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...]

Archive for Madness of North Wales

Shock, Mutilate and Poison: The Medical Mission

Changeling

Editorial Note: This post interrupts the Crusoe series.

The comments from Deirdre Oliver and “Truth” posted below assume Crusoe and I are one and in attacking me they risk derailing a position being laid out by Dr Crusoe. Dr Crusoe and I share some views or her posts would not feature here but while the issues about ECT have some relationship with the position she was staking out about drug regulation it seems better to separate out the attacks on me from the wider debate.

Anyone who wants to engage more fully should ideally read the attached chapters from the History of Shock Treatment – The Swinging Pendulum, A New Chapter? & Irrational Science. It is worth visiting Let Them Eat Prozac The Shock Controversy, where saving some items that might have been embarrassing to those attacking me, things that have come up before are posted. Also worth reading are Better to Die RxISKing it One and Two – the text of an address to ISEPP in Los Angeles last November. This talk was going to be posted by ISEPP – it is close in content to a talk given recently in Yale that has been posted.

So this post is responding to some of the comments that seem to come after it.

I am as constant as the Nothern Star

Caesar’s words that sealed his assassination – or words from Joni Mitchell. Take your pick.

The initial charge from Deirdre Oliver – see below – accused me of lacking consistency. She and many anti-ECT activists find it bewildering that I don’t call for ECT to be banned. It seems inconsistent to them to campaign against the toxic effects of drugs and not to call for ECT to be banned.

I have never called for a treatment to be banned – not SSRIs, not antipsychotics, not benzodiazepines, not psychosurgery and not any of the therapies that have been linked to a recovery of memories of abuse that never happened. My beef has been to get the hazards of treatment, whatever they are from whatever branch of medicine, put on the map so people can be better placed to decide whether or not to take the risks involved or to work out what has happened to them should treatment go wrong.

Getting to grips with the hazards should leave people better placed to decide if the primary problem was bad luck, a negligent therapist, or a systematic cover-up by an industry or other group promoting a treatment in a misleading way.

The cover up

Having gone into the background research, probably more than anyone else on earth, on what companies knew about the hazards of their drugs, and what those linked to ECT knew about the hazards of ECT, my view is that companies unquestionably engaged in and likely still engage in negligent and sometimes perhaps even fraudulent behavior when it comes to the hazards of drugs. Because drug treatments within mental health are used somewhere between 10,000 and 100,000 times more commonly than ECT, the consequences of this company behavior are far more devastating than any ECT cover-up could be – were there a cover-up.

I seem to be able to spot a cover up where others can’t. AllTrials for instance looks to me something that suits industry all too well. But there is no ECT cover-up that I can find.

Those who defend ECT can be wary and defensive. This is not surprising in the face of implacable hostility, and little support from the rest of medicine. Yet the person who most clearly put on the map the idea that ECT involves an organic insult was Max Fink, the person most excoriated by the critics of ECT. It has been very difficult to get clear-cut test evidence of enduring cognitive dysfunction on ECT; one of the few bits there is comes from Max Fink. D.O. below cites Charlie Kellner raising the possibility that the next generation of scanners may reveal harms on ECT. Kellner has been the editor of Convulsive Therapy, the lead investigator on the CORE ECT studies, and one of the major figures behind ECT. The fact that he thinks some scans might show something suggests an openness to the data here just not found among drug company apologists.

When I wrote a celebration of activist movements in ECT’s history (The Swinging Pendulum – above), and the efforts to use abuses linked to ECT to promote informed consent across all of medicine, I got a lot of my leads from Max Fink. When I supported the publication of Linda Andre’s Doctors of Deception (see comments), some of those concerned for the treatment weren’t enthusiastic because unlike D.O below they didn’t think it was meticulously researched, but no-one vilified me or ostracized me.

The research evidence

The critics cite evidence of brain damage in a paper by Hartelius and memory dysfunction in a paper by Janis – both dating back to the 1950s – or they invoke brain scans. The Hartelius’ study comes up again and again and came up a short while back in a set of exchanges on the Critical Psychiatry website between Barney Carroll and the CP network that more than fulfilled the English definition of fair play – at least 11 against 1 (as in cricket). Peter Breggin weighed in with the Hartelius paper. Carroll provided an analysis of this – attached here. This is a must read. Exchanges like this lead to silence on the CP site or to someone like Barney Carroll simply not having their contribution posted.

None of this is to say there isn’t brain damage on ECT. Poisons, poison. Mutilation, mutilates. And a convulsion is never a good thing. Some generation of scanner or other tests will reveal damage linked to ECT. But the same scanners will reveal as much or more damage linked to antipsychotics and antidepressants. What then?

In the meantime having worked with a variety of colleagues on scanning and cognitive testing protocols in an attempt to elucidate the harms ECT causes, I can report that with the best will in the world it isn’t easy to draw up a protocol that gets to where the critics seem to want to get. Their response is that the failure to come up with results that nails ECT points to a cover-up but what is being missed is that current scanners are pretty useless for anything fine-grained and cognitive function testing is little better.

ECT is linked to autobiographical memory problems – but so are the benzodiazepines. It’s easy to demonstrate this for the benzodiazepines but far more difficult in the case of ECT. There is nothing distinctive that ECT causes that drug treatments don’t cause in spades and no-one who gets ECT doesn’t get drugs also.

In terms of the severity of the conditions it treats, from resistant Parkinson’s disease, through Neuroleptic Malignant Syndrome and catatonia to psychotic depression, the benefit-risk ratio may be better for ECT than for anything else in psychiatry – when used for those conditions. This doesn’t mean it doesn’t cause problems. Unnecessary convulsions are never good.

Led the wrong way?

This brings us to legal actions. On the drug side, the actions that I have been involved in have never been against doctors. They have been directed at companies. These actions have brought a huge amount of material about the sequestration of trial data, ghostwriting of articles and public relations sponsored harassment of people trying to raise the hazards of treatment into the public domain. When juries have convicted in cases of birth defects, or suicide or dependence linked to antidepressants, it has been on the question of whether companies had good cause to warn and failed to do so. It has not been about getting treatments banned.

I have found it difficult to be party to legal actions against doctors in circumstances where drug treatments have been involved as it has seemed to me difficult to hold them responsible for the air they breathe. It is not unreasonable for them to depend on the literature that appears in respectable journals like BMJ and NEJM, although we may be nearing a point when juries decide otherwise.

A possibly even greater problem in medicine that RxISK.org seeks to address is the often abusive treatment that many of us receive that is made possible by a power-imbalance between doctors and the rest of us.

If not broken, the mental health system is wobbling badly, and there are an increasing number of people trapped within it, the learning disabled, the elderly and anyone who has an adverse response to a drug, who are at increasing risk of being treated for the consequences of prior treatment, and whose lives are being blighted and shortened as a result. I’ve been writing about this for nearly two decades – see Foreword: Dying for a Cure – and spent a good deal of the last two years working on a way to formulate the issues that might provide a platform for anyone having unnecessary treatment inflicted on them whether ECT or drugs, in community or inpatient settings, to escape from under the juggernaut.

How do we tackle being powered out? This happens across medicine – its not just a mental health issue but mental health activists are more aware of the issues than anyone else. Diverting them into calls for getting treatments banned is a great way to prevent them bringing a revolution in all of healthcare. Success in getting ECT banned might also be a good way to make a market for the next pro-convulsant treatment – Ketamine analogues.

Having at one point researched most of the major ECT legal cases for The Swinging Pendulum chapter above, the difference between ECT and pharmaceutical cases is striking. The ECT cases should be about medical negligence but time and again plaintiffs have ended up with experts on a mission to get ECT banned completely, when it might have been better to seek out an expert who concedes that ECT may be helpful but in their case was used abusively. And the plaintiffs have lost.

Romance

The call to ban ECT is linked to ideas that mental illness doesn’t exist – and indeed that disease doesn’t exist given the benefits ECT can produce in NMS and Parkinson’s disease. There is a romance to the idea that disease doesn’t exist but ninety-nine percent of the population just ain’t going to go there.

Romance might sound pejorative. I was going to say ethical nobility. When anesthesia was developed in the nineteenth century, it led some, who could not accept the idea of benefiting the many at the expense of the few, to agonies. There was an ethical nobility to such agonies in 1860, but most of us would regard their rehearsal now as romantic. Some of us split the difference and regard the bargain medicine has made as Faustian, but when it comes to the crunch of cancer or the maelstrom of melancholia we take the bargain and opt for anesthesia or ECT.

See Sherwin Nuland’s extraordinary TED talk on ECT. But for every Nuland who gets the call right, the Devil probably wins in having ECT inflicted on someone who shouldn’t have it – but s/he wins even more comfortably when it comes to drugs.

At the end of the day, I don’t see it as my role to decide for anyone what treatments they should or shouldn’t have. The message that the benefits you can get from me are linked to poisons, mutilations and shocks would reduce the use of all treatments across medicine, however anyone thinks they help, but they would still be given by some doctors to more than those who stand to benefit, or be demanded by some who don’t figure on meeting Dirty Harry.

The resistance to the message that medicines are poisons is not confined to mental health. Delivered at a recent event at the Hay-on-Wye HowTheLightGetsIn Festival, the message was not well received but it’s difficult in any other area of medicine to imagine hostility of the type that the critics of ECT mount, unless orchestrated by the pharmaceutical industry.

ECT is the most disputed treatment in all of medicine. This hostility was once actively fed by Pharma with adverts for chlorpromazine and other psychotropic drugs portraying a switch to their medicine as a way to eliminate Cuckoo Nest scenarios. Pharma have done some brilliant things in the mental health domain. One was their linking of concerns about the risks of suicide on SSRIs to Scientology. This was doctor Rope-a-Doping. The same has been done to ECT. From the 1960s onwards Pharma influence has made it steadily more difficult and its now close to impossible to get symposia on ECT into APA or other mainstream psychiatry meetings – this is activist Rope-a-Doping.

A true story

In one of the comments below, Johanna Ryan notes the mystique ECT has among some doctors. I’ve never really noticed it. It’s difficult to believe any doctors see ECT as anything other than Shocking. It would be great if they saw drugs as poisons in the same way. Some say they’d have ECT themselves if they ever became melancholic but an increasing number of them have never used it or seen it used. The only person recorded as seeing ECT as anything other than shocking was Ken Kesey, the author of One Flew over the Cuckoo’s Nest, who rigged an apparatus up in his garage thinking it might offer something similar to an LSD trip.

But ECT is iconic in other ways. Clint Eastwood’s movie The Changeling opens with the line – This is a True Story. Not based on a True Story but an actual True Story. The Changeling portrays the horrors of psychiatry as they have been since One Flew over the Cuckoo’s Nest – through involuntary ECT, The problem is the heroine’s incarceration happened 10 years before ECT was invented. There is something about ECT that all but compels people to use it as a symbol of the horrors of mental health systems. There is something about health which means we ignore where the real problems are coming from when ECT and anything else is used.

The people most likely to profit out of Dirty Harry turning into a pussycat or talking to an empty chair are Lilly, GSK and Pfizer. Sorting out the honchos who make the treatments that cause the most damage would take care of the problems linked to ECT en passant, but we’ll be a long time waiting for Harry to tell a drug company executive to make his day.

Meanwhile in another part of town….

Choosing ECT Rachel Perkins

Ad hominem

Lost in Medication: The Crusoe Report 3

Lost in Medication. Ask your doctor about the sexual side-effects of your meds. Based on Adam and Eve painting by Lucas Cranach the Elder in 1526

Lost in Medication. Ask your doctor about the sexual side-effects of your meds. Based on Adam and Eve painting by Lucas Cranach the Elder in 1526

Editorial Note: This follows Restoring Health part 1 and What’s Poisoning Health part 2 of the Crusoe Report in response to the Witty Magna Carta posts.

A medicine is a mix of a chemical that pharmaceutical companies produce and knowledge about how to use the chemical – that we produce.

Making even basic chemicals was beyond us for millennia. But once the process was cracked, discoveries and inventions came thick and fast. Making chemicals that could be used to treat diseases was beyond us for even longer but the pace of discovery began to pick up in the middle of the nineteenth century. The realization of what needed to be done to give a chemical a chance of becoming a medicine led to the hunt for a Magic Bullet. But even as the process became more rational the role of serendipity remained and remains enormous as the discovery of penicillin and so many other medicines demonstrates.

Huge amounts of knowledge are buried in the production of these chemicals that might be drugs. Some of that knowledge came from the pharmaceutical industry, especially the knowledge about how to mass produce the new chemicals to a quality standard. A lot came from university, institute or other research laboratories.

Patents or prizes?

The emergence of these new medicines led to vigorous disputes as to how much an industry like the chemical industry needed to be incentivized to produce new drugs. Venice was the first economy to use patents and the English adopted the idea as a reward system in 1624 to stimulate commerce. At this point patenting seemed a better bet for something like building up a business that traded in goods rather than a means of fostering discovery. When there was a need for a radical breakthrough, Prizes looked like a better bet. The best illustration of this is the story behind the Prize offered for the discovery of how to determine Longitude won by John Harrison in the 1740s.

At a time when chemical companies could produce little of any value to medicine, the French revolutionaries, ordinarily hostile to all things English, and with other things on their mind like guillotining a King, figured it was a revolutionary thing to do to allow patents on medicines. The Germans initially frowned on this idea but later opted for process patents – I could get a patent on my way to make Prozac but not on Prozac itself. If you find a different way to make Prozac, you could make it. The Americans who were much later to the game, from the get-go let companies have product patents – if I patent Prozac you can’t make it even by another method. I have a monopoly on it.

Process patents seem more the thing for the modern age with its emphasis on intellectual property rights than product patents that actively discourage innovation. And for a century the American pharmaceutical industry lagged behind all others, until political developments leveled the playing field and forced the Europeans in the 1960s to play by product patent rules and then the rest of the World to do so too through TRIPS in the 1980s, after which drug development slowed down.

Making a medicine

But here’s the rub, whatever patent system or Prizes we offer them, companies just produce chemicals. It is we who produce medicines. A medicine is a chemical with information and the information comes from us.

In the 1950s, the information came from doctors giving us the new pill and both of us monitoring what happened. That was the ideal but some of them gave us a pill without telling us it was new, and some of the guys handing out these new drugs were people you probably wouldn’t want to take something new and potentially dangerous from. Whether we were fully on board or not though, this was a system where the knowledge was produced in a hands-on way by us and our doctors. If the drug didn’t obviously do something useful or clearly did something harmful it was either removed from the market or the knowledge of what could go wrong found its way pretty directly into clinical practice.

These new chemicals interfered with biology in a way that only poisons had done before. The need to get the information component right was brought home horrifically in 1961 when thalidomide stripped babies of their arms or legs and deformed them in multiple other ways.

Producing Health can never be just a matter of Consuming Chemicals.

The wages of fear

A wave of panic washed over the political establishment at the sight of armless babies. There was a reflex need to be seen to raise the bar for pharmaceutical companies bringing drugs to market. If these companies were going to make money out of people at their most vulnerable, they would have to pass through the eye of a needle. They would have to show in clinical trials that their drugs worked. And those of us who entered these trials would have to be informed that the drug was something not yet on the market so that we could make up our own mind whether to take the risks or not.

This sounds like and is portrayed as something good being drawn from an appalling tragedy, except that clinical trials had only just been invented and no-one realized they weren’t up to the task, except Louis Lasagna, one of their inventors and their main promoter – (See Marilyn’s Curse and related Lasagna series posts).

It took time for the problems to appear. In the 1960s, whether in trials or just by trial and error, the knowledge that made these new drugs into treatments that saved lives came from us. The doctors who gave the drugs were local – they knew us and our communities. In the first trials the doctors were treating patients they knew and when the trial was over and they broke the blind they were able to make sense of the findings in terms of the things they remembered seeing or hearing about directly from the patient.

And so in the decades just after the greatest cataclysm in human history, the risks we took in taking new drugs, whether in trials or just under the observation of our doctors, on behalf of people we knew, ushered in the most extraordinary period of medical advance in all of human history.

But it is exactly this space to mull over what you are seeing and hearing or experiencing that trials have now now left as road kill as they have become the fuel for Fast Medicine.

The risks in destroying knowledge

The initial rationale for trials was that they would be run on drugs or in situations where it was just not obvious that the treatment was helping or that the risks were worth taking. For things that were evident, there was no need for further evidence.

When things aren’t evident and we decide to run a trial, we take a calculated gamble on something risky – and probably well over ninety percent of trials that get run involve risks not worth taking.

To test something out you first need to hypnotize doctors and patients. The blinding in a trial means more than the idea that neither the doctor nor the patient know what the drug is – they can often guess. It means you limit their vision. You get both to focus intensely on whether there is any sign of benefit – to the exclusion of all else. Drugs do a hundred different things but in a trial everyone is guided to ignore the ninety-nine other things and focus on just one thing – does this drug work for whatever it is the company is interested in.

In fact we have introduced another complication which is we ask does it work for depression or to stop heart attacks. Just as SSRIs do, a drug might so obviously blunt or numb reactions that you don’t need a trial to demonstrate this – or so obviously lower cholesterol levels that you don’t need a trial to show this. This blunting or lowering cholesterol can be helpful or not, but rather than call this working, we want to see if this helps depression or prevent heart attacks. When the trials finally squeeze out an answer that you can’t say these SSRIs are of no benefit, we in fact have no idea how the benefit has come about. Or if the trial finds that lowering cholesterol makes no difference, we have no idea why not.

Look at it this way. Alcohol can be very good for social anxiety. Everyone who takes it for this purpose knows what they are doing, and knows how it helps. If we ran a trial of alcohol for social anxiety, and on some rating scale could show some benefit, you would be asked to forget any ideas you had about how alcohol might be helping and just accept a company line that it “works” and therefore you should be taking it – for the rest of your life in all probability.

In the same way, our knowledge of how SSRIs help – they numb – is discarded in favor of the company or expert knowledge that these things work. Into this knowledge vacuum, companies were able to insert all kinds of baloney about serotonin and continue to offer up the hocus-pocus of chemical imbalances – See So Long and Thanks.

The great hypnosis

The great hypnosis involves a post-hypnotic suggestion – that out of the trial will come gold standard knowledge of what drugs do.

We are being told forget our ability to produce knowledge – to produce medicines. They have put us through a machine that erases any inconvenient observations we may have. Our only role now is to consume the pills they give us and to swallow without question the information they provide with them. We have been made into consumers; we are no longer seen as producers.

The hypnosis is pretty dense. In SSRI trials, one hundred per cent of us had genital numbing and a change in sexual function but less than 5% of us apparently noticed this or at least had it recorded by the doctor – many of these trialists are third raters you wouldn’t want to be treated by. To this day we don’t know how many of us return to normal sexually or emotionally after taking an SSRI even just for the 6 weeks of a trial.

So when your son or daughter rocks up to a doctor (visiting is too twentieth century) with the disturbing information that they have stopped functioning sexually, that they could smear chili paste on their genitals and they wouldn’t feel a thing so numb are they, he will check the product label and not finding anything like this there will tell them it’s all in the mind, or this is their depression speaking.

The more they protest, the firmer the noose of neurosis will tighten around their neck.

If you were in one of these trials where your attention was diverted away from the effects of these drugs on sexual functioning or when you tried to make an observation the doctor didn’t record it, the fact that you took risks in a trial for the benefit of your family and friends and community is now being used to skewer your family and friends, just as surely as your work in a lead smelter for most of the twentieth century poisoned any family or friends you had living nearby.

At least working in a smelter you were paid for the work you did.

Many of the trials on which our safety now depends have now moved to places like Bhopal in India or the townships of South Africa where the patients may not exist or if they are injured they can be disposed of without any trace of the problem appearing on the record. The “knowledge” that comes from these trials is deemed by the FDA, the MHRA, AllTrials, the Cochrane Collaboration and Barack Obama as the only real knowledge there is. Your experience by comparison is anecdotal – irrelevant.

If you’re a politician who hasn’t lobbied to make access to clinical trial data freely available, you’re a politician who would lobby to keep the lead smelter running in your district and the level at which lead in blood is regarded as dangerous as high as possible. Hey if kids poisoned by lead are hyperactive – well isn’t that what we have Ritalin for?

The garden of good and evil

Earth teems with life. It’s difficult not to be productive amidst this abundance. It takes the degraded circumstances of a concentration camp to turn humans into just consumers and even there the human spirit can find meaning.

In the Garden, there were trees we could eat from that our parents and others had spent lots of time cultivating, whose fruit were Medicinal. But there was also a Tree, the Fruit of which Wisdom made clear we should avoid. Consuming this Fruit, which we hadn’t been involved in husbanding, we were told would lead to Exile.

The Fruit of this Tree looks Medicinal – but it’s not life giving.

It’s profoundly alienating because of one more feature to the Clinical Trial process, at least within the current regulatory system, which is that it locates the problem, the taint, the original sin in us. If trials show ADHD responds to Ritalin, it must mean the kid is defective.

Which lets politicians say or maybe nudge – “Why look at goddamned lead levels – you want to drive jobs out of this country? If you want to make this world a better place, just keep taking the pills. All of them”.

If Medicine is to be Safe, we need to reclaim our birthright as producers of Medicines.

To be continued.

 

See comments – J Rees’ article is Here.

Magna What? The Embarassing Side Effects of Drugs

Magna Farta

This post is designed to be read with the Drugs and Smell post on RxISK. Click on the image to read the small text.

Into the Matrixx

The second drug in the Anosmia Table in the Drugs and Smell post is Zinc Gluconate which was traded under the name Zicam. For anyone concerned about adverse events this is one of the most important drugs in History.

Zicam was marketed by Matrixx Pharmaceuticals. The company’s shareholders became concerned about reports it could produce anosmia and parosmia and asked to “look at the books”. The Board said no. The shareholders took them to court and ultimately to the Supreme Court. The company defense was that all it had were animal studies that were not statistically significant and some anecdotal reports of a problem, but as nothing had been properly linked to treatment there was no need to tell the shareholders. The Supreme Court disagreed.

If you are going to gamble with your money, the Supremes figure you are entitled to make up your own mind what the data means but not it seems if you are someone gambling with your life or your child’s life or perhaps the life of child yet to be born or a doctor gambling with your patient’s life.

Blind doctoring

The Supreme Court decision doesn’t stand quite alone though. There is an extraordinary legal case from 1981, Oksenholt vs. Lederle Laboratories, which no one seems to have picked up on.

Dr Oksenholt was sued by a patient whom he had put on a treatment for tuberculosis, Myambutol. This had caused her to go blind. He settled the case with her for $100,000 and then sued the drug company for withholding information from him that their drug could cause someone to go blind. He won the case. He also won $50,000 damages and an unspecified amount for future loss of earnings and $5 million punitive damages. See Oksenholt.

None of the doctors who gave medication to any of the Mass Shooters of recent years or Airline Pilots who have crashed – and there have been many on antidepressants – have interrogated companies legally about the with-holding of data. There is a precedent there for them.

Oksenholt v Lederle Laboratories

This is the third post in the Magna Carta series, a place-holder while we try to FOIA or otherwise find the missing Crusoe Report mentioned in the Witty Report last week. It’s the twenty-first post in the Persecution series.

Illustration: Magna Farta, 2015 created by Billiam James

Magna Pharma

Magna Carta

This post on the eight hundredth anniversary of the signing of Magna Carta is the second in a Magna Carta series, and the twentieth in the Persecution series.

Faced in 2012 with questions about the $3 Billion fine imposed on GSK – triggered by a sequence of events starting with Study 329, – is it just the cost of doing business? Andrew Witty snapped back:

“Although corporate malfeasance cases end up looking very big, they often have their origin in just… one or two people who didn’t quite do the right thing. It’s not about the big piece. The 100,000 people who work for GSK are just like you, right? I’m sure everybody who reads the BMJ has friends who work for drug companies. They’re normal people… Many of them are doctors.

Witty A: Report to the President on changing the system

Accounts of what led to the 2022 Amendments to the Food and Drugs Act vary wildly. Some point to the new President’s first grandson being born with Tetralogy of Fallot linked to the mother’s antidepressant intake. Conspiracy theories invoked Marilyn’s Curse. They noted things like the coincidence of initials between the unknown American Woman whose baby had a Tetralogy of Fallot and Andrew Witty (See American Woman and American Woman 2). Others thought it was triggered by the increasing evidence of cognitive failure in more than one previous President linked by some to the fact both were on Statins.

Whatever the reason, Andrew Witty was recruited from GSK to rewrite the Charter between the people and Pharma. Here is a précis of his option appraisal.

1. Regulation & science

The licensing of drugs is a bureaucratic procedure that has nothing to do with science. As things stand, the way FDA goes about approving drugs has enough of the appearances of science so that most doctors and patients are fooled into thinking there has been a science based decision when there hasn’t.

To an extent the public can’t imagine, the bureaucrats are just interested in getting boxes ticked and to paraphrase Tom Lehrer, “When the drugs go up who cares where they come down, that’s not my department”.

Regulation is completely incompatible with science. Science seeks uncertainty, whereas regulation seeks to abolish uncertainty.

We in GSK thought it must be crystal clear that Pharma does regulation and not science when to support a legal action against the European Medicines’ Agency Data Access policies in 2013 that proposed to let doctors and others see our clinical trial data we argued that this “data” was simply the result of a regulatory exercise and regulators ordinarily maintain the confidentiality of submissions on products they regulate.

This was the winning option in the opinion of the Courts. Some of my colleagues had doubts about our ability to win using this argument while maintaining the illusion that companies do science. The argument was a blow to the self-esteem (amour propre) of FDA and EMA who, while asleep at the wheel, like to claim they base their actions on science.

But medicine predictably noticed nothing. As Thomas More said about the Nobles of England – they’d have slept through the Sermon on the Mount.  The only time they woke up was at Runnymede when there was something in it for them – (see Magna Carta).

2. The effectiveness fly in the 1962 ointment

Regulation needs to be disentangled from science. This cannot easily be done while the 1962 Amendments to the Food and Drugs Act contain an effectiveness criterion. The idea of forcing companies to show their drugs worked was a well-intentioned move but a disaster all round – a simple solution to a complex problem that has made things worse.

In the new regulations to mark the sixtieth anniversary of the 1962 regulations the word effectiveness needs to be replaced by safety.

For those who want companies to say what a drug is for, we can revert to the wording before 1962 by stating a drug should have a clear effect on a structure or function of the body.

Getting rid of the effectiveness criterion would do a lot of things. First it would make it a lot cheaper to develop new drugs. As a result, the cost of drugs would fall, more new drugs would be brought on the market and after marketing a lot of discoveries would be made. We could look forward to a new era of Wonder Drugs to rival the 1950s.

Second it would get rid of off-label marketing at a stroke.

Third it would mean that doctors and patients would have to be personally convinced a drug was actually helping them rather than depend on company claims that it was.

Fourth it there would be much less company clinical trial data and campaigns like BMJ and the Cochrane collaboration to access the data would likely wither on the vine. It would even be safe to appoint Peter Doshi and Tom Jefferson as data access Csars.

3. Evidence based medicine

Whether a drug works or not is not critical to companies but it is critical to medicine and patients. This is a question that cannot be left to industry. As with a lot of these things women have blazed the way as in trials like the Women’s Health Initiative study of HRT. There were earlier trials run by medicine like this during the 1960s but everyone has forgotten them – it’s so long since medicine ran a serious trial.

This would be real evidence based medicine.

One of the consequences of this is that it would likely mean that a full appreciation of the risks and benefits to be obtained from a treatment would only really be clear several years after the launch of a new compound when the proper clinical trials began reporting. What doctors do while waiting for these results to come in is the key issue. Our hunch is that hope is the most powerful incentive of all for most patients and most doctors. No regulatory system will ever change that.

4. Prescription-only arrangements

Quite simply these need to be dismantled. Anyone who doesn’t understand this doesn’t understand marketing – most doctors.

If prescription-only privileges are to be retained in some modified form, only those who do understand the need to abolish them should be involved in any modification.

There are a range of things that could be done such as:

  • Requiring doctors to have a training post in a company marketing department before qualification.
  • All editors of medical journals should have had a spell working in industry first – those without industry experience are too lilly-livered to take to the dance-floor with the amount of confidence needed to pull off any tricky steps.
  • Rewarding doctors for reporting adverse events
  • Penalizing doctors if they do not report them at a certain rate per year.
  • Maintain certain drugs on prescription-only such as cancer chemotherapies where patients are particularly vulnerable and the treatments particularly toxic.

5. Abolish medicine

Where alchemists, homeopaths, chiropractors and others, who have slavishly copied medicine, failed to make inroads, we have been able to walk in and leave with the Crown Jewels.

Using clinical trials and ghostwritten articles – the appearances of medicine – we have infected the body of medicine with an AIDs-like virus turning medicine’s defenses against itself. The insertion of these sophisticated adverts into the medical literature has triggered a Clinical Auto-Immune Deficiency (CID) reaction that leads most doctors and scientists to turn as viciously as they would turn on a quack on anyone who questions the results of these ghostwritten articles and trials that have no data and sometimes no patients. It’s been amazing to watch.

Physicians have had decades to find a way to get this cuckoo’s egg out of the nest of science. They could have based clinical practice only on investigations whose data is publicly available. They could have used the Human Rights of their patients as a lever – it is not for instance possible for any doctor to prescribe any branded medicine with informed consent as things stand at present.

But they haven’t done anything like this. The branches of medicine linked to the prescribing of branded products are finished as a profession. They have no brand value.

The market has now developed so that nurses, pharmacists, clinical psychologists and others can take over the role of prescribing drugs and are far less expensive than doctors.

If medicine has any value and we believe in market forces, abolishing it might lead to a solution. If people and governments come to think they need a set of experts who have brand value when it comes to good quality information on drugs, a new profession will be called into being.

Other physicians practicing in areas of medicine where branded products have little penetration could be allowed to continue.

One issue for others to consider is whether areas of medicine that are heavy users of medical devices are as badly affected as mainstream medicine.

A further option might be a promotion of patient co-operatives. Groups like ACOR.org are making a significant difference to healthcare. They might find it far easier to work with nurse and pharmacist prescribers than with doctors.

6. Boycott

One of the few things that might have influenced my behavior as CEO of GSK would have been a boycott. Record fines and even jail time are not deterrents. Almost everyone views these as a cost of doing business already. A jailed CEO might even boost share value.

We in GSK know that boycotts can hurt. In the crisis over making ARVs available to South Africa for AIDs the threat of a boycott was the only time our Board substantially altered its position.

The boycott would be aimed at getting companies to hand over Adverse Event data. Groups like AllTrials – which we did a lot to nurture – are campaigning for efficacy data. It’s been interesting to watch them punch themselves out on this issue which is tied to disease indications that don’t exist, and center on meaningless surrogate markers, and are produced for bureaucratic purposes only. These data are frankly close to worthless and are not what we have been trying to hide anyway.

What we have been hiding has always been the adverse event data.

7. Rewards

In 1962, in the frantic panic triggered by thalidomide all the wrong options were picked – the effectiveness criterion, prescription-only arrangements, and controlled trials. They all looked good at the time but companies are a bit like the dinosaurs in Jurassic Park, we are always going to find a way around the controls.

There was only one proposed change we really didn’t like and made sure we killed off – this was a proposed revision to the patent arrangements. Having US style product patents has been the key to the Pharma companies becoming Magna Pharma – the most profitable corporations on earth.

Companies need to be rewarded but the current product patents reward us beyond the dreams of avarice for delivering treatments that increasingly shorten life and increase disability.

There are other ways to cut this cake such as process patents, that would make blockbusters less valuable. Process patents would put a premium on diversifying the portfolio of compounds we hold rather than have us dependent on a small number of blockbusters.

At a stroke this would begin to turn us away from making everyone chronically diseased for life in order to make huge amounts of money out of them and away from just looking for drugs that millions will consume even though they don’t need them and turn us toward drugs that everyone will recognize are worth paying a lot of money for.

8. Access to data

The last decade has seen a huge fuss about access to Clinical Trial Data since we in GSK kicked open this door by posting the results of our trials on depressed children on the company website. We have been able to keep the lid on this and have fall back options such as the AllTrials proposals that if adopted will probably leave academics worse off vis-à-vis transparency than they are now.

We have taken some risks to win the argument so far by claiming that patients’ data is confidential – when pretty well everyone who volunteers for a company trial expects that independent experts will get to view the data at some point and would be horrified to find this is not the case. So far this has been a winning argument.

But the startling thing that everyone has missed so far and shows no signs of spotting is that there are thousands or hundreds of thousands of drug trials that remain completely unregistered, where there are no issues of clinical confidentiality. These are studies undertaken in healthy volunteers – normals. There is a compelling cases for ensuring these data are made fully available.

These contain the data we really want to hide – the adverse event data.

Companies will likely need an amnesty for some of the abuses of people that will come to light if the new regulations make these studies available to view.

9. Independent adverse event reporting

This is a key step.

We have taken astonishing steps to prevent decent reporting, or to denigrate reporting when it happens, and to manage the perception of risk rather than risks themselves. If the Nazis had access to our bag of tricks, there would be real and widespread doubt that the Holocaust ever happened.

For instance companies supported the development of an FDA MedWatcher App in 2013. This was widely applauded as we knew it would be. But it was in fact a way for companies to reduce the expense of maintaining a pharmacovigilance department, reduce their legal liabilities, and transform adverse events into anecdotes all in one go. Companies you see have a duty to follow up and decide if their drug caused the problem – FDA don’t have this duty.

But what was astonishing about all this was that pretty well everyone completely bought the idea that when it comes to working out whether a drug has caused a problem, a bureaucrat in FDA who is there because they don’t like meeting patients, has never treated the condition you have and never used the drug you are on, would be better placed than a good team of doctor, pharmacist and informed patient perhaps in touch with other good teams, to work out what’s going on.

If we’re good enough to get people to buy this, perhaps next April 1 we should see if we can persuade people the earth is flat.

Unless an independent patient organization gets involved in assembling real-time data and both doctors and patients combine to put risk mitigation programs in place, the other changes are less likely to work.

The bottom line is the average drug has at least 100 effects. Using clinical trials we have been hugely successful in hypnotizing doctors and patients to focus on one effect and to miss the other 99. This blind spot is the major driver of Pharmageddon (See Marilyn’s Curse).

If the climate change encroaching on healthcare is to be rolled back, we need someone to spit on some clay on the ground, make a paste, and rub it into the eyes of doctors or anyone who ends up prescribing.

10. Shareholding

Following the Supreme Court decision in the Matrixx case (note to self – check I am not confusing this with the movie), which said that while doctors and patients have no rights to access company adverse event data, shareholders have, one option is through Government to give everyone a shareholder stake or stakeholding in companies.

*****

There was a doctor on my panel who had a different point of view. Dr Crusoe. She produced a minority report which I will forward under separate cover.

A Magna Carta for Healthcare

Magna Carta

Editorial note: This is the first in a Magna Carta series, and the nineteenth in the Persecution series.

As the days lengthen and things warm up in England, historically it has been the time for the people to get restive.

Eight Hundred years ago, the people meant a group of us who counted – we called ourselves the Barons. There were other human beings – our serfs – who worked for us. Today, in theory even the serfs count.

Next Sunday, June 15, Eight Hundred years ago, we refused to accept King John’s right to rule in England as he had been doing, and confronted the king at Runnymede.

Today’s Barons are the Doctors. Doctors make a living out of the work done by the rest of the population – swallowing pills. These doctors are highly unlikely to confront Andrew Witty or any of the big beasts of the pharmacockracy – unless some of them do so as shareholders.

Eight Hundred years ago a charter was hammered out between us and the king that has since become known as Magna Carta. Today something similar is needed. The forthcoming publication of Study 329 will make clear why.

Up till June 15, John and other kings were absolute rulers, whose right to govern came directly from God rather than from the people. When this right was questioned the Pope weighed in on the side of the king, excommunicating anyone who questioned the authority of the monarch.

Magna Carta was based on two principles – the principle of No Taxation without Representation and the principle of Due Process. These principles are fundamental to most political systems today.

The area of politics that counts most for most of us is healthcare. Big Healthcare is now the biggest business in the United States and in the Western World. We desperately need a new compact between we the people and those who govern our healthcare – or at least a new compact between the doctors who make money for pharma by putting pills in our mouths and the Witty’s of this world.

No taxation without representation

No one bats an eyelid at the idea that the United States is pretty market oriented compared to the more communal or socialist systems found in Europe with Great Britain usually seen as sitting somewhere in the middle.

So it is surprising if you put UK PLC and US PLC into google and see what happens. Google recognizes UK PLC and Great Britain PLC but not US or United States PLC.

There was no google in the twentieth century. Had it been there, it would have started throwing up hits from the late 1960s when British Labour politicians (who used to be very socialist back then) started mooting the idea of UK PLC. The ex-Empire was now a company that had to make its way in the wider marketplace. The Government, we were told, was like the Board. It wasn’t quite clear if the rest of us were the shareholders. We had some notional control over the Board – we could vote them out. Election debates today still mention UK PLC –Scotland PLC hasn’t come on the radar yet.

It’s an odd way to see your country. Neither the US nor any European country views itself in this way. But then the Brits invented PLCs as well as Magna Carta and cricket.

The same idea lies behind the Magna Carta and a meeting of the shareholders of a company – there should be some trade-off between the financial input of the stakeholders in the company (country) and their ability to influence policy. It is worth paying money in the form of investments or taxes if the ship of state is being steered in a reasonable direction but not otherwise.

In health we pay either relatively directly or indirectly through insurance systems or government taxation for the benefits we receive. At present, our barons make money for pharma by putting pills in our mouths but pills that keep companies healthy rather than us healthy.

This happens because of a Flash Boy situation. The healthcare market (stock exchange) should produce better healthcare outcomes (channel money to genuinely productive ends). But neither the stock market nor healthcare support productive outcomes. Both have become a means to siphon money from the middle and working classes to a bunch of Flash Boys. This is possible because as with the stock market, in healthcare no-one gets to see the data behind the transactions. Drugs that are bad for us can be palmed off as life-saving without anyone being any the wiser and we are sold a costly bag of goods.

But we are not just being taxed in terms of the money we pay to consume drugs we don’t need. There is a tribute taken from our bodies also in terms of our participation in clinical trials. Companies need clinical trials to get their drugs on the market in order to make billions from them. These trials involve us taking risks with drugs that often prove too dangerous to market. We do so for free. Not only that but when some of us are killed or injured we collude with hiding the data of our injuries and deaths. We have no more status than serfs.

Or at least this was the way until the clinical trial operation was largely outsourced to India and Africa leaving UK PLC scrambling to persuade GSK, Roche and Pfizer that it is open for clinical trial business and willing to divert its NHS patients into company trials.

It’s this taxation drawn from our bodies that should fuel a demand for representation – we should have a say in deciding what we need medications for and we should have access to the data from trials to check on how it is being represented.

When trials run on our children lead to representations that paroxetine is effective and safe even though the actual data shows exactly the opposite – it’s time to intervene.

Due process

The other key element to Magna Carta was the idea that we are all equal before the law, kings and commoners, and that all have a right to a fair trial.

This principle established the rule of law and laid the basis for democracy. This is a basic Right that provides a basis for all other Rights.

Rather than assassinate the King or seethe with murderous fantasies (Anonymous) we can take him to Court. Rather than be executed at his whim, we have the right to a fair hearing by a Jury of our Peers (Just for the record Peers means other Noblemen).

The capacity of plaintiffs in the United States to take legal actions when they or their families are injured by treatments probably stands between the CEOs of pharmaceutical companies and an attempt to exact physical retribution (See Data Wars and Pharmaceutical Rape).

But even in the United States, there is a real problem. When we participate in clinical trials today, companies get to sequester the data from these trials in flagrant breach of the ethics and norms of science and yet parade their representations of those results as science. The participation of some of us in those trials puts all of us in a state of legal jeopardy. In the US, we may get our day in Court, but we will have the data from clinical trials in which our friends and families participated used against us.

We have entered a bizarre Wonderland where Queen John or Andrew can say off with our head if she wishes to or can say what happens on a drug is what I say happens – regardless of what in fact does happen.

It’s a world where increasingly we will be told by Sense about Science in the UK and related bodies in the US, Canada, Australia or wherever that to question the judgments of the scientific literature is to engage in an irrational War on Science itself. We may have a right to Due Process in the US (nowhere else) but even in the US Courts are no longer a place where rationality prevails.

Not a Peep from the Pope about the right to Due Process or Representation.

Meanwhile David Cameron on behalf of UK PLC has launched into an anti-corruption crusade – but there won’t be a word about this lack of due process or the extraordinary corruption of the scientific literature – on which hinges vastly more money than was ever dreamt of by Sepp Blatter and FIFA.

42 or Thereabouts

42 answer

See previous posts – Switch on Anti-Depression Today and So Long and Thanks for all the Serotonin.

In response to the recent BMJ editorial on Serotonin and Depression, there were seventeen letters of which three were published, along with my response. These are copied below along with the best letter – by Barney Carroll – which wasn’t published. Make your own mind up as to why.

Another piece of minor intrigue is that this editorial, originally entitled So Long and Thanks for all the Serotonin, a title BMJ felt uncomfortable with, registered well on Altmetric – an index that tracks how much Buzz an article is generating. When I started looking at this, the article was rated at 43 on Altmetric and then moved down to 40 passing through 42 en route. It will presumably pass back through 42 at some point as it gets displaced by Buzzier pieces. Amusing given the Hitch-Hiker link.

serotonin and depression

Healy states the obvious

As a matter of clinical science, the notion of a simple serotonin deficiency in depression ended 45 years ago, when the proposed therapeutic utility of monoamine neurotransmitter precursors was disconfirmed.1 There has been little incisive progress since then, owing to major missteps in the intervening years – for starters, the foolish introduction of generic major depression in lieu of clinically differentiated types of depression as the focus of investigations;2 the displacement of disinterested clinical science by corporate experimercials;3 the corruption of journals and of educational forums by key opinion leaders who promoted corporate marketing narratives;4 and the capture of research funding agencies and regulatory agencies by commercial forces. The discomfort that David Healy’s editorial has caused in some quarters reflects a general embarrassment at the emptiness of current research in mood disorders. The yield has not been commensurate with the billions of dollars thrown at the problem – to the point where most corporations have exited the field out of a healthy self-interest. Little wonder, then, that those who have reason to be embarrassed are now throwing the book at Dr. Healy for stating the obvious.

REFERENCES
1. Carroll B.J. Monoamine precursors in the treatment of depression, in «Clinical Pharmacology and Therapeutics» 12, 743-76 (1971).
2. Carroll B.J. Bringing back melancholia, in «Bipolar Disorders» 14, 1-5 (2012).
3. Carroll B.J. Sertraline and the Cheshire cat in geriatric depression, in «American Journal of Psychiatry» 161, 1145-1146 (2004).
4. Carroll B.J., Rubin R.T. The high cost of non-disclosure, in «Clinical Psychiatry News» 34(10), 27 (2006).

Bernard Carroll

Serotonin and depression – Healy does a disservice to psychiatrists

Alexander E Langford,  South London and the Maudsley NHS Foundation Trust

David Healy does a great disservice to jobbing psychiatrists with this editorial. By portraying them as ‘co-opted into a myth’ about low levels of serotonin being the sole cause of depression he paints them as gullible, and by stating that the same theory is ‘an easy shorthand for communication with patients’ he paints us as lazy and reductionist in our appraisal of the complex and diverse causes of depression.

In reality, good psychiatrists are and always have been only too ready to admit that they are unsure how antidepressants work. Serotonin does play an important role – likely via factors like neurogenesis and gene expression downstream from synapses – but modern psychiatry is way ahead of where Healy seems to think it is. The picture is far more complex. The fact that ketamine has been shown to be useful in depression does not ‘cast doubt on the link between serotonin and depression’, it rather confirms that the neurobiological underpinnings are as multifaceted as we think.

In any case, whatever their mode of action, SSRIs do work. Even the most stringent of analyses (i.e. Kirsch) support this. There is no good evidence that SSRIs work any less well than TCAs for depression , and the SSRIs have not become so commonplace in clinical practice due to some form of pharma-doctor conspiracy, as Healy would suggest, but because the older TCAs have a far less admirable side-effect profile and were also lethal in overdose. The safety of our patients should always come first, and they are far less safe without treatment for their depression.

Healy D. Serotonin and depression. BMJ 2015;350:h1771. (21 April.)

Serotonin and depression: myth or legend?

Philip J Cowen, Professor of Psychopharmacology, University of Oxford,

David Healy’s observations on serotonin and depression make interesting , if familiar, reading [1]. However, I was struck by the remarkable claim that the focus on serotonin has led to the ‘eclipse of cortisol’ in mood disorder research. A quick search in Scopus with ‘cortisol’ and ‘depression’ revealed a rapidly increasing number of published articles from the late 1990s, continuing unabated to the present time. Only last year saw the completion in the UK of a large placebo-controlled study which examined the effects of inhibiting cortisol synthesis in patients with depression refractory to SSRIs[2]. David also manages to suggest that ketamine has been shown superior to SSRIs in melancholic depression whereas no such comparison has been carried out. He further implies that the work of Andrews and colleagues is based on the intellectually paralysing notion that low serotonin causes depression whereas in fact these authors argue exactly the opposite [3].

Should one confront myths by constructing different ones? As an avid BMJ reader I find myself increasingly confused by this question. For if scientific narratives are manifestations of competing power claims and vested interests perhaps there isn’t really a ‘fact of the matter’- the important thing is to be on the right side. I agree with David.

  1. Lacasse JR, Leo J. Serotonin and depression: A disconnect between the advertisements and the scientific literature. PLoS Med 2005; 2: e392 DOI: 10.1371/journal.pmed.0020392 (http://medicine.plosjournals.org).
  2. Watson S, Anderson IM, Apekey TA, et al. Antiglucocorticoid augmentation of antidepressants in depression: The ADD study. J Psychopharmacology 2014; 28 (suppl): A38.
  3. Andrews PW, Bharwani A, Lee K R, et al. Is serotonin an upper or a downer? The evolution of the serotonergic system and its role in depression and the antidepressant response. Neurosci Biobehavior Rev 2015; 51: 164-188.

Serotonin and depression – personalized pharmacotherapy: an interim solution?

Adam M Chekroud. Yale University, USA

Prof. Healy offers an engaging historical perspective on the rise of serotonergic antidepressants that questions their efficacy and biological plausibility. However, this focus on low serotonin levels is a distraction that is basically irrelevant to whether serotonergic antidepressants are effective treatments for depression. It is important to note that response to serotonergic antidepressants appears to be heterogeneous rather than universally poor.  Unbiased trajectory-based analysis of over 2500 patients treated with SSRI antidepressants or placebo indicated that the majority of patients (over 75%) showed a superior response to patients treated with placebo.  However, nearly one quarter of patients treated with SSRIs showed a poorer response than patients treated with placebo. This suggests that in these patients, SSRI treatment actually interferes with their capacity to mount a placebo response, or perhaps even their capacity for resilience to depression [1]. This raises the critical issue of whether there are ways to identify those patients who would seem to be better off avoiding SSRIs and to divert these individuals to other treatments for their depression.

One factor reducing the effectiveness of antidepressants treatment is our inability to personalize pharmacotherapy, i.e., clinicians have no mechanism for predicting whether a particular patient will respond to a specific antidepressant. Instead, the process of matching patients and treatments requires a prolonged period of trial and error, delaying clinical improvement and increasing the risks and costs associated with treatment. Despite important progress in trying to identify depressed patients at high risk of treatment resistance [2], Psychiatry continues to lag behind other specialties like Cardiology and Oncology in which personalized treatment selection is far better established [3,4].

Developing more generally effective treatments and more rapidly effective treatments would be extremely important advances for public health.  However, in the absence of any such silver bullet, we advocate the development and implementation of innovative statistical methods to get the best available drug to each patient, as an interim solution. Personalized pharmacotherapy may still enable us to “save lives and restore function”. Giving up on these patients is not an option.

  1. Gueorguieva R, Mallinckrodt C, Krystal JH. Trajectories of Depression Severity in Clinical Trials of Duloxetine: Insights Into Antidepressant and Placebo Responses. Arch. Gen. Psychiatry. 2011;68:1227–37. doi:10.1001/archgenpsychiatry.2011.132
  2. Perlis RH. A clinical risk stratification tool for predicting treatment resistance in major depressive disorder. Biol Psychiatry 2013;74:7–14. doi:10.1016/j.biopsych.2012.12.007
  3. Kumbhani DJ, Wells BJ, Lincoff AM, et al. Predictive models for short- and long-term adverse outcomes following discharge in a contemporary population with acute coronary syndromes. Am J Cardiovasc Dis 2013;3:39–52.http://www.ncbi.nlm.nih.gov/pubmed/23467552
  4. Roobol MJ, Carlsson S V. Risk stratification in prostate cancer screening. Nat Rev Urol 2013;10:38–48. doi:10.1038/nrurol.2012.225

A pleasing look of truth

I wrote an almost identical editorial as this in 1991 (1). Covering the marketing of serotonin in 1997 (2), I cited Jerome Gaub’s 1767 opinion of Leibniz’ views on the relations of the mind to the body – it is a “fable whose novelty has recommended it, whose recommendation has spread it, whose spread has polished it, refined and adorned it with.. a pleasing look of truth” (3)

I use SSRIs.  Nevertheless I believe the SSRI era will soon stand as one of the most shameful in the history of medicine.  The shame does not stem from what pharmaceutical companies have done, which is just as might have been expected.  The shame will be seen to have arisen from the failure of doctors to know as much as they should have done about medicines they dish out so liberally.  A recent study showing how a dollop of neuroscience dressing can disguise otherwise meaningless material should be compulsory reading for doctors who are after all the true consumers of these drugs (4).

But perhaps an even greater shame will be seen to lie with the fact that this has been an era in which the bulk of publications on on-patent drugs in our best journals were ghostwritten, an era in which the journals refused to demand access to trial data as the price of publication – nowhere more clearly demonstrated than in the area of antidepressant studies on children.  It has been an era when industry has controlled journals, by spending money on some of them and by intimidating others into self-control.

  1. Healy D. The Marketing of 5HT.  British J of Psychiatry, 1991; 158, 737‑742.
  2. Healy D. The Antidepressant Era. Harvard University Press, Cambridge Ma 1997.
  3. Rather LJ. Mind and Body in 18th Century Medicine. Wellcome Historical Medical Library, London, P 17. 1965
  4. Weisberg DS, Keil FC, Goodstein J, Rawson E, Gray JR The Seductive Allure of Neuroscience Explanations. J Cogn Neurosci. 2008; 20, 470–477.

 

Meanwhile the patient information leaflets for pretty well all antidepressants and wannabe antidepressants like quetiapine as of today continue to promote versions of the Low Serotonin Hypothesis (thanks to Julie P for pointing this out).

Citalopram patient information leaflet

This should incense a lot of people.

Compulsory Vaccination and the Media – The Australian Experience

no vaccinations

Editorial Note: This is another post on the vaccination and censorship theme. Elizabeth Hart’s comments, over the past few weeks in response to some of the posts here, on efforts to stifle debate have been balanced and eloquent. Given the growing number of new journalism outlets, such as The Conversation, that portray themselves as tackling cutting edge issues fearlessly but in fact do no such thing it is a pleasure to help her get a message out that the editor of The Conversation has ignored.

Her interest in the issues began in an unusual way – after her dog died from a booster dose. Checking into it she became aware that pet vaccination is big business and one that has does more for the health of Vets than Pets. This is what radicalized her.

For the attention of:
Mr Andrew Jaspan
Executive Director and Editor
The Conversation

Mr Jaspan

I suggest there are serious problems of bias and censorship at The Conversation and I question whether you are fulfilling your charter.

The Conversation is very ‘pro-vaccination’, there is little in the way of critical analysis of vaccine products. For example The Conversation has helped promote HPV vaccination. I suggest HPV vaccination is controversial, see for example my summary which discusses the questionable way HPV vaccination was initiated in Australia when Tony Abbott was Health Minister in 2006.

The Conversation should be mindful that it has conflicts of interest in that it receives funding from universities that receive funding from the pharmaceutical industry for vaccine research. It seems to me that The Conversation is a marketing arm for the university and research sector.

Today comments were closed down on The Conversation article “Forget ‘no jab, no pay’ schemes, there are better ways to boost vaccination”.

Comments were also recently closed down on “Want to boost vaccination? Don’t punish parents, build their trust” and “’No jab, no pay’ policy has a serious ethical sting”.

I had posted detailed and referenced comments on these articles relevant to vaccine policy and practice, with some still awaiting a response. I had planned to post more comments, but I have now been thwarted in this regard, as ‘the conversation’ has been closed down. Opportunities for serious discussion on vaccination policy and practice are limited in the current hostile climate, and The Conversation does not help by curtailing debate.

Mr Jaspan, Prime Minister Tony Abbott’s announcement that vaccination will be compulsory to obtain family tax benefits is a very serious matter. We are on a slippery slope when governments mandate medical interventions such as vaccination.

There are serious problems with transparency and accountability for vaccination policy in Australia, and I have recently raised this matter with Prime Minister Abbott, see my letter dated 21 January 2015.  There is a serious problem of potential conflicts of interest and lack of disclosure by people influencing vaccination policy.

Tony Abbott, and Opposition Leader Bill Shorten, have reacted to the crude “No Jab, No Play” campaign by News Corp Australia media, e.g. The Sunday Telegraph.

It appears the vigilante pro-vaccination group SAVN (Stop the Australian (Anti) Vaccination Network) was also instrumental in this campaign. It also appears The Conversation is a supporter of SAVN, as evidenced by its publishing articles by self-avowed SAVN members, e.g. Rachael Dunlop and Patrick Stokes. It is notable that Patrick Stokes’ membership of SAVN is not included in the Disclosure Statement on his article “No, you’re not entitled to your opinion”.

I have tried to raise serious discussion about vaccination and individual vaccine products on The Conversation as my ‘activity’ illustrates, but I have often been impeded by followers of the SAVN who colonise comments threads on vaccination articles on The Conversation.

I was astonished today to discover that SAVN member Patrick Stokes has the ability to ‘hide’ (i.e. censor) comments on articles on vaccination on The Conversation, (see discussion between Patrick Stokes and Adam Bonner on “Forget ‘no jab, no pay’ schemes, there are better ways to boost vaccination”). Patrick Stokes is hardly an impartial arbiter, on what basis have you given him this power?

I also suggest there are serious problems at The Conversation in regards to proper disclosure of authors’ potential conflicts of interest. In this regard see my discussion with Professor C Raina MacIntyre on the “Want to boost vaccination? Don’t punish parents, build their trust” comments thread.

It is also ironic that experts on vaccination such as Professor MacIntyre and A/Professor Kristine Macartney do not appear to understand the difference between ‘vaccination’ and ‘immunisation’, and incorrectly use these words interchangeably, another point I raised on their articles. If ‘experts’ are so careless with the basics, what else are they getting wrong?

Mr Jaspan, compulsory vaccination is at odds with the requirement for ‘valid consent’ before vaccination, see Section 2.1.3 of The Australian Immunisation Handbook.

I suggest there should be an investigation into the aggressive campaign to make vaccination compulsory in Australia, and the tactics used by News Corp Australia, SAVN, and The Conversation.

Yours sincerely

Elizabeth Hart

http://over-vaccination.net/

Elizabeth Hart

The Couric Incident: HPV Vaccine & Mass Bullying

Katie Couric

Editorial Note: This post is by John Stone at my invitation. I am broadly speaking pro-Vaccination and reluctant to stray into the Vaccination Wars but the issues about free debate in recent posts seem most acute in this domain. Anyone who even thinks about questioning is vilified.

There are important public policy issues involved in MMR but less so with the HPV vaccine and the Flu Shot. For many working in healthcare, the Flu Shot is worrying. While in Britain it is not compulsory, there is a lot of pressure even though the case for having it seems weak. Elsewhere Flu Shots have been made compulsory. I’m sure many of us wonder what we would do if put on the spot like this.

Some of the strongest Vaccination advocates double up as Pro-Transparency campaigners. A Furor Vaxicanus just doesn’t seem to match up with transparency. John Stone is a Vaccine Safety Advocate who to my mind has also been one of the most reasonable voices commenting on some of the posts on this site over the last year. I don’t know John from a bar of soap (as we’d say in Dublin).

But I do know Rokuro Hama whose work John cites here. Rokuro and the group behind MedWatcher Japan are the most extraordinary courageous scientists and lawyers and all round safety advocates there are. Their MedCheck Bulletin is being made available in English for the first time this week and will be worth following – see MedCheck.

The point being raised by Rokuro goes to the heart of Evidence Based Medicine. When “girls” complain of serious problems after Gardasil or Cervarix, what weight do we put on what they say? What weight do we put on what we know about the biology of the HPV vaccine? What weight do we put on the fact that any effort to ask about this runs into media flak from SMC UK,  or SMC Australia, SMC Canada or SMC USA?      

Katie

In 2012 Katie Couric was the best paid media presenter in the United States, referred to as America’s Darling. Late in November 2013 it was announce that Couric was to give room in her ABC Television show Katie to the subject of vaccine injury from HPV vaccine. The result was an immediate furore.

Wiki recalls aspects of this historic episode:

In December 2013, Couric ran a segment on the HPV vaccine…which critics accused of being too sympathetic to the scientifically unsupported claims that this vaccine was dangerous…For example, Seth Mnookin accused her broadcast of employing false balance. In addition, Alexandra Sifferlin, of Time magazine, compared Couric to Jenny McCarthy, a well-known anti-vaccine celebrity…On December 10, 2013, a week after the original segment was aired, Couric posted an article on The Huffington Post responding to this criticism, in which she stated:

“I felt it was a subject well worth exploring. Following the show, and in fact before it even aired, there was criticism that the program was too anti-vaccine and anti-science, and in retrospect, some of that criticism was valid. We simply spent too much time on the serious adverse events that have been reported in very rare cases following the vaccine. More emphasis should have been given to the safety and efficacy of the HPV vaccines.”

The show which was falling in the ratings was due to be taken off the air the following summer was suddenly terminated 19 December, but not before a follow-up program had been screened giving all its room to the vaccine advocates. This was obviously a huge professional humiliation for Couric, but it was not the whole of the story: on Couric’s website a gigantic battle raged between families of injured people supporting the show and an angry mob of “skeptics” – many of them Australians – who ridiculed them. There were probably more than twelve thousand posted comments in all: more than a thousand apparently came from the keyboard of ubiquitous vaccine program advocate Prof Dorit Reiss, an academic (but not qualified lawyer) from Hastings law school in San Francisco, which is in partnership with Kaiser Permanente who were hired by Merck to study the post-marketing effects of their HPV vaccine Gardasil. Kaiser Permanente are also partners with Centers for Disease Control. While Reiss was more well-mannered than most of the vaccine advocates she dismissed any attempt to discuss vaccine injury as anecdotal, and her tactics were copied and deployed more brutally others. Many people, of course, speculated on how she could post so often while carrying out her professional duties at Hastings.

The episode also closely echoed a campaign earlier in the year to have Jenny McCarthy – widely labelled “anti-vaccinationist” – excluded from broadcasting, an episode which also involved Reiss and her colleagues at Voices for Vaccines. V4V also parades as not accepting pharma money but is in fact an off-shoot of Task Force for Global Health, which does accept pharma money, and is in partnership with the Centers for Disease Control. It is interesting to note that the chair of Task Force’s Board of Directors is leading Atlanta product liability lawyer Jane Fugate Thorpe.

The view from Japan

It should be evident, whatever the words of Couric after the event, that these are not stories about science asserting itself but of corporate leverage and internet bullying. The strategies and their effect say nothing about the quality of the science at all. They speak to the ethics of the proponents. It is particularly salutary to view these events against the background of a recent review of the evidence in the independent Japan Institute of Pharmacovigilance  bulletin Med Check – The Informed Prescriber (editor-in-chief Rokuro Hama). Hama is also a special advisor to the Cochrane Collaboration:

Harm of HPV

Abstract: Incidence of serious adverse reactions to HPV vaccine is 3.2% per year according to our  recalculation using the latest data (3,200 cases per 100,000 person years). This is almost equivalent to the incidence rate of serious adverse events within 1.2 years after the first vaccination (annual rate of 2.8%) reported in the randomized controlled trials (RCT) of Cervarix. In Cervarix RCTs, the excess incidence of serious reactions, autoimmune diseases and death after 3.4 years comparing with those during 1.2-3.4 years was calculated as 4,000 patients, 630 patients and over 100 deaths per 100,000 person-years respectively. These might also occur in Japan. As to the epidemiological surveys from Europe and North America that Japanese Ministry of Health, Labour and Welfare (MHLW) based on as the evidence for safety of the vaccine have flaws in their methodologies. One study confuses prevalence with incidence, and the other two have serious bias derived from “healthy vaccinee effect”. While there is no evidence confirming that HPV vaccination decreases incidence of and mortality from cervical cancer yet, supposing that the vaccine could halve the cervical cancer mortality, the expected maximum benefit would be two deaths per 100,000 person-years at the most. Hence, the harm experienced is overwhelmingly greater than the benefit expected.

The DisUnited Kingdom

In the United Kingdom media reporting of the harms of HPV vaccines has died out since 2009. An article in the Sunday Express by Lucy Johnston, much sneered at by Ben Goldacre in the Guardian, reported much the same thing as Med Check:

The cervical cancer vaccine may be riskier and more deadly than the cancer it is designed to prevent, a leading expert who developed the drug has warned. She also claimed the jab would do nothing to reduce the rates of cervical cancer in the UK. Speaking exclusively to the Sunday Express, Dr Diane Harper, who was involved in the clinical trials of the controversial drug Cervarix, said the jab was being ‘overmarketed’ and parents should be properly warned about the potential side effects.

It looks as if the article was withdrawn after a complaint by Dr Harper because she had alluded to the aggressive marketing of Gardasil by Merck in the US when the main topic was GSK’s Cervarix and this was not clear in the otherwise sound report. Be that as it may this is still a vaccine where the benefits are six years later still entirely theoretical and speculative and there are apparently many injured young women.

They and their families should be allowed to speak to the world without harassment. The public pay for these very expensive vaccines twice, first through the public purse, then through the harms they inflict. 

So Long and Thanks for all the Serotonin

Leunig depression cartoon

The BMJ article on Serotonin and Depression has stirred some interest. There are some highly technical comments on the BMJ site but of course the key point behind the piece is the rather obvious fact that twenty-five years ago many people were saying it was all a myth. The extraordinary Michael Leunig nailed it twenty years ago in the sketch above. (Leunig is wonderful across the board and razor sharp on medicine and mental health).

So did the BMJ know what they were doing when they sent the article to the Science Media Centre leading to the extraordinary new Switch on Anti-Depression (SAD) theory?

I thought they were making a mistake, but maybe not. The figures for impact from Altmetric show a lot of interest.

serotonin and depression

There are good grounds for a lot of people to be very angry.

The lawyers for several pharmaceutical companies for instance claim to be very angry and upset by recent posts mentioning that finding out about things such as the idea that lowered serotonin was a myth could provoke murderous fantasies in some people, most of whom would do nothing but simmer and seethe. They have been even more upset at the suggestion that while some of us can view all this as “academic” others might be radicalized and might storm the offices of pharmaceutical companies or journals.

See War on Civilization and Pharmaceutical Rape.

serotonin and depression

Our rulers are exquisitely aware of the potential for violence in those who are oppressed – those who are powered out. The violence inflicted on us – mostly by White Males – from Ferguson and Charleston to Baltimore playing out across television screens for the last year offers just one example. They expect Us to be as violent back as they are to US, and they tend to take pre-emptive action. At the first FDA Prozac and suicide hearings, the Chairman Daniel Casey wore a bullet-proof vest.

Clearly there has been no endorsement here for violent action but as one correspondent (MMC) put it, we sent Marlboro Man packing and something similar is needed here.

serotonin and depression

Better Die on your Feet than Live on your Knees sounds violent but was in fact the rallying cry of the Non-Violent Resistance movement that began in Ireland in the 1870s with Michael Davitt and later extended to Mahatma Gandhi and Martin Luther King.

If you want to see what is involved, fill a RxISK report on your behalf or someone close to you and take it to your/their doctor. There is a good chance you’ll find out just how violent the system is.

But keep knocking until you find a doctor who listens, let us know about them and we can build networks that can change medicine. It is only going to change from the Bottom Up.

Switch on Anti-Depression Today

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Science Media Centre roundup

Expert reaction to editorial on serotonin and depression as published in The BMJ (British Medical Journal)*

Dr Clare Stanford, Reader in Experimental Psychopharmacology, UCL, said:

“Prof David Healy’s article treads a path that is well-worn but out of date. He argues that selective serotonin re-uptake inhibitors (SSRI) antidepressants are used because of a pervasive myth that they boost serotonin levels, but this is something of a straw man. He makes the mistake of assuming that antidepressants reverse a functional abnormality in the brain that causes depression. Actually, the theory that low ‘levels’ of serotonin in the brain (whatever that means, functionally) causes depression died many years ago, in spite of the fact that a deficit in the synthesis of serotonin in the brain can trigger relapse of depression in some patients who are in remission: a fact which he also fails to mention.

“By contrast, the monoamine theory of ‘anti-depression’ is alive and kicking. There is plenty of evidence that SSRIs increase communication from neurones that release serotonin, as well as other monoamine transmitters, and that the ensuing downstream changes, such as creation of new neurons (neurogenesis) or modification of gene expression, can ameliorate depression.

“In short, SSRIs probably switch-on anti-depression, rather than switch-off depression (which could explain the rapid efficacy of ketamine).”

“I am sure that most clinicians and scientists will be dismayed that a flawed argument is used to underpin a suggestion that the use of older tricyclic antidepressants, which are so dangerous in overdose, is always preferable to the SSRIs.”

 So long and thanks for all the fish

The BMJ editorial that the Science Media Centre are referring to is Serotonin and Depression. It was originally called So Long and Thanks for all the Serotonin.

The first thing about the Science Media Centre comment is it’s wild. It completely misreads the editorial it’s commenting on – at no point does the editorial say I or any academic ever believed the serotonin hypothesis or changed our beliefs because it has now been debunked.

In an extraordinarily brief space Clare Stanford introduces a whole new concept Switching on Anti-Depression – that no one I know has ever heard of. And also manages to say that there was never any evidence for the serotonin hypothesis but that the serotonin hypothesis is right anyway.

It’s hard to believe Clare Stanford wrote something like this.

Which raises the question – who are the Science Media Centre? There were several posts last June about the Science Media Centre and Sense about Science – see Follow the RhetoricFirst Admit no HarmFollow the LawsuitFollow the Patient – cover aspects of what’s at stake. This is an organization that under the umbrella of taking a responsible approach to science ends up denigrating a lot of work or researchers that raise concerns about anything that might harm a corporation’s products.

Following the successful establishment of a UK SMC, comparable groups have been set up in Australia, New Zealand and Canada. See SMC Feasiblity Study for a document apparently stemming from a consultation exercise about what a Canadian SMC might look like.

Earlier this year a fuss blew up about coverage of HPV vaccines in the Toronto Star. The Star backtracked from its article, persuaded in part it would seem by input from SMC Canada that the Sixty cases of injured girls they had were just “anecdotes”.

The BMJ and other journals and media outlets divert a large amount of their content via the British SMC these days. They seem to think that this will increase coverage of their content – when the SMC is much more interested ordinarily to close down stories like this one rather than open them up. “We get our experts – who are usually media trained – to tell your journalists why you don’t want to bother with this story”.

Why do BMJ do this?

Who are the US equivalent of SMC?