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 Hiding the Bodies

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.

What’s Poisoning Health: The Crusoe Report 2

Mother Bird

How did we get to the point where healthcare itself is sick – where we have as Annemarie Mol brings out become consumers of healthcare products rather than people whom doctors and nurses care for when we are at our most vulnerable?

The breach of trust in modern healthcare comes close to a mother poisoning her babies in their infancy.

From luxury to basic

Back in the 1950s or 1960s depending on where you lived many of our parents thought about buying a car. It was a time when people didn’t need cars. They could get to work easily by bus, train or bike. The local shops were close so you could walk to get all the bits and pieces you needed or send a child who would usually run.

A car was a luxury.

But when enough people bought them, cars began to become a necessity. Cars made it possible to live further out of town and living further out you needed a car. Work was now too far away for a bus. The local shops weren’t local in the way they had been before. You shopped at weekends for the week in supermarkets and to get there you needed a car. And pretty soon the range of things in local shops began to seem limited.

As the number of cars grew, cities changed and the city itself became a vehicle to sell cars. This is what marketing departments dream of – where everything conspires to sell the product. Once our way of living meant we needed cars, companies could market types of cars without having to persuade you that you needed a car.

Cars can be a great thing. If we get taken seriously ill having an ambulance to get us to hospital quickly may be life-saving. But cars are also inextricably linked to a climate change, a permanent change in the world in which we live, a change of the kind that most of us as individuals find hard to see how we could influence.

Most of us find it equally hard to see how we can resist the climate change taking place in healthcare – fabulously illustrated this week with all the hype surrounding Solanezumab, which seems all about bolstering the share price of Eli Lilly and creating an industry that will persuade people over the age of 50 to start taking it and similar drugs, and pays little heed to the agitation and despair that may be occasioned in many, and the almost Witch in Macbeth like “Keep the word of promise to our ears while breaking it to our Hope”.

Car, TV and dinner

In much the same way as they did with cars, many of our parents in the 1960s wondered if we needed a TV. You didn’t need to have a TV back then but it just looked like a good idea. A little luxury.

But soon afterwards, when Kennedy was shot, and the news ever more often began to break on TV, life without a TV  became inconceivable to many.

It was the same with computers. Lots of us got told by real computer geeks in the 1980s, we didn’t need computers – for what we did all we needed were electronic typewriters. But as TVs hooked up with computers to create the informational super highway we have entered a world now where you absolutely have to be hooked up or you’re not alive. There isn’t an option. Everything conspires to sell the product.

The informational super highway looked close to adverse effect free until Edward Snowden revealed there could be risks to all this that we weren’t aware of. And of course if you are not hooked up you might get a bunch of US SEALs breaking down your door one day and killing you because, well if you aren’t hooked up to the superhighway, you must be up to something bad. (Monty Python’s Spanish Inquisition in modern form).

There seems to be no way back. Nothing the individual can do.

Slow medicine

Except as mentioned in Crusoe Report – 1, we have found ways to resist the Fast Foods from Supermarkets that also began to come on stream in the 1960s. They were once a luxury but now are seen as second rate.

In just the same way as for food, cars and televisions, back in the 1960s drugs were not the only answer to health care problems. They were a necessity in some cases like an ambulance is a necessity but in many other cases an option or even a luxury.

Doctors were people you expected would know you and your family and community and would know when to tell a teenager that being lovesick was not an illness or parents that adolescence was not pre-psychosis, or pregnant women that having an occasional glass of wine was probably a lot safer than having most drugs during pregnancy. They were people who had the common sense to rarely have you on several different drugs at the same time.

When effective drugs came on stream for the first time, many of these doctors realized that they were dealing with poisons because they saw side effects they had never seen before – the deafness that came from streptomycin, the limbless babies following thalidomide. These new tools needed to be treated with respect. This was not a world in which statistical benefits on concocted indicators would have appeared on the front page of newspapers.

We have been swept into a world where as opposed to being regarded as poisons that could be tremendously useful if used wisely, drugs are seen as fertilizers – to be sprinkled as widely as possible and begun as early in life as possible – solanezumab from birth?

Why not? If at a time of growing evidence that antidepressants cause profound problems for the children born of women taking them in pregnancy, there can be serious proposals to stamp these drugs with the image of a pregnant woman to overcome the scruples women might have about taking antidepressants during pregnancy, some academic out there can be relied upon to propose solanezumab from birth and newspapers to frontpage it and governments to support it rather than take action against the corporations producing the heavy metals that are likely causing the problem to begin with.

Just as cars and climate change are inextricably linked to oil, Fast Medicine and the changing climate in healthcare are inextricably linked to the controlled trial. Why engage with the changing the world when statistical surgery and data suction can give you figures to die for?

To be continued…

Restoring Health: The Crusoe Report 1

Crusoe map

The diplomatic thing would be to say there is some agreement between the Witty Report and this one. There is certainly some overlap in suggested solutions.

We could perhaps even agree that the real problem is the failure of medicine rather than pharma malfeasance. But the fault-line runs deeper.

There are two or maybe three forces, depending on the way you look at it, that have created the whirlpool into which we are now being sucked. One set of forces lies in the push to consumption and the other lies in the nature of modern medicines.

A patch of ground

Lots of us used to have a small patch of ground where we grew vegetables or herbs – or maybe just flowers. Some of us still do. We produce our own food rather than buy it. Not so long ago most of us used to produce food or at least ate food produced by people we knew or were not far removed from.

Until very recently, after we bought food, we produced our own meals and usually did so for families or for a few people at the same time. Now when we buy food it’s often in the form of processed meals where all you need to do is hit a button on the microwave. There is no production. It’s all consumption. We might once have produced the fire that cooked our food, it’s now bought in in the form of a microwave.

Producing meals did more than provide food.  It helped produce children and families and communities. Now the children will often come in from school to an empty house and press a button on the microwave. Who knows what’s in the meals. It might look like food but the food processing industry is increasingly getting away from anything that would have been recognized as food a few years ago. And eating meals this way is not producing a community.

Consuming convenience foods isn’t all bad. If you’re Beethoven absorbed in producing The Ode to Joy, being able to hit a button on the microwave might be a blessing – provided when you go to the supermarket to pick up something you’re not paralyzed trying to pick between exotic looking food packages that promise so much to the eyes but which you know will break their promises to your hope when you dig a fork into them.

Choice is one of the problems that consumption brings with it.

Annemarie Mol brings this out dramatically in The Logic of Care – one of the greatest books ever written about medicine.

I am pregnant and 36. A national committee of experts in the Netherlands where I live, has looked at the statistics and suggested that pregnant women over 35 should have an amniocentesis in case of Down’s Syndrome…  I follow the advice. I take a day off and go to the hospital… I lie down on the examination table and feel the ultrasound probe moving over my belly. Still in my field work habits, or just to break the silence, I say to the nurse who is preparing the long needle that will be inserted into my womb: ‘I hope it all goes okay.’ We both know that a small percentage of women have a spontaneous abortion as a result of the procedure. The nurse snaps back: ‘Well, it is your own choice.’

This is no longer a system in which people are working together to produce health. This is an industry with products available for consumption or not. It has extraordinarily sophisticated ways to persuade your doctor to consume its products by putting them in your mouth. Often close to forcing you to take them, most of which you don’t need.

Infertile

Very few of us can justify consuming Fast Foods by appealing to the symphony we are working on. Most of us consume our burger while consuming the latest Infotainment from systems that make information and entertainment. While the world may now have become a Village – just like food, the Village News is divorced from the connections that villages and food once had.  Its global gossip.

Even the so-called scientific articles about the drugs you might consume are infotainment divorced from the things that actually happened when a drug was given in a controlled trial. The articles are almost always written by a ghost-writer who has never prescribed a drug in her life.

There is a balance we all need to find between producing and consuming. If part of our time is spent working for someone else who is producing stuff for others to consume and the rest of our time is spent consuming yet other stuff, without us actually producing anything, we end up infertile – alienated, men would say – and probably unhealthy or at greater risk of becoming unhealthy.

Recipe

For millennia, the production of food and health were entwined. The Rx symbol for a prescription is an abbreviation of Recipe. The implication of the saying that it takes a Village to produce a Child is that the child is healthy. The knowledge of how to bring up children, ward off infections, alleviate problems using certain foods or herbs has been something passed down in families and communities. The pharmaceutical industry knows all about this. Trying to market ADHD, they found that the greatest barrier to getting treatment accepted was the presence of a grandmother who might caution against the child being treated because he’s just the same as his father was and look her son has turned out just fine.

The Village we live in now is not one in which one woman will tell another who has just been told that the bone scanner shows some bone thinning that getting out and running or working the garden is the best way to avoid fractures. It is a Village in which women will be pressured through fear to take bisphosphonates – among the most horrific drugs ever pushed – and will end up living greatly restricted and non-productive lives as a result.

Slow medicine

Back in the 1950s pharmaceutical companies participated in the production of health. New antibiotics saved lives and got people off sick beds and back to work. This was a health that made us wealthier. It made sense for nations to think about providing treatments like this for free.

But now companies produce medical goods for consumption. These come tagged as health-giving. But where once you took the risk that went with drugs when you were in crisis, now your healthcare provider likely summons you in for checks and puts you on treatments you didn’t ask for. Where once the norm was a short course of a treatment like an antibiotic until you were well and except in the case of insulin it was extraordinarily rare to be on a treatment for life, now it’s unusual to find people not on anything and very unusual to find anyone over 50 not on several drugs for the rest of their lives. We are harming ourselves to make drug companies healthy, and even the United States is working as hard as it can to make sure that as many people as possible get as much access to drugs as possible.

How did we get to this point?

For anyone who thinks the only way to fight the alienating forces of the modern world is to join ISIS or some other fundamentalist movement or to drop out of the Euro, the food domain shows that it is possible to fight back against “a sterile modernity”. Fast Foods don’t have it all their own way. The Slow Food movement – a movement that began in Southern Europe – looks like its here to stay. We need to building a Slow Medicine movement.

To be continued.

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.

Sense about Science: Follow the Lawsuit

Lawsuit

Editorial Note: This is a third in a series of posts about Sense about Science and Access to Clinical Trial Data that began with Follow the Rhetoric and followed up with First Admit no Harm.

There are some facts in the last few posts. There are also some extrapolations that may not be right.

Tracey Brown has gone on the Parliamentary Record to make clear what AllTrials are asking for – its not the data and not even full Clinical Study Reports. If this is the AllTrials position, it is easy see why GSK felt they could sign up. Even ghostwriting companies have signed up. But perhaps AllTrials have moved on.

It may be that the GSK periscope is an invention of subversives within GSK who saw a way to persuade AW1 that this would block access to the data for ever – all the time intending to gradually make it more and more user friendly and accessible. Perhaps AW1 is the mastermind trying to leverage things forward.

Partnering pharma

I’ve been a consultant to pharma and an expert for both plaintiffs and pharmaceutical companies in lawsuits. These contacts definitely bias me – as much by virtue of the people you meet as the money you might be paid. Under oath when asked if I’m biased I have always said yes – absolutely.

But I’ve never thought when it comes to science that it matters whether I or anyone linked to RxISK are moral or even nice people. Science might be better served if I’ve got some strange biases or am being paid to try and find the flaws in an argument. The key thing is access to the data, and given access to the data the more biases the better. Sometimes it takes a true weirdo to see how the data hangs together.

Being motivated whether because you have suffered an adverse event or because you’re being paid makes a difference to the effort you put in to solving problems. But at the end of the day, if you aren’t free to access the data it’s not science. If you’re a doctor and accept not being given access to the data – such as all doctors and statins – that’s quackery not medicine.

Science moves ahead, when people with different biases have their views challenged by the data. This is the very definition of science as opposed to philosophy or the humanities or business.

Medicine moves ahead when things happen to patients and when doctors and patients work to understand what has happened.

Business would likely do better in the long run if it built on this framework of doctors and patients working together to generate new knowledge. But instead at the moment business is not open for business on this issue. Why?

Study 329 & the lawsuit that didn’t bark

Linked to Peter Doshi’s RIAT initiative, a group of us are working on re-authoring Study 329 – close to the most famous RCT of all time. In this study GSK’s paroxetine (Paxil) was compared to imipramine and placebo in a group of children.

Those of us taking on this re-authoring job were among the first to be introduced to the GSMA-ESK scope – a periscope for looking at the data on which the GSK seagull regularly sits blocking the view.

The periscope gives the outside world the illusion GSK are offering transparency but it’s not meaningful transparency.

But periscopes are not the crux of the matter.

Damaging children

Children became suicidal on paroxetine in Study 329.

Before they had the results of Study 329, GSK had seen patients in clinical practice and clinical trials become suicidal and homicidal on paroxetine where the company had coded the event as caused by their drug. They knew the profile of what happens when an SSRI causes a problem. In their adult trials from the late 1980s, there was a doubling of the rate of suicidal acts on paroxetine compared to placebo.

They have run clinical trials that use the fact that paroxetine caused people to become suicidal to hide the fact that paroxetine caused people to become suicidal.

In breach of FDA regulations they had moved wash-out suicidal acts into the placebo column in clinical trials to hide the problem.

But in public, they have consistently denied there is a problem.

In Study 329, paroxetine didn’t work and wasn’t safe. Sally Laden ghostwrote the 329 paper and made paroxetine safe and effective. There were 22 authors on the authorship line, possibly none of which barring company personnel had seen the full dataset.

Informed consent?

The consent form says that in this trial you will be treated in just the same way as you would in normal clinical practice. Even from the protocol it was clear this was a lie.

The children taking imipramine were to be force titrated to 300mg where possible – this is just not normal clinical practice. This is double the standard dose for adults. It’s dangerous and seems designed to make imipramine look worse than paroxetine.

Even so imipramine wasn’t worse than paroxetine. There was a statistically significant elevation in the number of children on paroxetine who had a suicidal event in this trial alone compared to placebo.

In normal clinical practice if someone becomes suicidal on an SSRI it would be usual to make the link for them and tell them that in future they should try an antidepressant from another group. They are much more likely than the average person to become suicidal if exposed to another SSRI.

If the drug has caused the problem, it’s very important to their self-image that they know this. They are being done a further injury, in this case an unnecessary one, if this information is withheld from them.

Have any of the children who became suicidal on paroxetine been told that paroxetine may have caused their problem?

No.

Whose baby is it?

GSK say it’s the doctors – the non-authors of the paper – who know these children, whose responsibility it is to say whatever needs to be said to any of these children.

These are doctors who refuse to retract a paper that has been deemed fraudulent by New York State Attorney General Elliott Spitzer’s office. (Elliott Spitzer of Good Wife fame).

To come full circle, this is the paper that led to the data access story we have today. In response to a fraud charge in 2004, GSK agreed to post the CSRs on the company website in downloadable (non-periscope form).

Without Study 329 and the subsequent fraud charge and later $3 billion fine, GSK would likely never have felt the need to sign on to AllTrials.

Tomorrow and tomorrow and tomorrow

This is not a piece of history. This is our future.

Right now today GSK are refusing to tell the children who have been injured by their drug in Study 329 that they were injured by their drug. Tomorrow GSK will do the same and tomorrow and tomorrow.

Their drugs never injure people.

The reason GSK, Pfizer, Lilly and AbbVie don’t want anyone to get access to the data is so that no-one can access the damage. No-one can find out about the Dan Markingsons who die or are injured in company trials.

They are not doing this out of a concern for Dan Markingson’s confidentiality. They are doing it in order to avoid being sued.

This, Ben and Iain, is why I think GSK are playing the confidentiality card.

What do you think? And what should we do about it?

The cowardice of a pampered society

Tracey Brown and Dick Taverne of Sense about Science (SAS) have a publication:

Over-precautionary Tales: The precautionary principle represents the cowardice of a pampered society.

Is this Sense about Science?

What would the real SAS – the Short Arm Squad – say?

See SAS to Lisbeth

Sense about Science: Follow the Rhetoric

rhetoric

Editorial Note: This is the first of four posts about the link between Sense about Science and AllTrials triggered by the post Fucked and comments afterward by Ben Goldacre, Tracey Brown and others which raised these links.

My first contact with Sense about Science was linked to the Simon Singh affair. Singh had made some relatively innocuous statements about chiropractic and been sued for libel as a result. The case became a cause celebre – there was widespread support for his position among the scientific community and widespread concern about an inappropriate deployment of British Libel Law.

I supported him. I ended up on the mailing list for Libel Reform. As both of us had been on the receiving end of efforts to shut us up on academic issues, I met him when we were both invited to a workshop on academic freedom in 2011 in Cambridge.

It made sense that Singh’s efforts to change the libel laws was linked to an organization called Sense about Science, and by association Sense about Science seemed a good thing. It didn’t seem unreasonable to me either to have Sense about Science linked to AllTrials when AllTrials took shape.

The cowardice of a pampered society

Long, long before I had ever heard of Sense about Science I’d read Living Marxism and thought it a breath of fresh air. Marxism like this felt like it might even stand a chance in the marketplace.

Looking at the Sense about Science website now, I realise I know some of its trustees and even have stayed in one of their houses. The people I know are reasonable people. Others must think they are reasonable too as these trustees have ended up as Presidents of Royal Colleges for instance – very much part of the establishment as Dick Taverne the founder of Sense about Science is. I’d imagine Tracey Brown is engaging and interesting also.

Being a consultant to a pharmaceutical or tobacco company or the military is no bar to being engaging. I have several friends who have been consultants for all three and the greatest help in terms of adverse events has come from people employed within Pharma.

I’m sure Andrew Witty (AW 1) is also engaging and interesting. Guido Rasi of the European Medicines’ Agency is handsome, charming, engaging, sophisticated, dresses in great suits and had me believing him after a meeting at EMA eighteen months ago on data access that he wanted me to keep in touch.

And many of the views that Sense about Science espouse are ones that should be heard. They think the precautionary principle is over-precautionary – “Over-precautionary Tales: The precautionary principle represents the cowardice of a pampered society”. That people who smoke should be responsible for their own behaviour. That we need GM foods. That climate change has been overplayed.

The problem arises with views that aim to capture or pre-empt debate and rather than being views for debate are part of an agenda that is being implemented. Not that being part of an agenda to be implemented is wrong either, but a political program deserves more scrutiny and anyone engaging with such views deserves to know that the person opposite them is not holding incidental views. It’s good to know when you’re dealing with a believer.

Risk management

The common focus in Sense about Science views is on risk – the risk to corporations and other interested parties such as governments of things being perceived by the public as risky rather than the risk to you and me from treatments or climate change.

Within the pharmaceutical domain, the luckiest break for the Sensible Scientists was Andrew Wakefield (AW 2). Wakefield’s paper on the risks of the MMR vaccine gave the British and other governments a wonderful example of how a scientific paper can cause a huge scare that threatens lives and corporate profits. Managing the fall-off in vaccination uptake was a significant national event.

While many people fought shy of the MMR vaccine, perhaps even Tony Blair himself, this was an event that the public – me included – could readily understand and we were quite prepared to turn on Wakefield as the perpetrator, the bogeyman, the visible manifestation of why we needed sense about science.

In the UK, the most potent weapon on the lips of the academic puppets sitting on corporate hands ever since has been that Godlee or Jefferson is another Wakefield. In the fuss about the BMJ’s article about the hazards of statins a few weeks ago, Rory Collins, one of the industry associated statin supporters, accused Fiona Godlee, the editor of BMJ, of potentially being far worse than Andrew Wakefield.

Elsewhere in the world, where AW is not a household name, the accusation is one of being an anti-vaccinationist or being someone who pays heed to the TV actress Jenny McCarthy.

Many of the people I know who seem to have been approached to be a Trustee of Sense about Science would have readily signed up to an organization offering to bring sense to bear on scientific issues like this. I might have signed up myself if approached and unaware of its background.

Ben Goldacre began life taking on health fads and health scares like MMR (AW 2) for which he got a GSK sponsored prize (AW 1).

Fighting fire with fire

But something else has happened over the last decade since Sense about Science has been set up.

Doctors in general like a quiet life. Not unreasonably, they assume that what the regulators and their professional bodies say on issues are likely to be right. Doctors are also horribly vulnerable to complaints from patients or colleagues should they speak out about something. In addition for the last two decades, many of them are likely aware that they increasingly face a world where if they speak up about some treatment related problem – to do with Vioxx, Avandia, or SSRIs – they will be subject to vituperative rhetoric and be branded as being in league with the forces of darkness – in a way that would never have happened twenty years ago.

The rhetoric gets at doctors where it hurts. It’s been designed by people who understand doctors better than they understand themselves, and know just what to say to make them feel uncomfortable.

Some of the Sense about Science trustees that I know who have been subject to death threats from people unhappy with their scientific views could be forgiven for thinking its maybe no bad thing to fight fire with a little bit of fire.

Before coming to AllTrials, two housekeeping points. Another important and increasing criticism is that critics are anti-capitalist. We’ll tackle this in a third SaS post.

Yet another defence has been that raising questions linked to Sense about Science is just a smear tactic. This will be tackled in a fourth SaS post.

The AllTrials coalition

AllTrials is a coalition between the BMJ, PLoS, the Cochrane Collaboration, Sense about Science, the Centre for Evidence Based Medicine (Carl Heneghan), the Dartmouth Institute for Health Policy and Clinical Practice, the James Lind Library (Iain Chalmers) and Ben Goldacre.

It called for the registration of all trials and their results to be shared as open data. It probably took off so well because this ask was simple and vague. Even GSK could sign up.

In embryo this looked like a great thing. The idea that getting only the appearances of greater access might be harmful is too subtle a point for most people. And we don’t like to think that good intentions can be hazardous.

From outside it’s hard to know what might be going on in the AllTrials bedroom. The BMJ, and PLoS can be expected to go along with proposals that ask for the registration of trials and it’s hard to argue against greater access to the data from trials. Their editors, Fiona Godlee and Virginia Barbour, working within constraints have taken their journals to places no man would ever dare.

I know nothing about Dartmouth or the CEBM.

Cochrane is a mixed bag – Peter Gøtzsche, Tom Jefferson and Peter Doshi have done more to drive this debate forward than anyone else.

The Sense about Science website is a masterpiece of non-direction but their track record suggests a clear focus even if all their trustees don’t realise it. GSK, one of the major signatories to AllTrials, have an even more focussed agenda.

When the music stops

Iain Chalmers and Ben Goldacre are the two who are hardest to read. It came as a huge surprise to many to see Iain co-author an editorial with Patrick Vaillance a senior figure within GSK, accepting the view that patient level data was out of bounds.

Ben has eloquently told Pharma on many occasions that people will simply not accept the sequestration of data. But what is data?

For AllTrials and EMA it now looks like Clinical Study Reports (CSRs) are data. This is likely not what most people understand by data. It’s certainly not my understanding.

CSRs are a company’s first edited report on what the underlying data looks like – the point at which they begin to mislead themselves. If companies know these and only these are going to be made public they will very rapidly become tools designed to mislead the rest of us. These are the documents that even when the company didn’t think they might become public have already coded suicidal events as episodes of emotional lability. Without access to the data its impossible to know what is reliable and what isn’t.

The data are contained in what are called Clinical Record Forms (CRFs).

After a study is finished, a company will ghostwrite an article like the infamous Keller et al article in Study 329. For every page of this article there will be roughly 100 pages to the CSR from which it is drawn – or 500 pages if the company is being fully transparent. Behind this lie the CRFs. For every published page in a standard article there are between 5000 – 10,000 pages of CRFs. This is as close to the data – the patients – as we are ever likely to get. In some cases the real data never exist.

Here and here are EMA’s proposals about how CSRs will be redacted, and here is Ben’s acceptance of this redaction and apparent buying the line that CSRs contain commercially confidential information.

At the moment with the music stopped Iain and Ben look like they are in bed with Tracy, Guido and Andrew. Are they in bed just to stay in the game, still hoping to make the right call at the right time?

The time is now.

Fucked

Editorial Note: Apologies for the Language

A year and a half ago this blog ran a series of posts about access to clinical trial data – reporting on how industry were going to engineer the appearances of transparency. See Won’t get Fooled Again, Access to Clinical Trial Data, and The Data Access Wars.

Do academics have wild dreams?

Several months later, soon after being fined $3 Billion, GSK trumpeted their endorsement of transparency by signing up to the AllTrials campaign and declaring their intention to put in place a method to allow researchers access to clinical trial data that would go beyond the wildest dreams of researchers. See April Fool in Harlow, and GSK’s Transparency and Access Journey.

Its all to easy to imagine a marketing department figuring that academics don’t have very wild dreams.

When GSK signed up to AllTrials Ben Goldacre rolled over and purred. The BMJ featured Andrew Witty on their front cover as the candidate of hope.

Rain on the parade

In contrast, on this blog, 1boringoldman and on RxISK a small group have warned consistently that this was not good news. That what would be put in place was a mechanism that gave the appearances of transparency but in fact would lock academics into agreeing with GSK and other companies as to what the outcomes of their trials have been.

No one wanted to rain on the AllTrials parade – it never seems like a good idea to fracture a coalition. RxISK put the AllTrials logo on its front page.

Not content with a few academic ghost authors, GSK’s maneuver has put industry well on the way to making Academia a ghost, a glove puppet manipulated by company marketing departments.

Meanwhile Iain Chalmers co-wrote an editorial with GSK endorsing the GSK approach (The Attitude of Chicks to Trojans and Horses) and the British Government produced a document on clinical trial data access that could have been written in GSK central.

The GSMA-ESK model

The great hope for those dismayed at all this lay with EMA who following Peter Gøtzsche’s initiative and a European Ombudsman’s ruling looked like a beacon of hope. But this week EMA has come out and said it is going to put in place the GSK model of data access.

Everyone is in a spin. AllTrials are asking for more donations to continue their successful campaign.

As someone who has been working the GSK system, I can say with confidence that this is a disaster.

The key thing that companies are trying to hide are the data on adverse events. To get to grips with the adverse events in a clinical trial is a bit like playing the children’s game Memory – where you have a bunch of cards with faces turned face down and you get to pick up two and then have to remember where in the mixture those two were when you later turn up a possible match.

Patterns of deception

In the same way, picking up adverse events is about recognizing patterns – patterns of events, and patterns of deception.

To do this you have to be able to spread maybe a hundred documents out over a big area and dip back into them if something in one document reminds you of something in another. The new GSMA-ESK remote access system simply won’t allow this.

Not only will it not allow this but it is about to make things far far worse than they are at present.

At the moment when it comes to studies like Study 329, GSK have been stuck by a Court order with putting the Company’s Study Reports up on the web where they can be downloaded and pored over – all 5,500 pages of them for Study 329. They have refused to do the same for the 77,000 pages of raw data from Study 329, making it available to a small group of us through a remote desktop system.

For all other trials – future and past – investigators won’t even be able to get the Company Study Reports in usable form. They too will only be accessed remotely.

For anyone who wants to look at the efficacy of a drug this might just about work for outcomes that involve rating scale scores or lipid levels. The efficacy of drugs is pretty well all that most Cochrane groups, Iain Chalmers and Ben Goldacre are interested in. The Cochrane exceptions have been Tom Jefferson, Peter Doshi and the Tamiflu group.

But this system is a bust when it comes to adverse events and it won’t work if the efficacy outcomes are in any way complex.

What can be done?

The first point to make is this. Clinical trials are not all they are cracked up to be. Even if well designed, not using surrogate outcomes, of sufficient duration, done on patients who actually exist, and not written up by ghostwriters, clinical trials systematically get the wrong answer, especially on adverse events.  Clinical trials are the gold standard way to hide adverse events.

One of the risks of the data access wars is that it will put an unwarranted premium on clinical trials and their data – and in this way play straight into pharma’s hands. This is what led “Crusoe” to warn Peter Gøtzsche a year ago that his data access crusade might backfire – See Marilyn’s Curse.

Let’s make no mistake here – it’s morally indefensible that there is not full access to the data from scientific experiments. In this sense Peter is right and his outrage is well-placed and close to magnificent.

But, ceteribus paribus, it would be better for mankind if all clinical trial data were sunk to the bottom of the sea rather than being made visible to academics stuck in a submarine and only able to view things through a periscope, which is what the GSMA-ESK system offers.

It might have been better if AbbVie had won their legal action. Instead EMA’s accomodation with them has fucked us all.

Rape is a loaded word these days but in so far as what is happening is an abuse of consent and will primarily do harm to women and children it perhaps come close to being the best word. Consent processes in clinical trials were about telling you you were on a new drug that might be dangerous or might be involved in a marketing trial. Instead they have become a way for companies to justify hiding your data on the basis of a confidentiality clause they have slipped into the forms. See When Does Yes Mean No. Iain Chalmers, Ben Goldacre and AllTrials appear to have signed up to this.

Whether raped or fucked, the Dan Markingson case is a stunning example of what has gone wrong – the Markingson petition is probably a much better petition to sign if you really want to save yourself and others you know and love than the AllTrials one.

Let’s do the AbbVie again

Second the data companies are really hiding is their adverse event data. There are other ways to collect adverse event data.

We invited you 18 months ago to join an AbbVie – Let’s Do The AbbVie Again. This Irish invention is the reverse of a boycott – another Irish invention.

A boycott of a company’s drug would mean you don’t get the benefit. If you decide to AbbVie a company’s drug, you – we – can all make these drugs better by reporting on the effects they have.

Company efforts are geared more than anything else to ensuring that doctors and patients don’t report adverse events or ensuring that these events don’t register. If you really want to get up their nose, if you really want to send the marketing departments into a spin, if you really want a company CEO to blow a fuse, this is what you need to do.

Companies want to transform adverse events into non-information. You can stop this happening. If an event happens to you on a drug, you are in possession of the missing information. It’s our tolerance of the patients who have Disappeared in clinical trials that is killing medicine as we have known it.

AbbVie with us and then sit back and take pleasure in a marketer who says “Thank you for helping us make our drugs better – without you we couldn’t do it”.

Now there is of course a huge conflict of interest here. RxISK.org was set up precisely for this purpose – to register adverse events. But we will hand all events on to FDA or MHRA or whoever you want us to. What we will also do though, and we invite any doctors or others out there with backbone to help us do it, is to decide when a drug is causing an event – this is something no regulator will ever do for you or for anyone.

Boycott

The other option is a Boycott. Doctors could refuse to prescribe drugs for which the information was not fully available. The Panalba and Thalidomide cases have shown that this is the one thing industry is scared of – Report to the President.

If I made claims about a drug to my colleagues but refused to show them the data, they’d have no problem telling me to get lost. I’d be boycotted from here to kingdom come. But when it comes to industry, 99% of doctors lack balls.

Doctors have been given a license to degrade us by treating us like addicts – the origins of prescription-only status. They have been given a license to print money – we can only get our drugs through them. The very least they could do in return is show some backbone.

But this is a decadent situation and decadence rarely breeds courage.

Emily’s balls

The boycott was likely invented by Irish women. The Abbvie was too. There is one bulwark still standing in the way of GSMA-ESK. It’s the European Ombudsman, an Irish woman – Emily O’Reilly.

Lullaby

childrens books

Editorial Note: Another study published this week suggests that the issue of birth defects on antidepressants rather than suicide or homicide may yet end up as the Mark of Cain by which these drugs are remembered. This post first appeared on RxISK.org and can be viewed here.

Hush, little baby, don’t say a word,
Mama’s gonna buy you a mockingbird.
If that mockingbird won’t sing,
Mama’s gonna buy you a diamond ring
If that diamond ring turns brass,
Mama’s gonna buy you a looking glass.
If that looking glass falls down,
All the better for the sweet little babies in town.

In the beginning

The first report of antidepressants causing birth defects goes back to 1972.

In the 1980s the companies making SSRIs undertook animal studies to look at the behavioral effects of antidepressants on the offspring of animals given the drugs during pregnancy. These were difficult studies to do because the companies at the same time had to avoid generating evidence of major birth defects, when there was good reason to think the drugs might cause birth defects. The studies that were done gave evidence of both developmental delay and birth defects. This evidence never saw the light of day.

Then a strange study appeared from Motherisk in Toronto claiming there were no behavioral problems in children borne to mothers on SSRIs. The methods used were just what you might have used if you didn’t want to find a problem. This was such an unconvincing study it almost came labeled with Smell a Rat.

In the last five years several decently done studies have been published all pointing to problems such as increased rates of Autistic Spectrum Disorder (ASD) or Developmental Delay (DD) in children born to mothers who have been on antidepressants, primarily serotonin reuptake inhibitors through pregnancy. Aside from the Motherisk study, there is no study saying there is no problem.

A new study and new concerns

On Monday a new study by Harrington and colleagues was published with the finding that there is a three to four-fold increase in the rates of Autistic Spectrum Disorder and Developmental Delay in children, especially boys born to mothers who have been on antidepressants through pregnancy. This has already had considerable media coverage.

There are further studies with comparable findings in the offing.

Added to all the evidence from animal studies and epidemiology studies that SSRIs double the rate of major birth defects, double the rate of miscarriages, and increase rates of voluntary terminations, this extra evidence really suggests that these drugs should all be pregnancy category D if not category X.

Not only this but it looks as though the SSRIs may redefine what it means to be a teratogen. Other teratogens produce their effects in the first trimester of pregnancy when organs are first being formed. But it looks like antidepressants used in the third trimester can lead to autistic spectrum disorder and developmental delay.

Pregnancy category D

Pregnancy drug category C which is what most antidepressants currently are means ‘Use with Caution’. Category D means ‘Do Not Use’. Here’s what a Category D warning would look like:

Category D: (See WARNINGS sectionPregnancy Teratogenic Effects: Pregnancy).

SSRIs can potentially cause fetal harm when administered to pregnant women. If LEXAPRO-PRISTIQ-CYMBALTA  is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Because of experience with other members of the SSRI class, LEXAPRO-PRISTIQ-CYMBALTA is assumed to be capable of causing an increased risk of congenital abnormalities when administered to a pregnant woman during the first trimester. Because use of these drugs is rarely a matter of urgency, their use during the first trimester should almost always be avoided. The possibility that a woman of childbearing potential may be pregnant at the time of institution of therapy should be considered. Patients should be advised that if they become pregnant during therapy or intend to become pregnant they should communicate with their physicians about the desirability of discontinuing the drug.

When these issues have come up before on RxISK we have tried to engage Mumsnet and anyone else who thinks that putting material like this into the public domain is just scare mongering. We should be much more responsible. (See I’m not Pre-Pregnant, I just have a Womb, and linked posts – The Dark is for Mushrooms, not for Women, and Preventing Precaution and Mumsnet).

A warning like this does indeed look off-putting and scary. There has been almost no response from women.

Why benzos and not SSRIs?

But the extraordinary thing about it is that this is the warning that’s on benzodiazepines in the USA. Substitute benzodiazepine for SSRI and XANAX for LEXAPRO-PRISTIQ-CYMBALTA and you have the XANAX warning.

Even more amazing is the fact that there is not a fraction of the animal studies or epidemiological data pointing to pregnancy risks on benzodiazepines comparable to the data there is for the antidepressants.

The MHRA is Britain’s FDA equivalent. Asking them about the pregnancy risk of benzodiazepines turns up no evidence in the last 20 years that they are aware of indicating a risk from benzodiazepines. According to MHRA, they have been advising women not to take benzodiazepines from the get-go and the warnings were strengthened when the marketing of SSRIs got into full swing in the 1990s and SSRI companies were doing a great deal to blacken the name of the benzodiazepines.

There is nothing about the UK warnings that looks half as scary as the FDA warning, but FDA provide no link to the evidence base for this warning.

The best explanation for this warning is that its a hang-over from efforts twenty years ago by SSRI companies to elimination benzos and replace them with a group of drugs that cause as many if not more problems. This was a supremely successful marketing campaign to make Valium seem darker and scarier than Prozac. On the street Valium sounds almost as dangerous as Heroin – while within mental health care if forced to take Valium or Prozac for life, nine out of ten staff would take Valium. Prozac – and other SSRIs – are by far the darker drugs.

Meanwhile back in Denmark

Meanwhile Back in Denmark, as elsewhere, there is a drive to screen all pregnant women for depression and get them on antidepressants. Women are being bullied and harassed into treatment by unfounded claims that leaving a depression untreated will cause birth defects and developmental delay.

Peter Gøtzsche, one of Denmark’s leading epidemiologists, a longtime skeptic about many screening programs, and more recently someone who has been publicly wondering whether psychiatry needs to be compulsorily detained because of the risk it poses to people in general (Psychiatry Gone Astray), gave a lecture 6 months ago to Danish doctors on the insanity of screening for depression in pregnancy.

A video of his lecture can be found here. The Transcript of the screening part is here. The section on screening is almost at the start. The horror on the video wonderfully transcends translation and perhaps is all the better because of Peter’s lack of training as a stand-up comedian.

Hush little baby don’t you cry
Momma’s gonna buy you an SSRI.

Get Real: Peter Gøtzsche Responds

Editorial Note: Two weeks ago we ran Peter Gøtzsche’s Psychiatry Gone Astray. There was a context – a Danish doctor had been found responsible for the suicide of a young man put on antidepressants. This and Peter’s article stirred up debate in Denmark drawing a hard to credit defensive response from senior Danish Psychiatrists.

Peter’s blog was critiqued by George Dawson on Real Psychiatry. An anonymous tweeter @psycrit said “a post about @DrDavidHealy‘s nuttiness turns into an amazing discussion, with unbelievably high-quality comments”. Apparently my nuttiness lies in having anything by Peter G on the site.

There should be new word for this kind of ad hominem attack – which also flavor’s Dr Dawson’s post. It’s ad hominem by association or ad parahominem.

A number of colleagues such as Barney Carroll thought Peter’s piece was over the top. There are major differences between Peter and I – he locates the problem within industry in a way that I don’t. But the correct analysis is not always what carries the day. People like Peter, Ben Goldacre and Bob Whitaker can be effective – the worry then is whether the change they deliver is the right one – are GSK really one of us now?

History will recognize Peter as the man who, among other achievements, prised open the question of access to RCT data, forcing the European Medicines’ Agency to open up their files. His motivation to do this came in part from a discovery of how appallingly bad the state of affairs in psychiatry IS. How almost all trials on which the field depends are ghostwritten, all data withheld and all dissent suppressed. Whatever it is this is not science and there has to be a good chance it’s killing and disabling more people prematurely than it helps.

What you hear from Peter is a howl of horror. The rest of us have got so inured to the situation we can no longer see how bad it is. The Allied troops arriving at concentration camps must have reacted the same way, where many inmates had gotten used to the situation.

It’s quite possible as George Dawson says that psychiatrists could make equivalent comments about other concentration camps in internal medicine. That doesn’t excuse what’s happening in either psychiatry or the rest of medicine. It’s time to Get Real or at least recognize how an outsider from the media or elsewhere would react if they found out what is really going on.

Peter’s response to George Dawson is here.

Unwarranted criticism of “Psychiatry Gone Astray”
Peter C. Gøtzsche Copenhagen

On 6 January 2014, I published the article “Psychiatry Gone Astray” in a major Danish newspaper (Politiken), which started an important debate about the use and abuse of psychiatric drugs. Numerous articles followed, some written by psychiatrists who agreed with my views. For more than a month, there wasn’t a single day without discussion of these issues on radio, TV or in newspapers, and there were also debates at departments of psychiatry. People in Norway and Sweden have thanked me for having started the discussion, saying that it’s impossible to have such public debates about psychiatry in their country, and I have received hundreds of emails from patients that have confirmed with their own stories that what I wrote in my article is true.

Three months earlier, I gave a one-hour lecture about these issues in Danish, which was filmed and put on You Tube with English subtitles: http://www.youtube.com/watch?v=i1LQiow_ZIQ. After only two weeks, it had been seen by over 10,000 people from over 100 countries.

What this tells me is that I must have hit something that is highly relevant to discuss. I therefore translated my article and David Healy uploaded it on his website: http://davidhealy.org/psychiatry-gone-astray/. It also came up on www.madinamerica.com, the website of the science journalist Robert Whitaker, who gives many lectures for psychiatrists and whose recent book, “Anatomy of an epidemic,” was an eyeopener to me, as was David Healy’s “Let them eat Prozac.”

On 8 February 2014, psychiatrist George Dawson wrote “An Obvious Response to ‘Psychiatry Gone Astray“‘ on his blog. Having read Dawson’s blog, I feel the final sentence in my article, which was not translated into English, becomes relevant: It will be difficult when the leaders in psychiatry are so blind to the facts that they will not see that their specialty is in deep crisis. It is also relevant to quote the opening sentences in my acticle:

“At the Nordic Cochrane Centre, we have researched antidepressants for several years and I have long wondered why leading professors of psychiatry base their practice on a number of erroneous myths. These myths are harmful to patients. Many psychiatrists are well aware that the myths do not hold and have told me so, but they don’t dare deviate from the official positions because of career concerns. Being a specialist in internal medicine, I don’t risk ruining my career by incurring the professors’ wrath and I shall try here to come to the rescue of the many conscientious but oppressed psychiatrists and patients by listing the worst myths and explain why they are harmful.”

I listed 10 myths in my article, which I shall repeat here, and will now rebut Dawson’s criticism of them. Dawson says that the myths I describe “are mythical in that they are from the mind of the author – I know of no psychiatrist who thinks this way.” As I have just indicated, there is no person as blind as he who will not see and no psychiatrist as deaf as he who will not listen. Everything I wrote in my article has been documented, most of it in my book “Deadly Medicines and Organised Crime,” and many responses on his own blog shows Dawson to be wrong.

Myth 1: Your disease is caused by a chemical imbalance in the brain

Dawson: “This is a red herring that is frequently marched out in the media and often connected with a conspiracy theory that psychiatrists are tools of pharmaceutical companies who probably originated this idea. What are the facts?”

The facts are abundant. Many papers written by psychiatrists have stated this, and it is also what most patients say that their psychiatrists tell them. I have lectured for patients and asked them, and every time most patients say they have been told exactly this hoax about a chemical imbalance. The drugs don’t cure a chemical imbalance; they create one, which is why it is difficult to get off them again.

Myth 2: It’s no problem to stop treatment with antidepressants

Dawson: “Another red herring.”

Dawson agrees that there may be “difficulty discontinuing antidepressants” but then tries to get off the hook by noting that this can also be seen with other drugs than psychiatric ones. Allow me to say that one illegal parking doesn’t make the next one legal. Dawson agrees with me but tries to say he doesn’t. Pretty weird.

Myth 3: Psychotropic drugs for mental illness are like insulin for diabetes

Dawson invents strawmen here, e.g. by saying “Am I getting prednisone for my asthma because I am deficient in prednisone?”

That’s totally off the point, as no asthma specialist would be as silly as many psychiatrists are. Again, most patients have told me that this is what their psychiatrists tell them, and professors of psychiatry have also propagated the myth publicly, e.g. in numerous interviews and in articles written by themselves.

Myth 4: Psychotropic drugs reduce the number of chronically ill patients

Dawson: “I don’t know of anyone who has actually suggested this.”

Pardon me, but Dawson must be both blind and deaf to have escaped this, which psychiatrists say and write all the time. Dawson finds the argument “demeaning to anyone with a severe psychiatric disorder who is interested in staying out of hospitals and being able to function or trying to avoid a suicide attempt. Being able to adhere to that kind of plan depends on multiple variables including taking medications,” and he furthermore says that, “It is reckless to suggest otherwise and any psychiatrist knows about severe adverse outcomes that have occurred as a result of stopping a medication.” Whitaker has documented at length in his book that the increased use of psychotropic drugs has led to an explosion in the number of chronically ill patients on lifelong disability pension and he has also explained and documented the mechanisms behind this.

Myth 5: Happy pills do not cause suicide in children and adolescents

Dawson believes that I reveal my “antipathy to medication used by psychiatrists” by referring to antidepressants as “happy pills.”

Dawson plays the antipsychiatry card here, which is the ultimate trump card psychiatrists use when they have no valid arguments. I consider the term happy pill extremely misleading, as, for example, half of those treated get their sex life disturbed, which has led me to call them unhappy pills whose main action is to ruin your sex life. However, since everybody uses the term (instead of the cumbersome “selective serotonin reuptake inhibitors”), including many psychiatrists, I also use it. Dawson says he has never met a psychiatrist who calls antidepressants “happy pills,” but what can you expect of a man who seems to be both blind and deaf? Dawson claims that “saying that happy pills are a cause of suicide is the equivalent of saying that “sugar medicine” (insulin) is a cause of hypoglycemia that harms children and therefore it should not be prescribed.” What exactly does Dawson mean by this smoke and mirrors? It is a fact, which the FDA has demonstrated, that SSRIs increase suicidal behaviour up to age 40, and package inserts warn about the risk of suicide and recommend not using SSRIs in children and adolescents. Then why do psychiatrists use them in this age group? To use Dawson’s allegory, we wouldn’t use insulin if it increased blood glucose and the risk of dying in a diabetic coma.

Myth 6: Happy pills have no side effects

Dawson’s naivity with respect to the drug industry is heartbreaking. About the incidence of sexual problems caused by SSRIs, he refers to FDA data. But what is buried in FDA archives is not what the companies tell doctors. It is true when I write that companies have said that only 5 % get sexual problems. The true rate of sexual problems is above 50%, and there are reports that these disturbances might become permanent, which agree with rat studies where the rats showed less interest in sex long after they had come off the drugs.

Myth 7: Happy pills are not addictive

Dawson says that ‘antidepressants aren’t addictive’.

They surely are, as half of the patients have difficulty coming off them again even with slow tapering and experience similar symptoms as patients who try to come off benzodiazepines.

Dawson claims that SSRIs have no street value and will not make you high, and that my comparison with amphetamine is completely off the mark and consistent with my general lack of knowledge of addiction. Allow me to say that there are striking similarities between the effects of amphetamine and SSRIs and also to quote a few sentences from my book:

“In 2004, the FDA issued a warning that antidepressants can cause a cluster of activating or stimulating symptoms such as agitation, panic attacks, insomnia and aggressiveness. Such effects were expected, as fluoxetine is similar to cocaine in its effects on serotonin (73). Interestingly, however, when the EMA in 2000 continued to deny that the use of SSRIs leads to dependence, it nonetheless stated that SSRIs ‘have been shown to reduce intake of addictive substances like cocaine and ethanol. The interpretation of this aspect is difficult’(77). The interpretation is only difficult for those who are so blind that they will not see.”

“Until 2003, the UK drug regulator propagated the falsehood that SSRIs are not addictive, but the same year, the World Health Organization published a report that noted that three SSRIs (fluoxetine, paroxetine and sertraline) were among the top 30 highest-ranking drugs for which drug dependence had ever been reported (62).”

Myth 8: The prevalence of depression has increased a lot

Dawson and I seem to agree that there is hardly any true increase in the prevalence of depression. The apparent increase is caused by lowering the criteria for what is considered a depression. I also agree with his argument that since 80% of antidepressants are prescribed by primary care physicians we might call this “Primary care gone astray.”

Myth 9: The main problem is not overtreatment, but undertreatment

Dawson’s main argument is that we should not blame psychiatrists for the overtreatment but the primary care prescribers. Well, they are certainly to blame but so are the psychiatrists. Although the Danish National Board of Health recommends that only one antipsychotic should be used at a time, this is not the case. According to a report by the Board of Health, only half of patients with schizophrenia received one antipsychotic drug, one third got two drugs, and the rest got three, four or even more drugs.

Myth 10: Antipsychotics prevent brain damage

Dawson calls my arguments “More rhetoric.”

They are not. Leading psychiatrists have written this and tell their patients that they need to take the drugs in order to prevent brain damage, although it has been documented that antipsychotics cause brain damage in a dose-dependent manner. Dawson continues his futile attempts at killing the messenger: “He also talks about antipsychotic medication with the arrogance of a person who does not have to treat acutely psychotic people and incredibly talks about these drugs killing people.” These drugs do kill people. Doesn’t Dawson know this? I have estimated that Eli Lilly has killed 200,000 people with Zyprexa, and that is just one of the many antipsychotic drugs.

Dawson ends by saying: “At the end of this refutation what have we learned? I am more skeptical than ever of David Healy and his web site.” Dawson is very much against that Healy put my article on his website and he seems to suggest again that one illegal parking makes the next one legal: “It is well known in the US that the 20 year CDC initiative to control antibiotic overprescribing is a failure.” So what? That doesn’t let the psychiatrists off the hook, does it? I think a dose of self-criticism would help not only Dawson, but many other psychiatrists, and their patients.

Dawson finally says that:

“internists have enough to focus on in their own specialty before criticizing an area that they obviously know so little about. The author here also states that he is affiliated with the Nordic Cochrane Center and I think that anyone who considers the output of that Institute should consider what he has written here and the relevant conflict of interest issues.”

These are the words of a desperate man. Short of good arguments, Dawson shoots in all directions. I have done research on SSRIs for several years; had a PhD student who defended her thesis on SSRIs in 2013; have access to unpublished clinical study reports on SSRIs from the European Medicines Agency that no one else outside the agency have access to, and which tells a completely different story to that in published trial reports; and I therefore know more about these drugs than most psychiatrists do. I don’t have a clue what my relevant conflict of interest should be about. I have none! Finally, the Nordic Cochrane Centre, which I established 20 years ago when I co-founded the Cochrane Collaboration and whose director I have been ever since, is highly respected for its research. As an example, I have published more than 50 papers in the big five (BMJ, Lancet, JAMA, NEJM, Annals), which very few people in the world have done. So I think my credentials and my centre are okay.

Peter C. Gøtzsche

Psychiatry Gone Astray

Editorial note: We follow up the Guilty post last week with a piece written by Peter Gøtzsche that has caused a stir in Denmark and provoked some of the Danish professors he critiques to respond.

Peter C. Gøtzsche

At the Nordic Cochrane Centre, we have researched antidepressants for several years and I have long wondered why leading professors of psychiatry base their practice on a number of erroneous myths. These myths are harmful to patients. Many psychiatrists are well aware that the myths do not hold and have told me so, but they don’t dare deviate from the official positions because of career concerns.

Being a specialist in internal medicine, I don’t risk ruining my career by incurring the professors’ wrath and I shall try here to come to the rescue of the many conscientious but oppressed psychiatrists and patients by listing the worst myths and explain why they are harmful.

Myth 1: Your disease is caused by a chemical imbalance in the brain

Most patients are told this but it is completely wrong. We have no idea about which interplay of psychosocial conditions, biochemical processes, receptors and neural pathways that lead to mental disorders and the theories that patients with depression lack serotonin and that patients with schizophrenia have too much dopamine have long been refuted. The truth is just the opposite. There is no chemical imbalance to begin with, but when treating mental illness with drugs, we create a chemical imbalance, an artificial condition that the brain tries to counteract.

This means that you get worse when you try to stop the medication. An alcoholic also gets worse when there is no more alcohol but this doesn’t mean that he lacked alcohol in the brain when he started drinking.

The vast majority of doctors harm their patients further by telling them that the withdrawal symptoms mean that they are still sick and still need the mediciation. In this way, the doctors turn people into chronic patients, including those who would have been fine even without any treatment at all. This is one of the main reasons that the number of patients with mental disorders is increasing, and that the number of patients who never come back into the labour market also increases. This is largely due to the drugs and not the disease.

Myth 2: It’s no problem to stop treatment with antidepressants

A Danish professor of psychiatry said this at a recent meeting for psychiatrists, just after I had explained that it was difficult for patients to quit. Fortunately, he was contradicted by two foreign professors also at the meeting. One of them had done a trial with patients suffering from panic disorder and agoraphobia and half of them found it difficult to stop even though they were slowly tapering off. It cannot be because the depression came back, as the patients were not depressed to begin with. The withdrawal symptoms are primarily due to the antidepressants and not the disease.

Myth 3: Psychotropic drugs for mental illness are like insulin for diabetes

Most patients with depression or schizophrenia have heard this falsehood over and over again, almost like a mantra, in TV, radio and newspapers. When you give insulin to a patient with diabetes, you give something the patient lacks, namely insulin. Since we’ve never been able to demonstrate that a patient with a mental disorder lacks something that people who are not sick don’t lack, it is wrong to use this analogy.

Patients with depression don’t lack serotonin, and there are actually drugs that work for depression although they lower serotonin. Moreover, in contrast to insulin, which just replaces what the patient is short of, and does nothing else, psychotropic drugs have a very wide range of effects throughout the body, many of which are harmful. So, also for this reason, the insulin analogy is extremely misleading.

Myth 4: Psychotropic drugs reduce the number of chronically ill patients

This is probably the worst myth of them all. US science journalist Robert Whitaker demonstrates convincingly in “Anatomy of an Epidemic” that the increasing use of drugs not only keeps patients stuck in the sick role, but also turns many problems that would have been transient into chronic diseases.

If there had been any truth in the insulin myth, we would have expected to see fewer patients who could not fend for themselves. However, the reverse has happened. The clearest evidence of this is also the most tragic, namely the fate of our children after we started treating them with drugs. In the United States, psychiatrists collect more money from drug makers than doctors in any other specialty and those who take most money tend to prescribe antipsychotics to children most often. This raises a suspicion of corruption of the academic judgement.

The consequences are damning. In 1987, just before the newer antidepressants (SSRIs or happy pills) came on the market, very few children in the United States were mentally disabled. Twenty years later it was over 500,000, which represents a 35-fold increase. The number of disabled mentally ill has exploded in all Western countries. One of the worst consequences is that the treatment with ADHD medications and happy pills has created an entirely new disease in about 10% of those treated – namely bipolar disorder – which we previously called manic depressive illness.

Leading psychiatrist have claimed that it is “very rare” that patients on antidepressants become bipolar. That’s not true. The number of children with bipolar increased 35-fold in the United States, which is a serious development, as we use antipsychotic drugs for this disorder. Antipsychotic drugs are very dangerous and one of the main reasons why patients with schizophrenia live 20 years shorter than others. I have estimated in my book, ‘Deadly Medicine and Organized Crime’, that just one of the many preparations, Zyprexa (olanzapine), has killed 200,000 patients worldwide.

Myth 5: Happy pills do not cause suicide in children and adolescents

Some professors are willing to admit that happy pills increase the incidence of suicidal behavior while denying that this necessarily leads to more suicides, although it is well documented that the two are closely related. Lundbeck’s CEO, Ulf Wiinberg, went even further in a radio programme in 2011 where he claimed that happy pills reduce the rate of suicide in children and adolescents. When the stunned reporter asked him why there then was a warning against this in the package inserts, he replied that he expected the leaflets would be changed by the authorities!

Suicides in healthy people, triggered by happy pills, have also been reported. The companies and the psychiatrists have consistently blamed the disease when patients commit suicide. It is true that depression increases the risk of suicide, but happy pills increase it even more, at least up to about age 40, according to a meta-analysis of 100,000 patients in randomized trials performed by the US Food and Drug Administration.

Myth 6: Happy pills have no side effects

At an international meeting on psychiatry in 2008, I criticized psychiatrists for wanting to screen many healthy people for depression. The recommended screening tests are so poor that one in three healthy people will be wrongly diagnosed as depressed. A professor replied that it didn’t matter that healthy people were treated as happy pills have no side effects!

Happy pills have many side effects. They remove both the top and the bottom of the emotions, which, according to some patients, feels like living under a cheese-dish cover. Patients care less about the consequences of their actions, lose empathy towards others, and can become very aggressive. In school shootings in the United States and elsewhere a striking number of people have been on antidepressants.

The companies tell us that only 5% get sexual problems with happy pills, but that’s not true. In a study designed to look at this problem, sexual disturbances developed in 59% of 1,022 patients who all had a normal sex life before they started an antidepressant. The symptoms include decreased libido, delayed or no orgasm or ejaculation, and erectile dysfunction, all at a high rate, and with a low tolerance among 40% of the patients. Happy pills should therefore not have been marketed for depression where the effect is rather small, but as pills that destroy your sex life.

Myth 7: Happy pills are not addictive

They surely are and it is no wonder because they are chemically related to and act like amphetamine. Happy pills are a kind of narcotic on prescription. The worst argument I have heard about the pills not causing dependency is that patients do not require higher doses. Shall we then also believe that cigarettes are not addictive? The vast majority of smokers consume the same number of cigarettes for years.

Myth 8: The prevalence of depression has increased a lot

A professor argued in a TV debate that the large consumption of happy pills wasn’t a problem because the incidence of depression had increased greatly in the last 50 years. I replied it was impossible to say much about this because the criteria for making the diagnosis had been lowered markedly during this period. If you wish to count elephants in Africa, you don’t lower the criteria for what constitutes an elephant and count all the wildebeest, too.

Myth 9: The main problem is not overtreatment, but undertreatment

Again, leading psychiatrists are completely out of touch with reality. In a 2007 survey, 51% of the 108 psychiatrists said that they used too much medicine and only 4 % said they used too little. In 2001–2003, 20% of the US population aged 18–54 years received treatment for emotional problems, and sales of happy pills are so high in Denmark that every one of us could be in treatment for 6 years of our lives. That is sick.

Myth 10: Antipsychotics prevent brain damage

Some professors say that schizophrenia causes brain damage and that it is therefore important to use antipsychotics. However, antipsychotics lead to shrinkage of the brain, and this effect is directly related to the dose and duration of the treatment. There is other good evidence to suggest that one should use antipsychotics as little as possible, as the patients then fare better in the long term. Indeed, one may completely avoid using antipsychotics in most patients with schizophrenia, which would significantly increase the chances that they will become healthy, and also increase life expectancy, as antipsychotics kill many patients.

How should we use psychotropic drugs?

I am not against using drugs, provided we know what we are doing and only use them in situations where they do more good than harm. Psychiatric drugs can be useful sometimes for some patients, especially in short-term treatment, in acute situations. But my studies in this area lead me to a very uncomfortable conclusion:

Our citizens would be far better off if we removed all the psychotropic drugs from the market, as doctors are unable to handle them. It is inescapable that their availability creates more harm than good. Psychiatrists should therefore do everything they can to treat as little as possible, in as short time as possible, or not at all, with psychotropic drugs.