Making medicines safer for all of us

Adverse drug events are now the fourth leading cause of death in hospitals.

It’s a reasonable bet they are an even greater cause of death in non-hospital settings where there is no one to monitor things going wrong and no one to intervene to save a life. In mental health, for instance, drug-induced problems are the leading cause of death — and these deaths happen in community rather than hospital settings.

There is also another drug crisis — we are failing to discover new drugs. [Read more...]

Author Archive for David Healy

Not the 2018 Sense about Science JM Prize Nominee

Editorial Note: This post continues from Outsourcing Fascism.  For more on James Coyne, see Rolf Harris to James Coyne.  

Coyne was the perfect candidate for a Sense about Science JM Prize until a few years ago.  He was the first to wade in and rubbish anyone who might have thought there was something wrong with a medication.  His dark past had not come to light. 

But too many people now know that there have been a string of universities who, rather like the Catholic Church handling pedophile priests, have gotten rid of him in some cases by giving him glowing references.  And Simon Wessely thought he was great. 

The clincher has probably been a recent blot on his copybook.  Even SAS , unless they go into full new politics mode and view anything inconvenient as fake, would find it difficult to Maddox him.  The latest episode – see below – led to a series of public domain communications from a number of leading figures in UK clinical psychology and related domains, which gives a feel for what happened.


For all the talk about ‘safe spaces’, universities have been remarkably reluctant to take action against a convicted domestic abuser in their midst – until now.

Bullying and point-scoring in the academic world is nothing new, although social media like Twitter and Facebook might be making it more visible. Recently, however, a letter to the Universities of Groningen and Stirling, has highlighted the extent of the problem and, in the case of one American professor, given a clue as to why it might sometimes be going on.

The unacceptable behaviour of Professor James Coyne became public knowledge during the reporting of a major research trial into ways of helping people struggling with chronic fatigue. Several national British newspapers reported leaked emails from Professor Coyne showing that he had referred to a male academic colleague as a ‘disgusting old fart neoliberal hypocrite’ and had told a female colleague ‘let’s get all this backchannel bullshit into the open, you ol’ sleazebag’

(The Times, 1.8.17Daily Mail online 18.11.17.;).

A frequent visitor to the UK, Professor Coyne is a former visiting professor at Stirling University and relentlessly attacks British mental health professionals and researchers on social media. But while one eminent professor recently lost his job for a joke about being distracted by women in the lab, Professor Coyne’s behaviour has gone unchecked, despite numerous complaints. He regularly accuses fellow professionals of unethical behaviour, racism and so on while using grossly sexist epithets to female professionals such as ‘bimbo’ and ‘bitch.’ On one occasion, his threatening behaviour (he was overheard saying; ‘I’m going to get that c***.’), a university is reported to have hired a bodyguard to protect a fellow lecturer ( ).

Matters became more serious with the publication of a blog by Professor Coyne on 15th November 2017 entitled; ‘Stop using the Adverse Childhood Experiences Checklist to make claims about trauma causing physical and mental health problems’ (  ). Purporting to be a critique of an assessment tool for traumatic events such as abuse, domestic violence and emotional neglect, the blog made the astonishing claim that behaviours fitting the definition of sexual abuse can be a ‘positive, liberating experience.’ Coyne’s actual words were: ‘There is so much ambiguity in endorsements of (ostensible) sexual abuse. Maybe it was a positive, liberating experience.’ He elaborated thus: ‘What if the “perpetrator” is the 20 year old boyfriend or girlfriend of a 14 year old?… Arguably, the event…..could actually be quite positive.’

Professor Coyne followed up with a series of provocative posts on social media including comments in tweets about the numerous professionals and survivors of abuse who protested: ‘moronic’, ‘what a low lifer’, ‘a sleazy troll’ ‘another appalling sleeze troll’; and so on. He has also castigated colleagues with comments such as: ‘a real asshole’, a ‘pompous buffoon’, a ‘puritanical classist prig’ and ‘a moralistic cloistered white prude’ for raising the issue.

Meanwhile, as colleagues were moved to complain about Professor Coyne’s behaviour, social media also revealed what may be clues explaining his behaviour. Professor Coyne has a history of arguing that psychological trauma is relatively unimportant as a cause of later mental health problems. This may have something to do with the fact that Professor Coyne himself has a history as a perpetrator of domestic violence, which has included substantial damages for the infliction of psychological trauma ( ).

The balance between academic freedom of expression and unacceptable behaviour is a fine one. The fact that Professor Coyne’s behaviour on social media – in minimizing the effects of traumatic experiences on our mental health, and abusing colleagues – reflects a history of abusive behaviour in the real world, may give a clue as to some of the origins of this repellent activity.

Finally, however, the tide may be turning. The Chair of the Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, (with whom Coyne claimed a professional affiliation) described Professor Coyne’s behaviour as ‘reprehensible’ in a letter to professional colleagues. She regretted the abuse that colleagues had been subjected to, and condemning his ‘appalling’ language and actions ( ).

The Dean of the University of Groningen also expressed condemnation of Professor Coyne’s ‘continuing unacceptable behaviour’ along with a ‘strong request’ for Coyne not to present himself as a current employee of the university ( ).

Presumably as a result of this criticism, Professor Coyne has subtly altered his profile on social media ( ), referring to his various university affiliations in the past tense. He continues to offer online guidance to junior colleagues, charging $75 for an online course. Given his reputation, it is difficult to regard this as value for money.


Formal complaint about James Coyne’s behaviour

Professor James Coyne is a clinical and health psychologist based in the US who is well known on social media for his abrasive and attacking interactions.

On his website and on social media, Professor Coyne claims the following affiliations:

  • Professor of Health Psychology at University Medical Center, Groningen, the Netherlands, teaching scientific writing and critical thinking.
  • Visiting Professor, Institute for Health, Health Care Policy & Aging Research, Rutgers, the State University of New Jersey.
  • Emeritus Professor of Psychology in Psychiatry Perelman School of Medicine at the University of Pennsylvania. He also claims on his website to be a blogger at PLOS Mind the Brain.

Following the publication of his recent blog claiming that experiences classified as what he calls ‘ostensible’ sexual abuse can be a ‘positive, liberating experience’, which aroused widespread shock on social media, a group of us wrote the following letter of complaint to the University of Groningen and copied it to the University of Pennsylvania and Rutgers University: 
We write, as a matter of deep and urgent concern, to make you aware of the behaviour of one of your colleagues, Professor James Coyne, who holds the position of Emeritus Professor in your Department. For many years, now, Professor Coyne’s behaviour on social media has crossed the boundaries of common decency, and could be characterised as bullying, harassing, offensive and defamatory. Of particular concern is Professor Coyne’s misogyny; with examples of him using language such as ‘bimbo’ and ‘bitch’ about professional women on social media. Professor Coyne’s unacceptable behaviour became public knowledge when several national British newspapers reported that leaked emails showed that he has referred to a male academic colleague as a ‘disgusting old fart neoliberal hypocrite’ and had told a female colleague ‘Let’s get all this backchannel bullshit into the open, you ol’ sleazebag’ (The Times; scientists-trade-insults- over-myalgic-encephalomyelitis-me-study-slk0cv5lj;

Daily Mail online;– regarding-flawed-study.html

Matters became even more serious with the publication of a blog on 15.11.17 titled: ‘Stop using the Adverse Childhood Experiences Checklist to make claims about trauma causing physical and mental health problems’ (– childhood-experiences-checklist-to-make-claims-about-trauma-causing-physical-and-mental-health-problems).

Purporting to be a critique of an assessment tool for traumatic events such as abuse, domestic violence and emotional neglect, the blog made the astonishing claim that behaviours fitting the definition of sexual abuse can be a ‘positive, liberating experience.’ Coyne’s actual words were: ‘There is so much ambiguity in endorsements of (ostensible) sexual abuse. Maybe it was a positive, liberating experience.’ He elaborated thus: ‘What if the “perpetrator” is the 20 year old boyfriend or girlfriend of a 14 year old?… Arguably, the event…..could actually be quite positive.’

As a group of mental health professionals, survivors of abuse and senior workers in related fields, we hope it is abundantly clear that sexual abuse is never a ‘positive, liberating experience’. We also hope it is not necessary to point out that a sexual relationship with a 14 year old is illegal, and that the situation in which an older person has persuaded the younger one that they are in a caring boyfriend/girlfriend relationship is a very common abuse scenario. We trust it is obvious to you that Professor Coyne’s stated views are not only deeply offensive, but utterly irresponsible given his professional status, and a clear breach of professional ethics.

We regret to tell you that Professor Coyne has responded to widespread horror on social media about his views in his traditional unacceptable style. He has directed these comments in tweets about the numerous professionals and survivors of abuse who have protested: ‘moronic’, ‘what a low lifer’, ‘a sleazy troll’, ‘another appalling sleeze troll’; and so on. He has also stated that Professor Kinderman is ‘a real asshole’, a ‘pompous buffoon’, a ‘puritanical classist prig’ and ‘a moralistic cloistered white prude’ for raising the issue. Meanwhile, his history as a convicted domestic abuser has come to light and now appears to be common knowledge (– unpublished/20030424_C232981_53_232981.OPN.PDF?ts=1396125300).

We understand that Professor Coyne has been the subject of formal complaints in addition to ours. We are frankly appalled that no effective action has been taken, and that Professor Coyne is still in post. You may be aware that his recent behaviour is causing outrage on social media, with numerous angry and horrified comments on several Facebook websites, including the UK Clinical Psychology Facebook group, and on Twitter ( Since his grossly unacceptable conduct has already been exposed in the national UK press, we are astonished, among other things, that you are prepared to risk the reputation to your University of continuing your links with a man who continues to behave in this manner.

We ask you to act urgently and decisively on this matter and to inform us of the outcome.

In an immediate and strongly-worded reply, the Chair of the Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, described Professor Coyne’s behaviour as ‘reprehensible‘. She regretted the ‘abuse’ that colleagues had been subjected to and joined us in condemning his ‘appalling’ language and actions. We welcome this statement and believe it reflects well on the Faculty.

The Chair also clarified that ‘Dr. Coyne has not worked at the University of Pennsylvania since 2013 and we do not anticipate any relationship with him in the future.’

The Dean of the University of Groningen also expressed condemnation of Professor Coyne’s ‘continuing unacceptable behaviour.’ The Dean said that a second letter had been sent to Professor Coyne about his professional misconduct on social media, along with a ‘strong request’ not to present himself as a current employee of the university.

The University of Rutgers has no mention of Professor Coyne on its faculty list.

We understand that Professor Coyne has been asked to step down from his role as blogger at PLOS. He is not currently registered as a practising clinical psychologist with the state licensing board of Pennsylvania.

As of 13th Dec 2017, his website has not been altered in accordance with the University of Groningen’s request, and nor have the additional inaccuracies been corrected.

Given this appalling history of misrepresentation, harassment, abuse and criminal behaviour, we advise people to be extremely cautious in their interactions with Professor Coyne and very sceptical about the accuracy of any blogs, articles or claims by him, either personal or academic.

Professor Richard Bentall, Professor of Clinical Psychology, U of Sheffield
Dr Jacqui Dillon, Chair, Hearing Voices Network England
Dr Alec Grant, Independent Scholar in Narrative Mental Health
Dr Lucy Johnstone, Consultant Clinical Psychologist
Professor Peter Kinderman, Professor of Clinical Psychology, U of Liverpool
Dr David Pilgrim, Visiting Professor of Clinical Psychology U of Southampton
Dr John Read, Professor of Clinical Psychology, U of East London
Dr Akima Thomas, Clinical Director of Women and Girls Network and W London Rape Crisis Centre
Jo Watson, UKCP Registered Psychotherapist

Editorial:  Its likely too difficult to nominate JC for a JM Prize.  I would like to call for your suggestions for someone else to nominate instead.


Outsourcing Fascism


In 2017 the Sense about Science (SAS) John Maddox (JM) Prize was awarded to to Riko Muranaka for her efforts to counter apparent misinformation about the HPV vaccine.

MedWatcher Japan are the group who have helped raise the profile of concerns about the HPV vaccine in Japan. When it comes to tackling the adverse effects of treatments, there is no more impressive group in the world and in response to their arguments – see Here – the Japanese government has reconsidered its position.

Key to an award of an SAS Prize is that Muranaka should have been threatened, and intimidated for her brave work standing up for truth.  I asked some MedWatcher contacts what the score was.  They said yep she’s saying she has been threatened but there is nothing much that can be done about it, as she would just use any complaints or even debate as evidence of persecution.

What’s going on?

Iron Fist in Iron Glove

In the 1980s the pharmaceutical industry began to outsource the running of clinical trials to contract research companies, the writing of articles on their drugs to medical writing companies, and a lot of drug development to biotech companies, who could be bought if they discovered something.

Between 1990 and 2002 when Sense about Science and the Science Media Centre appeared, industry realized they could outsource “fascism” too.

When a controversy blows up about a medical product today, it is rare to have the company behind the product wade into the controversy. They take a reputational hit if they do.  Instead, the Science Media Centre in the UK or equivalent bodies elsewhere or SAS wades in – supported increasingly by APA or RCP or other such bodies.

SMC and SAS offer plausible deniability. As Tony Blair seems to have told the Trump team, the Obama administration will never have asked Britain’s intelligence service to spy on Trump – but it will have been understood.

Industry also gets to exploit private enterprise. If a number of providers are competing for the contract. just as with ghostwriters whose job requires competing to find big name academic authors and journals, or CROs who in competing will sign up non-existent patients if need be to secure the next contract, industry can depend on its outsourced defenders to outdo each other in terms of heaping abuse on those who might disparage a company product.  They outsourced defenders are not bound by Good Communication Practice standards.

JM Prize

The following material – except my comments in orange – is taken from the SAS website.

The JM Prize recognises the work of individuals who promote sound science and evidence on a matter of public interest, facing difficulty or hostility in doing so.

It pays tribute to the attitude of JM who, in the words of his friend Walter Gratzer: “wrote prodigiously on all that was new and exciting in scientific discovery and technological advance, denouncing fearlessly what he believed to be wrong, dishonest or shoddy. He did it with humour and grace, but he never sidestepped controversy, which he seemed in fact to relish. His forthrightness brought him some enemies, often in high places, but many more friends. He changed attitudes and perceptions, and strove throughout his long working life for a better public understanding and appreciation of science.”

The winner of the JM Prize receives £2000, and an announcement of the winner is published in Nature. The award is presented each year at a reception in November.


Simon Wessely and Fang Shi-min are the two winners of the inaugural JM Prize for Standing up for Science

Fang Shi-min, a freelance science journalist based in Beijing, was awarded the Prize for his bravery and determination in standing up to threats to his life to uncover clinics promoting unproven treatments, and to bring a wide public readership to the importance of looking for evidence.

Simon Wessely, Professor of Psychological Medicine at King’s College London, was awarded the Prize for his ambition and courage in the field of ME (chronic fatigue syndrome) and Gulf War syndrome, and the way he has dealt bravely with intimidation and harassment when speaking about his work and that of colleagues.

Given his very close links to SAS and SMC, the award of an SAS Prize to SW smacks of SAS awarding the Prize to itself.

That said, it’s easy to get on with SW. I’ve been to his house and he to mine. There are certain things you don’t challenge acquaintances on. In this case one of those things was his belief that he’d had death threats and in general had had a hard time from people with Chronic Fatigue Syndrome who didn’t like his research. Long before this SAS prize came on the radar, he had assiduously been peddling this line, as the researchers working on CFS in general do.

One of the other things I didn’t challenge him on was James Coyne who SW thought was marvellous.

I’d first come across JC when the University of Toronto – and perhaps others – appeared to have outsourced the defending of their fragile little selves against the juggernaut that was Healy – after they’d fired me – to JC, who didn’t just say what U of T or others might have wanted to say but went wildly beyond that without his having ever met me or liaised with me in any shape or form whatsoever.

JC is a notable academic thug, a bully who picks on women in particular. Some people find him very intimidating in print but if you confront him he becomes your new best friend in a rather wheedling kind of way.  See Rolf Harris and James Coyne


David Nutt is the winner of the 2013 JM Prize for Standing up for Science.

The judges awarded the prize to Professor Nutt in recognition of the impact his thinking and actions have had in influencing evidence-based classification of drugs…, and his continued courage and commitment to rational debate, despite opposition and public criticism.

Professor Nutt was named chairman of the UK Government’s Advisory Council on the Misuse of Drugs (ACMD) in May 2008.  In 2009 Professor Nutt was dismissed from his role at the ACMD by Home Secretary Alan Johnson after speaking out about the Government’s policies on drugs being at odds with the evidence. Concerns among the scientific community following Professor Nutt’s dismissal led to the creation of the Principles for the Treatment of Independent Scientific Advice, which are now part of the Ministerial Code.

Again I know DN, well enough to share an early morning Caribbean jacuzzi with him when we were both jet-lagged.  I thought this award to DN was wonderful given that he had referred me to the GMC in 2006 – a professional death threat – for standing up for science in the face of pretty intimidating odds.

Curiously the weapon he used for the referral was an article by Coyne on the martyrdom of david healy. Something Coyne and the journal in which it appeared seem to have been too nervous to include in the print edition of the journal.

In throwing the case out the GMC put it all down to the usual rough and tumble academics get up to.


Emily Willingham and David Robert Grimes are the two winners of the 2014 JM Prize for Standing up for Science.

Emily Willingham, a US writer, has brought discussion about evidence, from school shootings to home birth, to large audiences through her writing. She has continued to reach across conflict and disputes about evidence to the people trying to make sense of them. She is facing a lawsuit for an article about the purported link between vaccines and autism.

David Grimes writes bravely on challenging and controversial issues, including nuclear power and climate change. He has persevered despite hostility and threats, such as on his writing about the evidence in the debate on abortion in IrelandHe does so while sustaining his career as a scientist at the University of Oxford.

If there is anyone around the place who sounds most like Coyne, without being JC, its DRG who has the same features of picking on women and being intimidating and just plain objectionable.  He wades in on medical, especially vaccination, issues, without having any background that would qualify him for doing so, and usually does so from the safety of a twitter feed or print media – he has been notably reluctant to engage with people in real time.


Edzard Ernst and Susan Jebb are the two winners of the 2015 JM Prize.

Edzard Ernst is recognised for his long commitment to applying scientific methodologies in research into complementary and alternative medicines and to communicating this need. Prof Ernst continued in his work despite personal attacks and attempts to undermine his research unit and end his employment. As a result, he has addressed a significant gap in the research base in this field and has brought insights into discussions with the public, policy makers, commentators, practitioners and other researchers.

Susan Jebb, Professor of Diet and Population Health at the University of Oxford, is recognised for her promotion of public understanding of nutrition on a diverse range of issues of public concern, from food supplements to dieting. Prof Jebb tackled misconceptions about sugar in the media and among the public, and endured personal attacks and accusations that industry funding compromised her integrity and advisory capabilities. Despite this experience, she continued to engage with the media and the public on issues of dietary advice, talking about the need for sound science and high quality research, and advocating for high standards of research governance.


Elizabeth Loftus awarded the 2016 JM Prize

Professor Loftus is best known for her ground-breaking work on the “misinformation effect” which demonstrates that the memories of eyewitnesses are altered after being exposed to incorrect information about an event, as well as her work on the creation and nature of false memories. In addition to her research, Loftus has appeared as an expert witness in numerous courtrooms, consulting or providing expert witness testimony for hundreds of cases. Her findings have altered the course of legal history, in showing that memory is not only unreliable, but also mutable.

This year’s nominations – the highest number received in any year – reflecting a growing recognition in the global science community of the importance of engaging in discussion about science in the public realm. In 2016, there were 72 nominations, with nominees from 17 different countries.


Riko Muranaka has been awarded the international 2017 JM Prize for promoting science and evidence on a matter of public interest, despite facing difficulty and hostility in doing so. A journalist and lecturer at Kyoto University, Dr Muranaka is recognised for her work championing the use of evidence in public discussions of the Human Papilloma Virus (HPV) vaccine.

The HPV vaccine is recognised by the scientific and medical community, and endorsed by the World Health Organisation as key to preventing cervical and other cancers. In Japan the vaccine has been subject to a national misinformation campaign to discredit its benefits, resulting in vaccination rates falling from 70% to less than 1%.

Dr Muranaka’s work to put the evidence for the safety of the vaccine clearly before the public has continued in the face of attempts to silence her with litigation and undermine her professional standing. In persisting, she has tried to ensure that a scientific account of the weight of evidence is available not only for Japanese families but for public health globally.

Keepers of the Flame

I have to take care what I say here, as SAS will put it forward as evidence that RM is totally deserving of her JM Prize.

The very existence of this post in fact proves they all deserve a JM Prize – maybe even a second one each.

One of the extraordinary characteristics of at least some of the recipients of the JM Prize, SAS, SMC and others is that despite having the backing of the establishment and some of the most powerful interest groups on earth, when up against individuals or at most a handful of people who have been damaged by drugs or vaccines, who are trying primarily to stand up for both science and decency, the SASers see, or at least paint, the struggle in terms of them as the few defenders of science trying desperately to keep a flickering flame alight in the face of overwhelming forces of darkness.

It’s as though the Catholic Church were to use claims their priests had abused children as evidence of the hostile forces surrounding them – and their role as the light that shines in the darkness that the darkness does not comprehend.   

The Lilly advert above seems to capture many of the psychodynamic ambiguities involved in this kind of positioning. 

To be continued with my nomination for the 2018 JM Prize.
Readers nominations for the Prize are welcome.


The Night Before Christmas and The Nights After

Twas the night before Christmas, when all through the house
Not a creature was stirring, not even a mouse;
The stockings were hung by the chimney with care,
In hopes that St. Nicholas soon would be there

The children were nestled all snug in their beds,
While visions of sugar-plums danced in their heads;
And mamma in her ‘kerchief, and I in my cap,
Had just settled down for a long winter’s nap

Caught Napping

The use of sedatives for hypnotic purposes has been a source of concern for over a century. Initially the benzodiazepines looked like a step forward. They were sold as better hypnotics than older sedatives like the barbiturates.  But combining benzodiazepine hypnotics with benzodiazepine anxiolytics from 1960 through to 1990 helped trigger the benzodiazepine addiction crisis.  People were being saturated with benzos around the clock, making dependence almost inevitable.

Primary care doctors came under fire in the late 1980s, with threats of legal action against them, usually stemming from key opinion leaders (psychopharmapartialists) advocating the new SSRI kids on the block.  Family doctors were encouraged to convert anxious patients (cases of Valium) into depressed ones (cases of Prozac).

At the same time, they were encouraged to prescribe the shorter acting Z-hypnotics rather than benzodiazepines.  Even though Z drugs, zopiclone, zolpidem and zaleplon, act on benzodiazepine receptors, industry pretty effectively persuaded doctors they were entirely different to benzodiazepines. They aren’t.

Z drugs brought another set of problems. The benzodiazepine crisis mistakenly put a premium on shorter acting drugs. The Z drugs were much shorter acting.  They helped people fall asleep but also woke them up again a few hours later – just as alcohol does. They also triggered sleep walking, sleep eating, sleep driving, and sleep homicide.

Z drug concerns opened a niche for Seroquel (quetiapine) – a niche that Mellaril (thioridazine) once occupied.  Both are sedative tranqulizers, closely related to clozapine (which began life as a sleeping pill).

Mellaril killed many people by causing QT interval problems before its use was restricted and it was later discontinued.  Seroquel and Clozapine also cause QT interval problems.  One of latest concerns is that Seroquel combined with opioids may lead to premature deaths with a company whistleblower recently claiming Astra-Zeneca have known about this problem for years.

Another “fake” hypnotic option has been pregabalin and gabapentin.  These drugs, which act on the same GABA system as the benzodiazepines, and are addictive, have crept into use as hypnotics on the back of their marketing for pain-management.  They have a limited use in a small number of neuropathic pains but are now being prescribed widely in primary care for pain in general. As some patients seem initially happy when they take them, doctors have loosened up about using them especially at night when pain has been cast as one of the main reasons people can’t get to sleep.

This leaves us in an extraordinary position.  Many family doctors react now with extreme caution when asked to prescribe a benzodiazepine.  They only hand out homeopathic doses and refuse to prescribe for longer than a few weeks.  This would be fine if they handled SSRIs, Seroquel and Pregabalin the same way but they don’t.

If forced to take diazepam, fluoxetine (or any other SSRI), or quetiapine (Seroquel), or pregabalin for a year, I would immediately opt to take diazepam and I’d imagine most mental health workers would too – yet this is the drug with the darkest reputation among both family doctors and the public at large.


Insomnia is not the same as sleeplessness.  Insomnia is a complaint about sleep not a statement about how much sleep you aren’t having.  The benzodiazepines bring this out most clearly in that people taking them report a better night’s sleep when according to sleep recordings they only fall asleep minutes earlier.  They report getting up fewer times during the night but it seems they simply don’t remember getting up when they have taken a benzodiazepine.

The propaganda behind the marketing of hypnotics stresses that sleeplessness kills – both physiologically kills and in practice kills because we make mistakes.  The captain of the Exxon Valdez was supposedly over-tired when he crashed the tanker leading to the worst oil spill before Deep Horizon – some of whose crew were probably missing sleep also or maybe on pregabalin.

But missing sleep and functioning for over-extended periods of time is not the same as insomnia.  Insomnia – the belief you are having poor sleep – almost cannot be cured with a pill.

Medication can sedate.  And for millennia in the face of crisis, we have knocked ourselves out with substances and equally recognized that doing this for more than a short period of time brings problems.

Enter Stage Left

Suvorexant (brand name: Belsomra) is the next stanza in the Hypnotic Before Christmas.  This new drug claims to help sleep by blocking the waking mechanism rather than by sedating.

Work on the basis of narcolepsy, as outlined in Pandemonium and Pandemrix and Pandemrix and Narcolepsy brought the existence of orexins to light. Suvorexant is an orexin receptor antagonist which has been approved for the treatment of “insomnia” in a range of countries from 2014 onwards.

In clinical trials participants in the treatment group were able to fall asleep 5.2 minutes quicker and slept 10.7 minutes longer than those in the placebo group. When suvorexant is taken daily, plasma level remains high even during daytime a few days after commencement.

At the moment we know almost nothing about its interaction with other medicines like antidepressants, benzodiazepines, anticonvulsants, antipsychotics or opioids – many of which are likely to be co-prescribed with it.

In addition to triggering arousal, orexins promote the growth of normal cells and inhibits the growth of tumor cells. Blocking it is tricky.

In clinical trials, drowsiness, memory impairment, parasomnias (nightmares, sleepwalking etc.), narcolepsy-like symptoms (including cataplexy, hypnagogic hallucination, sleep paralysis) and suicidal ideation all increased in a dose-dependent way.

Drowning not Waving

In clinical trials, there were more deaths on suvorexant than treatment as usual. One death in particular stands out – written off by the company as just a bizarre accident.

The woman in question drowned while swimming in the sea.  There are a lot pointers in the case that what happened was she developed cataplexy – emotion-induced paralysis – part of the narcolepsy syndrome. This is the feature of narcolepsy that made it so hard to investigate the condition in dobermans prone to narcolepsy because the emotion of sex caused them to slump on the job – Pandemrix and Narcolepsy.

There are probably tons of other things about narcolepsy that will shed light on the effects of Belsomra and vice versa – effects of Belsomra that will shed light on narcolepsy.  Our Narcolepsy sufferer in Pandemonium was almost as incapacitated by sleep apnoea as by narcolepsy.  This was puzzling. Women are much less likely to get sleep apnoea than men.  But the Belsomra trials threw up breathing problems including sleep apnoea, so this may be much more part of narcolepsy than we have previously recognized.

There are two publications about Belsomra worth reading.  One is by Quarterwatch – here.  The other by Medwatcher – here.

New Year Resolutions

It would be nice to think doctors would have a New Years resolution not to believe fairy-tales quite so quickly and not to leap on the next sleigh that turns up but unfortunately while they might wish it, this is a resolution that ain’t going to last more than a few days into the New Year.

When something strange happens to you on the latest new drug – if you start hallucinating reindeer – the first thing you should think is the drug caused it.  And if your doctor says the clinical trials don’t show this happening, tell him you have some difficult news for him – there is no such thing as Santa.

Pandemrix and Narcolepsy

Editorial Note: In Pandemonium and Pandemrix the question was when and what basis is it possible to agree with an obviously smart women, as AM is, that there must be a link between the Pandemrix she was given and  the narcolepsy she ended up with.  No one really tackled this head on.

The answer has to be that if she and other smart people figure there is a link in their cases, there likely is. There are other factors that can be taken into account, such as whether anything else happening at the time might have played a part, but for the most part sensible people are largely right when it comes to adverse effects.

But rather than go with AM’s hunch, we turn to epidemiologists or other merchants of doubt to tell us whether there could be a link or not.  This post covers another way into the issue. 

In  a Guardian article two months back Dreaming of a Cure  Henry Nicholls wrote:

Sleeping on the Job

One of my first jobs was to keep a lookout for lions. There are some occupations that are not suitable for someone with untreated narcolepsy and this is probably one of them. I was 22, a recent zoology graduate studying meerkats in the Kalahari desert in South Africa. We worked in pairs, one of us on foot, walking with meerkats, the other in the jeep scanning the horizon for danger. On many occasions, I awoke with the imprint of the steering wheel on my forehead, realising that meerkats and colleague had wandered out of sight. I would look for signs of life and, as the panic grew, signs of death. I can tell this story now only because no one got eaten.

I have not always been like this. For the first 20 years of my life, I had a healthy relationship with sleep. Shortly after my 21st birthday, though, I began to experience symptoms of narcolepsy, a rare disorder thought to affect about one in every 2,500 people. If people know one thing about narcolepsy, it’s that it involves frequent bouts of uncontrollable sleepiness. This is true, but the condition is so much more disabling, often accompanied by cataplexy (where a strong emotion causes loss of muscle tone and a ragdoll-like collapse), trippy dreams, sleep paralysis, frightening hallucinations and, paradoxically, fractured night-time sleep. There is no cure. Yet.

A lot has changed in 20 years. There is now overwhelming evidence that by far the most common cause of narcolepsy is an autoimmune attack, where the body’s immune system mishandles an upper respiratory infection and mistakenly wipes out the estimated 30,000 neurons in the centre of the brain. In an organ of up to 100bn cells, this might not sound like too much to worry about. But these are no ordinary cells. They are found in the hypothalamus, a small, evolutionarily ancient and important structure that helps regulate many of the body’s basic operations, including the daily seesaw between wakefulness and sleep. The cells in question are also the only ones in the brain that produce orexins (also known as hypocretins).

The Doberman Guide to Narcolepsy

In April 1972, a  poodle in Canada produced a litter of four. One of them, a silver-grey female called Monique, soon developed what her owners described as “drop attacks” when she tried to play. These did not look like sleep; they were mostly partial paralyses: her hind legs would go weak, her bottom would slump to the floor and her eyes would become still and glass-like. At other times, particularly when fed, Monique would be struck by a full-blown attack.

When vets at the University of Saskatchewan observed Monique, they suspected these were bouts of cataplexy, and hence figured this might be a case of narcolepsy with accompanying cataplexy. As luck would have it, Monique’s diagnosis coincided with the arrival of a peculiar circular from William Dement, a sleep specialist at Stanford University in California. He was on the lookout for narcoleptic dogs. The Saskatchewan vets wrote back to him immediately.

“Monique is very likely to collapse when she’s eating something she especially likes, or when she smells a new flower outside, or romps around,” Dement’s colleague Merrill Mitler told the Associated Press for a story that ran in dozens of US newspapers. “We hope to discover exactly where in the brain the dysfunction occurs that causes narcolepsy,” Mitler said soon after Monique’s arrival at Stanford. “This could be the first step towards developing a cure.”

I ask Mitler if the story of the discovery of narcolepsy is really as good as it appears. “In a word, yes,” he says. “In the 70s, we didn’t know what we didn’t know about narcolepsy.” There is simply no way anyone could have anticipated how profitable the research into Monique and other dogs would turn out to be. The plan at that stage, he admits, was simply to use the animals to test new drugs that might improve treatment of the symptoms and to carry out autopsies in case there were some obvious physical changes to the brain.

Word began to spread, and soon Dement and Mitler were looking after Monique and several other narcoleptic dogs. The fact that narcolepsy appeared to be more common in some breeds than others suggested there could be some kind of genetic basis to the disorder. Then came the breakthrough: a litter of around seven Doberman puppies, all of them with narcolepsy and cataplexy. “Within 24 hours or less we saw the first of the litter and then the last of the litter all collapse,” says Mitler. “There was a large group of us at Stanford and we collectively had our chins on the floor.”

It turned out that in labradors and dobermans, the disorder was inherited. Dement made the decision to focus on dobermans and, by the end of the 1970s, he was the proud custodian of a large colony and had established that narcolepsy in this breed was caused by the transmission of a single recessive gene. By the 1980s, methods of genetic analysis had advanced just enough to contemplate an effort to hunt down the defective doberman gene.


I can never reconstruct the combination of factors that led to the onset of my own narcolepsy, but the stage was set at the moment of my conception in 1972, at around the time of Monique’s birth in Saskatchewan. I inherited a particular version of a gene (known as HLA-DQB1*0602) that forms part of a set that helps the immune system distinguish friend from foe. HLA-DQB1*0602 is pretty common – around one in four people in Europe has a copy – but it plays a key role in many cases of narcolepsy, and is present in 98% of those with narcolepsy and cataplexy.

While other infections during my childhood, hormonal fluctuations and emotional stress may also have played a part, it was in late 1993 that I probably encountered a key pathogen – an influenza virus or streptococcus perhaps. It was this that took me to an autoimmune tipping point and resulted in the dismantling of my orexin system. In short, most cases of narcolepsy are probably the result of an unfortunate combination of events.

How do Cataplectic Dogs… ?

Most people with narcolepsy also have cataplexy – a state were a strong emotion from laughter to fear can cause a paralytic response so that the person might slump to the floor for instance leaving others thinking they have had an epileptic attack.  They also have hypnogogic and other hallucinations – which is where the featured image comes in.

Around this time, the doberman project in Stanford was on the verge of unravelling the genetic basis of narcolepsy. The man responsible was Emmanuel Mignot, who succeeded Dement as director of the Stanford Center for Sleep Sciences and Medicine.

Back in the 1980s, the idea of locating the gene for canine narcolepsy was off-the-scale ambitious. Breeding narcoleptic dobermans is harder than it sounds, as the afflicted tend to topple over mid-coitus, temporarily paralysed by a cataplectic thrill (a so-called “orgasmolepsy” that can occur in humans too). This impracticality aside, there was also the task of locating a gene whose sequence was not known, in a genome that was, at the time, a no-man’s land. “Most people said I was crazy,” says Mignot. It took him more than a decade, hundreds of dogs and more than $1m. And he was nearly beaten to it.

In January 1998, after more than a decade of painstaking mapping, and just as Mignot’s team was closing in on the gene, Luis de Lecea, at the Scripps Research Institute, and colleagues published a paper describing two novel brain peptides. They gave them the name “hypocretins” – an elision of hypothalamus (where they were found) and secretin (a gut hormone with a similar structure). They appeared to be chemical messengers acting exclusively inside the brain.

A team led by Masashi Yanagisawa at the University of Texas independently described the same peptides, though they called them “orexins” and added the structure of their receptors into the bargain. They speculated that the interaction of these proteins with their receptors might have something to do with regulating feeding behaviour. “We didn’t even think about sleep at all,” admits Yanagisawa, now director of the International Institute for Integrative Sleep Medicine at the University of Tsukuba in Japan.

By the spring of 1999, Mignot and his team had worked out that the recessive mutation had to lie in one of two genes. When he got wind that Yanagisawa had engineered a mouse lacking orexins that slept in a manner characteristic of narcolepsy, the race was on.

In weeks, Mignot and his team had submitted  a paper revealing a defect in the gene encoding one of the orexin receptors. “This result identifies hypocretins [orexins] as major sleep-modulating neurotransmitters and opens novel potential therapeutic approaches for narcoleptic patients,” they wrote. Yanagisawa and colleagues added their experimental evidence to the mix two weeks later in the same journal.

Under normal circumstances, a chemical messenger and its receptor work a lot like a key and lock. A key (the messenger) fits into a lock (its receptor) to open a door (cause a change within the target cell). In the case of Mignot’s Dobermans, a massive mutation had effectively jammed the lock of the orexin receptor, rendering the orexin useless.

Whether it’s the lock that doesn’t work, as in this case, or that the keys are missing, as they were in Yanagisawa’s mice, the upshot is the same. The door won’t open. The orexin system is broken. In human narcolepsy, there are many ways to break the orexin system. Occasionally, a brain tumour or head trauma is sufficient to do the damage. In most cases, however, narcolepsy is caused by the series of unfortunate events outlined above.

The orexin neurons are a very big deal, and not just for those like me who have lost them. Present in every major class of vertebrate, they have to be doing something seriously important.

When mouse neurons release orexin, all of a sudden, the mouse wakes up. When they stop, it falls asleep as rapidly as it woke.

In most other neural networks, there are parallel and multiple layers of security, so if something isn’t working properly, there are systems that can step in and pick up the slack. In the case of the orexins, however, there appears to be little or no backup at all.

What we now know about orexins also helps explain why losing just a few tens of thousands of cells should result in a disabling, multi-symptomatic disorder like narcolepsy – something that messes with wakefulness and sleep, body temperature, metabolism, feeding, motivation and mood. These proteins are giving us a privileged insight into how the human brain does what it does.


The pharmaceutical industry has not ignored the discovery of the orexin pathway. Within just 15 years of the publication  that linked a loss of orexin to narcolepsy, Merck had received FDA approval for suvorexant (Belsomra is the trade name), a molecule capable of getting through the blood-brain barrier and blocking orexin receptors.

A drug that promoted sleepiness was not the application that most people with narcolepsy were looking for. By preventing the orexins from binding to their receptors, Belsomra effectively creates an acute case of narcolepsy, but where the fog, ideally, will have started to lift by the morning.

The applications of Belsomra may be wider still, with clinical trials proposed to investigate its potential to help shift workers sleep during the hours of daylight, improve the sleep of Alzheimer’s patients, help those suffering from post-traumatic stress disorder, combat drug addiction and ease human panic disorder.


Editorial Note: This second section comes from other sources

In an attempt to battle the 2009 swine flu pandemic, two separate pharmaceutical companies developed vaccines for the causative H1N1 strain: Pandemrix, produced by GSK, and Focetria, created by Novartis.  Following Pandemrix use there was  arise in cases of narcolepsy that didn’t happen after Focetria, which was manufactured using a different H1N1 strain. The association was too strong for even GSK to ignore.

According to a new study the vaccine can trigger the generation of antibodies that targeted both the virus and a population of brain cells critical to the regulation of sleep-wake cycles.

This finding supports ideas that narcolepsy may be the result of an autoimmune reaction, where the body accidentally attacks itself. These suspicions were aroused after scientists discovered that a significant portion of disease sufferers possess a genetic variation within a family of immune molecules that distinguish foreign invaders from the self. Additionally, narcoleptics seem to generate higher levels of antibodies to pathogens following infection.

Another important observation is that the brains of narcolepsy patients seem to have fewer neurons responsible for the generation of a signaling chemical called hypocretin that, when attached to its corresponding receptor, helps maintain wakefulness. Consequently, narcoleptics also have less hypocretin in their brains.

So what could it be that is joining all of these dots? It turns out that a chunk of one of H1N1’s proteins closely resembles a portion of the hypocretin receptor. While this protein was found in both vaccines, it was present in significantly higher concentrations in Pandemrix.

This suggests the antibodies generated as a result of the vaccine could be cross-reactive, meaning they stuck to both their viral target and the hypocretin receptor. If this turned out to be the case, it could mean that the antibodies were triggering an autoimmune reaction.

To probe this hypothesis further, the researchers examined the blood of 20 individuals who developed narcolepsy following immunization with Pandemrix and compared them to six controls vaccinated with Focetria. Piecing together the clues, they found that 17 of those in the Pandemrix group had abnormally high levels of hypocretin receptor antibodies, whereas the controls did not.

The suggestion therefore is that in those genetically predisposed to the condition, the H1N1 protein that was present in high levels in Pandemrix, but not Focetria, successfully triggered the production of antibodies to the virus, but that these also bind to the hypocretin receptor. This could ultimately drive a targeted immune response towards the hypocretin cells, triggering their destruction, disrupting the regulation of sleep-wake cycles.

Editorial Notes:  So why this detour through biology?  In cases like AM’s outlined last week, the story should convince most people in its own right – down to the benefits of Prozac.  Prozac and other SSRIs are hugely helpful for the cataplexy that is an integral feature of a lot of narcoleptic syndromes.  Facing Prozac in a narrative like this though, people will mistakenly wonder about the mental stability of the person affected.  In this case the Prozac detail helps confirm there is nothing mentally wrong with AM. 

But we doubt individuals these days and rather than work with them, we look to outside sources.  Governments and others turn to epidemiologists, who specialise in pointing out that smoking couldn’t be causing cancer because people are smoking more and living longer now (in the 1960s) than they were in the 1920s.  There will always be an annual incidence of narcolepsy in which any new cases can be hidden.   

This turn to doubt is unfortunate not only because of the harm it does to AM but also because we will ignore what she is showing us about ourselves – who knew that our dreams can go on for forty minutes or more and end in a gift shop on the second floor. 

Life and healthcare would be very different if everyone who walks in through the door was a potential researcher – or a research couple: AM and her partner – rather than a burden. 

Pandemonium and Pandemrix

Editorial Note: At the heart of RxISK is the idea that if something goes wrong for you on some medication you are the person best placed to know if there is an issue.  But again and again when people raise a problem they find they are invalidated – nonsense, rubbish, its your illness or whatever.  

If it is pointed out medicine had the same response fifty years ago to mothers whose infants were unwell – she was seen as neurotic – but we’ve learned now to run with the mother’s instinct, and a question is asked – why is an adverse event so different? – the response is usually well if this was case you’d have to believe all those people who claim they have been injured by a vaccine and we’d have pandaemonium. 

In the case below, which involves the Flu Jab Pandemrix, the question is how do we go about establishing if this is a case of vaccine induced injury or not? 

Before the Jab

I had all the normal childhood illnesses and vaccinations. I had rubella and BGC as a teen, and a few tetanus jabs, all without adverse effect.

I later had two pregnancies to term, all wisdom teeth removed, an operation to remove a bursa on my hip following a fall that hurt my back and made me walk wonky, all without problems.

Before I was given Pandemrix I was working for the Department of Work and Pensions and running a small online business. Busy life, busy mum but this was just “normal”.  I was good. I was twice call handler of the year for the whole South East, constantly getting vouchers for going above and beyond, getting all the great and the good sitting to listen in with me on visits.


After I got the jab I immediately became ill with a severe flu like illness. I had two weeks off work. The time afterwards has become a blur as to diagnoses as no one knew what was wrong.

I was so tired.  Coming in from work at two, I would fall asleep till teatime. After tea and the kids had gone to bed I’d nod off on the settee. All I seemed to do was sleep. I worked term times and I remember coming back to work after the Summer holidays and my boss asking the usual did I have a nice holiday and me replying that all I seemed to do was sleep. I used to go to the loo if I felt myself falling asleep. Endless walks to the photocopier. I reduced my hours, went home early. Work became a disaster.

Everything ached.  After much coming and going to my GP I was referred to rheumatology. They said I had fibromyalgia. Maybe I do but this didn’t help or solve anything.

I took Prozac 20 mg because for 3 or 4 days a month I turned into a very different person fuelled by PMT. It was like switch being flicked.  I would go mental for a few days and flick back to me again. I used to write letters to people and organisations if something offended me. I went to the Docs after I chased someone in my car who I felt had cut me up and sat revving outside their house like something from Duel.

As I am the type of person who never puts her head above the parapet I knew I needed to resolve this and the Prozac did help.

Deeper and Down

Then I started hallucinating sounds, specifically our buzzer.  I would get up in a panic usually around four in the morning to answer it. I would try to get the kids up thinking we had slept in.

I was becoming forgetful, not recalling conversations or events. If I fell asleep on the sofa of a night watching a programme I would wake not knowing I had fallen asleep with my brain filling in detail that didn’t exist.  I dropped things a lot. I could be seen staring off into space. I flooded the flat downstairs twice leaving the kitchen tap running. I had a small kitchen fire after turning the hob onto an electric chip pan I had left there to cool. There were multiple similar leaving the cooker on events where I just damaged things without setting fire to anything. Thank goodness for smoke alarms.

At night my dreams were becoming very vocal.  I would often talk for up to an hour. My partner still talks about my lecture on a hydro energy plant where after about 40 minutes of my guided tour I said that “and on the second floor there will be shops”.

I seemed to be going to the GP every month. Apparently, I was depressed now. I didn’t feel depressed but I had no knowledge of mental health and assumed he knew better. More Prozac and now amitriptyline on top.

What was making me depressed was that I had no control of all these things happening to me.  I thought for a time I was getting early onset dementia or something.

I recall one such GP visit where I had gone in with my usual I am tired, everything hurts, I keep falling asleep and I was given more Prozac. I was due to drive to Birmingham and I was worried about this. I told him I was falling asleep driving, hoping he would tell me not to drive or take note or do something, anything because I was panicking inside about what was happening to me. I got platitudes and was shown the door.

A few months later I was signed off work – “depression”.  All I did was sleep.

Going to my GP was largely pointless but I did it anyway because I knew there was something wrong with me. I didn’t know what, and he seemed to see a woman in her forties, Prozac, bang, out the door.


My GP was off and I saw a lovely young doctor who listened and almost her first question was about my sleep. Did I snore? Sleepwalk? She referred me to a Sleep Studies unit.

It was not a quick process, the appointments were slow to come and the first two sleep studies were “inconclusive”.   I later found out this meant they had not recorded enough sleep time.  On the third one, they came in the morning and told me that I had not slept.  I said no, you are wrong, I slept great.  They were puzzled and asked – so you thought you slept?  I stayed all day and was put in a room for 15 minutes and watched still wired up etc. I fell asleep within minutes each time.

So, about a year after being referred I was diagnosed.

  • Sleep Apnea
  • Narcolepsy
  • Periodic limb movement disorder
  • Night terrors
  • Restless legs

Meanwhile, I had lost my job. My daughter told Andy, my partner, that I was hitting myself in the car and had all the windows open to stop falling asleep taking her to school and still I kept hitting curbs. So I had to stop driving.


Having the Pandermix flu jab changed everything in my life. I don’t have a life now. I have an existence which I hate. I try not to dwell on it because hey, I’m not dead but it is hard. I think what makes it worse for me is that the jab was given to me at work. I worked for the DWP. I have done various freedom of information requests but apparently the jab never happened and none of my records exist anymore.

So here I am. Hitting 50 next year, trying to work self-employed. Having the indignity of applying for support payments to the agency whose reports to the DWP saying I was unfit for work and unlikely to ever be so got me fired. But still they make me go to interviews and then write to tell me how capable I am.

I can’t be left alone. The narcolepsy is bad enough but the sleep apnea on top means that if I fall asleep, I could choke and die because I should wear a Bpap mask when I sleep. So I am babysat if my partner goes out.

I have just got the brace off my leg from when I fell down the stairs in August in my sleep when I went to answer the non-existent doorbell.

I sleep on the sofa a couple of nights a week to give Andy a break from my talking and general night mentals. I hate going to sleep knowing I am going to disturb him. Aside from the talking, and  skipping, running, and fighting, the night terrors are bad. It is as though I am in absolute mortal terror . I can’t talk. No words will come out but I get up my courage to give one massive scream or shout.  He is 11 years older than me and I am convinced I will give him a heart attack. One time, my dog wet herself and hid under the bed.

My night-times are worse if I overheat so have a fan right next to me and windows open.

I won’t go out in case I fall asleep as often my sleep talking quickly becomes sleep tourettes with very loud, very bad language.  If I get too animated my speech slurs. If I am fighting sleep my speech slurs and my neck and face muscles go into cataplexy.

One of the most painful things this condition has caused me was that it meant not going to see my once timid daughter, who got a scholarship to a really top school giving her speech as head girl on leavers day.  How could I go and risk being an embarrassment?


I take Ropinerole/Requip for the restless legs. It has been an absolute godsend. Took a while to get used to but it has genuinely been a lifesaver.

I take Modanafil but over time this has become less good. Other stimulants haven’t been any better. Modanafil caused my BP to soar – up to 230.

I have been offered Xyrem but I don’t want it. As far as I understand, once you are on that there is no where else to go. Like a drug of last resort.

I don’t know if it is harder to treat me because I am older than people with younger onset Narcolepsy. No one really tells me that. From my own perspective it is worse, because I know what I once was and what I have become. I imagine it is like going blind after having sight. Cruel.

Vaccine Caused?

So imagine you are back in 2009 when Pandemrix was being given to prevent Swine Flu.  How do you respond to this woman if she raises a link between her Narcolepsy and her Flu Shot?

The authoritative response was – there is no link.  Does all Hell (Pandaemonium) break loose if we don’t believe the authorities?  What kind of evidence, if any, might be used to stop people from closing down a sensible debate about these questions?

A Call to H*ARMS

Editorial Note:  This is the fourth and final post in the Trick or Treat series that started with Vampire Medicines. These posts need to be read linked to the RxISK MAP posts. These are the theoretical background.  The MAP posts are the practical – what needs to be done posts.

Access to Medicines

In the 1980, we faced one of the greatest medical crises of any century – AIDs.  At its height the epidemic was claiming 50,000 deaths per year in the US.

Facing the AIDS epidemic, some called on Homosexuals to change their lifestyles.  But AIDS was caused by a human immunodeficiency virus (HIV) rather than lifestyle issues.

The answer lay in developing a science base and producing treatments. The treatments that emerged have arguably been the only decently effective treatments that have been developed in the last 40 years with the exception of Glivec.

One the extraordinary things about the response to AIDS was how the homosexual community embraced the stigma and mobilized around finding a cure.

Another extraordinary feature was a celebrated Access to Medicines campaign that took shape around 2000, when it became clear the greatest number of cases were in underdeveloped regions of Africa, and that these patients were being charged First World prices.  Campaigners led by Bill Haddad, Jamie Love and Yussuf Hamid, working to ensure access to these life-saving treatments at affordable prices, drove the price down from from $50 per day to under 50 cents.

It was one of the greatest triumphs of the human spirit and an example of what medicine and the pharmaceutical contribution to medicine could be all about.

There is a less inspiring Access to Medicines campaign under way at present, with European politicians mobilizing to control the cost of the latest drugs to hit Western markets – drugs of much less benefit that the Triple Therapy AIDS cocktails.

Access to Real Medicines (ARMs)

Starting around 1980, a new virus emerged that has led to a new and lethal and global epidemic.  One drug group alone, the opioids, now causes 50,000 deaths per year in the US.

Treatment induced drug wrecks are the leading cause of death and disability on the planet. Studies suggest treatment accounts for up to a third of deaths in hospital settings, where deaths may be caused by chemotherapy or the cardiac effects of drugs but will be put down to cardiovascular causes or cancer.  The drug induced death rate can only be greater in community settings where most deaths occur and where people are less likely to have conditions that can be blamed as the cause.

As for disability rates, roughly 1 billion people are on SSRI and related antidepressants in Western settings – that’s 1 billion people with their sexual functioning disabled.  If only 0.1% of these get PSSD or PGAD, that’s 100,000 people with their sexual functioning possibly eliminated forever.  This is the disability toll from only one drug group and one set of problems.

Faced with a Drug Wreck epidemic, the medical establishment is playing a moral card and calling on doctors and patients to change their lifestyles – diagnose less and treat less.

The answer lies in restoring a science – adverse eventology.  And in creating a climate where adverse events can be recognized and people can be got off treatments if they are maiming and killing them – something that is increasingly impossible to do at the moment.

The Drug Wreck epidemic is caused by a clinical immunodeficiency virus (CIV) whose primary mode of transmission is through major journals like BMJ, NEJM, AJP, through which it takes out the white cells of adverse event knowledge.  See Vampire Medicines and Raiders of the Lost Drug Wreck.

No doctor willingly harms patients.  If she dishes out drugs it’s because she has not been told about the harms, or has had them dissed.  No patient would take chemicals glibly – but this is what is happening increasingly as the information needed to manage the risks linked to the chemicals we take has been steadily degraded.

The reason drugs are being dished out and taken on such a massive scale is because the harms have vanished. RCTs are one reason for this. Drugs have 100 effects.  Most of them vanish in RCTs, leaving us with Vampire Medicines – actors without a shadow.

Another reason is journal funk. Our major journals are scared shitless and will not publish anything hinting at any treatment harms. Because of journals and RCTs, doctors have stopped listening to or looking at their patients – if the adverse events aren’t recognized in places like our journals it is more than a doctor’s life is worth to notice them. We might be sitting in front of our doctors but we are effectively invisible.

The hiding of harms has contributed to a growing medical nastiness, when we raise them. Faced with adverse events, some doctors get very nasty. Sensing this, and having no way to know who will and who won’t get nasty, we become increasingly nervous to mention adverse events.

Just as in 2000 the world needed an Access to Medicines campaign, we now need an Access to Real Medicines campaign. The core message of this campaign would be that a Medicine is a chemical plus information and without full access to all the information we don’t have access to the Medicine. The chemicals have always been and will always be risky.  The information component has been steadily degraded since 1980 making today’s medicines riskier than the treatments we had back then.

This campaign would be about saving lives on a global basis rather than just in parts of the underdeveloped world.  The wealthy of America and Europe are probably at greater risk than anyone.

Battle Plan

  1. Insist on access to data. No company claim to be based on science should be acceptable without access to data.
  2. Doctors should refuse to prescribed medicines where there is no access to the data.
  3. Patients should refuse to take medicines when their doctors don’t have access to the trial data.
  4. Restore a Poison sign to all new medicines, and all medicines without data access.
  5. BMJ and other journals to tell their lawyers: We are publishing harms data, among which will be case reports and articles from shady customers like Jureidini and Healy – your job is to work out how to make that happen, otherwise, although we might be a successful business, we are doing harm and may need to wind up the operation.
  6. Work out how to shrink the drugs regulator back to food regulator size and make doctors aware of their regulatory role.
  7. Before thinking about independent trials, create an independent Harms/Safety body.
  8. In the absence of data (Cisparency) to enable us to judge whether possible conflicts of interest have been realized, concerns about conflicts of interest (Transparency) create a counter-productive moral panic. Conflicting views are an important element of what drives science forward and should be resolved by data.  Claims about conflict of interest should only feature exceptionally.
  9. Prepare for the day when robots that can learn take over prescribing.


Raiders of the Lost Drug Wreck

Editorial Note:  This post follows from Vampire Medicines and Cisparency and Transparency and links to Relationship Based Medicine on Rxisk.  The painting is of Joshua crossing the Jordan with the Arc of the Covenant – an image that catches the essential features of climactic scene of Raiders of the Lost Arc with Joshua in the Indiana Jones position.

In every generation, there is a slayer.  In this generation, s/he will probably be female.  She need not be a doctor.  She might work for a pharmaceutical company.  She could be a patient or a family member. She will likely be a woman, if only on a probabilistic basis, as more women are injured by medicines and more women are involved in the lives of people who have been injured and now more women are in medicine than men.  And as the BMJ has recently shown even in medical specialities, such as surgery, where until very recently it was common to hear it said women were just not suited, in fact they now do a better job than men. She might be the editor of a medical journal.

In-Diana, besides, looks much more like a girl’s name than a boy’s.

The Slightest Slope

Just as water flows down the slightest slope, so drugs flow at the slightest hint of benefit – in both cases the flow is inevitable unless there are bumps in the way. It’s a bit like taking an apple off a tree. Difficult not to.

Difficult not to, short of seeing the tail of a worm sticking out of the apple and wriggling.

This is where the harms come in.  There is no such thing as a Free Apple. Its only in paradise there are worm free apples. Down here at the very least they have pesticides on them.

Since the Fall, we have lived in a world of Good and Evil – where sometimes what seems like the greatest good turns out to be more harmful than helpful. We need to be alert and make judgement calls that balance harms. In medicine, we were making progress at balancing harms to the point where we could make a reasonable stab at using poisons to do good provided everyone knew what they were doing.

But since 1990 that balance has been lost and the divide between good and evil is getting more marked.  This might sound like a good thing but its not. We are increasingly ending up with fistfuls of medicines branded as All Good Zero Harms – Vampire Medicines. The systems most people now work in or seek medical help from with would shrink in horror from the idea of bringing good out of the use of a poison. We have infantilized. The infantilization is worse by systems that are becoming increasingly brutal to those trying to work within them and those seeking care from them.

Suffer the Children

One of the best symbols is what we are doing to children. There have been roughly 30 controlled trials of antidepressants in children labelled as being depressed – all negative. The Prozac trials the most negative of the lot.

Yet prescriptions for antidepressants are soaring among teenagers, especially girls, so that they may now be the most commonly prescribed drugs in this age group.

This is because of hints of efficacy and a sustained campaign to turn the evidence that there are harms – every trial done shows an excess of suicidal events on active treatment over placebo – into a “controversy”.  The average doctor has been led to believe this is just an arcane dispute among academics.  Nothing of consequence in the real world.

In the real world children’s mental health services are close to collapse because, despite money being poured in, children are waiting so long to be seen that given antidepressants by family docs – to help tide them over – they are attempting suicide while waiting. They then get seen by services who have no sense the suicide attempts might be drug induced and they get treated for something they don’t have.  Meanwhile, the money going into children’s services goes into screening, and auditors and managers rather than clinicians in an effort to ensure adherence to guidelines. The only reason things could be going wrong is non-adherence to the guidelines – guidelines that say give Prozac.

Get that Crucifix out of Here

Another place to see the problem is with vaccines.  BMJ have just bravely run a piece by Peter Doshi on the funding of vaccine propaganda groups. Few people other than Peter could have pulled off something like this.  Others would be too scared. Still the impression left is that everything would be fine if there were transparency about the sources of funding and conflicts of interest.

The real problem is that in vaccine-land its not possible to mention harms. There can be no discussion of the fact that HPV vaccine causes problems, flu vaccines are for the birds, the Swine Flu vaccine caused narcolepsy, hundreds are suing Merck as a result of the Shingles vaccine, and earlier iterations of the MMR were withdrawn because the authorities accepted they were causing problems.

Not only is there a denial that there could be any problems but vaccine proponents have become thuggish and fascist, with alt-health diatribes turning up in the most unexpected of places – the Guardian. It’s enough to make anyone who believes in vaccination despair. The analysis of the growing vaccine resistance in healthcare professionals pays no heed to this.  It scolds us for not telling the public that the safety of vaccines is monitored thoroughly – when this is self-evidently not true.

American Women

Medical academics now discuss company creativity at gaming efficacy in clinical trials – the way scholastics once debated the number of angels that might fit on the head of a pin.  But company creativity at gaming efficacy is like nothing compared to their creativity at gaming safety.  One of their best tricks is to get doctors and patients to report harms directly and independently to regulators.  You might have thought this would help but reporting adverse events to a regulator is like pouring water into sand.

This was brought out in two posts some time ago – American Woman and American Woman2.

An entire science has been lost here – the science of adverse events/ drug wrecks.  Doctors have no training in establishing when it is possible to say that drug X is causing problem Y.  They are told that RCTs tell them what a drug causes.

The irony of this is that with most drug wrecks the causal chain is commonly so clear, so lacking in ambiguity, there is no need for an RCT – PSSD and PGAD offer great examples of this.

We Need to Medicalize

Many well intentioned people think they are contributing to a resolution of this epidemic by getting involved in campaigns against Overdiagnosis and Overmedication (ODOM).  As things stand Overmedication Campaigns are like telling people they are a little Overweight – everyone agrees they need to change but, like Augustine of Hippo, they figure they will try to put it right but maybe not just yet. While everything works – is nutritious – or everything is good – like making a diagnosis – it’s difficult to stop feeding your diagnoses.

ODOM is like AllTrials – wonderful for industry.  It gives the “good guys” the feeling they are doing something while behind the fig leaf industry get to hide ever more transformations of medical culture and practice.  Centrally important to all this is that the proponents of ODOM or AllTrials be like BMJ and Fiona Godlee, its current editor, brave and beyond reproach and better again seen as trying to rein in industry.

But this won’t work. The only way the epidemic of treatment induced death and disability can be tackled is to return pharmacotherapy (not quite the same thing as medicine) to its roots which is that everything is a poison and physicians need to act accordingly.

We are Underdiagnosing the injuries being caused by treatment and Undertreating these injuries.  We need to medicalize the problem. A campaign to recognize harms and manage them would require a lot more cojones from journal editors, scientific advisers and consultants than we are currently likely to get from any of these sources.

Relationship Based Medicine

But medicalization is not just about recognizing harms.  It’s about managing harms in a relationship. We need to get back to a Relationship Based Medicine.  The relationship used to be authoritarian. It needs to become consensual. It needs to harness the abilities of those of us who as patients take risks with medicines to contribute not only to our own wellbeing but to the wellbeing of all.  A bunch of reasons why the slayer is likely to be a ….

Of course, doctors should probably also be told they are on the way out of business unless something like this happens.  If drugs work wonderfully well and are so free of harms, nurses and pharmacists would be much cheaper prescribers.

And looming on the horizon are robots that can learn. Pretty soon putting a robot in charge of prescribing for patients, providing they were granted leave to learn by killing a few hundred patients first, would lead to fewer people being injured and fewer dying than is happening at now.  If it was let learn rather than just follow a program, the first thing the robot would learn is to junk the evidence from RCTs.

Cisparency and Transparency

Editorial Note: This post continues Vampire Medicine and links to Reformation Day on RxISK and forthcoming posts – Here We Stand.

Between 2002 and 2004, giving antidepressants to teenagers and the risks of triggering suicidality became one of the most high profile issues in medicine.  Raising a profile should be the way to put things right but things are getting much worse.  The lack of access to services is leading to adolescents self-harming to such an extent this is now accepted by the British government as the area of greatest failure in Britain’s Healthcare System.

What’s gone wrong?

Blowing up the Fishpond

It was BBC’s Panorama and a Los Angeles law firm, Baum-Hedlund who initially raised concerns. Panorama threw a hand grenade into the mostly East Coast fish pond that was American medicine. This led to a series of FDA hearings in 2004, and a derailing of company plans to get their antidepressants licensed for children.

The central event was a document obtained by Panorama which revealed that Study 329, a trial comparing paroxetine, imipramine and placebo, had been negative but was going to be portrayed as positive.  New York State took a fraud action against GlaxoSmithKline.

The document crystallized recognition that close to every article on every on patent drug in any area of medicine was ghostwritten and there was zero access to clinical trial data.

Faced with this crisis, there were two obvious courses of action.

One was go after the docs who were willing to let their names be put on ghostwritten articles whose data they had never seen and who presented these data at meetings – for a fee.

The other was go after the data. In 2004, the British Guideline maker, NICE, considered the second option but funked it.

New York State thought they had secured a commitment from GSK to make the data available which would set a precedent for other companies.  But GSK ran rings around them, making some company authored study reports available that concealed everything about everybody that had anything to do with any of their trials.

The first was the sexy option.  It offered stories the media could understand – docs on company payrolls prepared to say anything. Everyone could understand Conflict of Interest and agree it was a bad thing. Chasing this fitted a zeitgeist which said all problems could be solved with Transparency.

The second was more difficult.  Unless you are involved in clinical care it sounds esoteric and geeky. It also risked blowing up a lot the guys we think of as the good guys like BMJ, Lancet, NEJM and JAMA. And it quickly became clear there would be resistance. Let’s call this Cisparency.

Stunned Amigos

When BBC threw their hand-grenade into the healthcare pond stunned fish floated to the surface. Baum-Hedlund picked the fish up and started dumping them on Congressional and Senatorial desks. Most of the fish were ugly and had thwarted data access stamped all over them. A few others were colorful eye-catching dudes.

The key desk turned out to be Senator Grassley’s, where a formidable woman, Emilia di Santo, ran the operation and an energetic staffer, Paul Thacker, got engaged.

Some colorful flashy fish called Alan, Marty and Charlie, the type to feature in Disney movies – a great title would be Three Amigos – caught senatorial or other eyes, rather than the uglier critters. There was nothing notable about the three flashy guys in terms of contributions to medical or mental health science, but at the time details about the conflicting interests of all three were tumbling into the public domain.  Charlie had become the poster boy for conflict of interest across medicine.

If you’re a Senator what’s not to like about a guy who was willing to let himself be featured on the front of a glossy publication as The Boss of Bosses with a question Is Charlie Nemo the most powerful man in psychiatry. Marty was the first author on Study 329, the trial that had kicked everything off, then on its way to becoming the most famous trial in medicine.

Nemo was a Harvey Weinstein like character, capable it seems of charm with those who played ball with him and of being a thug to others. Close to the entire field of US psychiatrists enabled him.

He was probably a greater embarrassment to GSK and other companies than he was to academic psychiatry. GSK could not have wanted him to behave like a loose cannon in the way he did. He was probably central to losing them the Tobin case, which led to Panorama interest, and a bunch of dead fish, which they are still grappling with.

Enter Stage Left

Because of the Toronto episode Paul Thacker called wanting to know anything if I could tell him about Nemo. I told him – nothing much apart from what is in the public domain.  I tried to persuade him Nemo was not the problem. He was irrelevant.  He could even do some good if he could be turned. He and some others like Stuart Montgomery could show us where some of the bodies were buried.  Chop their heads off and others would replace them.

PT wasn’t listening. Nemo had become too juicy a morsel to give up.  But very little came out of his investigations beyond what was already in the public domain.

Let the Sun Shine In

The collapse in August 2007 on the grounds of pre-emption of a Baum Hedlund lawsuit, centered on the suicide of a 13-yr-old boy while taking Paxil, coincided with the introduction in September of a Physicians Payments Sunshine Act by Senators Charles Grassley (R-IA) and Herb Kohl (D-WI).  This act aimed to “shine a much needed ray of sunlight on a situation that contributes to the exorbitant cost of health care”, according to co-sponsor Senator Charles Schumer (D-NY). It would require manufacturers of pharmaceuticals and medical devices with annual revenues of more than $100 million to disclose gifts or payments to physicians in any form, whether cash, trips, or other.

The most bizarre aspect of this was the idea that letting the Sunshine in would bring down drug costs – See Raiders.

But the Bill fit the perceptions of many ethicists, journalists and others that the root of the healthcare problem lay in payments to opinion leaders. Transparency was crowned king despite a complete lack of evidence of opinions being changed by payments.

This model locates opinion leaders as experts – the cream of the profession.  They are only the cream in the sense of being rich and thick. No pharmaceutical company wants someone who can think. The first qualification for being picked by pharma is to be mediocre, and the second is to remain on message.

The model views other doctors and patients as airheads who will rely on a few puppets made over as smart dudes to tell them what to think.  No one would pay any heed to what some cartoon puppets were saying were it not for the iron fist inside the puppets that has all too obviously silenced BMJ, JAMA, Lancet and NEJM – see Vampire Medicines.

The Benefits of Transparency

Baum Hedlund contacted Emilia di Santo again in 2007. It put the Ugly Fish back on her desk. While Grassley wrote to the Department of Health and FDA raising cisparency issues, the die was already cast.  The transparency fish were already sitting in their bowl, scales glinting in the bright sun light. Rather than chase cisparency, Grassley continued with the low hanging fruit of transparency, scooping up a number of other prominent psychiatric academics on the way none of whom seem to have been harmed by the attention.

Just this year Karen Wagner, one of those named and supposedly shamed became the current President of the American Association of Child and Adolescent Psychiatry, despite multiple depositions conceding her articles are all ghost-written and she wouldn’t know what to do with data even if she saw it.

On July 12, 2008, the New York Times reported:

“But now the profession itself is under attack in Congress, accused of allowing this relationship to become too cozy. After a series of stinging investigations of individual doctors’ arrangements with drug makers, Senator Charles E. Grassley, Republican of Iowa, is demanding that the American Psychiatric Association, the field’s premier professional organization, give an accounting of its financing.”

The following year APA voted Alan Schatzberg in as its President.

After a brief period under a cloud, Nemo moved from Emory to Miami and was welcomed into the bosom of places like London’s Institute of Psychiatry who know a thing or two about supporting people who have been vilified by the enemies of psychiatry. A President of the World Psychiatric Association in waiting?

On March 23 2010 Grassley and Kohl’s Physician Payment Sunshine Act was enacted as part of the Patient Protection and Affordable Care Act.

Sidelining Cisparency

The resolution of New York States’ fraud action against them in 2004 involved an agreement by GSK to post details of their clinical trials on their website. This led to a set of Clinical Study Reports (CSRs) for paroxetine trials in children being posted.

GSK also posted 3-7 page summary reports of trials in other therapeutic areas, including trials of their blood sugar lowering blockbuster, rosiglitazone (Avandia). Reviewing these summaries Steven Nissen, from the Cleveland Clinic, found an increased rate of mortality on Avandia compared to placebo. Avandia was withdrawn from the European market and restricted in the US. These data laid the basis for the Department of Justice to pursue GSK for both Paxil and Avandia.

In 2009. Peter Doshi from Johns Hopkins and Tom Jefferson from Rome, working with colleagues on a review of Tamiflu, Roche’s antiviral drug for influenza, became headline news, when the data they assembled suggested Tamiflu didn’t work.

Governments around the world had stockpiled billions of dollars’ worth of Tamiflu having been told it saved lives by reducing transmission of the virus, kept people out of hospital and got them back to work faster. Fiona Godlee and BMJ helped make Tamiflu a campaign for transparency.

Then in October 2012, facing criminal charges for promoting its antidepressants for unapproved uses and failing to report safety data about Avandia, GSK accepted a $3 Billion fine, then the largest settlement in a Department of Justice lawsuit.

Far from being on the back foot, just as they had out-maneuvered New York State in 2004, GSK took the initiative. They announced plans to make their clinical trial data available to researchers on a secure website, if an independent panel of experts agreed the research proposal met a scientific need – mature transparency.

A few weeks later, AllTrials was born. The idea might have begun with Fiona Godlee. The family present at the birth included Sense about Science, the Cochrane Collaboration, the Centre for Evidence Based Medicine, Iain Chalmers, along with BMJ and PLoS, with the lot now fronted by Ben Goldacre.

The AllTrials ask was for access to the protocols for all clinical trials. The impression given was that AllTrials was seeking access to clinical trial data. It wasn’t. It was named AllTrials rather than AllData. It supported proposals that might enable some investigators, approved by companies, to access certain efficacy data. Exactly what GSK were proposing.

GSK promptly signed up to AllTrials. Within a few months of a record fine in the US, Andrew Witty, GSK’s CEO, featured on the March 9 2013 cover of the BMJ hailed as the acceptable face of the pharmaceutical industry.

Spearing Nemo?

A few years later the time came to dump fish in a Chicago jury box in the Dolin case. Trying to spear Nemo wasn’t going to get anyone anywhere with a Windy City jury – he mightn’t have been visible in a Green River anyway.

It was the ugly brutes the jury got told about. GSK’s lawyers spent their time desperately trying to block any mention of Study 329 and trying to stop jurors seeing the harms data from paroxetine trials, or hearing about the ways the company had tried to thwart access to data.

GSK’ s lawyers went apoplectic at a mention of the idea that if you owe a bank a million dollars, you have a problem but if you owe a billion, the bank has a problem.  This could be reprized as – if Senator Grassley catches GSK out in a little lie – hidden payments to Nemo – GSK has a problem but if the entire thing is a lie Senator Grassley is fucked.

Transparency, efficacy and Nemo were irrelevant in Chicago. Its the Great White Lies about Harms that count, not a few little tiddlers.

To be continued..

Vampire Medicines

Editorial Note:  This is the first of four Trick or Treat posts.  They make most sense when read in conjunction with the RxISK Prize posts especially the series of 3 posts starting tomorrow.

In 1962 RCTs were added to the regulatory requirement for marketing medicines.  This looked like a definitive stake through the heart of hucksterism. No longer would we have to carry crucifixes and garlic around to ward off blood-suckers hawking ineffective remedies.

In 1962 doctors were viewed as the key element of the regulatory apparatus. A great part of their input centred on descriptions of the harms medicines could cause. In addition to news of the latest advances, medical meetings were filled with symposia and medical journals with articles on the harms of treatment and how to manage them.

Company funded RCTs, which played a minor part in clinical practice, were all done in hospitals and universities and academics had the data.

Around 1980, as new drugs got weaker and weaker, company trials became multi-centered, coordinated by CROs, written up by ghost writers, with academic names attached afterwards.  Everyone seemed as happy to enable this increasingly Hollywood like remake of medicine as they were to enable Harvey Weinstein.  In the process access to trial data was lost.

Richard Smith

The key event that marked a transition to the modern world came in 1990, when Teicher et al published 6 cases of people becoming suicidal on Prozac in the American Journal of Psychiatry.  According to all canons of causality, this paper offered undeniable evidence SSRIs can cause suicide. Hearings were convened to discuss the need for warnings.

But coincident with these hearings, BMJ published a meta-analysis of Prozac trials which Lilly claimed showed Prozac was not linked to suicidal events.  This paper had been rejected elsewhere, The BMJ reviewer was lukewarm. But Richard Smith, BMJ’s editor, perhaps spotting an opportunity to push a new kid in town, Evidence Based Medicine, and its shiny new meta-analytic machine, published.

The published data showed an increased risk on Prozac, which Lilly and BMJ ignored, claiming nothing was statistically significant.  Beyond this, Lilly played some of the tricks other companies later played – the small print shows the only placebo event hadn’t happened on placebo, so that technically there was a statistically significant  infinitely greater risk on Prozac.

The follow-up letters told RS he had been naïve and wrong. But no one accused him of conflict of interest. What could be wrong with letting good quality evidence (even though he got that wrong) triumph over anecdote?

The way this played in public was that the stories of suicides on Prozac were tragic but anecdotal.  The scientific evidence demonstrated that patients and doctors just can’t believe the evidence of their own eyes and ears. They have to be told what’s what by experts.

This dangerous and misguided message triumphed with regulators, and later in Courts.

This message killed any interest journals like AJP and BMJ had in taking Case Reports. Besides companies didn’t buy reprints of these, whereas they handed over huge amounts of money for reprints of ghost-written fraudulent RCTs with zero access to data, and even more for the best science money could buy – meta-analyses of these trials. Evidence Based Marketing was here.

Vampire Birth

A medicine is a chemical plus information. The information about the effects of chemicals should come primarily from practice on the ground, as in the early days of antibiotic or psychotropic drug use, or street drug use now, or from use of anti-retroviral combinations for AIDS in the 1990s.

When the benefit (not the harms) of a drug is equivocal, RCTs offer a means of examining efficacy ambiguities by focusing a magnifying lens on the ambiguity. They do this at a cost – ignoring safety.  They are an act of hypnosis that gets investigators to focus on one thing while ignoring everything else going on around them.

If we ignore the ignoring of safety, as we do, we compromise rather than enhance safety. The harms vanish. The drugs that come out of an RCT have no shadow – no harms.  They are vampire medicines. Put another way, all clinical trials (RCTs) cause harm but some can also be helpful. They pose the same problem AI and viruses do – if you create one, can you control the consequences?

Co-incidentally around the time vampires began to flourish, companies had poison symbols removed from medicines and from discourse.  Any mention of the celebrated medical wisdom that all medicines are poisons in an expert report will now be met by company motions to have the word poison struck as prejudicial.

Conflict Free Blood

If there was a conflict of interest involved in linking trials to regulation, it was born from hostility to pharmaceutical companies.

But it’s now clear that even if done by angels, RCTs are the gold standard way to hide adverse events.  Their intense focus on a primary outcome rather than the overall picture means that in even the most independent of studies they necessarily neglect adverse events.  Companies overlay a lot of creative hiding on this neglect but this is an extra source of difficulties not the primary problem.

It was doctors who used to go around with stakes. Regulatory bureaucrats never did. RCTs have made life easier for the bureaucrats.  According to the head of Britain’s MHRA, Ian Hudson, formerly of GSK, if events are not statistically significant – and strictly speaking as no adverse event is ever a primary outcome measure, they can’t be – then they aren’t happening.  BMJ helped consign stakes to the twentieth century.

If there was a conflict of interest involved in the move from RCT to Evidence Based Medicine (EBM), it was born from hostility to companies.

EBM was not unreasonable in the early 1990s but it has created a bandwagon that is now out of control contributing hugely to a conversion of poisons into fertilizers to be sprinkled as extensively as possible, from as young an age as possible.

If there was a conflict of interest involved in using trials to create Guidelines in the 1980s, it was born from hostility to pharmaceutical companies.

But now, if NICE and other Guidelines, based entirely as they are in the case of on-patent medicines, on ghostwritten articles whose data is inaccessible, hadn’t been created, Pharma would have to invent them.

Drug harms that took a year or two to come to light in the 1960s take a decade or two now.  In 2003 I predicted we were on our way to having lethal and common drug harms being contested years after the drug had gone off patent. In April 2017, the Dolin case in Chicago centred on just this issue – ten years after paroxetine had gone off patent.

These problems are not being contested because it is difficult to decide if a drug is causing a harm.  They are being contested because of the power of companies to shut down debate in journals like BMJ.

BMJ’s news item about the Dolin trial missed the key issues, and it wouldn’t have occurred to them they had a role in the development of the situation.

Rosemary’s Baby

If it was just one drug harm that might be fine but drug wrecks may well now be the leading source of death and disability on the planet.

BMJ helps this happen in its educational forums by making it clear for instance that giving antidepressants to minors is just fine – no mention of harms.

BMJ helps this happen in its educational forums by making it clear for instance that giving antidepressants in pregnancy – now the most commonly used drugs in pregnancy – is just fine despite a doubling the rate of birth defects and miscarriages and behavioural abnormalities in the children of those taking them.

Buffy the Vampire?

Richard Smith was succeeded by Fiona Godlee, as free of ties to industry as RS once was.

Starting with RS and then later with FG, I and others had a series of articles on drug harms rejected with an increasingly bizarre set of reasons offered for the rejections, and increasing involvement of BMJ’s legal department.

These rejections have two elements.  One is that across all journals anyone interested in a drug’s harms appears to be deemed ipso facto not just biased but perverted. It’s like wanting to publish something about sex around the time Dracula was written.

The second is anyone who has ever been in any way linked to a lawsuit as an expert against a company is deemed irredeemably conflicted.

For those of us working on the Restoration of Study 329, the review process became beyond odd. BMJ editors kept raising queries that had been answered and talking about conflict of interest.  To which our response was everyone is biased but the way conflicts are overcome in science is to turn to the data – it’s the data that reveals whether someone’s latent bias is operative or not.

BMJ just didn’t get it. My formulation up till then was that a belief conflict of interest is of supreme importance is incompatible with recognizing the importance of accessing the data.  This is still my view in the case of most of those who champion Sunshine.

But then a predicted legal review came into the 329 frame.

BMJ’s lawyers made it clear that if the journal had anything to do with Healy and Jureidini they would be providing GSK or other companies with grounds to claim bias and to sue. This is even though BMJ and GSK are partners in AllTrials and BMJ had a short while before featured Andrew Witty on its front cover as the acceptable face of pharma, helping GSK put a $3 billion fine behind them. Partnership?

BMJ is a business that can no longer support medical practice, a key part of which is describing harms. If a doctor is not prepared to go to Court to stand up for the harms she’s put her name to, she’s writing fiction – a bit like Bram Stoker saying in real life he doesn’t believe in vampires.

That the BMJ editor handling 329 was married to a man who worked for the law firm who defended GSK against a $3 billion Department of Justice fine didn’t seem to be any kind of conflict of interest.  But then patients who have committed suicide or homicide on these drugs aren’t going to sue BMJ.

When it comes to on-patent drugs, BMJ provide news stories about medicine, medical entertainment. They are less likely than the NY Times or BBC to check the integrity of their primary sources.

BMJ and all our major journals have been turned.

Oh for the Blood of a Teenage Girl!

Water and drugs flow down even the slightest gradient unless there is something in the way.

The BMJ got involved in the Tamiflu saga in 2009 making it the basis of a “transparency” campaign – see Cisparency and Transparency next week – and later AllTrials.

Tamiflu is an efficacy story not a harms story.  As Peter Doshi and Tom Jefferson accessed more and more efficacy data the efficacy of Tamiflu shrank to almost nothing. But it only takes 1% efficacy to sell pills provided there are no bumps in the way, and nothing has happened to dislodge Tamiflu from the top of the guideline heap for use in cases of Flu.

The story of antidepressants and teenage girls is even more remarkable. There are now 30 RCTs of SSRIs and related antidepressants for adolescents and children – 29.5 negative.  Fluoxetine/Prozac is the most negative of the lot – there are 7 trials in which it has failed to beat placebo on the primary outcome measure including the two that led to its licensing by FDA and MHRA and EMA.

Surely not – you thought Prozac worked for children.  Why have you not heard of this?  Same reason you never knew Harvey Weinstein was anything other than a nice guy – with the extra reason that whatever about other enablers, bureaucrats never ever admit they’ve made a mistake, and the academic media aren’t any better.

There is an excess of suicidal events on antidepressants in every one of these 30 trials. In the only notionally non-company trial, the investigators in 7 major publications in leading journals from this trial “managed to conceal” the 34 suicidal events on Fluoxetine versus 3 on placebo – this requires an Editorial Nelson to be not just blind in one eye but very short-sighted in the other.

The BMJ has done more than conceal harms. It “enabled” a transformation of these life-ending harms into a “controversy”, when in 2014 it published close to the shonkiest, most ridiculous article any major journal has ever published on anything – the Lu et al article.

There seems no point in submitting an almost entirely data-driven, opinion-free, article on what the trials in teenagers show to BMJ, even though antidepressants are now the most commonly prescribed drugs to teenage girls.

Even though last week, the British Secretary of State for Health declared adolescent mental health services the biggest single weakness in NHS provision.  The great concern is that teenagers are self-harming while waiting for access to secondary services – now why would that be?

A few weeks before, the grisliest case report ever appeared in one of the few media still concerned about primary sources (Panorama). It covered the killing of twelve people in Aurora by a 24 year old on an SSRI, Black Boxed up to 25.  This case report is totally backed up by the RCT data. BMJ played a stellar role in dissing any possible link to the drug – abetted by a posse of Psychiatric Association Presidents and ex-Presidents.

If on a Winter’s Night a Traveller…

With the creation of Dracula, Bram Stoker, a Dubliner, globalized the Celtic feast of Halloween. Both Dracula and Stoker left their place of origin and came to England.  When last heard of, Stoker was working a few blocks down the road from the BMJ office…

To be continued


If on a Winter’s Night a Traveler… Trick or Treat?

Its the end of October when every Irish person going back millennia  gets taken over by Halloween – not just the Celts, those who come and stay get bitten too, as Bram Stoker could tell you.

So there will be a series of 4 posts to mark the occasion, starting next week, previewed here.  These fit closely with the RxISX Prize posts and should be read in conjunction with them.

Not every title and subtitle will remain the same – and some still need to be inked in……

Vampire Medicines

  • Richard Smith
  • Vampire Birth
  • Conflict Free Blood
  • Rosemary’s Baby
  • Buffy
  • If on a Winter’s Night a Traveller….

Cisparency and Transparency

  • Blowing up the Fish Pond
  • Stunned Amigos
  • Enter Stage Left
  • Let the Sun Shine In
  • The Benefits of Transparency
  • Cisparency
  • Spearing Nemo

Raiders of the Lost Drug Wreck

A Call to H-Arms