Making medicines safer for all of us

These words are from David Foster Wallace.  I don’t know if he was speaking about the depression he had or the akathisia that antidepressants can cause.  Maybe he didn’t know and this contributed to his suicide.

This post needs to be read in conjunction with What to do about Sex on RxISK.  This post is about structural aspects to the problems not just of sexual dysfunction and suicidality caused by drugs but all other adverse events also.   The RxISK post is about the specific things people can do about a specific sexual dysfunction or adverse event such as suicide.

Structurally Speaking

Here’s the easy bit.

Raising Awareness

Its impossible to argue with the proposals after the last post by Heather, Tim and others to try to raise awareness about akathisia.  The word is confusing and it’s difficult not to think as Sally does that its obscurity, almost meaninglessness, has been a godsend to industry

Something like Drug Induced Emotional Turmoil (DIE.T) might have got the message over more effectively twenty years ago but MISSD and others have produced such good material on akathisia already that its not clear that going back is an option.

The tee-shirt ideas are great. I’ve been in touch with Bill James who has produced all of the really striking images we have had on RxISK.  It takes a while for images to come to Bill – and this time will likely take longer as the outlines of a song is what has turned up first.  There is no reason to wait around till more comes from Bill – quite the contrary the fact something else is happening should encourage more diverse effort.  As the message on RxISK and below puts it don’t be put off by experts – even expert artists.

FDA, MHRA, EMA, Health Canada etc

There is no point looking to a regulator to solve problems with any adverse effect on a drug.  Their brief is to supervise the wording of drug labels and adverts by drug companies primarily before a drug comes on the market.  It is not to ensure that patients or doctors are properly warned before they take a drug.

Being bureaucrats their job is to make sure they have a good reason for doing nothing.  This means for instance that there needs to be a hint from an RCT that a drug does something they can point to if politicians ask questions.  If a politician asks about akathisia, the regulator can say – ah but if we warn about that we will deter people from seeking treatment and lives will be lost.

This is why they are so vulnerable on the issue of SSRIs for children.  There is no benefit they can point to – not even for fluoxetine (Prozac).

Why did RxISK submit a petition to FDA, EMA and MHRA about PSSD?  You have to be seen to cover all the bases but there is no expectation that things will change.

Government

Government will never do anything companies don’t want. Even if you were to go on hunger-strike outside Congress or Parliament, it would count for nothing.

In the case of AIDS activists their protests got somewhere with Government and Regulators – primarily because they were asking for politicians to ease the regulations on companies.  ACT-UP wanted things made easy for Pharma.  This resulted in them getting early access to thalidomide and a host of other drugs that may have killed as many people as the virus did.

Guideline Bodies

Bodies like NICE and others who write guidelines base their recommendations on ghost written articles.  They have no access to the data.  They invariably recommend the latest high cost drug over superior lower cost but off-patent drugs because if they don’t pharma will threaten to pull out of a small country like Britain – and there are presumably other threats in the US.

The guideline makers are unwilling to share a platform with anyone who might raise the issue of access to data or what they do about ghost-written articles.

The SSRIs and children story is supremely inconvenient for NICE and other Guideline bodies but they don’t have to share a platform with anyone or answer questions from a journalist on the issues so don’t hold your breath.

Journals

Through till 1991, journals carried case reports of adverse events – Evident Based Medicine.  These reports contributed more to the progress of medicine than Evidence Based Medicine has done. But following the publication of the Beasley et al  1991 meta-analysis of Prozac trials in BMJ (which showed an increased suicide risks that BMJ reviewers and editor missed) – the which are you going to believe the anecdotes or the data article – journals like BMJ are now scared to publish case reports or anything about adverse events.  Besides which reprints of RCT and meta-analyses are so much more lucrative.

See Vampire Medicine and related posts – A Call to Harms.

It takes a brave journal to provide a forum for adverse events – see Villains and Heroes.

Pharma

These are largely marketing companies these days.  The research, clinical trials, medical writing, public relations (SAS and SMC) and increasingly pharmaco-vigilance has all been outsourced.  There is no-one at home who will understand the question being asked.

Some of the major breakthroughs though have come from people within pharma sending documents to people in the media or others.  Or taking the high risk route of filing a legal action against their own company.  They may get lucky and get money from it but there are more likely to just lose a job.  In general, people working in pharma have done vastly more than politicians, bureaucrats or clinicians to bring problems to light.

For every Schindler though, there are thousands of ordinary folk who by doing a good job (keeping to the rules and following orders) are at least as ethical as anyone injured by their drugs from thalidomide to Zyklon B and on.

Bereaved

There are a large number of people who read these blogs and comment and are desperate to find a way forward who have been injured by treatments or lost loved ones to treatment.

There is also a large number of people, perhaps an even larger number who have been injured by treatment and in particular who have lost loved ones to treatment who have become advocates for more treatment – who will front up programs to pick up schizophrenia or depression or osteoporosis or cancer at the earliest possible stage.  If only we’d picked things up in time, everything would have been okay.

This is the side Prince Harry or Camilla Parker-Bowles or Ivanka Trump are always going to end up on – they will all want to spread the good news of salvation through baptism and treatment.

Law

This is where Americans have an advantage.  They can take a lawsuit – although its incredibly difficult to do so. Europeans can’t. Winning a lawsuit can make a difference – 20 years later.  Tim Tobin won his case against GSK in 2001.  The benefits of that win are still making a difference.   But for the most part companies have become adept at shutting down any publicity that might stem from a legal loss.  Pretty well no doctors have heard that GSK lost the Tobin case or cases against them for dependence on paroxetine or birth defects on paroxetine or even the Dolin case.

NGOs

NGOs from the ACLU to Medecin sans Frontieres (MSF) to Open Society and others are committed to your rights.  This is great but in practice they are committed to your rights to treatment so drug companies actually rather like them.

The coin hasn’t dropped for any of NGOs that access to medicines should mean full access to all the information that transforms a chemical into a medicine. When it comes to harms, NGOs at the moment are part of the problem not part of the solution.

Activism

ACT-UP put activism on the map.  Its fizzled out. Its not clear that AIDS type activism can play a useful part in terms of raising the profile of adverse events.  It hasn’t so far.

RxISK put a much older form of Irish activism on the map – the Reverse Boycott.  We called this an AbbVie – Lets Do the AbbVie Again – which may be why it didn’t catch on. Basically this involves getting people to stop writing to companies or regulators asking them to be reasonable and bombarding them instead with reports of adverse events on drugs.  Only 1% of the serious adverse events on drugs are reported.

The ideal form of this would involve getting your doctor to submit a report also – this was the idea behind RxISK reporting.  The courts cannot ignore reports that have people’s names on them and is very unlikely to be able to ignore reports from both you and your doctor.

Companies dismiss your reports with the phrase – The plural of Anecdote is not Data.  Maybe we need a catchy slogan – Corroborates are Compelling.  Corroborates are Conclusive. Please suggest

But people seem scared to do this. This is an important discovery – people are scared silly.  Their doctors are even more scared.  We are facing a Structural Violence that almost no-one is talking about.

APA, RCP, Psych Central

The people who are failing everyone the most are doctors and their professional associations.  If the American President of their Psychiatric Association or Medical Association were to make it clear they thought some drug caused a problem, the pharmaceutical companies and regulators would have to act.  They’d be trumped.

Why would the President do this?  At the time of the 1962 regulations, FDA and other regulators were viewed as small beer – regulating advertisements.  The real people regulating medicine and keeping their patients safe were doctors.  Who for the most part had a good track record in putting conditions like tardive dyskinesia (1959) or dependence or drugs (1961) on the suicide that antidepressants can cause (1959) on the map.

For those with the time to let the dish go cold, the revenge will be that this ignoring of adverse events is going to put doctors out of business.  Just as salt that loses its flavour is useless, there is no point spending money on high cost prescribers if they can’t deliver anything that lower cost prescribers would and perhaps even less than robots soon will.

Social Media

You can’t depend on it.  The Spectre of Dissent post fell foul of Facebook.  It was removed.  If a post threatening to raise the profile of adverse events, even an effort to save children from suicide, ever looks like it might get anywhere, the chances are Facebook or other outlets will find some way to block it.  Facebook has 23 community standards – they’re worth a look at.  It will always be possible using one of them to limit the spread of unwelcome information.

RxISK has an Akathisia page.  In 2016 when it was put up it featured near the top of Google searches.  MISSD have produced a great video on akathisia but it has begun to slip down the rankings also.  We are being replaced by articles and sites like WebMD and related that focus only on the visible motor restlessness this condition involves.  Rather than outright block something – which feels like a Facebook own goal – this is a more subtle way to control the conversation.

Taper

There is a thing called the ZPD – Zone of Proximal Development – that mothers know about.  Its means knowing what A to encourage your child to do next to help him get to B and C and then D rather than trying to force him to get straight to D (the way his sister did).

We sometimes think that being reasonable – arranging meetings to talk to the regulators, or those other people we need to keep onside  – is taking the A step, after which B and C and then D will follow.  They won’t follow.  The regulators, and professionals may smile nicely but landing on A makes you an enemy of the people.  You will never be let get to B or C, never mind D.  We will hang on to the carriages being used to transport you to Auschwitz even when the Army are asking for them to try and shore up the Eastern front against the Russians.

This has led RxISK to Taper MD.  It may take 10 years for Taper to begin to make a difference but the trick is to go with the flow.  If  everyone wants to hear drugs work, and no-one wants to hear they might cause problems, then this is what we talk about.

Let’s get you maximal efficacy – this it turns out means 5 or ideally less than 5 drugs at any one time.  Clinicians and patients working together are going to have to perm from among the thousands of possible drugs a winning combination.  What the patient wants will be key to this.  This is what’s going to get people to D.

What to do about…

Meanwhile, for those trying to get a son rather than a daughter somewhere, you need a bunch of Anne-Maries – See What to do about Sex.  People with motivation can move mountains if they don’t sit around waiting for experts or other authority figures to do it for them.

The last post The Greatest Failure of What Used to be called Medicine provoked a lot of comment – or at least the photographic images in it did.  There was little discussion about the content of the post and what to do about the spectre of bureaucrats in the guideline and the regulatory apparatus hanging together when it comes to something like children hanging after antidepressants.

Gillian Anderson and others asked if its valid to use images like this?  Will it do “the cause” more harm than good – put off the people who need to listen?

In 1963 Thích Quảng Đức, a Buddhist monk, set himself on fire in Vietnam in protest against the South Vietnamese Government, soon to be supported in spades by the US Government.  JFK said “no news picture in history has generated as much emotion around the world as that one”.

The Americans didn’t listen.  It took over a decade to sort things out.

In 1969, Jan Palach set himself on fire in Prague in protest against the Soviet occupation.

Ireland, the home of Lynching, is also the home of the Hunger Strike, and the Boycott – non-violent ways to bring about change – Gandhi, Martin Luther King and others came later.  These moves often expose the violence in the system – hunger strikers are let die, the boycotters were shipped off to Australia,  Gandhi and King were assassinated.

There is unquestionably something honorable about dying or suffering yourself for a cause.

The people of Prague turned out en masse for Palach’s funeral and his death played a part in the later formation of Charter 77.  There is unquestionably something honorable – but does it work.

Re-Traumatising

Gillian and Maria Bradshaw raise points about re-traumatization.  Showing a photograph of a hanging child or a lynching will disturb people and this is an injury inflicted on them by the person showing the photograph – me in this case.

I don’t buy this.  The violence, trauma, disturbance is real but it comes from the system.  There is nothing more that the system would like but for everyone who has lost a loved one to a medical treatment to shut up.  They would love nothing more than to help generate the impression that someone who tries to raise concerns is an enemy of the people.

If a photograph of a hanging child traumatises some, well we probably should ensure we don’t talk about these things either.  Perhaps there should be trigger warnings on blog posts.  This is reverse Stockholm syndrome.  In Stockholm syndrome, people held captive by their hostage taker come out singing their sympathy for him.

In Saigon syndrome (we need a good name for this), anyone who tries to rescue people from a prison gets seen as an enemy of the people.  The doctors and clinical psychologists who come along to shelter you from something disturbing get seen as the White Knights.

These posts will disturb, unsettle and anger some?   Should they not happen?

Violence

I and others have gone down and will continue to go down a non-violent route.  This is what RxISK is all about.

One of RxISK’s main goals was to tackle the violence of the system by getting people not just to file RxISK reports but to take them to their doctors .  Among the most astonishing things this has shown is that people are too plain scared to do so.  They sense their doctors will get nasty.  And many doctors probably will get nasty, because doctors sense the system will get nasty with them if they don’t squash out dissent.

It is clear that pretty well everyone is being traumatised the whole time.  The momentary disturbance triggered by seeing a photograph hints at the pressure everyone is under.

This pressure is not going to go away unless we tackle it. Part of the difficulty in tackling it is alerting people to the fact that their problems don’t come from rogue doctors who make mistakes but from good doctors who keep to guidelines – based on junk.  There are few better symbols of the violence of the system than the craven attitude of bodies like NICE to the refusal of pharma to hand over the data.

Its not just NICE who are part of the problem – its non-governmental bodies (NGOs) like Medicins sans Frontiers (MSF), (Doctors without Borders), George Soros’ Open Society, Health Action International (HAI), the American  Civil Liberties Union (ACLU) and others involved in Access to Medicines campaigns who will fight the easy fight about the cost of drugs and not the fight about access to the data that turns a chemical into a medicine.

Its not just regulators, and guideline bodies and NGOs who are part of the problem, its everyone who turns to complementary medicine or antipsychiatry or who rejects the medical model one way or the other.

Its professional bodies like clinical psychologists who scream blue murder about trauma but never help a patient disabled by the side effects of drugs to stand up to the doctor who has put them on the drugs.

The system depends on everyone to quietly get on the trains that turn up to take us East.  This is a hazard of bureaucracy that was put on our radar by Max Weber a century ago.  There was a “there there now Max” response at the time and later outrage at the suggestion he might have been predicting the Holocaust.  We are nowhere nearer getting to grips with this than we were a century ago.

Dissent

Following the death of Jan Palach, Vaclav Havel and others set up Charter 77 to respond as they saw it to the bureaucratic dictatorship in which people in Eastern Europe found themselves.  Previous dictatorships had involved a minority and were temporary but the Soviet system ruled in the name of the majority and looked pretty permanent.  Havel didn’t want a turn to the West which he saw as pretty capable of going just the same way.

As Havel put it:

“A specter is haunting Eastern Europe, the specter of dissent…

You do not become a ‘dissident’ just because you decide one day to take up this most unusual career. You are thrown into it by your personal sense of responsibility, combined with a complex set of external circumstances. You are cast out of the existing structures and placed in a position of conflict with them. It begins as an attempt to do your work well and ends with being branded an enemy of society. … The dissident does not operate in the realm of genuine power. He is not seeking power. He has no desire for office and does not gather votes. He does not attempt to charm the public. He offers nothing and promises nothing. He can offer, if anything, only his own skin—and he offers it solely because he has no other way of affirming the truth he stands for. His actions simply articulate his dignity as a citizen, regardless of the cost.

It’s easy to resonate to these nice words now that we know Havel won – largely by accident.  It took a shipworker in Poland to galvanise things.

Feeling a warm glow in response to these words is rather like the warm glow that half the population of Dublin had when later claiming they were in the General Post Office (a small building) at the time of the Easter Rising when in fact most Dubliners were hostile to the revolutionaries at the time.  The Easter Rising was a curious mix of violence and self-sacrifice – almost like committing suicide by aiming what appears to be a gun at the police.

We need more than the stirring words in Havel’s quote.  Written before he won, the key insight is that you become an enemy of the people – even the people who have lost loved ones and been traumatised by the system.  Even for the Jews in 1942 or 43, those who took to the woods rather than getting on the trains were enemies putting everyone else’s life at risk.

If you win, the stone the builders rejected becomes the cornerstone.  If you don’t, the people call for crucifixion – pretty well force the powers that be down this route.

Editorial Note: This anonymous comment featured toward the end of the Murder or Accident post. It seemed worth transforming into a post in its own right. In the week of the US vote, a key question facing voters is where does all the pain come from.

A colleague and I gave a talk to family docs this year and we discussed the opioid epidemic, including the 1% risk of addiction myth in Letters to the Editor at NEJM. One Key Opinion Leader (KOL) is now acknowledging that he may have overstated the safety of opioids but maintains that they still have a role in chronic pain, see Dr Russell Portenoy here: http://www.wsj.com/articles/SB10001424127887324478304578173342657044604

He strikes a controversial chord with others involved in treating the outcomes of chronic pain killer addictions, like Dr A. Kolodny, see here: http://www.medpagetoday.com/painmanagement/painmanagement/47855

Other KOLs like Dr Jane Ballantyne, have made 180 degree turns regarding opioid use in chronic pain, this article is well worth the read: http://www.nytimes.com/2012/04/09/health/opioid-painkiller-prescriptions-pose-danger-without-oversight.html?_r=0

Challenging myths that have so much resources poured into them to maintain is very difficult. We were all taught that pain was the “fifth vital sign” by the American Pain Society (around the same time OxyContin approval occurred). You can see the sordid history, including how patient satisfaction scores may have a role in this epidemic, here: http://www.kevinmd.com/blog/2016/04/the-opioid-epidemic-its-time-to-place-blame-where-it-belongs.html

The US Docs probably had some scare put into them by the successful legal case brought against a doctor (Dr Chin) in 1998 who was charged for not treating pain adequately. Incidentally, this was the same time as the heavy marketing machine was revving up for Purdue. http://articles.latimes.com/2001/jun/15/news/mn-10726

The appalling story about Purdue/Abbott’s role in this public health disaster is outlined nicely here:

https://www.statnews.com/2016/09/22/abbott-oxycontin-crusade/

There has been very vocal opposition from pain advocacy groups and physicians when British Columbia adopted the March 2016 CDC pain guidelines that discuss opioids and state they are not effective and should not be used for chronic pain and that doses should not exceed 50 mg equivalents of morphine.

Pain BC is encouraging patients who have been affected by these new regulations to complain to the College! https://www.painbc.ca/news/howdothesenewopioidguidelinesaffectyou. Nothing strikes fear into physicians quite like a good old College complaint!

Although the evidence of harm is abundantly clearly (lack of efficacy in chronic pain, massive overdose deaths, lives in ruin, 80% of heroin users report starting drug use with physician prescriptions), both people and doctors choose to ignore this and some doctors fear College investigators. Sounds a lot like Dr Chin all over again…

Big Pharma’s influence in Canada continues. See here for Purdue’s lobbying of the Federal Government: http://canadians.org/blog/who-behind-canadas-opioid-epidemic. A coalition of chronic pain and addiction specialists signed a letter earlier this year, requesting that Federal Health Minister Philpott consider making oxycodone only available as a tamper resistant formulation (of which Purdue holds the patent). Sixty percent of the signatories have ties to industry. http://www.theglobeandmail.com/news/national/ottawa-urged-to-reconsider-tamper-resistant-oxycodone/article29813367/?utm_source=twitter.com&utm_medium=Referrer:+Social+Network+/+Media&utm_campaign=Shared+Web+Article+Links

Dr David Juurlink may have said it best in the Globe and Mail piece referenced above:

“It’s time we stopped listening to pain specialists. Their messages, which were wrong, got us into this mess in the first place,” “Many of these physicians are deeply in the pockets of the companies that make opioids and that stand to profit immensely from the sale of these new products.”

Ontario released a new “Strategy to Prevent Opioid Addiction and Overdose” on October 12, 2016. This milquetoast framework to our public health crisis makes several vague recommendations, one of which is to make more substitution therapy available, specifically access to buprenorphine/naloxone (Suboxone). The document fails to provide suggestions for how to carry this out nor does it make mention of the potential public health risks. Studies have shown that Suboxone is ten times more likely to be diverted than methadone (i.e. not taken by the intended person and diverted to illicit market). We may want to ask Finland for some advice (buprenorphine, has been at the top of drugs misused in that country): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3154701/

The provision of methadone (the other substitution treatment available) in the province received well-deserved criticism from the “Methadone Treatment and Services Advisory Committee”. http://health.gov.on.ca/en/public/programs/drugs/ons/docs/methadone_advisory_committee_report.pdf. Page 11 details some of the most egregious concerns:

 “Lack of access to comprehensive care in stand-alone fee for service clinics: Many of these clinics provide little more than urine drug screening and methadone prescribing and dispensing, leaving patients without access to primary care, mental health and addiction screening, brief intervention or counselling, and management of acute and chronic illnesses. Variation in the quality of clinical services: Some clinics require frequent attendance for urine drug screening and a brief office visit regardless of the state of recovery demonstrated by the patient. This is wasteful and can be harmful to patients’ recovery as attendance can be inconvenient and at times very challenging, particularly for those in rural and geographically isolated areas.”

Profit driven care has clearly moved the patient far way from being in the centre.
Some are sounding the clarion call of “another epidemic” happening where over 50,000 patients in Ontario are now on methadone https://substanceabusepolicy.biomedcentral.com/articles/10.1186/s13011-016-0055-4

Perhaps the most astonishing elephant in the room is “why are so many people in pain?” As a society we must look at the root drivers of this epidemic and that must also focus on prevention. We need to do some serious soul searching as a nation, as a community of peoples. We will need to address poverty, hopelessness, dislocation, safe housing, disintegration of community, lack of meaningful employment, adverse childhood experiences, resiliency, etc. if we have any hope of bringing this epidemic under control.

Comment

The links above are chilling. The video clip of Russell Pourtenoy is beyond belief.

It raises the question as to whether there is a growing amount of pain in the world as this US election suggests. The alternative is that doctors been adding to whatever pain and anxiety there is and to other dis-ease. While opioids and other pain-killers can give wonderful relief when given short term, as can benzodiazepines for anxiety, there is good evidence that given chronically opioids and benzos increase the amount of pain and anxiety we have – by altering physiological thresholds in the wrong direction.

Old style doctors, professionals, knew this. New style technocrats – we have the technology to fix your pain and anxiety – don’t know it.

It was and is an important part of caring for you to know the limits to what we can offer. But we now live in a world where choices like opioids are put on plate in front of you and your doctor and you are invited to choose. The right choice will supposedly deliver the jackpot – this is what marketing promises.

But somehow wisdom is never on the list of options – it can’t be – it’s not evidence based. It would be irrational to let you choose something that is not evidence based – like less medication or vaccines. That’s not a free choice.