion or 10.2% of the entire market. There were only three medications that would qualify as blockbuster drugs and being used by significant numbers of psychiatrists and they included Latuda (lurasidone), Chantix (varenicline), and Abilify Maintena (aripiprazole).  The blockbuster drugs listed are all concentrated in a few specialties. Several are from the same class.  For example both Eliquis and Xarelto are novel oral anticoagulants (NOACs).  The total market share of the top 15 drugs greatly surpasses any amounts every attained by psychiatric medications. That makes sense because many are treating conditions that have a high prevalence and these medications generally represent an advance in pharmacotherapy.

I posted this mostly to note the trends over time. Journalists and other commentators tend to get carried away with market snapshots. I have not really noticed any negative commentary about the fact that the current blockbuster drugs that have nothing to do with psychiatric disorders are generating much more pharmaceutical company income. I also have not heard any commentary on how there is a natural fluctuation in this market based on drug discovery and the current rules on patent exclusivity. Many of the previous psychiatric “blockbusters” are obviously rapidly losing market share now that there are generic versions. I would argue that the current data also may indicate that restrictions on current medications may be limiting their market share.

The issue of direct to consumer advertising has typically not been discussed in these opinion pieces.  I have seen Rexulti frequently in television ads.  The application is generally antidepressant augmentation - accompanied by a very fast and diluted compilation of symptoms of both tardive dyskinesia and neuroleptic malignant syndrome. How much do those ads contribute to the market growth of Rexulti? My speculation is quite a lot. It would not take much for a person taking an antidepressant and not experiencing adequate relief to call their primary care physician for the addition of Rexulti.  I have seen similar ads for Vraylar.

Looking only at market share and pharmaceutical revenue only provides a look at one cost of this market. There is a huge pharmaceutical benefit manager component that generates revenue primarily by requiring their authorization for specific medications and also packaging deals for managed-care organizations. There is definite cost what they do but they currently are allowed to force physicians to work for them for free.

I hope that this information allows people take a more skeptical look at political and journalistic pieces that use pharmaceutical sales numbers and specialty sales for one rhetorical purpose for another. I am specifically referring to the recent good old days of the psychiatric drug “blockbusters” where much of what was written was an indictment against psychiatry and those psychiatrists who either worked directly for pharmaceutical companies or received some minor perk. There was the conspiracy theory that pharmaceutical companies had influenced the DSM-5.  That is both unrealistic and it greatly exaggerates the importance of that book. The data illustrates that no amount of physician manipulation can maintain a pharmaceutical product as a “blockbuster” independent of market forces.  

Those market forces also have a significant political and regulatory component where the real conflict of interest lies.  Allow me to translate that to Congress and the FDA.

George Dawson, MD, DFAPA

Graphics Credit

The top table from PharmaCompass was posted with their permission. 


Disclaimer:

I had to identify and hand count the psychiatric drugs on the PharmaCompass web site from their graphic interface.  It is possible that I missed some or the count is off (they were not numbered).  Let me know if you detect any errors.

A Great Independent Film and Its Lessons

When I first saw the trailer for The Last Black Man in San Francisco I knew it was a movie I had to see. The trailer itself suggested great cinematography and a unique story. By the time I looked for it again at my local cinema it was gone. I subsequently learned it was critically acclaimed but did not make much at the box office. I was very pleased when I was working out two nights ago and it popped up as a streaming choice on Amazon. It turns out that this is an outstanding independent film and I will probably come back to it.

I have not reviewed a film on this blog for some time but will include the customary spoiler alert. Some people just prefer a global recommendation rather than details. At this point I am going to proceed with some details.  This film is primarily about the relationship between two young black men - Jimmie Fails and Montgomery “Mont” Allen. Over the course of the film we learn that they are best friends.  We also learn that they are both staying with Mont’s blind grandfather. The conditions are less than optimal. We see Jimmie sleeping on the floor of Mont’s room. We see all three men watching television and Mont providing a running commentary for his grandfather sometimes to Jimmie’s exasperation. We learn that Mont is an aspiring playwright and artist. We catch glimpses of his work and his grandfather is very encouraging.

In the opening scene Jimmie and Mont skateboard to a very large Victorian house in another part of San Francisco. We learn that Jimmie used to live in this house and that he said his grandfather built it in 1946. The opening scene at the house he is painting some windows but there is a couple in the house and the woman of that couple is very angry with him for not staying away from the house. Jimmy and Mont talk about maintaining various aspects of the house. At one point the couple moves out and they move in. They go so far as to get furniture from Jimmie’s aunt’s home and move that into the place. There is not a very clear plan for possession of the house. They eventually have some interactions with a realtor, a banker, and a county official. None of those interactions are productive in terms of helping them purchase or acquire rights to stay in the home. Jimmie eventually tells Mont that his plan is to stay there no matter what. We eventually learn that Jimmie’s grandfather really did not build the house and that it was constructed in the late 19^th century.

As Jimmie and Mont travel between Grandpa Allen’s home in the mansion they regularly encounter a group of young black men out of the street.  One of them was a tall young man named Kofi who Jimmie knew from the year he spent in a group home. They were both skateboarders.  Jimmie thought that Kofi was quite good and asked him if he was still skateboarding. Kofi said that he was not. The skateboarding theme was important because Jimmie appeared older than most skateboarders and as his father put it “dressed like a white boy” in a red flannel shirt and khaki pants. There was a lyrical scene when Jimmie was skating down the San Francisco hill to Jefferson Airplane - until he wiped out three quarters of the way down the hill. I took the skateboarding as a symbol of Jimmie being stuck in an earlier time and what he has to do with the skateboard in order to move on - confirms this later in the film.

Kofi was the only young man invited to the Victorian house by Jimmie and Mont. When he was there, they all seemed to enjoy themselves. That was in contrast to the confrontations that Jimmie and Mont had with the young group of men in general.  They had very different styles of interacting with these young men. Mont was nonconfrontational and seemed to take a didactic role with them in that in one scene was described as “directing”. Jimmie was more confrontational and at one point asked Mont about his style of interacting. Mont told him that by avoiding confrontation he was able to appreciate these other men for who they really were.

The dynamics between Mont, Jimmie, and this young group of men was one of the most interesting aspects of this film. Jimmie characterized this group as “talking shit”.  This is a colloquial expression for young men engaging in interactions that could be considered sarcastic or overtly mocking. In some cases physical threats are feigned and there is always some risk of bullying or actual physical confrontation. This type of behavior in young men is common and as far as I know occurs in all cultures. A common way of dealing with it is to just avoid it. Mont and Jimmie do not avoid it.  Mont continues with what I saw as an empathic but at times eccentric approach to the mocking. Jimmie tends to deal with it in a more straightforward way by making similar statements or feigning physical aggression. The risk of “talking shit” is highlighted when Jimmie and Mont learned that their friend Kofi was shot and killed by a gang in one of these confrontations.

Jimmie and Mont learned about Kofi’s death from the group of young men they encounter. Jimmie becomes very confrontational trying to learn about what actually happened and it appears that he is at risk for a physical confrontation with one of the men. Instead that man becomes very tearful, start sobbing, and embraces Jimmie in one of the more emotional scenes of the film.

Kofi’s death was the subject of a one-man play put on by Mont in the Victorian house. In the play he confronted the small audience of local people and what they really knew about Kofi. During the exercise he  elicits a number of superficial observations from the audience. He asked Jimmie for comments and he described the positive and negative aspects of his relationship with Kofi concluding “people aren’t one thing”. From there and in the same setting Mont confronts Jimmie about the fact that his grandfather did not build the house. Jimmie gets angry and leaves and all of the theatergoers file out after that.

Jimmie eventually accepts the reality that he will never be able to stay at the Victorian house that his family used to live in. He grows more uneasy staying with Mont and his grandfather.  He leaves one night, with a note behind to Mont thanking him for being his best friend.

That basic story line is set in what I would describe as a separate visual story. That story has elements of how people have been misplaced in San Francisco by the current housing crisis, how that toll has fallen unevenly and unfairly on people who are not making high incomes, and how people who show up for a job in that area might not have the same appreciation for the area as long-term residents do. There is the clear message that the plight of low income people is being ignored by responsible officials to the point that their health is endangered. At one point Jimmie asks the rhetorical question about why a millionaire is more entitled to stay in his old family home than he is.  From the visual standpoint the story is brilliantly told.

On an interpersonal level, this is a story about relationships between men. The main characters Mont and Jimmie are interesting and likable. I found myself rooting for them and hoping that nothing bad would happen to them. In the final scene Jimmie is rowing a small boat in Pacific swells by the Golden Gate Bridge.  He is not in any danger but you wonder where he is headed.

And you wish him well.

George Dawson, MD, DFAPA



Graphics Credit:

Shutterstock per their standard agreement. "Painted ladies from Alamo square park over San Francisco skyline during the day."   By Sergey Novikov.