This post links to Experts by Experience and Withdrawal, PSSD and Cholinergic Drugs on RxISK and The Marketing of Anticholinergic Maleficence here last week along a just published article The Past Present and Future which describes a medical ‘episode’ that gives you an insight on how the system ‘works’ and should leave you skeptical amost almost anything you might hear about drugs or vaccines.
A Folly is defined in dictionaries as an act of foolishness or an ornamental building with no practical purpose. Dublin’s most famous folly was built to block another rich man’s view of Dublin Bay – which stretches the definition of practical. The Anticholinergic Burden Folly is like a modern medical equivalent of Tulip-Mania – or Tulip-Phobia. Except, while doctors and academics have been exceptionally foolish, when it comes to anticholinergic drugs, there are pharmaceutical company marketing departments behind this mania who are anything but foolish.
The Anticholinergic Burden Folly
The Anticholinergic Burden Folly is one of the greatest medical follies of recent years. It comes from the same playbook as men treating women badly – seeing them as Madonna or Whore. Modern patented drugs are Madonnas while Anticholinergic Drugs are Whores – incapable of doing good. .
The Past Present and Future of Anticholinergic Drugs and The Marketing of Anticholinergic Maleficence point to the role of the ghostwritten medical literature on pharmaceuticals in generating perceptions like these. Both documents also compare this perception to the marketing myth created to sell SSRI antidepressants that depression involves low serotonin or a chemical imbalance.
A fuss blew up, a little over a year ago, when an article by Joanna Moncrieff, Mark Horowitz and colleagues claimed there was no evidence for a lowering of serotonin in depression. This was not an original claim but it got right up the noses of some of their London colleagues who have spent a year since trying to rubbish it and support pharmaceutical company marketing departments.
A second Ang, Horowitz and Moncrieff article slipped beneath the radar, which I had been asked to review by Emily Mendenhall, editor of Social Science and Medicine: Mental Health.
Moncrieff and colleagues had reviewed the 30 most cited texts on the biology of depression and 29 of the 30 referred to the established lowering of serotonin in depression. Joanna and Mark referred to their then work in progress pointing to a lack of evidence for this claim.
I nearly didn’t accept the invitation to review the article, because the serotonin story was old hat. I was glad I did as the medical literature finding was striking.
I suggested the authors could kill two birds with one stone – one being the low serotonin idea. They could also point to how ghostwriting created memes like low serotonin, which infect academic discourse with enormous consequences for those of us put on these drugs. Looking at the 29 out of 30 articles claiming it was Gospel Truth that Serotonin was Low in Depression, and the journals these revealed truths were published in, it was a racing certainty that most of them had been ghostwritten.
Emily was taken by this idea. She apparently asked the authors to build it into their revision but they said this was not something they could comment on – so she asked me to transform my review into a comment to appear with the article – as you will see.
The first set of emails all happen on April 2, 2022.
Emily
From: Emily Mendenhall
Date: Sat, 2 Apr 2022
To: DH
Dear Dr. Healy,
First, thank you sincerely for your service as a reviewer, and for your swift and important contribution. In thinking about your review, as well as the second very positive one, I anticipate accepting the article. However, in doing so, I wonder if you might respond to the manuscript? I would be very keen to publish your response to the manuscript alongside its publication. Would you be interested and willing to contribute such a piece?
Emily
David Healy 2 April 2022
Emily
How many words and did you have a format in mind ?
David
Emily
Most responses are short–under 1000 words. Would that be enough? We could give you a bit more if you would want more space but I do think this subject warrants some discussion. It would be like a normal SSM comment on a critical piece.
Emily
Comment
The Comment sent appears below. It is designed to say things that social scientists should be able to get behind but as you will see it also contains an element Emily was not expecting.
Science or Marketing? Comment on Is the chemical imbalance an ‘urban legend’? An exploration of the status of the serotonin theory of depression in the academic literature
The idea that an imbalance of our brain chemicals or a lowering of our serotonin might underpin swathes of our behavior is a cultural trope of our day (1). Investigating this, the authors of this paper have stumbled on something unusual (2). Some peer reviewed articles claim the idea is wrong, a view anyone can validate by asking to have their serotonin levels checked. The most cited articles in premier journals, however, endorse the imbalance claim as the height of scientific orthodoxy and the wider media and public go along with this (3).
A marketing trope about ‘following the science’ rather than actual science has won the day, as was predicted in 1991 (4). This is not just an antidepressant story. It applies to ADHD and all drugs that affect behavior, along with most drugs used to manage risks like statins and bisphosphonates. How is something like this possible?
We have known for over twenty years that there is a lack of access to clinical trial data in all articles about on patent medicines and that these articles are ghostwritten (5). We know that articles in the best journals claiming a trial have shown a drug to be safe and effective may contradict what a company has reported to FDA, or FDA themselves have concluded, about this same trial (6). But FDA do nothing to correct a publication stating this study has shown the drug to be safe and effective (6, 7).
FDA can equally do little to correct a known to be wrong trope like lowered serotonin levels. It can prohibit companies from making this claim but cannot stop an academic from making the claim as FDA do not regulate statements by academics. Companies can still use the trope citing the academic (8). FDA turn a blind eye to these claims being made by ghostwriters, for whose statements pharmaceutical companies are ultimately responsible, choosing to believe the academics on the authorship lines hold these views. Unless explicitly instructed not to, the ghosts continue to add important commercial messages about chemical imbalances to the reports of trials or derivative articles.
Neither the New England Journal of Medicine (NEJM) nor any of its reviewers are likely to pick up on these points or challenge the ‘authors’, any more than they are likely to seek access to the original trial data (9). NEJM articles now explicitly acknowledge the role of ghosts in their writing, while giving the impression that academics somehow oversee what is being done in their name.
The ghosts ensure the articles they write become the most cited articles by citing a growing stream of aligned reports and tropes, giving these tropes a veneer of science that must be followed, and equally not citing articles that might feature harms or other challenges to the marketing copy (5, 10).
The processes outlined here contribute significantly to an increasingly procedure driven healthcare, a development that is problematic if based on marketing copy. With Kuhnian paradigms, we had the sense that beliefs moved forward when the old guys died. Does the patent life of products now determine our beliefs?
Social scientists may soon need to grapple with these points not just as part of a critique of biomedicine. Two recent Nobel Prizes in the social and economic sciences have been given to proponents of RCTs. As this algorithmic based knowledge form comes into increasing use to evaluate the development of applications sponsored by interested parties, governments or corporations, unless social scientists understand operationalism better than doctors do, the social sciences risk being transformed the way medicine has been (11).
The capture of the social sciences is not just a future issue. There is no access to vaccine trial data (12), the vaccine trial articles in the NEJM are ghostwritten (13), and our willingness to be vaccinated today all but defines whether we are living an enlightened life, one that aligns with Pfizer’s ‘Science will Win’ slogan (14).
References
Healy D. Serotonin and Depression. The Marketing of a Myth. BMJ 2015; 350: h1771
Author S. Is the chemical imbalance an ‘urban legend’? An exploration of the status of the serotonin theory of depression in the academic literature. SSM: Mental Health
Davis JE. Chemically Imbalanced. Everyday Suffering, Medication and our Troubled Search for Self-Mastery. University of Chicago Press, Chicago 2020
Healy D. The marketing of 5HT: anxiety or depression. Brit J Psychiatry 1991; 158: 737‑742.
Healy D, Cattell D. The interface between authorship, industry, and science in the domain of therapeutics. British J of Psychiatry 2003; 182: 22-27
Healy D, Le Noury J, Wood J. Children of the Cure. Samizdat Press. Toronto, 2020.
Turner EH, Matthews AM, Linardatos E, Tell RA, Rosenthal R. Selective publication of antidepressant trials and its influence on apparent efficacy. New Eng J Med 2008; 358: 252-60.
Healy D. Let Them Eat Prozac. New York University Press, New York, 2004.
Fine P. Make Big Pharma provide their data. University World News January 18, 2009.
Sismondo S. Ghost-Managed Medicine. Mattering Press, Manchester UK. 2018.
Healy D. Shipwreck of the Singular. Healthcare’s Castaways. Samizdat Press, Toronto 2021
Thomas S. BMJ Podcast: Behind the Scenes in the Pfizer Vaccine Trial. 2021.
This is now stated at the end of all NEJM published vaccine RCTs.
Bourla A. Moonshot. Harper Business Books, New York, 2022.
Emily’s Dilemma
The next set of emails all took place on May 18 2022 and it seems Emily figures she is no longer dealing with Jekyll (David) but trying to manage Hyde (Dr Healy).
Emily
Science or Marketing? Comment on Is the chemical imbalance an ‘urban legend’? An exploration of the status of the serotonin theory of depression in the academic literature
Dear Dr Healy
Thank you for submitting your manuscript to SSM – Mental Health. I do think this commentary on the manuscript is an important one. However, after extensive internal discussion, we have decided not to accept this paper. The submission is written as a ‘letter to the editor’ manuscript type and, although it has provoked extensive discussion, we have decided that if you would like to rework these ideas into a 2000-3000 word commentary, then we would be happy to reconsider.
Again, I’m sorry this long drawn out process was not successful. We value your time and ideas, and thank you for lending your expertise.
Kind regards, Emily Mendenhall
David
Emily
You asked for a comment on an article that was less than 1000 words. I thought you would run it with the article.
David
Emily
David,
That was my plan and I hit major resistance from my co-Editors-in-Chief and Editorial staff, which I tried to work through. It has caused extensive internal discussion for the journal.
Thanks again for making the effort and providing the reviews. I hope we can publish a full-length article in the future.
Emily
David
Emily
Thanks for getting back. From the way you put it, it doesn’t sound like submitting anything else even vaguely on the same lines is likely to overcome the resistance.
As it turns out I have a 5000 word something else on similar lines – that doesn’t mention vaccines other than the merest hint – but its difficult to know whether it would be worth the trouble. Something quite different like this needs a sympathetic editor or at least not too much resistance
David
Emily
David,
It depends on the subject–I could send a 5000 word commentary out for review. Is it on mental health and vaccines?
Emily
David
Emily
Its a piece that I’m working on with two colleagues. We will in due course have a few versions – one for medical, one for economic and one for social policy forums. The medical one is the one I lead on. Its about a category error – company trials are not RCTs – they are Randomized Controlled Assays
The examples come from mental health and antidepressants because that’s my forte
The only reference to vaccines is about the vaccine trials in NEJM stating they are ghostwritten and the lead author for the Pfizer trial saying he has never seen the data. This makes those points incontrovertible and topical.
It will be 5000 words. It will also be light on references – that is because its about a category error. Its not an argument – more a case of look at it this way and many of the things people argue about vanish.
A surprising example of how swapping one word – Assay for Trial – can change so much.
Why a social science journal – when social scientists likely don’t know much about assays? Well doctors do know about assays but don’t know much about regulation or the possible policy implications of something like this and there is lots in there that social scientists would like about there being little or no raw data without an act of judgement.
In order for me and colleagues to work out if there is a chance of a marriage (perhaps after tweaking the wording to minimize resistance) it would be good to know what the resistance centered on.
Happy to talk about it if you don’t want to commit anything to print
David
Radio-silence from Emily – at that time a vigorous supporter of vaccine orthodoxy
Mad North North-West ?
Random behaviour was once seen as a sign of madness – folie, folly, foolishness. Random motion in sub-atomic particles or generally in physics was a sign of chaos until statistics helped us bring order out of the chaos.
Randomization, in the sense of making things chaotic in order to disturb order (bias), was introduced into the evaluation of drugs in the 1950s in the form of Randomized Controlled Trials (RCTs). Pharmaceutical companies quickly learned how to use RCTs as a magnet to get doctors, patients, regulators (bureaucrats), the media and politicians all lined up in neat ordered rows.
Once the Gagging Consumers are lined up (Doctors are the main consumers of patented medicines) the marketing then plays on them to produce a modern equivalent of what used to be called the Patented Medicine where consumers (the rest of us) were fooled by patent medicine hucksters selling worthless nostrums on the back of wild claims for beauty and success in addition to health.
Hamlet told Rosencrantz and Guildenstern he was pretty sane most of the time but he has a small element of madness in him that comes out when the wind blows from the North NorthWest quarter – a mixture of the Mistral wind from the North-West and the wind from the Mountains (Tramontana).
We are now pretty mad most of the time, but there is an element of sanity we might notice when we meet someone on an anticholinergic drug who seems fine and not showing any signs of dementia or if we ask for a blood or other test to check on our serotonin levels and find there is no such thing, or if we find we are more than briefly thinking about drug company claims that their drugs have no side effects.
The Randomization article Emily didn’t engage with has now been published and will feature next week.
The post Psychotropic Drug Follies first appeared on Dr. David Healy.