Making medicines safer for all of us

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

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

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

Author Archive for David Healy

RxISK Prize

Over on RxISK, we have launched a RxISK Prize.  The hope is to find an answer to the debilitating disorders of Post SSRI Sexual Dysfunction, PSSD, Post-Finasteride Syndrome, PFS, and Post Retinoid Sexual Dysfunction (PRSD).

Please check this out and pass the word on to any pharmacologist, physiologist, endocrinologist, biologist, electrical engineer, doctor, herbalist, and anyone else you can think of and get them to pass the word through their networks.  We need someone to find a cure, to whom we can hand over the Prize.

David Healy

 

Alt Medicine

                  

Editorial Note: When I raised the specter of the Science Media Center and Sense about Science recently, some of the Americans I knew fell about laughing, figuring we are still a long way off being as censored as the US of A is. After calming down, one of them Johanna Ryan wrote this post.

In June 2014 the BMJ published a study by Lu et al supposedly of teen suicide.  This was a group of researchers at Harvard University.  The study claimed to have found a “33% jump in suicide attempts” among US teens after the FDA placed a Black Box warning on antidepressants for young people.

It received an avalanche of publicity, none of which cast the faintest doubt on its alarmist conclusions.  With a publicity machine like this, it was no wonder most American journalists (and most doctors as well) hesitate even to mention any downside to antidepressants, lest they be accused of triggering a wave of teen suicides.

Dozens of leading academics wrote the BMJ to pour scorn on the study.  It is a good candidate for the most egregious article BMJ has ever published.  It showed neither a major decrease in antidepressant prescribing, nor a rise in teen suicides.  The increase in suicide attempts it claimed to find was actually a rise in insurance claims for “psychotropic drug overdoses”, many of which would not have been suicidal.

The Clay Center

The “Clay Center for Young Healthy Minds” was founded at Massachusetts General Hospital in 2013 and immediately took a lead role in press coverage of teen depression and suicide.  Gene Beresin and Steven Schlozman, two Mass General child psychiatrists, are its leading figures.  Beresin went on ABC News to promote the “study” and  its alleged finding of a 33% increase in teen suicides.  He and Schlozman co-wrote an Op Ed calling on FDA to repeal the Black Box warning, which Beresin called “the next closest thing to prohibition.”

The Clay Center is not a treatment or research institute.  It’s a media and communications project. Its dedicated to “educating” journalists, policymakers and the public about the virtues of the Mass General approach to childhood problems. Mass General  is known for an aggressive use of psychiatric medication in children.  In particular it’s known for the work of Dr. Joseph Biederman promoting the controversial diagnosis of “childhood bipolar disorder” and its management with antipsychotics in infants.

From the start it has forged a close alliance with the American Foundation for Suicide Prevention, an influential nonprofit whose leadership roster reads like a Who’s Who of American psychiatry.  Dr. Christine Moutier, AFSP’s current president and chief spokesperson, worked with Beresin in the 2014 media campaign.    Both are articulate, engaging and much more media-friendly than most leading academic psychiatrists like Biederman.  Both are also sufficiently far removed from the world of drug-company clinical trials and “key opinion leaders” that no sticky trail of Pharma money adheres to them personally.

I’ve found it useful (and occasionally fun) to keep tabs on what they say to various audiences.  Take this 2013 blog article, where they reassure everyone that the very small uptick in teen suicides in 2004 or so – which they allege was related to the Black Box warnings – was just a temporary blip, and suicide rates have re-stabilized.  Very much at odds with their 2014 hysteria campaign!

And this more recent article, in which they report that more youth are getting mental health treatment, but the increases are occurring among kids who are either mildly impaired, or “not impaired at all.”  They are nonetheless “delighted” that so many are seeking help!  No downside whatsoever when your child psych clinic fills up with kids who are “not impaired at all” (though they do worry that more disturbed children may still be undertreated).

Occasionally their promotions verge on the ridiculous: In August 2016, at the height of back-to-school season, the Clay Center solemnly announced that 50-60% of college students had a psychiatric disorder.

Landon T. Clay

The Clay Center owes its existence to two big, “transformational” philanthropic donations.  The biggest was from Landon T. and Lavinia Clay.   Landon Clay is a venture capitalist and head of a Boston-based investment fund called East Hill Management Company, LLC.  He was formerly head of Eaton Vance and ADE, two other major investment funds.  He’s an alumnus and major donor to Harvard University, and is (or was) on its Board of Overseers.

So why has this become the Clay family’s cause?  I expected a warm fuzzy story about how one of their children had a mental-health condition, or how Mrs. Clay was a schoolteacher who worked with troubled kids, or something similar.  I didn’t find it.

East Hill focuses on biotech ventures, and is advertised as investing in “disruptive innovations” developed at UK universities.  Its offices are in Rhode Island and Oxford, UK.  Landon Clay is a director of Plasso Technology Ltd., Glycoform Ltd., Arradiance Inc. and other biotech ventures in which East Hill invests.   He’s also given millions to Harvard for telescopes, a faculty chair in mathematics and other high-profile science projects.

Jeremy R. Knowles, twice Harvard’s Dean, was on East Hill’s Board until his death in 2008.  As Dean, Knowles was responsible for major expansions of scientific research, including the Harvard Brain Science Institute which is heavily involved in psychiatric research at Harvard and Mass General.  Knowles also served on the boards of Vertex Pharmaceuticals, Biogen, Celgene and the Howard Hughes Medical Institute (HHMI).

East Hill’s business model is to finance startup companies to develop various drugs, devices, etc., and then sell them to major corporations.  Their scientific advisory board also included Robert May, a “former President of the Royal Society” and Oxford zoology professor, now a member of the House of Lords.

East Hill has a link to Sense about Science, the British think-tank and media center: Oxitec Ltd., a company developing genetically-modified mosquitoes in a scheme to eradicate mosquito-borne tropical diseases such as dengue fever.  Oxitec claims its technology is safer and more sustainable than pesticides, but this claim has been controversial.  East Hill was a major investor, and Clay was on its board until it was sold in 2015.   Oxitec’s press officer, Chris Creese, has also been employed by or affiliated with SAS, and SAS has publicly defended the Oxitec project.

Elizabeth Hayden

The Clay Center’s other large donor is Elizabeth Hayden, billed as “an educator who has dedicated her life’s work to children and families.”  She is also the widow of James Hayden, a tech millionaire.  The Hayden Fund, set up in his memory, is administered by The Boston Foundation, an influential block of philanthropic capital with a finger in every political and economic pie in the Boston area.  The Hayden Fund is one of its “Donor Advised Funds” whose funders are actively involved in their charitable giving.

Ms. Hayden’s professional career seems to have been as a teacher and administrator in a few of the small, wealthy private schools patronized by the Clays.  She is also on the board of Stonehill College, a small Catholic college in Easton, Mass. where she and her husband both went to school.   A student of the sociology of the U.S. ruling class could have a field day with Stonehill.  Its board is 100% alumni, and amazingly influential for such a small place.  It includes Wall Street bankers, university presidents, political fundraisers and corporate execs – including a former head of Johnson & Johnson’s pharmaceutical division and a key political advisor to both Presidents Bush.

Elizabeth Hayden is said to have worked with Gene Beresin for years to make his media center project a reality.  She may have been the person who recruited the Clay family to the cause.

Alliances

The National Alliance on Mental Illness (NAMI) is listed as a key “partner” of the Clay Center, along with AFSP as mentioned above.  NAMI has played an enormous role in establishing the “chemical imbalance” concept of mental illness in the media and public discourse, and it has received six-figure donations from just about every psychotropic drugmaker in the market.

AFSP, in turn, has been involved in a retooling and expansion of official psychiatry’s support system in the past three years.   It has played a key role in founding a broader organization called the Action Alliance for Suicide Prevention, which draws in U.S. military and govern-mental agencies as well as corporate heavy hitters to back the brand of mental health care favored by Mass General, Charles Nemeroff and Big Pharma.

Its Board of Directors includes the CEO of AFSP along with top execs from Kaiser Permanente and Universal Health Services, the giant for-profit behavioral healthcare chain.  It also includes Thomas Insel of NIMH and Thomas Frieden of the CDC as Ex Officio members.

The Action Alliance does not seem to have a medical advisory board.  It can always count on the AFSP’s, which still includes Nemeroff as well as Jerrold Rosenbaum of Mass General.

It can also count on the Anxiety & Depression Association of America.  This group began as the humble Phobia Society in the 1980’s and became the Anxiety Disorders Association in 1990.  In 2012 it took on its current name, and a much larger structure.  ADAA is mainly a professionals’ organization, and its leadership is heavily stacked with Harvard, Mass General and Boston University faculty. The three groups – ADAA, AFSP and the Action Alliance – have collaborated on a survey of support for mental-health spending and other projects.

Media Links

The Clay Center website names WBUR, the Boston affiliate of National Public Radio, as an affiliate.  It also seems to have strong ties to WGBH, Boston’s PBS-TV channel.  Despite the “Public” in their titles, NPR and PBS get less than 10% of their money these days from the taxpayer.  About half is from corporate and foundation sources (the rest being from individual-donor fundraising).  Affiliates are often high-profile pet causes for local corporate philanthropy, which can tend to put limits on their independence.  WBUR’s CommonHealth health-reporting project handles the station’s work with the Clay Center and other powerful nonprofits.

The Clay Center can also draw on the considerable media networks already developed by NAMI and the AFSP.  Both are regarded as prime sources for “responsible” mental health information by most media – and both have relied heavily on funding and hands-on public relations support from Pharma to achieve that standing.

Because of the Sunshine Act and the general low opinion of Big Pharma shared by most Americans these days, complex nonprofit arrangements like the Clay Center will likely play a larger and larger role in advancing both drug research and a Pharma-centric health care system.  This may make it harder for most people to spot any conflict of interest. The fact that rich venture capitalists give you money doesn’t strike everyone as grounds for suspicion, and I can’t point to anything as naked and obvious as an investment by Landon T. Clay in pediatric psych medications.

However, it is biotech money flowing into Dr. Beresin’s beloved project, which is extremely helpful to the bottom lines of Harvard and Mass General.  That may not be sinister, but it is kind of self-serving, to say the least.  Sort of like Silicon Valley capitalists financing laptops for schoolchildren.  You may think laptops for schoolchildren are basically a good thing, but you can’t help noticing how good it is for Silicon Valley as well.  It also means that one particular viewpoint in medicine is being artificially inflated above others that might have more to offer troubled kids.  When busy reporters or public officials want to know “what the science says” about mental health, nonprofits like the Clay Center help insure they hear no inconvenient facts.

Kelly on WBUR

There is an interesting story Bob Fiddaman points out on his blog recently.

On May 18 2017, Chris Cornell, lead singer for Soundgarden committed suicide.  The media reported his wife’s hunch the Ativan he was taking had caused his suicide. WBUR ran an interview with Kelly Posner on May 25, the same Posner who headed up the Columbia Suicide Classification group FDA had turned to between the two PDAC hearings in February and September 2004.

Posner dismissed the link to suicide. When quizzed about the fact her group had reported the data that led to the Black Box, she responded that both FDA and she knew there was no link but they were stuck with trials that were not designed to look at the issue and FDA being very conservative and super-concerned about patient safety had been ultra-cautious and issued a Black Box Warning that was strictly speaking unnecessary. Posner was looking forward to a day in the near future when all the new and better designed research coming through the system would lead to the Black Box being removed, because it had had terrible unintended consequences – a drop in diagnoses of depression and a resulting increase in suicides.

This is presumably the work of Robert Gibbons and Lu for godsakes.  And what about the fact there is no evidence the drugs work?

Thirty years before a certain D J Trump began talking about fake news, medicine had entered a fake world. Thirty years before Alt Right and Alt Left we had Alt-Medicine  – as Study 329 makes clear.

 

The Junkies Take over the Asylum

Some markers first. I am a committed believer in what may now be a last millennium concept – the medical model. I think antidepressants – the older tricyclics and ECT, not the more recent SSRI and other antidepressants – can save lives. I figure conflict of interest, crucially important in other areas of life, is of minor importance if not irrelevant in science. Although by science I mean something that can only happen in the presence of publicly available data. 

This post links to Honey I Shrunk the Shrinks, What’s Going on Here, and to Grassy Knoll.

I used to sit on training scheme interview panels some years ago. We ended up being told we had to ask exactly the same question of every candidate. By accident I hit on a question and amazed by what I was hearing stuck to it:

Tell me about some mistakes you’ve made and what you’ve learnt from them?  

When women were asked this, they immediately looked comfortable and answers tumbled out of them. When men were asked, they looked puzzled and if they could be said to have hopped from foot to foot while sitting on a chair this is what they did.

Junk News

But of course if SMC are writing a brief for you, whether you are a female or male President of a College, they are unlikely to let you admit to mistakes.

The SMC mantra in the background of the recent Panorama fuss, aside from the weird plug about stigma, and the junk in the background to other artificially created concerns about related issues, is that Antidepressants Work and Save Lives.  Millions are benefiting, more and more each year, and its just not right to worry people with Bogeymen. These are the dog-whistles they expect the junkie opinion leaders they have helped create to parrot.

Allen Frances and others now tell us we can’t put DJT’s labeling of inconvenient facts as Fake News down to mental illness. For thirty years the presidents of the American Psychiatric Association and Royal College of Psychiatists (except one), along with Allen Frances, have endorsed a ghostwritten news in all the best journals with zero chance to fact check.  Endorsed a News so obviously Fake it beggars belief. They dismiss the inconvenient facts of suicides, homicides and other harms by an appeal to this Fake News. This is not a mental illness.

Antidepressants

One of the difficulties here is the word antidepressants.  From 1957 to 1987, this meant treatments that could produce a benefit in melancholia.  The tricyclic antidepressants and ECT did this and psychiatrists using these treatments judiciously may have saved some lives.

The word has now changed meaning completely. SSRIs and related “antidepressants” are ineffective in melancholia.  There are no trials showing they work for what until recently was regarded as depression.

The clinical trial evidence for SSRIs comes from people with much milder conditions, who are at little or no risk of dying if left untreated – as the placebo arm of these studies shows.

There is a myth that SSRIs and related drugs treat severe depression.  This comes from the trial data that shows that in people whose rating scale scores are little worse than many of us might have on a Monday morning, it is not possible to show any budge in the rating scale score.  You have to head to the severe end of normal to show a budge.  This is not severe depression.  Its probably not depression.  Its certainly not blood test positive depression as in Dexamethasone Suppression Test Positive depression. SSRIs don’t work in people who are DST +ve.

The SSRIs are essentially anxiolytics.  People toyed around with words like Serenics in the 1980s, when the drugs were first developed. They adopted the term antidepressant in part because the word didn’t suggest dependence. They adopted this word, knowing SSRIs cause dependence.

Antidepressants Save Lives

If by working we mean save lives, the clinical trial evidence base does not show SSRIs or recent antidepressants saving lives.  Quite the contrary.  In 2006, FDA called for all trials. They made a curious call that eliminated all data from taper periods, run in periods and had other odd features.  Even so they only got some trials.  Some other trials in which there were suicides and deaths just didn’t make it to FDA’s offices.

Despite all this, there was an excess of dead bodies in trials that combined involved 100,000 people on antidepressants compared to placebo.  These deaths were not just from suicide.

When the regulators finally put a Black Box on antidepressants it was because there was an excess of suicidal acts on these drugs – not because there was some evidence there could be a suicidal act on treatment.

Antidepressants Work

If by working we mean correcting an abnormality in serotonin or other systems, there is no evidence for this and never was.  Ideas about abnormalities in serotonin systems were fringe hypotheses before marketing copy transformed them into a biobabble that has degraded clinical encounters.

Antidepressants make people’s serotonin systems abnormal.  The longer you stay on them, the more abnormal your serotonin system becomes.

A lot of people seem to sense this, because pharmaceutical company research shows that more than half of those put on antidepressant stop by the end of the first month.

Millions are Benefiting

There is up to a 10% increase in people on antidepressants each year.  There are 65 million prescriptions in England per year. What does this mean?

Roughly the same amount of people get put on antidepressants for the first time each year. The increasing number on these pills comes from people continuing on them at the end of each year. Roughly 90% of the people now on antidepressants have been on them for a year or more.

Of this 90%, the bulk continue taking them because they can’t get off.

They may think the pills are saving their lives when they stop and feel awful and go back on them and feel better. And their lives may be saved but they are being saved by a treatment for withdrawal rather than for depression.

This is dependence – addiction in lay language. It’s difficult to know where this story is going to end – probably in a lot people being dismissed as neurotic or psychosomatic. The caravan will move on leaving a lot of dogs barking.

What Antidepressants Do

SSRIs change the genitals of 100% of the people who take them. They do so within an hour of the first tablet.  In most cases, this means numbing, but in some cases it may involve the opposite.  In almost all cases, except some men (and women) with premature ejaculation (or its equivalent), this leads to sexual dysfunction.

A significant number of people with sexual dysfunction will never recover normal function. A decade after stopping they will not be functioning normally and may not be functioning at all. We don’t in fact know how many people return to full sexual function after an SSRI. It may be less than half of those who have been on treatment for more than a few months.

Numbing

SSRIs and related antidepressants also produce an emotional numbness in most takers. This is at the core of their therapeutic action. We prefer to talk about these drugs “working” rather “numbing” because numbing doesn’t sound ethically quite right.

But SSRIs were developed to produce precisely this effect – not to correct a serotonin problem.

It would be helpful for people offered them to know this is what is being aimed at, and indeed more honest, even though some people might then say they’d prefer not to go down this route.

Women of Child-Bearing Years

Women of child-bearing years have been the target population for these drugs – even though from before their marketing there were strong warning signs these drugs might cause birth defects.

SSRIs double the rate of birth defects in children born to women who take them during the first trimester. These range from almost all cardiac defects through to spina bifida and other problems.

SSRIs also double the rate of autistic spectrum disorders and developmental delay in children born to women who have been on them in pregnancy.

SSRIs double rates of miscarriage – one of the biggest causes of nervous problems later.

SSRIs trigger alcoholism in a significant number of people, especially women. They can lead to compulsive drinking pregnancy and later Fetal Alcohol Syndrome.

Psychotropic Drugs in Children and Adolescents

Prozac is licensed for depression in adolescents. It doesn’t work. The Prozac trials are indistinguishable from paroxetine and other trials in showing no evidence of benefit and evidence of a great deal of harm.

It remains licensed because regulators are never willing to admit mistakes and the academics involved appear unwilling to come clean. It may be legitimate to talk about a conspiracy to hide its problems.

Children’s mental health is the place with the greatest divide in all of medicine between what the published evidence shows and academics say and what the data in fact shows.

Children’s mental health used to be the clearest place where the magic lay in the doctor rather than the pill. If this were still the case, there would be place for a judicious use of medication even though except for OCD there is not a lot of conventional evidence to support doing this in the case of SSRIs.

But the magic no longer lies in the clinicians.  Child Shrinks have become Model Shrinks – where a model means a shrunken replica of the real thing.

Children’s mental health services have become a horror story with children even more likely than adults to end up with a plethora of gateway diagnoses leading to shocking cocktails of treatment – this is in the UK not the US.

And its getting worse.  There are proposals to increase the numbers of child psychiatrists to meet an unmet need. This is a nightmare.

The Difference Between…

In response to the interview question above, Women like Blacks vis-a-vis Whites, or Irish vis-a-vis English can spot the mistakes they make.  The powerful can’t.  Who me?  Make a mistake?

The confidence that comes with power leads to a blindness to mistakes. Strangely, it also leads to extreme nastiness when faced with any evidence of a mistake.  The powerful feel very threatened by those they subjugate. They worry about death threats.  The surprise to me always has been that women and blacks and people whose lives are ripped apart by what was known to be junk information on a drug don’t in fact get violent with the junkies who have robbed and injured them for the sake of a quick fix.

This doesn’t mean that all women and Irish and BMEs are better than WASPs.  The Irish have shown themselves at least as capable of bigotry and nastiness as any other group on earth.

But you’d expect shrinks of all people to be aware of psychodynamics and defense mechanisms like this.

Upton Sinclair famously said you can’t depend on a man to understand something if his job depends on not understanding it.

Sinclair was so twentieth century.  APA and RCP today don’t seem able to understand things their jobs tomorrow depend on them understanding.  If drugs like the antidepressants work wonderfully well and are free of side effects, if it doesn’t require the magic an expert can bring to bring good out of the use of a poison, shrinks are toast. They will be replaced by cheaper prescribers, and Sinclair News (see next post) outfits and SMC will welcome the benefits.

Trains

Simon, the train above is about to leave Prague train station and head West.  It’s just before other trains start heading East.  Pius XII is about to start hearing, seeing and speaking no evil in case the people who produced Beethoven, Mozart and Goethe decide to destroy the Sistine Chapel.

There are more important things than the roof of a Chapel. Children are more important. You know this better than anyone.

Grassy Knoll or Slippery Slope?

Health Warning: Let me put down some markers before riffing on the Grassy Knoll theme. I am a committed believer in what may now be a last millenium concept – the medical model. I think antidepressants – the older tricyclics and ECT, not the more recent SSRI and other antidepressants – can save lives. I figure conflict of interest, crucially important in other areas of life, is of minor importance if not irrelevant in science. Although by science I mean something that can only happen in the presence of publicly available data. 

In the case of the antidepressants and other drugs, do people sit down in closed rooms to hatch a plot against “the people” for the sake of profits? Yep, they do. Is this a conspiracy theory?  No, its out in the open – nothing personal just business.

Is concern about the operations of the Science Media Center legitimate?  Yep. Is it because they’re engaged in a conspiracy? Well – they are in the business of managing perceptions. Is that a conspiracy – even if a well-intentioned one? Difficult call.  Anyone who bases their case on Robert Gibbons and related stuff as Pariente and others in SMC have done is either cynical or thick.  Sticking a litmus strip into the SMC bilge around Panorama caused the litmus strip to dissolve.

The vast bulk of the academic literature on on-patent drugs, excepting the diminishing number of articles talking about adverse effects, is ghostwritten.  Is this a conspiracy? Nope it out in the open but no one spots it on radars in front of them because for most its still as unbelievable as UFOs, or the idea we might incinerate millions of women, children, musicians, artists and scientists.

The entirety of the data from clinical trials of on-patent drugs is unavailable.  No-one gets to see it.  Is this a conspiracy?  Its force majeure – that’s French for fuck off.

The Presidents of American and European Physicians Associations (as well as Royal Colleges) remain quiet about this.  Is this a conspiracy? No. Its political maturity, as modeled by Pius XII in the 1940s.

Spitzer

On June 2 New York State’s Attorney General Elliot Spitzer filed a fraud action accusing GlaxoSmithKline of “repeated and persistent fraud” for concealing known problems with efficacy and safety of Paxil (paroxetine) for children and adolescents. He claimed GSK hid the fact that its Paxil trials failed to show efficacy in adolescents and in some cases it was more likely to cause suicidal thinking.

There was a basis for the charge given that Study 329 and other company pediatric trails may represent the greatest divide in all of medicine between what the academic literature says about the drugs and what the data actually show. There was also a smoking gun document unearthed by Panorama which appeared to show GSK intended to deceive doctors and patients with the publication of the Keller paper in 2001.

Spitzer held a press conference arguing his action would change the course of medicine for ever.  All companies would be pressured into making their data available to doctors – as it should be.  The media attention helped propel him to the Governorship two years later.

On August 26, GSK announced that it had resolved its case with New York.  It would pay a small amount of money and publicly disclose all of its clinical drug trials about the safety of paroxetine for children in a “Clinical Trials Registry”.

Showing a mastery of the art of turning problems into opportunities, GSK’s press release stated:

“We are pleased that the Attorney General believes the Clinical Trial Register we have been developing will provide useful information to the medical and scientific community,” said Mark Werner, Senior Vice President for US Legal Operations at GlaxoSmithKline. “We believe that GlaxoSmithKline’s initiative to launch this register is a responsible step in ensuring transparency of our clinical trial data.”

Spitzer was left seething.

He became Governor in 2006, but two years later he was forced to resign after being found in a compromising situation. The first season of The Good Wife and the last episode of Law and Order are thought to have based on these events. There was no end of speculation as to who was behind his downfall.

The Spitzer action didn’t change medicine one iota.  It may have helped a few weeks after with pushing through a Black Box Warning that FDA up till the last minute was dead set against.  But from GSK’s point of view, Paxil was off-patent, and the warnings may have helped sales of its Lamictal for bipolar disorder – a failure to diagnose which they knew a bunch of doctors were straining at the bit to say was the real reason all these kids were becoming suicidal.

Conspiracy? You have to admire GSK’s nimbleness.

Montgomery

In the late 1980s Stuart Montgomery in London hooked Eli Lilly into a placebo controlled trial of Prozac in patients with recurrent brief depressive disorder, aka intermittent brief depressive disorder, aka borderline personality disorder.  The data are unavailable.  An article was published years later concealing the suicidality data but tucked away in it was mention of the fact that placebo was roaringly better than Prozac.

A few years later Montgomery persuaded GSK to run the same trial in the same patient group, probably using some of the exact same patients, comparing Paxil (Seroxat) to placebo.  The trial ended early. No data were ever published. There was a much higher suicidal event rate on Paxil.

A few years after that again GSK ran a trial in Belgium in the same patient group.  Who know what the real figures are – I’ve seen several different sets.  In all of them there are very high suicidal act rates on Paxil and placebo – which was the point of the trial.

In 2006, under pressure on the suicidality front, GSK put out a press release, containing these figures.

 Paroxetine
Events/Patients
Placebo
Events/Patients
Risk
Major Depression
11/29430/1671Infinite
Brief Depression32/14735/1510.9
Total43/309035/18220.7

What this shows is that you can use a problem you know your drug causes to hide a problem your drug causes. This is effortlessly easy to do by mixing superficially similar but in fact different patient groups together.  It can be done for Parkinson’s disease, Back Pain, Cancers, and works particularly well when both the disorders and their treatment cause a problem.  It’s a harder trick to pull off when you use duloxetine for urinary incontinence and end up with suicidal women.

Anyone like Stuart Montgomery could have sat down and explained to the company what the pay off was going to be from what might have looked like a crazy move.

Company trials are full of moves like this.  Is this a conspiracy?  No – its a game.  On our side, we expect our academics, like Dr Wessely who bills himself as an expert in these kind of things, to spot what’s going on and prevent the buggers from scoring goals.

Goldacre

In 2012, GSK was hit with the then biggest fine in corporate history. As part of its response, as with Elliot Spitzer it took the moral high ground and made a big deal about banning free pens to doctors and eliminating payments to detailers (sales reps) by results. All payments to reps, along with the reps, were being eliminated anyway so this one was easy.

But for Andrew Witty to end up on the front page of the BMJ, just a few weeks after agreeing to the biggest fine in corporate history, billed as the acceptable face of the pharmaceutical industry and the Great White Hope, was a lot more impressive. It must have brought a smile to lots of faces, whatever about the Good Guys in the Department of Justice.

In between paying the fine, and canonization, AllTrials had launched. Most people heard access to trial data but AllTrials proposed nothing like this.  They were focused on efficacy as adjudged by experts not data as trawled by people.  And in a dangerous world, efficacy sells drugs. Its the nuclear option.  Why take risks – nuke it. There is nothing about AllTrials that is not going to increase the sales of drugs.  And all sorts of the great and good were swinging their thuribles and chanting “Transparency”, Transparency” around the new sacrament.

Andrew jumped on board.  What was not to like about this? Nobody rooting through the data to find evidence of a Third Shooter.

Did Ben Goldacre and Iain Chalmers conspire to offer him a Get out of Jail Free card. Its irrelevant. All it needs is someone in GSK to be able to spot a Get out of Jail Free card in front of their nose and able to persuade the CEO to grab it.  And 100,000 people work for GSK so there was every chance this would happen.

The Business Model

The business model of the pharmaceutical industry is:

Pay us what we want because we do research to produce new drugs and if you don’t pay us we will stop doing this and you will die.

Its the next best thing to the barrel of a gun.

They don’t invest the money in making new drugs.  The track record in this area is worse and worse. The money goes into maintaining power. With sufficient lawyers, regulators and academics, its a bit like retaining so many monkeys, you can be sure of ending up with a Mozart symphony or Shakespearean play from time to time.  The other thing as any great sports coach will tell you is Focus.  Industry have a focus – the bottom line.

Medics on the other hand and shrinks in particular are the least focused people in the world – except for those who jump ship into private practice.

Watching Medic behavior however is a good way to check which way the wind is blowing. When there is a dominant power, a bully, medics usually line up to right of the bully. Its called identification with the aggressor. When the Catholic Church held an iron grip on thinking in Ireland, far from offering a voice of liberalism, Irish Medicine took ethical positions on abortion, contraception and everything else to do with sex to the right of the Church.  It often left Church leaders looking rather – well Andrew Witty like.

Anyone who expects doctors to save them would probably have thought the Maginot Line looked wonderful, and voted for the canonization of Pius XII.

(Was that a conspiracy?  Well he did have a woman who looked after him and she was German, wryly described by some as the most powerful German in the Vatican…..).

(Yanis Varoufakis’ Adults in the Room is a wonderful take on what its like to deal with a dominant power and the ventriloquist’s dummies, the Irish or Lithuanians, who do the speaking for them. Or how people will be clapping your back one minute over a stein of beer and then selling you out the next).

 

From the Grassy Knoll

Editorial Note: The image is of Science Media Centre funding from their website. This post links to Whats Going on Here, Honey I Shrunk the Shrinks, and to the two Prescription for Murder Posts on RxISK.   When AF’s email came in first, it seemed far from private as he now claims. The choice of people seemed anything but accidental – especially SW.  It seemed likely SW would engage on the SMC topic. 

From: Wessely, Simon <simon.wessely@kcl.ac.uk>
Date: 6 August 2017 at 20:41
Subject: Re: Thanks David.
To: David Healy <david.healy54@googlemail.com>
Cc: “Summergrad, Paul” , Allen Frances <allenfrancesmd@gmail.com>, Jeffrey Lieberman, Bernard Carroll , Ronald Pies

Honestly David.  This SMC stuff is just daft.   Look at the website and look at the daily digests they do.  They asked a lot of experts to comment on the panorama programme. A lot. If people had given different opinions they would have included them.  They always do.  The facts are that no one on the list did.  A lot were on holiday I grant you but I don’t think that made any difference.

It’s nowt to do with them.

RCPsych certainly did provide a lot of media comments – that’s our job. Sadly not my job any more as I stepped down but I was v pleased with them.

Simon

From: Wessely, Simon <simon.wessely@kcl.ac.uk>
Date: 6 August 2017 at 20:43

Presumably david you think that SMC gave the Sunday Times their big splash pre transmission – ‘Killer Pills’

Was that acceptable journalism?

Come on!

From: David Healy <david.healy54@googlemail.com>
Date: 6 August 2017 at 20:52

As far as I know, the ST piece didn’t have a lot to do with panorama.  That was a journalist who has written a rather good book, who has a compelling case for negligent treatment and who had the wit to take advantage of the fact that panorama was due later that week.

I do think SMC are dangerous and I that you need to consider whether it isn’t effectively operating as an outsourced public relations outfit for pharma among others.  I also think its doing the College no favors to be as tightly linked to them as they are.

I think Dr Burns’ credibility is in rather less good shape as a result as her involvement with them

David

From: Wessely, Simon <simon.wessely@kcl.ac.uk>
Date: 6 August 2017 at 21:40
David.  Are you seriously suggesting that the ST trailer was nothing to do with product placement by panorama ?

It’s not a crime.  It’s normal practice and we all know it

And finally – and I mean finally – look at the rules for donations to SMC and the accounts

You have a case.  I don’t think it’s right but no matter.   Have always enjoyed debating you as you very well know and even more enjoyed drinking with you very well know

But you don’t do your corner any good by going into third shooter and grassy knoll territory.

Ok. Hope you are in Berlin. Shorter and I will be downing a few Steins.  I hope you will be there

Simon

From: David Healy <david.healy54@googlemail.com>
Date: 6 August 2017 at 21:57

S

So whats third shooter about this?

https://davidhealy.org/honey-i-shrunk-the-shrinks/

Or the very many other SMC pieces linked to this story since, all of which misrepresent what the program was about

Or what’s third shooter about the college docs showing SMC efforts to co-ordinate my views about the So Long and Thanks for all the Serotonin piece. I can send this if you really want to see them

In my view SMC have done and are doing a lot to degrade the quality of debate in British psychiatry.  In my view no pharmaceutical company could reasonably be expected to be without an SMC.  It would be bizarre for business with so much at stake not to have something like this.  The idea that SMC wouldn’t exist and wouldn’t be doing exactly what I suggest is a fantasy.

As regards your enjoying debating with me – I can’t remember when that was.

David

Science  Media Centre

SMC began in 2002 in part to contain negative media coverage of GM Foods which seemed bad for business in UK PLC. One of the other factors cited early on was the rough time certain academics such as Simon Wessely were getting when they put forward views about Chronic Fatigue Syndrome (CFS). SMC was and is closely linked to Sense about Science, which began at the same time. They had key founders in common.

The Trustees are:

  • Jonathan Baker Professor of Journalism, U of Essex, (ex-Head of Newsgathering, BBC)
  • Adrian Bull External Relations Director, National Nuclear Laboratory
  • Karen Chadwick Head of Commercial Finance, Wellcome Trust
  • Julian Hitchcock Partner, Marriott Harrison LLP
  • Dr Helen Jamison Head of Media Relations, Wellcome Trust
  • Prof. Ottoline Leyser Professor of Plant Development, Sainsbury Laboratory, U of Cambridge
  • Prof. Mike Rawlins Former Chair of NICE
  • Jo Revill Chief Executive, British Society for Immunology
  • Fran Unsworth Director World Service Group, BBC
  • Prof. Simon Wessely Professor of Psychological Medicine, Kings College London

“When a story breaks – whether it’s the latest flu epidemic, health scare or a potential nuclear crisis – the SMC persuades leading experts to drop everything and engage with the story, then contacts journalists at all the major news outlets to offer those experts for interviews or immediate comment”.

“The SMC has a track record of recruiting experts to its media database on topical issues and considerable experience and expertise helping them speak to the media. The SMC should therefore prioritise recruitment of experts working in high-profile fields that attract controversy”.

The people most aware of SMC and SAS up till this have been from the environmental movement – Friends of the Earth etc, as befits the origins of SMC in trying to influence the debate on GM foods.

Their commitment to CFS has been pretty constant too. As one of the comments on What’s going on Here mentions, SMC have recently co-ordinated comments on the PACE study of CFS.  This is a British study that has generated more interest in the US than the UK, in part because the authors have resolutely refused to part with the data and because there has been outcome switching worthy of Study 329.

The brand is obviously working because it has spread to Canada, Australia, New Zealand and elsewhere.  SMC recently forced the Toronto Star to back down over a story about HPV.

There has been a move to America also which generated this US assessment of its background and M.O. – basically endorsing corporate views.  The stated aim is to promote mainstream science but a science that doesn’t question, and get us to question, is worse than salt that has lost its flavor – the appearances of salt are worthless, the appearances of science are dangerous.

Brush with a Hitman

I had a first brush with SMC in 2015 when BMJ commissioned a piece about SSRIs and serotonin mythology. They had difficulties with the idea of calling it So Long and Thanks for all the Serotonin, but eventually it ran. From around the time it came out or earlier there were comments – the one that caught my eye was from Clare Stanford – because like Wendy Burns’ Panorama comments these were bizarre. It came with a whole new idea – Switch on Anti-Depression Today.

The comments about that article were almost identical to the ones about the Panorama program.  Telling people there was no evidence for a serotonin theory and never had been would provoke people to murderous rage, and I would be responsible for this.

To repeat what I wrote then, the powers that be (AF, SW etc) are scared silly of the people. Their reactions scream guilt. They scream that if we ever found out what they had done to us, we would rise up and they would be in trouble.  Just to be clear, I am not advocating anyone rise up, I am describing the body language of the Bishops and Cardinals of medicine.

What I didn’t know then was that the BMJ had sent the editorial and a press release of the piece to SMC.  On April 20th SMC sent both to their bank of experts including the Royal College asking for comments “from my limited understanding this could be quite controversial as it essentially suggests there is no link between serotonin and depression”. It worked its way across a few desks in the College to Dr Wessely’s desk – “this could be a big story Simon.  Would you perhaps like to comment?”

The next brush was over Study 329, an earthquake in therapeutics.  There was very little reaction from GSK to this, other than a perfunctory comment almost coinciding with publication.  This didn’t seem so astonishing; after all they had recently been fined $3 billion linked to this study and so comment was always likely to be constrained.

But it looked very like the ball was passed to GSK’s partners, Sense about Science, and in smart order Tracey Browne, Ben Goldacre and Iain Chalmers all came out to defend this wonderful, most marvelously transparent company.

The God that Didn’t Bark

One of the most surprising things about the Panorama program was that neither GSK nor Pfizer barked. Given a right of reply by BBC they said almost nothing. You will look in vain around other media outlets to find anything from them. No screaming blue murder or irresponsibility.

Thirty years ago when Prozac ran into trouble first, the standard thing was for companies to mobilize “friends” when faced with difficulties.  This is not all bad.  We want companies to defend products. With the right give and take a middle ground can be found.  But over the last few decades like the Cheshire cat, companies have been fading into the background leaving only a grin behind.

Or rather a hell of a lot of barking behind – by what appear to be others.

The Dog that Did

Before the Panorama program came out and before she had seen it Wendy Burns, the new President of the College, who has no background in these issues, had made a fool of herself in the Times commenting on things that had nothing to do with program.  See Honey I shrunk the shrinks.

Wendy Burn

http://www.sciencemediacentre.org/?s=antidepressants&cat=

The same holds true for Carmine Pariente in the Lancet who turns up regularly in these slots.  To have something come out the Lancet so quickly shows a real sure-footedness on the grassy knoll.

Carmine Pariente

www.download.thelancet.com/pb-assets/Lancet/pdfs/S2215036617303127.pdf

A host of tweets from all kinds of people including Ben Goldacre, until he ran into an upper cut from Shelley Jofre, followed.

James Thomas (@James_M_Thomas) | Twitter

My complaint about the #BBCPanorama ‘Prescription for Murder?’ show broadcast … Panorama ?, Science Media Ctr UK … Prof Social Research & Policy at EPPI-Centre

MHRUK (@MHRUKCharity) | Twitter

Check out the latest Tweets from MHRUK … Here’s a blogpost from Science Media Centre on recent #Panorama programme on … news-blog/post /a-prescription-for …

https://twitter.com/MHRUKCharity/status/891589217494740992

Ed Sykes from the Science Media Centre explains why we must rely on research to inform investigative journalism in light of Panorama’s recent episode on the link between antidepressants and homicidal behaviours.   This gushing little piece is laid out in full below  

https://www.mqmentalhealth.org/news-blog/post/a-prescription-for-stigma-why-evidence-matters

BBC News

https://twitter.com/MHRUKCharity/status/890478505514987520

http://www.sane.org.uk/resources/news/show_news/816

Media centre. News releases and … Following last night’s BBC Panorama episode – ‘A Prescription for Murder?’ … The PMCPA is a division of ABPI which is a company …

Following last night’s BBC Panorama episode – ‘A Prescription for Murder?’ – Dr Sheuli Porkess, ABPI’s Head of Medical Affairs and Clinical Research, gives her reaction to the program and its views on SSRI medicines.

http://www.abpi.org.uk/our-work/news/Pages/Having-a-responsible-conversation-about-mental-health.aspx

https://www.rethink.org/media-centre/2017/07/rethink-mental-illness-responds-to-bbc-panorama-prescription-for-murder

http://www.khq.com/story/36030700/mental-health-watchdog-says-uk-tv-documentary-prescription-for-murder-should-prompt-us-investigations-into-psychotropic-drug-violence

Watering the Lamppost

There is a Lamppost on the grassy knoll that dogs use a lot.  Its not clear if the drunks looking for their keys there get the smell.

Ed Sykes from the Science Media Centre explains why we must rely on research to inform investigative journalism in light of Panorama’s recent episode on the link between antidepressants and homicidal behaviours.

Imagine a pill, taken by millions of people every day, that unwittingly turns some of us into murderers. That was the scenario laid out in the recent Panorama on antidepressants, it was the message trailed in the media in advance of the show and it was the line used in the press release to drum up interest. That ‘s a very powerful and scary message, and when you’re talking about a drug that saves thousands of lives every year – and that already has a bad public image – then we need to be extra careful.

Putting people off antidepressants costs lives.

Antidepressants are not perfect, they have many side-effects, it can take a long time for people to find one that works for them and they don’t solve the problems that drive people into depression in the first place. People should be aware of these problems and we should discuss them openly. At the same time, we should be celebrating investigative journalism because it can be a massive force for good and I’d love to see more of it, but with any topic it needs to be done well, and when there’s a risk of people stopping a life-saving medication then that’s especially true.

So why was I concerned by the programme? What riled so many other people? I fully believe that antidepressants can change someone’s behaviour, and that we should be asking whether the negative side-effects are really outweighed by the benefits.

But to do that, we need to see evidence, not simply be given a case study.

The programme focused almost exclusively on the case of James Holmes, known as the Batman killer after opening fire in a cinema showing the Dark Knight Rises. We were shown the timeline of events leading up to the massacre, we heard from his parents and from a couple of psychiatrists involved in the case. But where was the evidence that the murders were linked to the medication?

I spend my days working with researchers on all aspects of mental health and neuroscience, these are people who dedicate their lives to sifting through the data to see whether we are imagining patterns or are blind to what the stats are telling us. Many of them are investigating exactly these questions around antidepressants.

Professor Seena Fazel is known around the world for his work investigating whether antidepressants lead to an increase in violence. The research doesn’t show any evidence for an increase in people over 25. In younger people, there is evidence of a slight increase but we still can’t say if this is due to antidepressants. It’s complex as young people are taking more alcohol and other recreational drugs, and some of these people are actually suffering from severe personality problems that make them violent in the first place. It’s fascinating work using data from tens of thousands of people and I would have sat engrossed for an hour hearing about what the figures show. But even if Seena’s work did show antidepressants caused people to be more violent, that would still be a big step away from turning someone into a murderer.

It’s not just Seena and his datasets who don’t see the evidence for saying antidepressants turn people into murderers. I contacted around I00 researchers who work on various aspects of depression and antidepressants and the only message that kept coming back to me was that there was just no good evidence to suggest that antidepressants turn people into murderers. Yet in the show we were presented with one psychiatrist who said he thought the drugs weren’t to blame, one who thought they definitely were and one who thought we should be looking into it. It seemed as though the field is split evenly on this and that the evidence is up for grabs – this isn’t representative of the views of the mainstream science community; it may be ‘balanced’ but it isn’t measured.  This kind of false balance has been blogged about many times before.

The main evidence the programme seemed to be giving us, alongside the case studies, was the result of a Freedom of Information request to the Medicines & Healthcare products Regulatory Authority (MHRA). The MHRA is responsible for many aspects of healthcare, including a Yellow Card system that records all the bad side-effects linked to any drugs. The Panorama team informed us that their investigation had unearthed 28 cases linking antidepressants to murder and 32 to murderous thoughts. The show did point out that these were just reports, not conclusions that the drugs had caused murder. But what they failed to mention was that these reports to the MHRA can be made by anyone. You or I could go on their website right now and make a report, it doesn’t necessarily mean it was a medical professional who reported it or that the report was supported by strong evidence . Maybe each of these reports was made by a healthcare professional and was supported by good evidence, but Panorama didn’t show it to us.

The programme did well in reminding viewers not to stop taking medication without speaking to a medical professional first, but it also kept repeating that in rare circumstances these drugs might be turning people into murderers. The EU defines a rare disease as affecting fewer than 5 in 10,000 people, but when there are a lot of people involved then even a rare event should start to appear quite a lot. Around 1 in 10 people in the UK experience some form of depression during their life, there were 61 million prescriptions for antidepressants in 2015 alone, probably more than 500 million during the last three decades. So even if all 60 of the Yellow Card reports to the MHRA had all definitely been a case of the drug turning someone into a murderer that would be around I per 800,000 prescriptions. There are only 600,000 people living in Glasgow. These circumstances aren’t rare, they’ re vanishingly small.

What viewers of this Panorama didn’t see was a measured, proportionate account of the huge wealth of evidence on this topic. Through false balance, by not showing the evidence, and by not giving some much-needed context what could have been an insightful programme left people misinformed. Antidepressants would benefit from investigative journalism – there are good questions about over-prescribing and prescribing for the wrong reasons, but there are also concerns about under­ prescribing and how a really useful drug is still being shunned by many. With a thorough investigation we could learn a lot about how much the drugs do change people’s personalities, whether using them stops us from investing in psychological therapies, if they result in social problems being ignored and even whether they do lead to violence or murder – but to have that debate we need to see the evidence, not just rely on one case study, no matter how distressing.

Ed Sykes is Head of Mental Health and Neuroscience at the Science Media Centre.

 

What’s going on Here?

Editorial Note:  This arrived out of the blue. The list of those copied in makes it look like its anything but spontaneous. Simon Wessely is recently vacated president of Royal College of Psychiatrists, and one of the Trustees of the Science Media Centre.  Paul Summergrad and Jeff Lieberman are former presidents of APA.  JL offered views on the Holmes case. There is no indication AF has actually watched the program.

From: Allen Frances <allenfrancesmd@gmail.com>
Date: 6 August 2017 at 00:53
Subject: Dear David.
To: David Healy <David.Healy54@googlemail.com>
Cc: Simon Wessely , Barney Carroll , Paul Summergrad , Jeffrey Lieberman , Ronald Pies

I have watched this story play out with deep misgivings. I know you meant well, but also know you went way overboard categorically declaring meds to be the causal factor in this mass murder, when there were so many other possible contributing factors and no real proof meds were among them. It reduces your credibility when you make such extreme statements and also makes it harder for people like me who are trying to curb medication excess, while encouraging its proper use (against the false claims of extremists who somehow blame all psych problems on meds). I know how much flak you have already taken and that you must feel backed into a corner. My recommendation would be that you issue further clarification on the difficulty of establishing causality and the essential benefits, as well as the considerable risks, of psych meds. To do otherwise makes you responsible for patients going off, or refusing to start, meds they may desperately need. Protecting people ffrom unneeded meds is your noble calling, but should not result in your unneceessarily scaring people off needed meds. What do you think?

Allen Frances (@AllenFrancesMD) tweeted at 4:06 PM on Sat, Aug 05, 2017:
I constantly caution re misuse of psych meds
But its extreme to blame mass murder on them
Ignores role of psych disorder/guns/social context https://t.co/gpJ2JpHOzw

On Aug 6, 2017 4:36 AM,
“David Healy” <david.healy54@googlemail.com> wrote:

Allen

With all due respects you are a long way wide of the mark.

First, aside from a carefully orchestrated campaign, the response from patients and many others has been very positive.

I think the best way into this is to give you two things to read – a piece in the BMJ by Gwen Adshead attached and a response below.

Re: Antidepressants and murder: justice denied

Dr Adshead misses the point behind this program. This was not a program attempting to prove antidepressants can cause homicide. This has already been conceded by prosecutors, regulators and company personnel. As early as 1982, Pfizer personnel had noted that this class of drug (SSRI) were known to cause these reactions.

Nor was it about whether sertraline caused James Holmes to commit murder. Having spent time with the man, my view is that it did, and more could have been done to persuade viewers of this.

The key issue was this. If it has been conceded this drug can cause events like this, and if a case could be made that it did so in this instance, why did Holmes’ legal team not run it?

The answer in part lies in the fact that academic literature on SSRIs is almost entirely ghost-written and there is no access to the data generated by the RCTs of these drugs. The BMJ and other journals play a part in this situation. This means that to acquit Holmes, a lawyer has to persuade a jury that most academics and journals are guilty of failing to adhere to the norms of science.

Holmes was in a Guildford Four quandary. Paraphrasing Lord Denning in that case ” If his [their] story is right, it is such an appalling vista it cannot be. Wrongfully convicted prisoners should stay in jail rather than be freed and risk a loss of public confidence in the law”.

Holmes had a public defender. If he had been wealthy enough to afford a lawyer who relished the challenge, or if the crime was less horrific, things might have been different. The rest of us who end up on the wrong end of one of the close to 100 drugs, including respiratory, skin and cardiac drugs, that prosecutors or companies have indicated can cause violence risk ending up in the same legal quandary Holmes was/is in.

There have been a lot of comments, coordinated by the Science Media Centre, that this program cast aspersions on a useful group of drugs. We need to find some balance between raising alarms about a drug and ensuring we do not compromise an innocent person’s right to a fair trial.

*#@

Let me spell out some things in further detail. The Panorama program had vastly more detail on Holmes and his assessment than it could deal with and likely ended up being too subtle for its own good (or maybe for my good).  To call this a failure of BBC journalism is as far removed from the truth as you can get.  It was one of the best things they have ever done in my opinion.

Second, they do refer to Pfizer judgments their drug can cause psychosis and aggression – which Pfizer opted to put in the label as of 1994 (See the link below). Vanishingly few doctors understand what is going on here.  They see a label saying something like “there have been reports of violence and psychosis on our drug so we are including these here” and read this as – look at this wonderfully transparent and responsible company who are putting in the label even whacko reports from nutters and scientologists – am I going to believe this?  Don’t be ridiculous.

In fact what is going on is Pfizer and other companies have reports that no matter what way they spin it they cannot explain it in any other way but that our drug has probably caused this.

This is consistent with Pfizer determinations from their healthy volunteer studies in 1982 that sertraline can cause behavioral reactions including agitation/suicidality and aggression/ homicidality and that this class of drug (SSRI) are well recognized to do this.  1982 !

Part of the problem the field has is that the data is inaccessible. If anyone can tell me how anyone can offer expert views in the absence of the data, I’d be interested to hear it.  The more we go on with this charade of basing views or guidelines on ghostwritten articles, the less credibility we will all have.  Surely Study 329 brought this point home.

The second point is this.  Before this program came out, the Science Media Centre had lined up statements from high ranking figures including Wendy Burn President of the Royal College of Psychiatrists to slam the program – in terms that had nothing to do with what was in the program – her statement talks about stigmatizing mental illness.  WB later confessed she hadn’t seen the program when she made the statement.  She has no expertise in this area.  It’s not clear to me she authored her view. SMC have continued to coordinate inputs that have little to do with the real issues at the heart of the program.

Who are SMC?  They are linked to Sense about Science.  Simon can probably tell you more. My take is the original idea was reasonable – scientists like him were under attack from what might loosely called activists.  He probably had much less hostility to cope with than I have had defending ECT.  But the idea was to ensure that proper science got a hearing.

The reality today is that funded by public money and almost any major corporation you can think of whose interests intersect with healthcare, SMC get preprints of all articles from BMJ for instance – such as my piece some years ago – So Long and thanks for all the Serotonin – and approach the Royal College to get experts who can diss the piece when it appears.  (I wouldn’t make a statement like this without the documents to back it up).

This is stifling proper science.  It has become nasty and risks being fascist. It’s dangerous for both patients and medics.  As I’ve tried to tell SW on several occasions unless medicine embraces the idea that the magic of medicine and doctors is that we bring good out of the use of a poison, we are fucked.

If the drugs are wonderfully effective, and free from problems other than notional ones, then we are costly prescribers and it is no accident we are at present being phased out.   This may not be a problem for you Allen but it is for my children and everyone else in that generation.

If the drugs do what the guidelines would suggest, then managers can tell shrinks what to do and we are losing our jobs if we don’t comply.  This is not a world in which you had to practice Allen but I can tell you its not pleasant.

As a hard core supporter of the medical model and someone who doesn’t advocate for anything other than physical treatments, I look at the current state of psychiatry and a lot of medicine with increasing dismay and would make sure anyone thinking of taking up psychiatry knows it is an increasingly grim profession where the excitement if any lies in working out how we have messed up so badly and how to turn things round.

Re reducing the burden of over-medication – well 10% of the UK and most other major countries are on antidepressants.  There is no increase in the numbers being put on them year on year.  The yearly increase comes from those toppling over into chronic use at the end of their first year of use.  When I began practicing we figured antidepressants should be used for 3 months – perhaps 6 months occasionally.  Of the 10% of people in the UK on these drugs, 90% roughly are on them for  more than a year primarily because they can’t get off – there are several reasons why this might be.

Here is a link to the P program.

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

It’s worth watching.  But remember it’s subtle.  They left out lots – including the healthy volunteer material and the clips of Bill Reid saying he knew nothing about the drugs and there was no point asking him about drugs – you’d better get someone else to comment on that.

After watching, the issues I’d be interested in hearing views on are the following:

  1. Having offered comparatively few views in cases involving SSRIs, mostly views that the drug has played no part in whatever event, I believe there are a number of innocent people wrongly convicted and many people who will never get a fair trial.  What can we do about this?
  2. Recognizing that prosecutors in the case of Zoloft, companies in the case of all these drugs, and the data where it is available, make it close to incontestable that SSRIs in principle can cause violence, and recognizing that patients are far more sensible than we usually give them credit for and can manage a genuine debate, how do we conduct a debate about these issues?
  3. It seems to me we are failing the F Scott Fitzgerald test: “The test of a first rate intelligence is the ability to hold two opposed ideas in the mind at the same time, and still retain the ability to function”.  Why might this be?
  4. Are organizations like SMC a good thing or not and if a good thing do they need a new brief – looking after the interests of a profession rather than the interests of corporations and their products?

David

From: Allen Frances <allenfrancesmd@gmail.com>
Date: 6 August 2017 at 14:20

David,

You make my point much more eloquently & succinctly than I ever could with this quotation at the end of your response:

It seems to me we are failing the F Scott Fitzgerald test: “The test of a first rate intelligence is the ability to hold two opposed ideas in the mind at the same time, and still retain the ability to function”.  Why might this be?

I think you need to address your own question to yourself- why might it be that you (who obviously otherwise have the highest intelligence), are so willing to go propagate the one sided extremes emphasizing the potential for bad complications from meds without being able to hold as well the opposed idea that for many the meds are desperately needed and of very favorable risk/benefit. In my view, your being unable to hold these 2 opposing ideas greatly reduces your effectiveness as reformer of psychiatry and risks disaster for patients who do need meds.

I also don’t understand how you can be so sure of yourself and make such definitive statements about an inherently multicausal act. How can you or anyone prove it was just meds that caused murder. You must know that nothing in psychiatry and human behavior is that simple, but you seem not to know the possible harms that follow when you make it seem so.

I fear that the great good you have done and will do in pointing out the risks/harms of meds is tarnished by your radically extreme position and inability to also appreciate benefits. I know we have been over this many times before and don’t want to make what must be a difficult time more difficult. My goal is not to change your mind, but to open it a little and to suggest that you are now embattled not just because there are some corrupt forces aligned against you, but also because you have gone overboard in taking an indefensible one sided position.

Thanks for the dialog. Even if it goes nowhere I felt compelled to once again raise our differences. Hope the dust settles.

Best Al

David Healy <david.healy54@googlemail.com>
Date: 6 August 2017 at 14:44

Allen

You are either not reading what I’ve written or not thinking about it.

I would hardly say I believe in the medical model probably even more than you and advocate nothing but physical treatments if they didn’t do some good.

I think you are making the mistake of thinking good comes out of the use of a pill – when in fact it comes from doctors use of pills – or not.  And if we don’t keep doctors and patients fully informed of all the effects of pills they are much less likely to be able to bring benefits out of them.

Can you tell me where you get the idea I am embattled from?  I expect an SMC campaign – this is just the rough and tumble that someone who is concerned about patients and the profession has to put up with these days.  Aside from this I am not aware of much else – certainly nothing of substance that engages the issues.

Its not me being so sure of myself.  Companies have been sure in the case of close to 1000 different meds that they have caused psychosis and over several hundred that they have caused violence.

This has been the case for Zoloft for over two decades.  Do you think you’re looking after the interests of patients saying nothing about this?

D

From: Allen Frances <allenfrancesmd@gmail.com>
Date: 6 August 2017 at 18:45

It is not deceiving the public to take a balanced position that meds can benefit and meds can harm.

It is deceiving the public to assert with certainty that you know meds caused this mass murder.

And the vulnerable populations I worry about (& you should too) are not the many worried well who are over medicated, but the few very ill who desperately need meds & will be scared off them by your overly dramatic and unsupportable claims to omniscience that Holmes acted only their influence. Every act can have unintended harmful consequences. You are nobly trying to help people, but the extremity of your views and unwarranted certainty hurts others.

From: David Healy <david.healy54@googlemail.com>
Date: 6 August 2017 at 20:20

Allen

I was puzzled “extremity of my views” – about the medical model or access to data  – until I realized you were talking about my old style twentieth century making a diagnosis as opposed to taking a brain scan.

Having interviewed the man at some length and seen 24 hours of others interview him on tape and having read many other reports – all from people who quite happily say they know nothing about the effects of the drugs, and having had access to vast amounts of other material – computer records, texts etc – and having gone into it not thinking the drug played a part – I only went because the lawyers insisted – yes I am very happy this would not have happened but for the drug in this case.  Holmes has no sense that I thought that.

I remain the only person with any expertise in the drugs in this case who has interviewed him etc – so I don’t really know what basis you have for thinking my views extreme.

I have no idea what it would take to get you to realise this is not about Holmes innocence or guilt – he is gone away forever and would have preferred to be dead.  The issue is that very few people in the US or UK in anything remotely resembling this situation are getting a fair trial.

Long before Holmes I approached ACLU about this issue – who wanted nothing to do with it for fear of jeopardising prisoners access to healthcare.  I realize there is an access to healthcare issue in the US but I don;t think the people on this list need to act like you are an embattled minority.  Your job is to change this so both those not getting care and those not getting justice get a better deal

David.

 

 

Honey I Shrunk the Shrinks

 

Editorial Note: Prior to the Panorama program Prescription for Murder tonight,  a flurry of experts denounced the scaremongering. This didn’t just happen by accident.  The denunciation effort was also more intense than the pressure brought to bear on the original Panorama programs in 2002-2004. The change is in part down to the fact that Sense about Science, which co-ordinates the Science Media Centre/Center, was set up for this and related purposes in 2003.  

It would take a brave investigative journalist to investigate the SMC and SAS. No-one has been brave enough so far.

Some of the comments below are unfortunate.  It seems counterproductive to have the new president of the Royal College defend antidepressants, as her predecessor did, rather than defend psychiatrists.  If the pills are so good and so free of side effects, some politician is going to wake up some day to a new possibility – Honey I shrunk the shrinks and replaced them with nurses and pharmacists and we all are going to save a lot of money. 

From: Edward Sykes [mailto:edward@sciencemediacentre.org]
Sent: 25 July 2017 13:11
To: edward@sciencemediacentre.org
Subject: SMC Roundup: Antidepressants and murder

Science Media Centre Roundup

Expert comments on whether antidepressants can lead people to become a murderer, as is being reported in advance of the upcoming Panorama programme ‘A Prescription for Murder?’*

Prof Wendy Burn, President of The Royal College of Psychiatrists, said:

“We are disappointed with recent coverage about antidepressants, especially since the reporting so far has not included a comment from the College.

“For many milder episodes of depression talking therapies will be recommended as the first line of treatment.  For moderate to severe depression, antidepressants are an evidence based treatment. Their prescription should be reviewed regularly in line with clear national guidance. We know that more of the people living with mental illness now seek medical advice and we believe this explains the increase in the number of people being prescribed antidepressants. For many, these drugs have had a beneficial effect on mood and have helped reduce suicidal thoughts or self-harm.

“In all treatments – from Cancer to heart disease – medicines which do good can also do harm. This applies in psychiatry. Current evidence from large scale studies continues to show that for antidepressants the benefits outweigh the risks, which is why it is important to highlight that the experience raised by the author in the recent Sunday Times article is extremely rare.

“Any patient who is unsettled by this media coverage, or feels pressurised to stop taking an antidepressant drug, should not abruptly discontinue their prescribed treatment. Instead, they should make an appointment with their family doctor or mental health professional to discuss any concerns they might have. They should together make a joint decision about whether to continue antidepressant treatment.

“This decision should be made on their own individual experience and should be informed by how effective their treatment has been in helping to reduce depressive and anxiety symptoms, any side effects which might have occurred, and the risks of a recurrence of illness, if treatment is stopped prematurely.”

Prof Shirley Reynolds, Professor of Evidence Based Psychological Therapies, Director of Charlie Waller Institute, University of Reading, said:

“If the Sunday Times article is correct then the upcoming Panorama (A Prescription for Murder?) focuses on a BMJ study that came out last year that looked at suicidality and aggression during antidepressant treatment. Unfortunately, as we wrote in our letter published in The BMJ, that study had flaws in presentation and logic and the results were further misrepresented by the BMJ press release.

“The term ‘suicide’ was used when the data actually only referred to ‘suicidal behaviour which is a hugely important difference. The data in the study didn’t actually show any instances of suicide in children or adolescents. The authors also stated that antidepressants are known to increase the risk of suicide in children and adolescents, which is not factually correct and the references cited do not support their assertion.

“Furthermore neither the paper itself nor the editorial actually pointed out the significant fact that of the five antidepressants mentioned in the article only two (fluoxetine and sertraline) are currently recommended by the National Institute for Health and Care Excellence for the treatment of depression in young people.

“This matters because if people stop taking their drugs then that really can lead to an increase in suicides. A review of 574 youth suicides reported that only 1.6% had received antidepressants.

“Young people need access to a range of individualised evidence based treatments. The possible risks of harm from antidepressants (or psychological therapy) must always be balanced against the benefits of treatment and the increased risk of suicide in severe, untreated depression, but we must be very careful about turning people away from the very therapies that can help them.”

Prof Carmine Pariante, Professor of Biological Psychiatry, King’s College London’s Institute of Psychiatry, Psychology & Neuroscience, said:

“There is no good evidence that antidepressants increase the risk of violent behaviour, and the extremely rare (and tragic) cases that are cited in support of this theory could be explained by chance: antidepressants are prescribed relatively widely, and so by chance someone on antidepressants will commit a violent act. Moreover, people on antidepressants may be suffering from some forms of mental disorder or distress that may, albeit very occasionally, increase the risk of reacting impulsively or violently.

“With 7% of the UK population and 11% of the US population currently taking an antidepressant, we would have clearly seen an increased risk of violence if there was one. With alcohol, for example, there is a clear evidence that it is linked to at least half of all cases of violent assaults, child abuse, domestic violence as well as homicides and murders.

“In contrast, we know very well that every time an alarm reduces the rates of prescription for antidepressants, suicide rates increase, including in adolescent and young adults. The risk of suicide attempt in patients treated with the commonly use ‘SSRI’ antidepressants is approximately one-third that of patients who are not treated with an SSRI. And this is without even considering the life-saving effects that these medications have on patients’ recovery from their mental health problems.”

Prof Allan Young, Professor of Mood Disorders, King’s College London’s Institute of Psychiatry, Psychology & Neuroscience , said:

“Antidepressants are widely used and at the same time that the MHRA is constantly monitoring reports, scientists are continually doing studies looking into any side-effects. We have to be really careful that there is good evidence for the claims we make and if we find serious effects then we shout about them because we want to help patients.

“If there was good evidence of antidepressants turning people into murderers then we would certainly be looking into that. It is an extremely strong claim and therefore needs to be backed by strong evidence. So many people take antidepressants that we will always be able to find some coincidences, but it takes a lot more evidence to mean it’s more than that.”

Prof Seena Fazel, Professor of Forensic Psychiatry, University of Oxford, said:

“I have spent some years looking at the impact of psychiatric disorders and treatments on violent behaviour and the data is quite complex. The first thing to say is that there is no clear evidence of a link between antidepressants and violent behaviour in older people. In young people the latest stats do show something, but we cannot say that antidepressants are making people more aggressive as we can’t tease apart whether it’s the antidepressants or the fact that young people on antidepressants are also using alcohol, and some actually have severe personality problems which can make them more violent in the first place.

“The whole picture is further complicated by the fact that we don’t have much really high quality data and most data comes from trials which are actually looking at things like verbal aggression, rather than actual violent acts. We are trying to get round this by looking at data from countries where national crime registers can be linked to records of individuals with depression. We can then look for any differences in individuals who are prescribed SSRIs versus those who are not. You can also compare the same person twice – once when they use antidepressants and once when they don’t.

“With colleagues at the Karolinska Institute, we did one such study based on all people in Sweden from 2006 to 2009, which amounted to around 850,000 individuals taking SSRIs. What we found was a complex picture although two patterns emerged – for 80% of individuals who were prescribed SSRIs and were aged over 25 years, there was no clear association with violent crime. In those aged 15-24 years old, there was an association with increased rates of violent crimes (and also violent arrests and non-fatal accidents), however that’s not as clear as it sound as this association was stronger in those receiving sub-therapeutic doses of SSRIs, suggesting that partial treatment of the underlying depression may be one explanation for this link in younger people.”

* As reported in the Sunday TimesDaily Mail and The Sun

Declared interests    None declared

Note to editors

The Science Media Centre is an independent venture working to promote the voices, stories and views from the scientific community to the news media when science is in the headlines. Over 100 supporters including scientific institutions, media groups, charities, universities and corporate organisations provide a donation to support the Centre achieving its objectives. The SMC makes all organisational and editorial decisions independently of funders. This press release contains the personal opinions of those acknowledged, and represents neither the views of the SMC nor any other organisation unless specifically stated.

The Science Media Centre can also help you find an expert on a topical area of science, we have over 2000 media friendly scientists and engineers on our database and you can call us on 020 7611 8300 if you need an expert to interview.

The SMC has asked the experts in the above Roundup to declare any interests which may be regarded by a reasonable and objective third party as giving rise to a conflict, and their responses are included above.

For more details see our website www.sciencemediacentre.org, please e-mail the Science Media Centre with your comments on our service atsmc@sciencemediacentre.org

Dr Edward Sykes
Senior Press Manager and Head of Mental Health & Neuroscience

Science Media Centre
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Baby Boomerang

Editorial Note: This post continues a sequence of posts about well-intentioned efforts to produce change that may have produced the wrong change – see Boomerang and Boomerang 2.

The contraceptive pill, the Pill, came into our lives in 1960. Almost immediately there were reports of young women with deep vein thrombosis (DVT) and pulmonary embolus and in some cases death from thrombosis. As expected industry denied there could be a problem – DVTs happen, women are prone to them, pregnancy leads to more of them than anything else. Many medical and religious experts thought there had been shockingly little research on the Pill and it should be banned until a lot more was known about it. AMA and FDA undertook studies and reviewed the evidence and concluded there was nothing to it. In the middle there were a few experts like Louis Lasagna who said that if a bunch of young women start turning up with DVTs while on the Pill, there were compelling grounds to think the pill could cause thrombosis, but having been told the risks women needed to be let make their own minds up about it. This position probably cost him job in Johns Hopkins.

The original Pill was a high dose Estrogen pill. In 1968 a British study reported that high dose Estrogen pills were linked to far more thrombosis that just introduced low dose pills. There was panic.  The British regulator convened meetings.  The options were to phase out the high dose pill or begin to insert information for the patient with each package explaining the risks.  British medicine was against interfering with the doctor patient relationship and so the regulator effectively banned high dose pills.  The change was so rapid that pharmacies didn’t have time to stock up and there was chaos.

The following year Barbara Seaman’s The Doctors Case Against the Pill spread the panic to the United States. Senator Gaylord Nelson convened Hearings on January 4 1970 to review the situation. These hearings gave rise to the photo above – the forerunner of the all male Trump cabinet photo in January this year for the signing of the order limiting access to funding for any organizations having any truck with abortion.

The Nelson experts were all male. One of them John Davis, concealing his financial interests, made a pitch for IUDs and the soon to be introduced Dalkon Shield which had a huge uptake partly because of concerns about the Pill.  The Dalkon Shield caused horrific injuries and put the the company marketing it A.H. Robins out of business – in part because they spent so much time denying there could be a problem.

Girls

Nelson was pro-generic drugs, pro-consumers and generally progressive. So perhaps he did what he did next on purpose!  When two women from the Women’s Liberation Front stood up to protest what was going on, and refused to sit down, he asked the Girls to settle themselves.

All of a sudden a consumer movement that was having difficulties getting heard had hundreds of thousands more followers. Drugs beyond the Pill became an issue for women, who turned up in force at later hearings on tranquilizers.

Bill Haddad’s National Consumer League for Prescription Drugs had women experts and women presenters at hearings, and men began to become a touch more wary about women like Abby Meyer, a self-styled little old housewife from Connecticut, when she began talking about an Orphan Drugs Bill.

DTCA

Rather than remove high dose Pills, the FDA resolved the Pill controversy by opting for patient inserts to inform women. The AMA objected. It was the role of the doctor to have discussions with his patients. In the end there was a compromise, dispensing an almost unintelligible and opaque insert was left to the doctor’s discretion.

Some years later in 1978, the Carter Administration announced a Drug Regulation Reform Bill, more often thought of as a Kennedy Bill.   This planned to extend patient inserts to all medication and make them more intelligible.

It also proposed among other things to let companies post the prices of their drugs.  The generic industry was just coming into being and the hunch was that visible evidence of lower prices might help the switch and save costs. The National Consumers Prescription Drug League welcomed these changes. The Carter Bill went nowhere but …..

In 1983, on television in Florida, the Boots Pharmaceutical company ran the first Direct to Consumer Advert for a pharmaceutical.  A brief 40 second slot telling consumers that Boot’s own brand of ibuprofen, the original drug, was cheaper than some of the copies they might be sold.

They were instructed to take down the advert, while the FTC considered the propriety of this move. After thinking about it for two years, during which they had representations from companies like Lilly that this was not a good idea – it would be burdensome for industry – FTC sanctioned the move on the basis that consumers had patient information now anyway and had welcomed information about prices.

Before inserts doctors were the fall guys if something went wrong on a medication – it was their duty to warn. Companies had no duties to warn patients. After inserts and DTCA, doctors remain the fall guy – as GSK’s efforts to pin the blame on Dr Sachman in the Dolin case illustrates. You gotta have a fall guy.

 

Change in Chicago: Boomerang 2

In 1983, the year before Henry Waxman got the Waxman-Hatch Act on the Statute Books he got the Orphan Drugs Act passed.  Here’s how it happened.

In a wonderful 2016 self-publication, Abbey Meyer, a self-styled Connecticut housewife, outlines a story that began when her eldest son David was born in 1968.  The book is downloadable for free and is well written and compelling.

When David was only a few years old he began to show signs of what her doctor called tics. As problems grew at school, she became increasingly concerned for him.

Then one Sunday in a newspaper she read an article about Tourette Syndrome. This led to clinical appointments and treatment.  The standard drug, haloperidol, turned David into a zombie. He was enrolled in a clinical trial of a new drug pimozide, which was better, but supplies were cut off in 1976 when McNeil pharmaceuticals opted not to develop it further. Her doctor used the term orphan drug to explain what was going on.

An Orphan Drug was one that was likely to end up being used by less than 200,000 people – which the pharmaceutical industry figured was their break even point. Unless that many people took the drug, they claimed they were unlikely to make a return on their investment.  Around 1980 concern was growing that this might mean no new drugs for Multiple Sclerosis, or Epilepsy or Lou-Gehrig’s Disease (Amyotrophic Lateral Sclerosis – ALS).

Meyer was astonished. She became active.  Among the first people she tied up with was Marjorie Guthrie, the wife of Woody Guthrie who was campaigning for orphan diseases. A group of women mobilized pretty quickly. Muriel Seligman from Los Angeles had a son Adam with severe Tourette’s.  She approached her Congressman, Henry Waxman.  Waxman convened a hearing in June 1980 inviting all pharmaceutical companies. None turned up. There was no-one at the hearing apart from a few families with rare diseases and a reporter from the Los Angeles Times.

On the back of an LA Times article, Meyer was contacted by Jack Klugman who ran the Quincy MD show a widely watched medical series on TV. Klugman bought the idea of an episode that would have a boy (an actor playing Adam Seligman) testify at a Congressional Hearing in very emotional terms about the damage caused by lack of treatment.

The show Seldom Silent, Never Heard ran in March 1981. Its a must watch. There are 5 minute clips out there showing the key scene when Adam Seligman makes a pitch to Congress – but I can’t find the link at the moment.

Thousands of letters flooded in. Waxman convened a follow up hearing at which Quincy (Klugman) testified in person. There was standing room only. The Wall Street Journal laughed at Waxman and the idea that Congress might take advice from actors.  But Nancy Kassebaum introduced a bill in the Senate, which Waxman introduced in the house that passed both houses in December 1982 and was signed into law by Ronald Reagan in January 1983.

A few days later, Meyer and others formed the National Organization for Rare Diseases (NORD) and began cataloguing all the conditions that might qualify – there were over 6000.

By this stage she had met Bill Haddad. Haddad, as Chair of the Generic Pharmaceutical Industry Association, was chasing a Bill to regularize the position of generic drugs – that later became Hatch-Waxman.  Among other things he had made it clear that if the branded industry didn’t bring orphan drugs to the market, the generic companies would.

Haddad provided funds for an office for NORD in Danbury Connecticut. When the landlord heard what NORD was up to, he asked whether this meant AIDS patients might be visiting the premises. Meyer hadn’t thought of this possibility. The landlord told her she would have to go elsewhere but after a later “meal” with one of her supporters he made a several thousand dollar donation.

AZT turned out to be the first drug approved under Orphan Drug provisions, with almost all other drugs for AIDS and its associated infections being approved in the same way.

A key contact Meyer got from Haddad was Agnes Varis, the owner of AgVar a generic company. Varis was connected to everyone in the generic industry and the Democratic party.

At this stage rare diseases were assuming a shape fronted by ALS, multiple sclerosis (MS) and hemophilia. A drug called copaxone had shown benefit for MS but Meyer couldn’t persuade a branded company to pick it up.  Among other things the patent status was obscure.  It had been discovered in the Weizman Institute in Israel.

Varis strong-armed Teva, a small generic company based in Israel and the US to pick it up.  It was approved under the Orphan Drugs Act and went on to blockbuster status, earning Teva over $1 Billion per year, and making Teva the leading generic company.

Get on the Train

Meyer’s book is a compelling read.  But its difficult to avoid a slight feeling of deliverance from a ghetto on trains that turn up to transport us East to safety.

As of 2016, the branded drug industry is a $1,275 Billion dollar industry half of whose profits ($638 Billion) come from drugs brought to market in the standard way. The other half ($637 Billion) comes from drugs availing of the Orphan Drug provisions which allow for an easier ride through FDA and a longer period of monopoly.

The orphans have included Merck’s Vioxx, Lilly’s Cialis, Astra’s Crestor, Bristol Myers Squibb’s Abilify, Botox and many others among the best-selling drugs of recent years.

While it is possible to close some loopholes that lead to blockbusters being named orphans, the precedent of allowing high prices for drugs that will supposedly only ever occupy niche markets has laid a business model for personalized medicines.  If genetic tests ever permit a tailoring of medicines to specific patient groups, the orphan argument will apply.

For most of this period, the Wall Street Journal had Henry Waxman as one of its prize targets claiming that he was to progress what the Troll under the bridge was in the Billy Goats Gruff.

But without mentioning him, as early as 2005 WSJ was trumpeting the fact that Orphan Drugs Act had been the savior of the pharmaceutical industry – not that an industry earning $638 billion from other sources really needs saving.

 

Change in Chicago: Boomerang

When it comes to branded and generic drugs, the listing of key issues in this image misses a trick. The labels are identical.

This lack of difference is a consequence of the 1984 Hatch-Waxman Act which after two decades of dispute staked out a boundary between generic and branded pharmaceutical companies, part of which in the case of their drugs required the generic companies to take over the label of the branded drug when they entered the market.

The Cost of Drugs

The issue of branded and generic took shape in the 1950s.  Before then the primary way companies controlled drug niches – monopolized on the sale of profitable drugs – was through branding rather than patents. This meant there were a lot of branded generics and a lot of companies who manufactured drugs for other companies who branded and marketed.

The branding and marketing cost money and was the major component of a drug’s price – that and profit taking. If consumers could access “raw” medicines the same way they can access unbranded other products, they would be able to save money. And driving down the price of drugs was the main goal of Estes Kefauver’s hearings on the pharmaceutical industry that led to the 1962 Amendments to the Food and Drugs Act.

Kefauver failed in his goal of containing prices.  Other changes his amendments introduced, such as the need to prove a drug worked before marketing and the use of controlled trials to achieve this, drove the price of drugs up. As prices rose during the 1960s, for a variety of reasons support for the idea of increasing the flow of generic drugs began to grow.

The main block to the use of generics was legal.  Most American states for instance had anti-substitution laws, meaning that, if a doctor wrote a script for a branded drug, a pharmacist could not substitute a cheaper generic drug.

Battle lines were drawn between the consumer movement, a relatively powerful lobby in the 1960s, and the branded industry who for the most part were operating behind a shield of doctors.

The push to repeal anti-substitution laws and greater use of generics was portrayed as a push for socialized medicine and an infringement of the sacred relationship between doctor and patient. Do you want your doctor to give you the best or the cheapest drug?

Pharmacists were warned about the risks of being sued by patients if they were to intervene and swap drugs and something then went wrong.

Staring in 1974 with Kentucky a trickle of states repealed their anti-substitution laws, while Oklahoma refused to do so.  The key moment came in 1978 when New York opted to allow substitution.  This was key because where other states had lists allowing twenty or thirty drugs to be substituted, using cloak and dagger methods Bill Haddad in New York had created a list of 800 FDA supported substitutions.  It was this rather than Haddad’s later involvement with Orrin Hatch and Henry Waxman that brought generics into play.

Tidying Up?

Hatch-Waxman tidied up the loose ends.  It gave the branded industry a modest amount of patent extension and streamlined the process for generic drugs to enter the market.

A central element of the deal involved the label generic companies would run.  Generic companies can make chemicals but the branded companies run the trials and collect the early data on a drug that makes the label and transforms a chemical into a medicine. The best deal seemed to be for generic companies to take over the branded label lock stock and barrel.

When the Supreme Court ruled in 2011 that generic companies could not be sued in a failure to warn case, because they had not done the warning, this set up a predictable clash.  In 2001 when Prozac went off patent and Barr Laboratories brought out a generic fluoxetine, it was clear that at some point the question of suicide on a generic SSRI would become an issues.

The Dolin case is where the rubber hits the road. Some higher court will have to decide on the merits of allowing GlaxoSmithKline to be sued when Stewart Dolin committed suicide while taking generic paroxetine rather than Paxil.  This may take some years to sort out, with every iteration in the legal process cementing Stewart Dolin’s name in legal history.

Boomerang

Meanwhile, the cost of branded drugs around 1962 was less than $10 Billion per year.  In 1984, the year of Hatch-Waxman, it was slightly over $20 Billion per year.  It is now a $1,200 Billion per year operation.

Somehow every action in the pharmaceutical sphere has a way of turning out exactly the opposite of what its promoter intended.