Introduction

Doctors have been prescribing this incredible drug more and more as they believe it to be of use in such a wide variety of conditions. It was first approved for schizophrenia (and therefore called an ‘anti-psychotic’) but then it seemed helpful in cases of depression, of all kinds, so is also regarded by many as a ‘mood stabiliser’ and anti-depressant and anti-manic agent. More recently still, it has been used in generalised anxiety disorder and sleep disturbance (and who does not suffer from those?), also for disturbed behaviour in old people, especially those in nursing homes: there are so many of them and they can be so ‘time-intensive’ and they will keep trying to get up out of their chairs (so much better if they just sleep their time away). We must not forget the little ones, what about ADHD, or whatever they have that is making them a pest. Yes, quetiapine may be the answer. And, there is more: it is finding a use in PTSD, anorexia nervosa, OCD, borderline personality disorder: indeed, there is an argument for just putting in the water supply.

The pharmaceutical company continue to be pleased with the sales, which I believe are now getting close to $100 billion; if only that pesky patent law could be altered, surely someone can come up Trump(s) on this one! that would be a Tr(i)ump(h). He might oblige.

I hope and trust no-one has read this far without realising that I am employing humour and sarcasm, because if I did not I would be so enraged about the whole obscene farce surrounding quetiapine that you would have been reading a tirade of abuse against the drug company, my gullible colleagues, and all the people involved in publishing the third-rate so-called ‘scientific papers’ about this drug.

No surprise; I am about to expound on just how bad and how dishonest it all is.

Who remembers ‘Flanders and Swan’? Even the young ones may have heard the ‘Hippopotamus’ song ‘Mud, mud, glorious mud’: in this context, I am reminded more of their witty song about the newly discovered multi-purpose vegetable called the ‘Wompom’, which provides everything imaginable

‘… the flesh in the heart of a wompom has the flavour of porterhouse steak,

and the juice is a liquor that will get you higher quicker,

and you’ll still get up next morning when you wake.

Take a break and listen, and if you get angry about the stuff below, listen again, it will bring a smile back.

https://www.youtube.com/watch?v=CsaNgsoQcO4

I choose the words ‘incredible’ and ‘believe’ in my first sentence because, as the old saying goes ‘If it sounds too good to be true, it is too good to be true’. Science is about replicated evidence, not belief, or impressions created by promotion and spin doctors. Doctors are especially susceptible to spin precisely because they think it affects others, but not them.

Unbelievable claims: ‘post-truth’ era science

There is neither good evidence that quetiapine has any useful pharmacological effect other than increased appetite, weight gain and sedation, nor that its’ hundredfold price differential over other available drugs (e.g. promazine or doxepin) is justified. These effects result from its’ most potent pharmacological property, by far, H1 antagonism. In other words, it is good for hay-fever! (see table).

Quetiapine’s potency is about 100 times greater at H1 vs D2 receptors: if it was marketed on the same basis as the SSRIs it might called a super-selective histamine blocker (SSHB)! I have been surprised while doing this update of quetiapine that none of the papers I have reviewed even mention, never mind discuss, its H1 potency: we certainly are living in the ‘post-truth’ era!

Here is the seminal paper linking weight gain and H1 potency from Solomon Snyder’s lab (1), and others (2-4). If you are a psychiatrist, and you do not know who Snyder is then you should be ashamed of yourself https://en.wikipedia.org/wiki/Solomon_H._Snyder

There is no evidence or reason for supposing quetiapine possesses useful or unknown new properties (see ‘fast-off’ below). Indeed, from a pharmacological point of view this drug regresses us to the dawn of psychopharmacology in the 1940s (see table below).

It is the first drug in the modern era to be prescribed widely for sleep, anxiety, depression and schizophrenia: it is either a miracle, or the most stupendous con-job ever perpetrated on patients, and the eternally gullible psychiatric fraternity.

Part of the reason the link between weight gain and psychotropic drugs (many have H1 potency) was slow to be recognised was that very few doctors bothered to weigh people, and if they did they never used properly calibrated accurate scales: I always weighed patients at every visit (on proper accurate scales) and it was obvious with the old TCAs that those with higher H1 potency caused more weight gain, like-wise with the anti-psychotics. I remember writing something about this around twenty years ago — I was astonished to find that most of the papers relied on patient self-reports of weight gain! That gives a vivid insight into how hopelessly unscientific most psychiatrists are — I wanted to shout at them, ‘haven’t you got a f**king set of scales’! One fellow took my breath away when he replied that proper scientific scales were too expensive.

Mutton dressed as lamb

A brief explanation may help. Many papers on the history of psycho-pharmacology relate how the tricyclic nucleus of the aniline dye, methylene blue, led to the discovery — France, the 1940s — of the first antipsychotic drug, chlorpromazine, and its’ structural analogues, the first tricyclic antidepressant (imipramine), and the first generation of antihistamines, promethazine (good old ‘Phenergan’). All these ‘tricyclic’ drugs are still on the market, including the ‘proto-typical’ promazine.

Promazine was regarded as too weak to be useful, and as is obvious from the names, led to the development of chlor-promazine (Largactil), the first antipsychotic drug. Adding electro-negative elements such as chlorine increases the potency of many tricyclics — hence, add chlorine, and imipramine becomes the much more potent ‘chlor-imipramine’, viz. clomipramine (Anafranil).

The table below gives the well-replicated pharmacological data demonstrating clearly that quetiapine is no different to promazine; on the face of it, we have returned to the 1940s.

Some drug, some progress.

Remember Winston? ‘Some chicken, some neck’. Ottawa 1942

https://www.youtube.com/watch?v=y6JxSHmVB5g

Table of Affinities (Ki nM)        

  D2 5-HT2A H1
Promethazine   250 170 1
Promazine       200 15 2
Chlorpromazine                   2 5 2
Quetiapine        500 150 7
Doxepin 350 25 0.2

Data from the PDSP database (approximate means from several sources, not all HCR data). https://kidbdev.med.unc.edu/databases/pdsp.php

Most drugs seem to need low single figure affinity potency (i.e. <10 nM) to produce clinical effects. An affinity of 500 nM is regarded as insignificant.

Note: For structure and 3D configuration See http://www.drugbank.ca/

What does it all mean?

What does it all mean? Much could be written about this; however, the rule of parsimony suggests that the simplest explanation is likely to be correct: the simplest explanation is that since there is so little pharmacological difference between promazine and quetiapine the likelihood of there being any substantial difference in their therapeutic efficacy in schizophrenia, or anything else, is small. I would say close to zero.

The same must be said of quetiapine’s supposed benefits for treating, or augmenting, depression. In that context, there is no basis for supposing it to be superior to doxepin, which is a useless anti-depressant, but the most potent anti-allergy drug on the world market — still, after 50 years!

The potencies in the table mean that for quetiapine we would expect no substantial effect in humans, other than H1 antagonism (viz. increased appetite, sedation), unless it is used in doses of around 1,000 mg daily, close to its toxicity threshold (the max recommended doses are between 300 – 800 mg, depending on indication).

A quick lesson from history

Incidentally, I have put doxepin in the table because it is similar and contains historical precedents and lessons. It was of course originally classified as a tricyclic antidepressant, despite its’ noradrenaline reuptake inhibitor potency being so weak as to be of no consequence whatsoever. It is one of the most potent antihistamines known, about equipotent to mirtazapine. That property (H1 antagonism) inevitably makes it increase appetite (promoting weight gain) and produce sedation, sleepiness and reduction of anxiety. Hence, over the decades, it has been used as a hypnotic and anxiolytic: indeed, around the time of my TCA review paper, which expounded on the usefulness of doxepin, ((5), see table 5), it was reformulated and marketed as a hypnotic in the USA (Silenor). There are dozens of similar drugs with antihistamine activity that have been used for appetite stimulation and sleep, as well as allergies, over the last 50 years (diphenhydramine, doxylamine, cyproheptadine, trimipramine, hydroxazine, promazine, promethazine, carbinoxamine, dimenhydrinate etc.).

For many years (mis-guided) psychiatrists used doxepin as an antidepressant, and some may still think it works: its most prominent clinical effect was of course sleepiness and weight gain which is inevitable because of its extremely potent H1 antagonism. It was useless as an antidepressant, except that it improved appetite, sleep and anxiety symptoms. That produces substantial improvements in depression the rating scales (see below) used to assess depression and hence allows it to be ‘misclassified’ as an antidepressant, even though it does not improve the core symptoms of anergia and anhedonia. This paragraph could be repeated with quetiapine (or mirtazapine) substituted for doxepin. It took psychiatrists 30 or more years to realise doxepin was useless, I don't suppose they will become enlightened about quetiapine any more quickly, since there is no reason to suppose the present generation are any smarter than the previous one. Indeed, they probably suffer from the disadvantage that they are even more influenced and indoctrinated by drug company ‘education’ and promotional material than previous generations.

Is there an explanation?

It is certainly possible to produce all sorts of far-fetched pharmacological theories that might account for a possible different in effect of Promazine and Quetiapine, even though current assay techniques indicate they are so similar. However, to be convincing such evidence would have to be reliably replicated by different research groups and a plausible mechanism linking any such effect with well-established clinical differences would need to be demonstrated. As those who have read a few of my commentaries will know, all sorts of theories have been advanced about all sorts of things in psycho-pharmacology over the last 50 years. Few have proved ‘true’, even when they emanated from independent sources. All the RCTs originate from the pharmaceutical manufacturer and are thus even less likely to be corroborated and substantiated by additional independent research (6-8).

The evidence adduced in relation to the supposed therapeutic effect, never mind superiority of, quetiapine is pathetic; but more of that later.

The key issue is this: is there any sound evidential basis for supposing quetiapine is, despite being so-like promazine pharmacologically, somehow magically different in a way we do not yet understand, that confers advantage? Pigs might fly.

The 'fast-off' idea

The main explanation put forward is the so-called 'fast-off' idea (see also discussion of another unconvincing ‘explanation’ re 5-HT2A receptors here). This idea suggests that the key difference with atypical antipsychotics is that they dissociate from their binding with the D2 receptor much more quickly, like 100 times more quickly, than the traditional antipsychotics (9, 10). Put simply, the evidence for this is unconvincing and not well replicated and the techniques used to establish this are new, uncertain, and of unproven reliability. The most recent research suggests little or no association between ‘fast-off’ properties and ‘atypical’ characteristics, whatever they are conceived to be (11).

It is also notable that most of the publications on this topic seem to come from one author, Seeman: that should always make one sceptical, just like Meltzer and the 5-HT2A story. It is premature to justify, or base, any clinical actions on such a nebulous notion. The notion that the weaker the D2 binding, the better it works, reminds one of homeopathy!

A medline search for ‘atypical antipsychotics’ and ‘fast-off’ yields only 6 results since Seeman’s 2002 paper: one would think, after 15 years, if there was mileage in this idea, that the drug company would be throwing some of their billions of dollars of profits at researchers to ‘prove’ it. Or do they know full-well that it is baloney?

Then again, if you are making that many billions why would you care about anything!

PET Studies show low and transient D2 binding (12-16) and minimal effect on prolactin.

The number of publications doubting the efficacy of quetiapine is small: here is one which is a bit feeble, and does not even mention histamine (17):

https://www.nps.org.au/australian-prescriber/articles/concerns-about-quetiapine-3#r4

‘Evidence’ from clinical trials

Antagonism of H1 receptors improves appetite, sleep and anxiety. In the frequently used Montgomery-Asberg depression rating scale***, appetite, sleep, anxiety, and concentration (often impaired due to anxiety) each rate up to a max of 6 points (severe) out of a total of ten items (i.e. max total score id 60 pts). Thus, they make up 24 pts. out of the total of 60. The Hamilton scale is little different.

*** Another example of a shit rating scale: it has almost no rating of the core symptoms relating to psychomotor retardation like drive, energy, motivation, interest; nor of anhedonia, enjoyment, pleasure, satisfaction. So it is rating anxiety more than biological depression.

The claimed improvements from quetiapine (11 papers in a recent ‘meta-analysis’, all drug-company sponsored (18), see also (19-21)) average only 4-5 pts ***. A child from the bottom of the maths class can figure out that easily adds up to 5-10 points, just from sedative effects. Not rocket science is it!

*** Incidentally, the usual variations of ‘inter-rater reliability’ (i.e. how different the scores will be if 2 raters asses the same patient) is of that order, viz. ~ 5 pts. I very much doubt if any of those trials tested their inter-rater reliability. Such points help one to appreciate that the scientific standard of these trials is extremely poor.

Look at the scale for yourself: https://psychology-tools.com/montgomery-asberg-depression-rating-scale/ see how small the changes in appetite, sleep, anxiety and concentration need to be to produce this small degree of improvement.

It should also be noted that most of the studies on schizophrenia emanate from China. The evidence of fraud and bias is even worse for Chinese studies than others (22, 23)

And that is called evidence.

These improvements are most convincingly explained by its sedative antihistamine property which is substantiated by the fact that the improvement is manifest in less than one week, and at low doses (< 50 mg daily). Such doses can only be effecting H1 receptors (thus producing sedative, anxiolytic and sleep promoting changes), at those doses there would be absolutely no effect on D2 (or any other) receptors. A recent large study of 1,000 patients showed most managed to take it for less than 3 months and only at a dose of 25 – 40 mg a day (21, 24), and the prominent effects were, wait for it, you guessed, yes, tiredness and sleepiness!

As far as schizophrenia is concerned the latest summary from the Cochrane review is: ‘Most data that have been reported within existing comparisons are of very limited value because of assumptions and biases within them’ (25). And much data emanates from China where fraud and bias is even worse (22, 23). Like I said before, just no good evidence of different or superior effectiveness.

Conclusion

  1. No reliable pharmacological data exists that would even suggest quetiapine is likely to be any use for depression except as an anti-histamine and therefore sedative and anxiolytic. But doxepin would be better and 100 x less expensive.
  2. No reliable clinical data exists indicating useful superiority for schizophrenia.
  3. No reliable clinical data exists indicating usefulness for any form of depression.

Quetiapine is an very expensive drug of minimal usefulness. The world would probably be better off without it. I suggest clinicians who ‘believe’ this works might read the story of Sir Arthur Conan Doyle and the ‘Cottingley Fairies’.

References

1.         Kim, SF, Huang, AS, Snowman, AM, Teuscher, C, et al., Antipsychotic drug-induced weight gain mediated by histamine H1 receptor-linked activation of hypothalamic AMP-kinase. Proc Natl Acad Sci USA, 2007. 104(9): p. 3456-9.

https://www.ncbi.nlm.nih.gov/pubmed/17360666

2.         Salvi, V, Mencacci, C, and Barone-Adesi, F, H1-histamine receptor affinity predicts weight gain with antidepressants. Eur. Neuropsychopharmacol., 2016.

http://dx.doi.org/10.1016/j.euroneuro.2016.08.012

3.         Nasrallah, HA, Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol. Psychiatry, 2008. 13(1): p. 27-35.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17848919

4.         Kroeze, WK, Hufeisen, SJ, Popadak, BA, Renock, SM, et al., H1-histamine receptor affinity predicts short-term weight gain for typical and atypical antipsychotic drugs. Neuropsychopharmacology, 2003. 28(3): p. 519-26.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12629531

5.         Gillman, PK, Tricyclic antidepressant pharmacology and therapeutic drug interactions updated. Br J Pharmacol, 2007. 151(6): p. 737-48.

http://onlinelibrary.wiley.com/doi/10.1038/sj.bjp.0707253/pdf

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17471183

6.         Ioannidis, J, Lies, Damned Lies, and Medical Science. Atlantic, 2010. November 17th.

http://www.theatlantic.com/magazine/archive/2010/11/lies-damned-lies-and-medical-science/8269/

7.         Ioannidis, JP, Why most published research findings are false. PLoS Med, 2005. 2(8): p. e124.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16060722

8.         Naci, H and Ioannidis, JP, How good is “evidence” from clinical studies of drug effects and why might such evidence fail in the prediction of the clinical utility of drugs? Annu. Rev. Pharmacol. Toxicol., 2015. 55: p. 169-189.

9.         Seeman, P, Atypical antipsychotics: mechanism of action. Can. J. Psychiatry., 2002. 47(1): p. 27-38.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11873706

10.       Vauquelin, G, Bostoen, S, Vanderheyden, P, and Seeman, P, Clozapine, atypical antipsychotics, and the benefits of fast-off D2 dopamine receptor antagonism. Naunyn. Schmiedebergs Arch. Pharmacol., 2012. 385(4): p. 337-72.

https://www.ncbi.nlm.nih.gov/pubmed/22331262

11.       Sahlholm, K, Zeberg, H, Nilsson, J, Ögren, SO, et al., The fast-off hypothesis revisited: A functional kinetic study of antipsychotic antagonism of the dopamine D 2 receptor. Eur. Neuropsychopharmacol., 2016. 26(3): p. 467-476.

12.       Nord, M, Nyberg, S, Brogren, J, Jucaite, A, et al., Comparison of D dopamine receptor occupancy after oral administration of quetiapine fumarate immediate-release and extended-release formulations in healthy subjects. Int J Neuropsychopharmacol, 2011. 14(10): p. 1357-66.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=21477416

13.       Vernaleken, I, Janouschek, H, Raptis, M, Hellmann, S, et al., Dopamine D2/3 receptor occupancy by quetiapine in striatal and extrastriatal areas. Int J Neuropsychopharmacol, 2010. 13(7): p. 951-60.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20392299

14.       Nikisch, G, Baumann, P, Kiessling, B, Reinert, M, et al., Relationship between dopamine D2 receptor occupancy, clinical response, and drug and monoamine metabolites levels in plasma and cerebrospinal fluid. A pilot study in patients suffering from first-episode schizophrenia treated with quetiapine. J. Psychiatr. Res., 2010. 44(12): p. 754-9.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20176367

15.       Sparshatt, A, Taylor, D, Patel, MX, and Kapur, S, Relationship between daily dose, plasma concentrations, dopamine receptor occupancy, and clinical response to quetiapine: a review. The Journal of clinical psychiatry, 2011. 72(8): p. 1108-1123.

16.       Sparshatt, A, Jones, S, and Taylor, D, Quetiapine: dose-response relationship in schizophrenia. CNS Drugs, 2008. 22(1): p. 49-68; discussion 69-72.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18072814

17.       Brett, J, Concerns about quetiapine. Aust Prescr, 2015. 38(3): p. 95-7.

https://www.ncbi.nlm.nih.gov/pubmed/26648630

18.       Suttajit, S, Srisurapanont, M, Maneeton, N, and Maneeton, B, Quetiapine for acute bipolar depression: a systematic review and meta-analysis. Drug Des Devel Ther, 2014. 8: p. 827-38.

https://www.ncbi.nlm.nih.gov/pubmed/25028535

19.       Maneeton, N, Maneeton, B, Woottiluk, P, Likhitsathian, S, et al., Quetiapine monotherapy in acute treatment of generalized anxiety disorder: a systematic review and meta-analysis of randomized controlled trials. Drug Des Devel Ther, 2016. 10: p. 259-76.

https://www.ncbi.nlm.nih.gov/pubmed/26834458

20.       McIntyre, RS, Muzina, DJ, Adams, A, Lourenco, MT, et al., Quetiapine XR efficacy and tolerability as monotherapy and as adjunctive treatment to conventional antidepressants in the acute and maintenance treatment of major depressive disorder: a review of registration trials. Expert Opin Pharmacother, 2009. 10(18): p. 3061-75.

https://www.ncbi.nlm.nih.gov/pubmed/19954275

21.       Pringsheim, T, Gardner, D, and Patten, SB, Adjunctive treatment with quetiapine for major depressive disorder: are the benefits of treatment worth the risks? BMJ, 2015. 350: p. h569.

https://www.ncbi.nlm.nih.gov/pubmed/25739588

22.       White, J, Fraud fighter: 'Faked research is endemic in China' New Scientist, 2012(2891): p. http://www.newscientist.com/article/mg21628910.300-fraud-fighter-faked-research-is-endemic-in-china.html.

23.       Miyar, J and Adams, CE, Content and quality of 10,000 controlled trials in schizophrenia over 60 years. Schizophr. Bull., 2013. 39(1): p. 226-9 https://academic.oup.com/schizophreniabulletin/article/39/1/226/1889747/Content-and-Quality-of-10-000-Controlled-Trials-in.

https://www.ncbi.nlm.nih.gov/pubmed/22290267

24.       Pae, CU, Wang, SM, Han, C, Lee, SJ, et al., Quetiapine augmentation for depression: dosing pattern in routine practice. Int. Clin. Psychopharmacol., 2015. 30(1): p. 54-8.

http://www.ncbi.nlm.nih.gov/pubmed/25371174

25.       Asmal, L, Flegar, SJ, Wang, J, Rummel-Kluge, C, et al., Quetiapine versus other atypical antipsychotics for schizophrenia. Cochrane Database Syst Rev, 2013. 11: p. CD006625.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=24249315

This commentary incorporates suggestions for combatting the tidal waves of bad and dishonest science, flooding over us all via the medical journals that we read. Quite a long time ago I wrote about the dishonest practices and bad science in the field of atypical antipsychotic drugs, which have been a multi-billion-dollar source of income for big pharma for a couple of decades now. The original piece that I posted on this website about ‘Antipsychotics and Humpty Dumpty’ was republished in the Carlat psychiatry report in an abbreviated form, sometime later (1).

In that article I made passing reference to risperidone and the chicanery that had been engaged in to make it appear good (Huston et al.), better than haloperidol — which was of course going out of patent — and better than the other competing ‘newer’ drugs.

In the process of researching that commentary I contacted the Prof Leucht (2), who had written the meta-analysis relating to the relative merits of various of these drugs, including risperidone. I was enquiring of him why they had not referenced and discussed the paper ‘Redundancy, disaggregation, and the integrity of medical research’, by Huston et al. (3)*** when discussing the possibility of bias, fraud, and unpublished studies etc. His answer was that they were simply not aware of it. I do not suppose they searched the scientific data using words like fraud, dishonesty, etc. Many doctors are insufficiently ‘street-wise’ and insufficiently sceptical, or cynical. See also (4).

*** The title is a science-journal-acceptable way of saying ‘lying and cheating’.

That is an example of how even carefully done meta-analysis is often seriously flawed without anyone noticing it (except me, it seems). A sort of ‘whoops, we did not know the castle was built on sand’ moment.

I have done quite a lot of writing about bad science and fraud in science (see main menu ‘Bias in science’), but no amount of writing about it is going to change anything unless people decide enough is enough and take actions.

There are so many quotes and references one could give on this subject that it is difficult to choose: I will offer you the words of the retiring British medical journal editor of some years, Richard Smith (5, 6), that ‘Journals have devolved into information laundering operations for the pharmaceutical industry’: but see also my other commentaries on bad science, especially ‘Why Most New Antidepressants Are Ineffective: And How Pharmaceutical Companies Have Deceived Doctors’.

Part of Smith’s writing is a sort of mea culpa about why it took him so long to realize he was being duped as editor of a top medical journal. I will record the fact that I wrote to him, in response to something in the BMJ, a while before he resigned, to tell him I thought he was being duped. I like to think I may have played a small part in his ‘conversion’.

So, I wonder if this series of articles about risperidone (Risperdal™) in the ‘Huffington Post’ will precipitate anything useful? other than spreading the appreciation of the negative aspects of naked capitalism. Capitalism caught in flagrante delicto, as it were.

http://highline.huffingtonpost.com/miracleindustry/americas-most-admired-lawbreaker/

The big picture: information generation and dissemination

The misleading drug trials that permit big pharma to get their drugs approved are possible mainly because big pharma often has control of all the data from clinical trials (doctors have very naively allowed them to gain that control), that is but the tip of the ice-berg. Big pharma exerts considerable control over post-graduate medical education, medical journals, and the whole environment of information that doctors are exposed to on a day-to-day basis. Furthermore, big pharma has gained a strong influence over, or even control of, much of the process of legislation about drug licensing, the FDA, the formation of clinical guidelines, and more.

What are the ‘nutrients’ that have nourished this mutant growth of big pharma control?

The first essential element is getting the data. Patients, who all sign consent forms agreeing to participate in drug trials, and doctors who 'allow' them to do that, are giving big pharma control 'on a plate'. It is like putting the fox in charge of the hen-house. Anyone wishing to understand that a bit more just needs to look at the Huston review (3). If they have possession of the raw data (possession is nine-tenths of the law) they can manipulate it free from control and scrutiny — and we know, beyond any conceivable doubt, they do that ruthlessly and repeatedly (see Huston), despite multi-million dollar penalties for infringements. When one is raking in billions (not millions), that is just a minor cost of doing business.

Trials cannot be carried out without the essential raw material of patients! If patients only signed ‘consent’ forms that stipulated that the raw data must be held and controlled by to an independent party, that would be the beginning of the end of the story — a knockout blow. TKO in the first round, as they say.

There are various other somewhat similar measures that could be enacted as well, perhaps another key one would be to do with the metrics of ‘success’ used to assess researchers, and which determine their chances of progress and promotion. At present the system encourages poor research, multiple small publications (salami publishing) and puts so much pressure on most, that good people do less reviewing for journals. The huge proliferation of published journal titles means that more and more less expert people are acting as ‘referees/reviewers’ and the quality of published work is declining. In my area, much of what is published is simply rubbish. The proliferation of poorer quality material makes the finding of the better stuff more and more difficult, especially now that less researchers utilize the services of independent professional librarians (Journal cost to libraries have become so great that many places can no longer afford a librarian).

So, what goes naturally, hand-in-hand with the above, is a system for ‘rating’ (post-publication), the quality and value of material. That is quite straightforward if you think about what Google have achieved with search engines and advertisements. Such a system would link in to weighing the ‘publication’ metrics of authors in a way that would enable appointments committees and funding agencies to improve their decision making.

The proliferation of 3rd rate publications makes it harder and harder to figure out who is doing good work, and easier for big pharma to artificially elevate the apparent excellence of their chosen, groomed, candidates and place them in prestigious and influential positions (there are various ways they can do that, the bottom line is ‘money talks’). There is little reliable data on this, but I am sure it is much more widespread and consequential than most doctors appreciate. This proliferation of 3rd rate publications*** also makes it hard for ‘ordinary’ doctors, who may not have the ability to accurately deduce the quality of their source, to know what to trust and rely on when they wish to inform themselves with quality information. After I retired from clinical work and began publishing and writing much more, especially about bad and fraudulent science, I went through a period of being angry. I was angry because these dishonest people had caused me to waste so much of my intellectual effort wading through lies and rubbish to reach something approaching good and true science. I could have achieved so much more if I had not so frequently been lied to and conned.

*** There has been a burgeoning of the number of journals devoted to publishing case reports (from < 10 on 2005 to nearly 200 in 2016 (7).

Therefore, any measures that facilitate the better quality science getting a more prominent exposure to doctors will do a lot of good. The IT technology to achieve this already exists and could be applied tomorrow. Let me outline an illustration of this. An algorithm like the ones used in search engines, and to decide on the adverts you are shown, could give a score to published papers weighed by factors like: how long people have spent reading the material, what their professional and publication ranking in the field is, what score they give it on a scale (a more sophisticated version of ‘like’ feature), etc. Not exactly rocket science. So, if I spend a long time reading a paper on ST (as a world expert in that field) that should have a much bigger influence on its’ rating than if a nurse-practitioner from Woop Woop gives it a five-star rating. Such a system does not involve any kind of suppression of ‘non-mainstream’ ideas or any ‘censorship’, it just enhances people’s ability to know what has rated as good science by those more expert.

Big pharma is the predominant influence over clinical drug trials. Those who control clinical trials also control clinical guidelines, and clinical practice and most importantly, healthcare expenditure on drugs. They also strongly influence the general emphasis of healthcare spending. That pretty much covers all bases!

By, ‘the general emphasis of healthcare spending’ I mean, for instance, allocating money to anti-depressants drugs, rather than social and psychological services for the huge numbers of people classified as having ‘depressive illness’. Or, cardiac drugs, rather than sending people to the gym and teaching them to eat healthily.

Another thing many people would not even dream was happening is big pharma’s influence over classification of illness via DSM. That much expands their market.

I could go on: but, the point is that a lion’s share of the problem starts with patients giving-up their data unconditionally, which has allowed big pharma to high-jack the whole process, with very profitable results.

Doctors have acted as pathetic, wimpish bystanders and I am ashamed to call myself a doctor (well, I don’t, I am a clinical neuro-pharmacologist!).

Gillman’s solution

The first step in the campaign to correct this awful & crazy situation is to retain control of the data! This would require some sort of umbrella patient-trials organisation to protect and represent patients, who could supervise the 'data-collection/protection' process.

It would be simple to form an independent board of non-pharma research scientists, and other representatives (e.g. community, law etc.), to hold all the 'raw' trial data, and provide it to any bona fide researcher to analyse. There are many other similar changes that could be made — but the above is the first essential step.

That idea requires no new laws, no government intervention (although that could help), just the concerted action of individuals. Stop agreeing to participate in clinical trials (stop giving money to the church): things will change very quickly. If patient advocacy and support organizations pick up that baton, and run with it there would be trembling hands, pale faces, and hyper-active descending colons, in big pharma boardrooms over-night.

The message: 'if patients give their data away unconditionally, they are asking to be screwed, and they have been screwed, and they will continue to be screwed'. Just like people who give money to, or support, the Catholic church (except in that case they are asking for their children to be screwed).

Perhaps I will talk another time about what academia could do, along the same lines, to change the way papers are assessed, and academic promotion regulated. But I am afraid there are many wimps in that camp, so someone may have to put a bomb under them. And indeed, the bomb is the above. If they do not implement such changes then they could be ‘black-listed’ from participating in clinical trials. Patients could achieve that change without any help from laws, government or anyone else.

You have the power, if you wish to use it.

Sadly, my colleagues in the medical profession are somewhat naive and/or lacking in moral fortitude. Or are they just greedily taking big pharma money (If you think I am exaggerating, there is a web site that tells you how many $$$$$ your doctor has got from big pharma (for giving ‘education talks’ to nurses, para-medical staff of all sorts, and even their colleagues).

And we wonder why doctors have not been leaders in dealing with these crucial ethical and scientific issues.

Enough said.

PS. The dogma of RCTs as a gold standard

The dogma of RCTs as the gold standard has contributed greatly to the present situation in which those who control trials control clinical practice, via ‘clinical guidelines’, and aided by the pseudo-science of ‘meta-analysis’, which I now call the phrenology of the third millenium.

Healy D, Cattell D. Interface between authorship, industry and science in the domain of therapeutics. British Journal of Psychiatry (2003) 183: 22-27 & Charlton BG. Conflicts of interest in medical science: peer usage, peer review and 'CoI consultancy?' (editorial). Medical Hypotheses. 2004; 63: 181-186.

References

1.         Gillman, PK, Atypical antipsychotics: where is the science, where is the evidence. The Carlat Psychiatry Report, 2013. 11(1): p. 3-5.

http://pro.psychcentral.com/atypical-antipsychotics-where-is-the-science-where-is-the-evidence/006014.html

2.         Leucht, S, Kissling, W, and Davis, JM, Second-generation antipsychotics for schizophrenia: can we resolve the conflict? Psychol Med, 2009. 39(10): p. 1591-602.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19335931

3.         Huston, P and Moher, D, Redundancy, disaggregation, and the integrity of medical research. Lancet, 1996. 347(9007): p. 1024-6.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8606568

4.         McLaren, N, Psychiatry as Bullshit. Ethical Human Psychology and Psychiatry, 2016. 18(1): p. 48-57 http://theaimn.com/psychiatry-as-bullshit/.

5.         Smith, RL, Medical Journals Are an Extension of the Marketing Arm of Pharmaceutical Companies. PLoS Med, 2005. 2: p. e138.

http://www.plosmedicine.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0020138

6.         Smith, R, Travelling but never arriving: reflections of a retiring editor. Br. Med. J., 2004. 329(7460): p. 242-244.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15284125

7.         Akers, KG, New journals for publishing medical case reports. Journal of the Medical Library Association: JMLA, 2016. 104(2): p. 146 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4816468/.

I am still sometimes asked if nifedipine should be given to patients for them to take as a ‘rescue medication’ if it is thought they may be having a hypertensive episode resulting from consuming tyramine, whilst taking MAOIs.

No, no and no. Do not give nifedipine, to anyone, ever.

This commentary is supplementary to the comments I have already made in the full version of the MAOI monograph which states clearly that ‘immediate-release’ or ‘short-acting’ nifedipne should not be given to patients. Indeed, it would never be used by a hypertension expert, even under close observation in hospital.

Pain and anxiety exacerbate hypertension, so remaining calm and using a benzodiazepine, which will lower BP safely and to a significant and sufficient extent (1-4), is the most useful and safe initial step. It is most unlikely that urgent hospital and specialist assessment will be required, unless a very large ingestion of tyramine is suspected (nowadays that would almost have to be ‘deliberate’), and observation and BP monitoring shows BP increasing beyond 220 mm/Hg or so over a prolonged time (2 hours).

A great majority of BP elevations nowadays are going to be mild, from relatively small amounts of tyramine, and will last only an hour or two and require no intervention.

Evidently, and a little surprisingly, it is still not uncommon practice for doctors, including psychiatrists, to give such medication, usually nifedipine, to patients to self-administer. At least one published article I recall seeing quite recently suggested that strategy, and doubtless many websites do.

Right away, let me advise that for some years it has been possible to state, confidently and emphatically, that using nifedipine (or any other BP ‘rescue’ drug) to rapidly lower BP during a hypertensive urgency is absolutely contra-indicated (hypertensive urgency is BP > 180/120, three measurements, taken whilst calm and at rest!).

The evidence is sufficiently clear that a doctor who advised nifedipine might well lose any resulting damages claim.

I hear a chorus: ‘But surely that risk is worth it to prevent a ‘stroke’ … .’ No, it is not.

The first mistaken assumption to tackle is this: the idea that a tyramine reaction will raise someone’s BP, higher and higher, until their head explodes. That simply is not a plausible scenario. There are two good reasons for that: first, even people with elevated risk, who have known A-V malformations, survive years of episodes of high BP, then might get a sub-arachnoid haemorrhage while just sitting on the toilet.

Second, the degree of elevation of BP caused by ingestion of tyramine is generally no greater than elevations produced by a host of other factors. These include, exercise, sex, stress, driving, anxiety, lifting weights, taking amphetamines (speed, ice) – in fact just living.

Foods have much lower levels of tyramine now, than in past decades. To ingest sufficient tyramine to raise BP high enough, for long enough, to precipitate encephalopathy, heart failure or renal damage would now be nigh on impossible (that is what some of the old cases reports from the 1960s involved, hypertensive encephalopathy and heart failure – not acute sub-arachnoid haemorrhage).

The relatively short duration of BP elevation precipitated by excess tyramine will rarely be more than an hour or two, and the risk of such elevation ‘causing’ sub-arachnoid haemorrhage is minuscule. Again, I hear people say, ‘but I had a case …’. Yes, cases like that do occur, but a myriad of episodes of BP elevation, that are an inevitable part of life, pass without consequence. If you have a defective boat which sinks when it encounters a decent-sized wave, it makes no sense to blame that particular wave. Like waves, BP goes up and down all the time. The ‘fight and flight’ response raises BP as high as tyramine (the mechanism is, after all, the same, viz. sudden release of adrenaline). If evolution had equipped us with such weak blood vessels that they popped regularly when our BP went high, our species would not have survived.

History

A review twenty years ago (in 1996) stated ‘Not surprisingly, sublingual nifedipine was pulled from the antihypertensive arsenal for hypertensive emergencies after its dismal risk/benefit ratio was publicized, and its widespread use came to a screeching halt (5, 6). It was too good and acted too fast (hence the slow release formulations!).

The product labelling, twenty years ago, for short-acting nifedipine included specific warnings against using the agent for acute blood pressure reduction and for controlling essential hypertension and the FDA declined to approve it for the use of acute hypertension because of its unpredictability and unproven effect and the documented risks. The National Heart Lung and Blood Institute issued a statement saying, in part, that “short-acting nifedipine should be used with great caution (if at all), especially at higher doses, in the treatment of hypertension, angina, and MI.” (7) and it was suggested that the practice should be prohibited (5).

Well, the ‘screeching halt’ bit did not quite happen, despite all the above. Not all doctors are aware of the dangers, it would seem. Another recent review bemoans that ‘old habits die hard’ even when the evidence against them has been substantial and existed for many years. The nifedipine story is certainly an example of that (8), its use has undoubtedly been the cause of many strokes – this is still happening, two decades after the initial warning from the FDA.

When I first prepared the MAOI monograph years ago, I spoke to several physicians with experience in this area and they are all related cases they knew of cerebral injury e.g. cortical blindness, precipitated by nifedipine-induced hypotension.

Thus, for two decades, the overwhelming weight of opinion amongst hypertension experts is that oral nifedipine is not only strongly contraindicated in acute hypertension, but should probably never be used at all.

Powerful BP lowering drugs must only be used under expert supervision in hospital because of the risk of catastrophic consequences from hypoperfusion caused by sudden reduction in blood pressure. This can cause cerebral infarction (9, 10), cortical blindness (11, 12), cardiac insufficiency, angina and renal damage.

If excessive tyramine is ingested the blood pressure starts to increase from about half an hour after ingestion (sooner for liquids on an empty stomach), and remains elevated for 1 – 2 hours: the magnitude and duration of that elevation is dose related, so unless a large amount of tyramine has been ingested (50 – 100 mg) the reaction will be short-lived (about one hour).

An SBP of 180 mmHg or more, sustained over 3 measurements in 10 minutes or so, performed in a calm setting with an accurate sphygmomanometer is now referred to as a ‘hypertensive urgency’. Only if ‘end organ’ dysfunction is present it is called a ‘hypertensive emergency’. End organ dysfunction is uncommon unless DBP is greater than 130 mmHg (13).

In hypertensive urgencies the treatment aim is to reduce BP slowly over 24 – 48 hrs. Since tyramine reactions are self-limiting over 2 – 4 hrs., or rather less with present, typically smaller, tyramine ingestions, it is clear they will very rarely require intervention. The exception to this might be when a large (> 100 mg) ‘deliberate’ tyramine ingestion has occurred and SBP is in excess of 220/130 mm/Hg.

Rapid reduction of hypertension (i.e. within 2 – 4 hours) carries a serious risk of catastrophic adverse effects (13-16) and such treatment is probably inadvisable, even if initiated in a specialist hospital setting.

Several of these recent reviews about hypertensive urgencies make very strong statements about premature treatment and about excessively rapid reductions of blood pressure.

  1. Flanigan: “Often the urgency is more in the mind of the treating physician than in the body of the patient … The compulsive need to treat reaches the pathological in some physicians, especially during the early years in their careers”.
  2. Marik: “Rapid reduction of BP may be associated with significant morbidity … causing ischemia and infarction. it must be lowered in a slow and controlled fashion [over 24 – 48 hrs.] to prevent organ hypoperfusion.”
  3. *Sub-lingual nifedipine is very strongly contra-indicated (11, 16-18). It can result in uncontrollable hypotension and hypo-perfusion which may cause stroke or sudden permanent blindness. Indeed some experts have suggested instant/rapid-release formulations of nifedipine should be prohibited(5, 19) and that it should never be given to patients to self-administer.

References

1.         McCormack, D and Buckley, N, Psychostimulant poisoning. Australian Prescriber, 2006. 29: p. 109–11.

http://www.australianprescriber.com/magazine/29/4/article/824.pdf

2.         Murray, L, Daly, F, Little, M, and Cadogan, M, Toxicology handbook. 2011: Elsevier Australia.

3.         Grossman, E, Nadler, M, Sharabi, Y, Thaler, M, et al., Antianxiety treatment in patients with excessive hypertension. Am. J. Hypertens., 2005. 18(9 Pt 1): p. 1174-7.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16182105

4.         Yilmaz, S, Pekdemir, M, Tural, U, and Uygun, M, Comparison of alprazolam versus captopril in high blood pressure: a randomized controlled trial. Blood Press., 2011. 20(4): p. 239-43.

http://www.ncbi.nlm.nih.gov/pubmed/21288144

5.         Grossman, E, Messerli, FH, Grodzicki, T, and Kowey, P, Should a moratorium be placed on sublingual nifedipine capsules given for hypertensive emergencies and pseudoemergencies? JAMA, 1996. 276(16): p. 1328-1331.

6.         Messerli, FH and Eslava, DJ, Treatment of hypertensive emergencies: blood pressure cosmetics or outcome evidence? J. Hum. Hypertens., 2008. 22(9): p. 585-6.

https://www.ncbi.nlm.nih.gov/pubmed/18432257

7.         Chobanian, AV, Bakris, GL, Black, HR, Cushman, WC, et al., Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension, 2003. 42(6): p. 1206-52.

https://www.ncbi.nlm.nih.gov/pubmed/14656957

8.         Chou, C-L, Chou, C-Y, Hsu, C-C, Chou, Y-C, et al., Old Habits Die Hard: A Nationwide Utilization Study of Short-Acting Nifedipine in Taiwan. PloS one, 2014. 9(3): p. e91858 http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0091858.

9.         Gemici, K, Baran, I, Bakar, M, Demircan, C, et al., Evaluation of the effect of the sublingually administered nifedipine and captopril via transcranial doppler ultrasonography during hypertensive crisis. Blood Press., 2003. 12(1): p. 46-8.

https://www.ncbi.nlm.nih.gov/pubmed/12699135

10.       Ishibashi, Y, Shimada, T, Yoshitomi, H, Sano, K, et al., Sublingual nifedipine in elderly patients: even a low dose induces myocardial ischaemia. Clin. Exp. Pharmacol. Physiol., 1999. 26(5-6): p. 404-10.

https://www.ncbi.nlm.nih.gov/pubmed/10386229

11.       Bulling, M and Burns, R, Occipital cortical "angina" induced by nifedipine. Med. J. Aust., 1988. 148(5): p. 266.

http://www.ncbi.nlm.nih.gov/pubmed/3343961

12.       Morton, C and Hickey-Dwyer, M, Cortical blindness after nifedipine treatment. BMJ, 1992. 305(6855): p. 693.

http://www.ncbi.nlm.nih.gov/pubmed/1393116

13.       Marik, PE and Rivera, R, Hypertensive emergencies: an update. Curr Opin Crit Care, 2011. 17(6): p. 569-80.

http://www.ncbi.nlm.nih.gov/pubmed/21986463

14.       Flanigan, JS and Vitberg, D, Hypertensive emergency and severe hypertension: what to treat, who to treat, and how to treat. Med. Clin. North Am., 2006. 90(3): p. 439-51.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16473099

15.       Migneco, A, Ojetti, V, De Lorenzo, A, Silveri, NG, et al., Hypertensive crises: diagnosis and management in the emergency room. Eur. Rev. Med. Pharmacol. Sci., 2004. 8(4): p. 143-52.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15636400

16.       Feldstein, C, Management of hypertensive crises. Am. J. Ther., 2007. 14(2): p. 135-9.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17414580

17.       Marik, PE and Varon, J, Hypertensive crises: challenges and management. Chest, 2007. 131(6): p. 1949-62.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17565029

18.       Schwartz, M, Naschitz, JE, Yeshurun, D, and Sharf, B, Oral nifedipine in the treatment of hypertensive urgency: cerebrovascular accident following a single dose. Arch Intern Med, 1990. 150(3): p. 686-7.

http://www.ncbi.nlm.nih.gov/pubmed/2310288

19.       Burton, TJ and Wilkinson, IB, The dangers of immediate-release nifedipine in the emergency treatment of hypertension. J. Hum. Hypertens., 2008. 22(4): p. 301-2.

http://www.ncbi.nlm.nih.gov/pubmed/18239624

This section on diurnal variation of mood was added in 2017, after talking to someone with depression over Skype, and explaining about diurnal variation. That reminded me of an analogy I used.

Persistent diurnal variation of mood is one of the more reliable markers of a biological depression. However, something I have observed over the years, which does not seem to crop up in the literature, is this: the improvement of mood that occurs in the afternoons and evenings, and the return of severe symptoms on waking next morning, is something that gradually gets less noticeable if the illnesses becomes more severe and has been present for some time. In other words, as the illness is developing, diurnal variation is most noticeable; if-and-when the illness reaches a severe degree, then diurnal variation becomes less noticeable. People just feel like ‘death-warmed-up’ the whole time.

The converse is also true. As more severe illnesses start to improve and respond to treatment, the early improvement is usually most noticeable in the afternoons and evenings, but then, when people wake up next morning, they feel as bad as ever. If you ask someone with severe illness ‘what is your first thought about the day ahead when you awake’, the answer is frequently ‘OMGAD’ (Many suffers guess that immediately, I spell out that acronym below***). Hence the heading of this piece, ‘A cruel trick’. I am sure that this phenomenon has been responsible for many people giving up on treatment, or despairing of improvement, because they feel better in the afternoon and think the illness is improving, only to wake up as-bad-as-ever the next morning. If no one has provided the above explanation that phenomenon is a profoundly discouraging experience.

Remember the ‘waves on the beach’ analogy above, remember to compare like with like, i.e. afternoons with afternoons, or mornings with mornings, and remember to compare averages of several days, with a gap of a few days in between, to judge change. Also, as I often commented to patients ‘I do not care how you feel’. That made people stop and listen! Instead I want to know what you have done, compared to before. This point was illustrated only a few days ago, in another skype ‘consultation’: ‘How are you going’? ‘I am more anxious …’. This person felt they were not improving. But a couple of brief questions made things clear. They had in fact managed to go shopping, alone, twice in that week, in order to get the ingredients to cook a meal (for the first time in a while) and also been to a drinks party and ‘coped quite well and enjoyed it, a bit’. And there was more! No wonder anxiety had increased. In relation to this remember ‘Salami tactics’ above, and the aphorisms, ‘Slow and steady wins the race’, ‘Do not try to run before you can walk’, and ‘Do not bite off more than you can chew’.

If people are doing more activity that is strong evidence they have more drive and energy: if that core symptom is improving one can be quite sure they are getting better. As president Nixon is quoted as saying, ‘When you’ve got them by the balls, their hearts and minds are sure to follow’.

Enough said.

The acronym: *** ‘Oh my god, another day’. 

Introduction

I have written this commentary for several reasons. I could have written it long ago, and do so now because the time for restraint and silence is past. My research and teaching, and the content of this website, is about psychopharmacology, so this is somewhat peripheral to my errand.

The first reason is articulated by Edmund Burke’s attributed words, ‘The only thing necessary for the triumph of evil is for good men to do nothing.’ I this instance professional experts like me, who have special confidential knowledge, and skills and experience at evaluating people’s stories and motivations, must speak of what they know about wrongdoing in the churches etc., ‘for the record’: to stay silent is to do nothing.

The second reason is to offer reassurance to the legions of people, who have been abused in many and various ways, that their accounts are believable and believed, by sensible observers, and professional experts. Take note of the ongoing Royal commission findings.

Third, to remind everyone how the ‘simple inaction’ of not supporting (that may also mean ‘not believing’) is the power they already possess to foster change.

I am focussing on my experience of treating Catholic ‘clergy’ and consulting in a Catholic private hospital, since they have made themselves the center of attention in what seems like an endlessly repeating sick ‘real-life’ TV drama (see today’s episode).

I also proffer my clear conclusion that preventing these perversions*** requires nothing less than removing the power and privilege accorded to this dysfunctional institution. Installing new actors and directors to run the show will change nothing. This is because what drives all this is not just individuals, but the nature of the institution itself.

*** Throughout, I use the word ‘perversions’ in both senses defined by the SOED.

The simple realization that the inaction (of not supporting) is one key step is empowering, because it shows that ‘adherents’ could choose to end it all, simply by ceasing to support and believe. Neither fairies nor monsters exist for people who do not believe in them. It is such a simple way to further diminish the steadily dwindling remnants of this unbelievable erstwhile theocracy (well, not quite ‘erstwhile theocracy’, since the Vatican still exists).

This commentary pertains particularly to my first-hand experience, as a specialist psychiatrist, of Catholics and of the misbehaviours of Catholic ‘non-laity’ (clergy of whatever gender, species, title or presumed authority).

I shall say ‘they’ and ‘them’ from now on, because they deserve no self-granted grandiose titles, dwellings, robes (bit of a give-away there?) or descriptions. Many of them have mediocre intellects and modest educational achievements that would make it less easy for them to attain similar status or position in the ‘outside’ world.

NB. Definition: Clergyman. ‘A man who undertakes the management of our spiritual affairs as a method of bettering his temporal ones’. Ambrose Bierce.

I now offer this variant of Ambrose Bierce’s acerbic observation:

‘A man who undertakes the betterment of our moral life as a method of bettering his own opportunities for an immoral life’. Ken Gillman.

Perhaps, from this record of my experience, people adversely affected by the misbehaviour of ‘them’ may be reassured about the complete justification for the disbelief, that any ‘man-of-the-world’ must experience, of the chorus of denials we hear (forgetting, lying about, turning-a-blind-eye to, whatever evasive tactic or euphemism for perfidy is employed). Be robustly assured that ‘external’ observers and experts like me are convinced, beyond doubt, from their professional experience, that the evidence of wrong-doing that is now evident is but the tip of the iceberg: a large proportion of them are indeed practitioners of various types of perversions (not just sexual) and are also cowardly (but well-practiced) liars who are utterly undeserving of their privileged position in society. Relegation to the role of ‘translocation of ordure’ is for many of them closer to their deserved position in society.

Any psychologist who can come up with a way to enable the deceived, bullied and betrayed supporters of this institution to gain insight into its cruel bullying premises and wicked practices, would be doing society a great service. Such insight would facilitate removal of support for ‘them’ so they would wither and fade away, faster.

As a recipient of abuse, or a friend or a supporter of sufferers, try to educate people that any support for the institution, makes them, by proxy, abusers themselves. This is because the very existence and continuation of the institution inevitably means continuation of abuse and perversions. Simply being a passive observer involves a degree of collusion, as does merely attending one of their churches: the quotation attributed to Edmund Burke says it all: ‘The only thing necessary for the triumph of evil is for good men to do nothing.’ That sentiment has been a major motivator for me to write this commentary. I must tell what I know, and give my expert opinion, or I too am a complicit bystander: but I can only tell a part of what I know, it would take too long to tell all of it, and some of it simply would not be believed by most people.

As I write this, in the early part of 2017, we seem to be drowning in a sea of news about the perverted behaviour of enormous numbers of people in institutions, mostly religious, and especially Catholic (news here in Australia – but I am quite sure it is equally bad where-ever Catholics have a presence, as documented in the book by the famous Australian jurist, Geoffrey Robertson QC ‘The Case of the Pope’).

Pervasive and persistent perversion

I need hardly have said ‘as I write this’ because opinions such as those I am expressing have been given by informed persons over the last couple of thousand years of the Catholic church's domination of Western religious thought and western society.

Perversion’s very persistence and pervasiveness is what indicates it is part of the warp and weft of the institution itself. There will be, in all times and places, individuals who will thrive in, dominate over, and pervert, any institution with such a belief system and structure.

I state, ‘any informed person’, with due recognition of the fact that until more recent times the church's domination of society, at all levels and in all professions, was such that it was simple for them to suppress knowledge and criticism rather effectively (books, especially the contents of the bible, knowledge, their own bad behaviour – I know, bad behaviour may seem an understatement, but if understatement is not employed we will exhaust hyperbole in no time).

A powerful example of the deep insidious roots of a belief-distorted mentality, from my personal experience, is given below (in anecdote 1), when I was accused by a (Catholic) medical colleague of uttering the words of the devil (perhaps he could have arranged an exorcism foe me! – see below). It will shame, enrage or amuse, depending on your viewpoint.

As their ability to achieve universal domination and bullying has been steadily eroded, by education, knowledge, science, rationalism, and secular society, the extent of their undesirable behaviours in so many spheres have become more and more apparent to more and more people. I doubt not that perversion has been just as frequent throughout the history of the church. It has just been revealed more often, and to more people, in our age.

If belief about their deity, and the assembled writings associated with their message, makes ordinary mortals torture and burn to death other people, just for translating it from one language into another***, then one might easily suppose that all the perversions we have been informed about in recent times might have been accomplished with ease and an unruffled conscience, before breakfast.

***A reminder, for those less familiar with the history of their perverted practices: poor Tyndale was murdered and burned, essentially for translating the bible into English. So much for church claims to lead the improvement of the moral behaviour of society! There was a death penalty for possession of the bible in English. If this reminds you of the sorts of behaviours by other religious groups currently reported daily in the international news, and if you still think religion advances moral outlooks and behaviours, then I suggest you have a bit of explaining to do, and that will involve you in some pretty tortuous and tiring mental gymnastics.

I do not propose to expend a great deal of my time, or my readers time, in discussing religious belief and the Catholic church. Essentially, belief is the adoption of precepts and ideas for which there is no sound reason or reproducible evidence, usually against the laws of nature and what common experience demonstrates to be the case – miracles, divinely inspired prophets (very few of whom agree with each other on even the most fundamental of facts), inscriptions found on mountains in remote locations which have a habit of mysteriously disappearing, etc. One believes in fairies, but one deduces (if only vicariously) Darwin’s theory of evolution (or any other scientific ‘theory’) from evidence. Such evidence is not a unique one-off experience by an individual. It is reproducible, and to an extent modifiable, by anyone, at any time, who wishes to go and dig up a few fossils. Fossils were not ‘revealed’ to Darwin, only to then disappear from human perception, leaving only his word. As Carl Sagan said (in the tradition of Hume), ‘extraordinary claims require extraordinary evidence’. And indeed, Darwin produced extraordinary evidence, and a very great deal of it. So much, that those able to understand even simple science, cannot doubt or contradict it. How spectacularly different that is to the belief demanded (often under threat) of a potential adherent to a religion.

Definition: Faith. belief in one instance of the extra-ordinary, related in another tongue, from another land, by persons of unknown sobriety, which contradicts what we know to be true here and today.

My experience of ‘channelling’ the devil

As a doctor of reasonably broad experience I can affirm that most of these people are up to no good, and many of the others know, or suspect, that the rest of them are up to no good. That leaves few who are truly innocent and blameless, in the ‘Burkian’ sense. The oft repeated story that they did not know ‘that sort of thing’ was going on might very occasionally be true, because some of them may be that naïve. The phrase, ‘lying for God’, covers it for the rest of them. That rapidly morphs into lying for their own good. Many of them become fluent and frequent liars.

When they revealed to me their behaviours and their problems in consultations, I would often ask, what happens when you confess? What help and guidance does that give you? The standard reply was ‘Oh! I wouldn't confess to that’.

Time for another definition in the spirit of Bierce

Definition: Confessional. A place for perfecting and practicing the arts of lying and denying.

It is also essential to appreciate that an enormous amount of self-selection, and selective screening, of who gets into the church, and who progresses once in it, has been going on for centuries. As with any powerful, hierarchical and secretive organisation these elements inevitably foster perversion and corruption. The added element of celibacy in the Catholic church means that it is almost inevitable that a substantial proportion of the entrants will be unusual personalities, by whatever criteria one applies to such things.

The indications are clear, that the church’s tendency to attracted abnormal personalities has always been prominent, and is probably becoming more pronounced as the church, and educated western societies, move further apart – I am told most Australian seminaries have empty echoing rooms, and many parishes now need to import their incumbents from Africa. The immigration department could put a stop to that one right away! Especially since we do not know which ones are paedophiles (the United Nations, no less, have been blocked by the Vatican on child protection issues – because those measures would allow extradition of thousands of paedophile Catholic priests to face prosecution, which at present cannot be done).

My experience was that they had more than their fair share of nasty, bullying, pathetic, neurotic, inadequate men, quite often of rather second-rate intellect, like Cardinal Pell from Australia***, who presided over a process supposedly to help those who had been abused, whilst having very convincing evidence hanging over him that he too had an abnormal physical interest in young boys. To be specific, he spent a lot of time at the Ballarat swimming pool where he physically handled many boys, playing in the pool, and where he spent long spells naked in the changing rooms in the presence of young lads. That much seems hard to deny – what else? I, for one, am not awarding any prizes for the answer to that.

So, Pell dealing with accusations of abuse. Talk about setting set the fox to guard the henhouse!

Thus, the bizarre greenhouse of the Catholic Church allows these odious specimens to grow and thrive.

*** This courageous and principled gentleman finds his health insufficiently robust to make a trip from his refuge in the Vatican (what a timely appointment) back to Australia to answer questions at the commission of enquiry, relating to abuse, including by him. It is easy to learn for yourself how specific, and in my professional opinion, convincing, the many accusations against Pell are.

https://www.youtube.com/watch?v=f_tz7DBEmiE

I think he might find himself to be well enough to attend a ceremony to honour a new (fast-tracked) saint. Is his health really any worse than the millions of retirees who jet about the world daily? His excuses for non-attendance at the Royal commission have been accepted.

Definition: Saint. A dead sinner revised and edited. Bierce.

A here is a lovely song in Pell’s honour

https://www.youtube.com/watch?v=EtHOmforqxk

When a grossly disordered group of people like this are permitted to retain money and power, with no accountability, one will always have the perfect recipe for perpetuating perversions and much else undesirable and unpleasant: that is made self-evident by these tediously ongoing revelations.

The lesson from this is simple and revealed by history. It is utterly impossible for them to self-regulate. This obscene farce will continue for as long as they are permitted to retain the status, power, privileges and influence that our naïvely deluded society still allows them to retain. Until a sufficient proportion of the population demand the removal of their status and powers and make them answerable fully to all the proper constraints of society, nothing will change, Royal commissions or whatever.

It has always puzzled me that so few clergy have been assaulted by family members, or church property or churches burned down. I wonder if those who insure them are re-assessing the level of risk and may be thinking of upping the premiums a bit! Think of it like this: churches get hit by lightning just as frequently as other buildings, so that indicates ‘God’s’ influence, or opinion, over such matters.

Stop supporting. Stop believing, neither fairies not angels exist, however comforting such ideas may be. To continue supporting is to collude in, and be complicit in, a panoply of perversions.

Anecdote 1

It is important to understand that ‘belief’ will turn apparently educated people into irrational and immoral people: no religion can escape that trap. Belief is antithetical to rational thinking, the more fervent the belief, the greater the distortion of rationality. Once belief is established it can pervert any action, or inaction, and justify it, because it is ‘in God’s name’ or for the church, not necessarily quite the same thing.

Remind yourself, what I relate here happened close to the dawn of the third millennium! Not in the dark ages - the halcyon days of the church when there was no accountability whatsoever.

After I had been practising in town for a few years as a specialist I established a psychiatric unit at the local private Catholic hospital. They engaged in all sorts of dubious behaviours. I remember discovering that on Sundays, when I was not around, they were taking psychotic patients into the chapel to cure them by speaking in tongues, or casting out devils, or whatever (medieval madness that I presumed, till then, had disappeared from civilized countries).

In due course things started to go more seriously amiss, because senior nuns in the hospital were exercising their sexual predilections in a manner that became harmful to the hospital, and to other staff who were not ‘in on the act’. I decided to advise them to curb these activities, and as a first step in that process I arranged a meeting at my home with the senior Catholic doctor on the board of the hospital. What I had to tell him need not be described in detail, in outline it was simply that inappropriate sexual relationships were occurring involving this nun in charge of the hospital. As an atheist, there was nothing in that to concern me (only adults were involved), except that it was resulting in other members of staff who were aware of the situation being dismissed, disadvantaged etc., and it was bad for the proper operation of the hospital.

So, this doctor, a fellow specialist at the hospital, arrived. I sat him down at the table and began succinctly to tell him the problem. I said that there was a serious situation that was harming the running and reputation of the hospital that involved Sister X who was having a lesbian … .

Well readers, believe it or not, that is as far as I got, well, at least as much as he heard. This grown professional man heard no more of what I said because he thrust his fingers into his ears and started repeating over and over in a loud voice something like the following: "this is the Devil speaking, I will not listen, this is the Devil speaking, I will not listen …".

He went on repeating that until he saw my lips stop moving. At that point, he got up from the table and left hurriedly, saying, in Parthian style, ‘over his shoulder’, as he went, "I'm not calling you a liar, but …".

I must say that I thought, as a psychiatrist, I was knowledgeable about psychology and the extent to which belief systems distort people's rational processes, but this first-hand example of such an extraordinary piece of behaviour illustrates the enormity of the problem. It left me appalled and aghast: but with laughter not far behind. Belief turns people who might otherwise be rational into immoral idiots***. Is there any other way to describe that educated professional person’s behaviour? Not in my book. Could you have respected that man? I hope not.

Never forget, there are millions more just like him.

I did not let it rest there. I ‘persuaded’ the board to act. No prizes for guessing what they did with her: Africa, I seem to recall. Needless to say, I was ‘persona non grata’, and my unit closed.

*** I must record how one of the oldest nuns, a dear lady, who I am quite sure knew exactly what was going on, came up to me in the hospital, after all this had unfolded, and took me gently to one side (I was of course being shunned by most). She indicated the sign of the ‘Sisters of Mercy’ and whispered to me, ‘they should take that down’, and tottered away. So, you see, some people can transcend the power of belief and see the truth! But I guess she said nothing, except to me, and one can understand that: she was too old for Africa.

If there is anybody out there who rates the chances of these abused people, who have been mistreated by the church for so long, being listened to by the church and its followers in anything approaching a sane and fair hearing, let them ponder my account. This was a doctor dealing with a fellow professional. What chance would a child, or a lay-person, have, if they related their account to a priest, or policeman, teacher, or even their own parent.

Such knowledge and experience makes it hard not to have sympathy with the view that religion poisons everything, as expressed by Hitchens in his book ‘God is not great’. Poisoning the trust between a parent (who will react similarly to my colleague above), and a child, is surely up near the top of the ratings in the ‘league table of wickedness’. Young children pick up the not-so-subtle clues which tell them that making any adverse comment about the clergy will attract instant, and sometimes severe, disapproval and censure (just as your dog learns to read you). Indeed, it is all part of the ‘grooming’ process. What a horrible and insidious way of poisoning a child’s perception and trust.

But, such events and consequences are inevitable, they are built into their system as much as gold and interest rates are part of capitalism.

Addendum

This commentary could go on forever: however, one cannot let this one, from today’s news, go by unremarked on. I thought I had become inured, but I suggest you look at this next link only if you have a strong stomach and but little imagination, it is about the Irish single-mothers’ home:

http://www.abc.net.au/news/2017-03-07/ireland-dead-babies-found-in-sewer-may-prompt-inquiry-widening/8330504

And on the same day, I saw this (it is not an excerpt from Mr Brown’s ‘Da Vinci Code’, it is real life): ‘Mastering the devil: A sociological analysis of the practice of a Catholic exorcist’ which indicates they are still performing many thousands of these rituals.

http://journals.sagepub.com/doi/abs/10.1177/0011392116686817

and

https://www.youtube.com/watch?v=WgaV-3epSEU

and if you think Pell has any vestige of a decent intellect this might make you question that

https://www.youtube.com/watch?v=LX7tz78RVEI