Making medicines safer for all of us

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

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

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

Archive for August 2012

The Tree Must Go

Tree in the countryside

Crusoe had a chance to view the new facility – the brainchild of one of the world’s wealthiest men, who had made his name in a race to sequence the genetic code. He had famously used his own DNA in the process. He later went on to create synthetic life and it was from synthetic biology He made his fortune.

The inspiration to recreate Eden came from watching an old movie, The Truman Show, in which Truman Burbank, played by JC, is cocooned in a world in which everyone else is an extra in his life and everything is stage-managed.

Why not do it properly with real people? They could be designed free of genetic disorders. Their main use for drugs would then be for psychedelic or hallucinogen purposes where every dose produces a different outcome in contrast to the numbing uniformity of twenty-first century drugs.

A range of projects in a number of different countries had shown how to create self-contained environments. Curiosity’s trip to Mars in 2012 had confirmed the presence of extensive subterranean water, making all else possible. The new facility was set up. Unlike the Truman Show, its occupants were unlikely to come into contact with outsiders for several centuries, perhaps millennia.

Synthetic biology had made it possible to design species to fit the new ecosystem. No-one of course could know beforehand what in fact would happen when these species began to interact. In other words, the place would almost instantly begin to have a history, and slip out of control. Whether He realized this or not was less clear. Maybe He had a fantasy about being able to intervene.

The most important moment was designing the woman to take control of the Garden. The man came from stem cells retrieved from the marrow in one of her ribs.The first couple were just about to be woken up in the Garden, when Crusoe arrived. She was in time to see the final check that everything was in order. One last round for Health and Safety. It was then they noticed the tree, growing on a slope. A firstborn son out climbing who slipped could have a dangerous drop on the downhill side. The tree must go they said.

The New World had a history. Ultra-short story writing became its dominant art form. The form developed when someone dreamt one night of the following: “For sale, baby shoes, never worn“. The shortest was “Crusoe, we say, was saved”.

The Oedipus Effect

Crusoe was called to see the woman. It all began she said when on the way home after a successful board meeting, taking shelter from a sudden downpour, he stepped into an empty building. There he saw something. Perhaps it was the nutmeg with the meal or the mushrooms that did it. A bunch of children, he said, sitting looking at a stockmarket ticker tape. Many of them appeared limbless, had cleft palates or clubfeet or were otherwise deformed. Others had the scar of some operation down their breastbone or elsewhere, some with the stitches still in.

All hail the Thane of Delaware one sang, as the ticker tape showed a share-price rise. All hail the Thane of Pennsylvania another said as the share-price rose further. All hail Mr. President the last one said as the share-price rose yet higher.

He came home astonished. He couldn’t see what she could. But she said, tearfully turning to Crusoe, things had not worked out. The treatments coming through had been nothing like the breakthrough treatments of a few decades before. Far from getting people well, more were dying earlier. Younger and younger children were being put on some of the foulest drugs on earth. She had thought no-one in their right mind would prescribe such drugs to children or pregnant women but there seemed to be nothing that could stop it happening. The last years of a person’s life, the years of sere and yellow leaf, became the most profitable years for the company. Few of the elderly went to their graves on less than 30-40 pills per day. The country was in thrall.

There was wailing across the land but no-one seemed to have an idea how to bring about change. Some broke into and occupied buildings, but what good could this do when it was impossible for doctors to do anything other than what the evidence said. A series of traitors leaked documents but these resulted in no more than minor embarrassments.

When the Thane of Indiana’s wife became depressed in the midst of all this, she was put on treatment and committed suicide.

She sometimes wondered if he was on something he had become so unfeeling. Never more so than when one of his closest friends on the way up suggested they needed to change course, and soon after was terminated. The man she married would never have done this. Not to someone who had been through so much with him, without whose help he would never have made it.

There was no option he said. As long as the clinical trial data pointed the one way, there was no other rational option for the country but to follow it. Unless someone was to show the entire body of clinical trials was worthless marketing copy, there was no way to undo the system – and what chaos would ensue then. He had even mockingly on one occasion said no-one born of man could bring the system down.

The security around him recently had become total. She was sure they had profiled her and knew she posed no threat. Or else thought her death would make no difference. They knew she was infertile.

“But I had a test-tube baby before I met him and gave him up for adoption”. “Has he just contacted you?” Crusoe asked.

For The Oedipus Effect – see The Antidepressant Era. Re parable, a startling number of US Senators, Governors, Secretaries of State, and even Presidents have had senior roles within the pharmaceutical industry, which is based in Delaware, Indiana, Pennsylvania and New Jersey.

Suffer The Little Children

Illustration of sick child in hospital

This post was written by Dr Irene Campbell-Taylor, a former Clinical Neuroscientist and Assistant Professor of Medicine at the University of Toronto.

This phrase means, of course, to allow the little children but today I want to write about children who are suffering in the other sense. The word “patient” comes from the Latin patire, to suffer or to endure. The children I write of here are suffering what I can only call medical abuse. Anyone interested however marginally in controlling what Big Pharma is doing should watch the PBS program “The Medicated Child”.

We become outraged at the actions of pharmaceutical manufacturers that negatively affect young adults, the middle aged and the elderly but when one sees the pharmaceutical abuse of children, outrage takes on a whole new meaning.

They “make me more like I’m supposed to be”

The most striking thing about this program is, of course, the number of antidepressants and antipsychotics these children are given, often from toddler age. It is deeply disturbing to hear parents declare that they have become convinced that their child needs to be constantly drugged and will probably continue to need these medications for life. When one mother expresses concern about the effect these may be having on her child’s development, she is, politely but definitely, dismissed. It is even more distressing to hear a thirteen year old say that she has to take several medications because they “make me more like I’m supposed to be.” Who decides how she’s “supposed to be”? It is to weep.

Having worked for many years with children and adults who have developmental and/or cognitive impairments, I couldn’t help but be amazed at the physical signs and behavioural aspects that, in this film, are repeatedly missed by pediatricians and psychiatrists. In several of the children in the program, I would want to investigate the possibility of a genetic condition, the physical aspects are so clear.

The parents are brainwashed

The parents are, in a word, brainwashed. Over and over we hear that “if we stop the medications his behaviour returns, sometimes worse.” Have none of these physicians ever heard of withdrawal syndrome? To illustrate just how far this propaganda has spread, we hear that the schoolteachers are suggesting medications. And being listened to by parents.

The “tantrums”, aggression and self-harm that lead to this appalling medication cascade don’t seem to be examined for what they might actually represent. There are genetic conditions in which these are prevalent behaviours and require specific approaches, depending on the particular disorder. But let’s imagine we are three years old again and are afraid of something real or anticipate fear or feel pain that we can’t express. What are we going to do to get the message across? What if you’re three years old and have been abused? How might you react? I’m not suggesting that this is the case with any of the children in the program but I have seen a sufficient number of children who have been physically and sexually abused, at ages you probably wouldn’t believe, to keep it in the forefront as a possible explanation for behaviours that have been described as “oppositional”, “aggressive”, “violent” and so on but now are…BIPOLAR.

I hardly know where to begin. Bipolar disorder in adults is extremely rare and to have the arrogance to assert, on the basis of no evidence whatsoever, that it is common in children is staggering. It is probably possible to do as Dr Biedermann has done, to take the signs of several disorders, overlap them, pick out those that occur in common and create a whole new disease.

Biederman and the drug companies

It is important to note that Massachusetts General Hospital disclosed sanctions against Drs. Joseph Biederman, Thomas Spencer and Timothy Wilens for violating hospital ethics guidelines by failing to adequately report, internally, seven-figure payments they received from drug companies. The disciplinary actions include:

  • They must refrain from “all industry-sponsored outside activities” for one year.
  • For two years after the ban ends, they must obtain permission from Mass. General and Harvard Medical School before engaging in any industry-sponsored, paid outside activities and then must report back afterward.
  • They must undergo certain training (type not specified).
  • They face delays before being considered for “promotion or advancement.”

Each disclosed previously undeclared payments of over $1M each from pharmaceutical companies. It is inevitable that the integrity of their work has become, at best, questionable yet many psychiatrists and other physicians cling to the conviction that juvenile bipolar disorder is a real disorder probably because it gives them something to do about it – treat it with the same drugs they give to adults.

This is medical battery

To proceed, with no supporting evidence, to prescribe ever-increasing dosages of powerful drugs, never intended for children is, in my opinion, malpractice including medical battery because who is capable of giving informed consent? Certainly not the child and the parents are not told that there’s no scientific evidence for any of this and we really don’t know what we’re doing. Informed consent is, I submit, impossible.

I am not even going to touch the theories around “abnormal amygdala”. It may very well be the case that there is an influence but even if there is, we are far from knowing what it means. Courchesne, many years ago, identified children who have what I insist on calling “true autism” as opposed to the “autistic spectrum disorders” now prevalent. He found that they were born with a part of the brain called the cerebellum smaller than normal. Similarly, persons with Down syndrome have abnormally sized parts of the cerebellum, but in different areas than in the person with autism. This is all very well but so far hasn’t led to effective treatment although in the future we may have some sort of breakthrough based on these initial findings.

There is, however, a growing reliance on MRI and PET scanning as though these were diagnostic instead of mere tools to aid in diagnosis. This month, in the American Journal of Psychiatry, we find a chilling report of the evaluation of “92 children who were at high risk for developing autism, because they had older siblings with the disorder. At age six months, the children underwent (MRI) imaging. Additional imaging data was obtained from most of the children at 12 months and/or 24 months old. Behavioral assessments were also performed at 24 months. Twenty-eight of the 92 children met the criteria for autism spectrum disorders at 24 months.” There are literally dozens of genetic abnormalities that carry the label of “susceptibility to autism” but from this report, I can’t see that any genetic investigation was conducted. The researchers apparently made the assumption that if an older sibling had one of the “autistic spectrum disorders”, the infant was at risk and, lo and behold, by age two, they were so diagnosed. Well, when you’re a hammer, everything looks like nail and, if you can increase the numbers of MRIs and, in turn, massively increase the probability of selling drugs on a scale never seen before, so much the better – except for the children, of course.

Now, let’s consider lithium as a treatment for bipolar disorder. When swallowed, lithium becomes widely distributed in the central nervous system and interacts with a number of substances. Lithium is known to be responsible for significant amounts of weight gain as do several of the antipsychotics such as olanzapine. Lithium also increases water output into the urine, a condition called nephrogenic diabetes insipidus. It increases appetite and thirst, and reduces the activity of thyroid hormone (hypothyroidism). And we give this to children. The recent discussion about mercury and arsenic as medications seems somehow connected. I hope that one day soon we will come to regard lithium given to children as a treatment with same disbelief that we now consider mercury, white lead and arsenic.

Can we talk about Jacob

The adverse reactions to antipsychotics, antidepressants and similar medications are very clear in the young fellow called Jacob in the program. By age nine he was showing an unusual neck and head movement. The narrator refers to these movement disorders as “tics” and, while not accurate, serves as well as anything to describe abnormal muscle movement as a result of the drugs he was taking. In Jacob, the neck muscles are the ones most involved in that involuntary contraction of the muscles at the side, back and front of his neck cause his head to roll. Apparently, no-one has introduced a simple method of controlling this when it starts and that is to touch the chin or the back of the head gently when it is about to happen. This breaks the cycle. Of course, it should never have occurred in the first place and is entirely due to the antipsychotics he is ingesting like candy. The other effect the medications have had, is on his speech. He is dysarthric, that is unclear in articulation, a common side effect of antipsychotic medications. He is at increased risk of choking because of disruption of the muscles used for speaking and swallowing and this is something I find patients and parents are never told.

Why go to see a doctor?

Fewer and fewer health professionals seem to learn about the multiplicity of ways in which one can identify and treat the behaviours that are identified in these children as “pathologic”. No-one seems to care about treating the child and not the “disease” or getting entire families into programs that will examine what factors, environmental, familial or genetic may be causing or maintaining the perceived problems. But, of course, as one pediatrician says,” When you see a new child every fifteen minutes….” We have allowed a very wrong turn in the assessment and treatment of all of us, at all ages for conditions that are too often misidentified and then, for want of knowing about anything else, dismissed with drugs that have unknown and untold effects on DNA, physical functioning and mood.

The prescription pad is the only thing doctors now have. As the little fellow in the film, asked why he is going to see Dr X, reply gleefully and accurately, “To get medicine!”

Krystallized

BBC Radio Four’s Today program ran a piece on August 2 in response to an NHS report showing a startling 500% rise in prescriptions for antidepressants since the advent of SSRIs and a 9% rise last year. Close to 47m prescriptions were dispensed in the NHS in 2011 for anti-depressants and sleeping pills. There has been a rise year on year for the last two decades.

“Antidepressants work” and “antidepressants save lives”

In response to questioning on Today, Professor Clare Gerada, of the Royal College of General Practitioners, trotted out the standard lines “antidepressants work” and “antidepressants save lives”. Would we be worried if there was a rise in the use of statins or anti-cancer drugs?

The UK twittersphere exploded with tweeters taking sides. When challenged on the issue of antidepressants working Dr. Gerada insisted they do. There were predictable tweets from individuals who stated antidepressants saved my life – although as is often the case with such comments the person will often add that it was only on the fourth or fifth antidepressant that they were helped.

Claims that antidepressants work and save lives are not evidence based

Claims that antidepressants work and antidepressants save lives are not evidence based. There is no question that antidepressants do things and in this sense “work” (RxISK position paper on antidepressants). If the trials had undertaken to demonstrate SSRIs have an acute onset anxiolytic effect this could have been conclusively demonstrated. But the clinical trials that were done were undertaken to see if antidepressants “work” for depression and this has not been shown. They haven’t even been shown to “work” marginally better than placebo, as is often claimed.

What has been shown is that these drugs have “effects” on rating scales that regulators such as FDA can interpret as evidence they “might” work. This is quite different to demonstrating that the drugs get people back to work or save lives. It is indeed a moot point whether the law has been broken in the licensing of antidepressants in that the 1962 FDA statutes state that the agency will approve drugs that have been shown to be effective.

The rating scales moreover have been rating scales completed by doctors where some of the benefits may stem from sedative, anxiolytic or appetite enhancing side effects of antidepressants. On rating scales completed by patients, or scales less sensitive to the side effects of the medication, there is no evidence even for a rating scale benefit.

Pharmaceutical companies will sue

Pharmaceutical companies will quickly sue anyone who says things that the company believes it can prove in court are unsupported or injurious to the reputation of its product, as happened to Prescrire. (See also Welcome to Data Based Medicine). It is against this background that I am saying that antidepressants such as Cymbalta or Pristiq or Zoloft have not been shown in clinical trials to work.

Having made this point, I also have to say that I use antidepressants. They can have clear therapeutic effects. These effects are typically concealed by trials. If used judiciously I hope I can sometimes put such effects to good use. Whether on balance I do more good than harm is something neither I nor any other doctor can know, in the way we can know when we give an antibiotic for a life-threatening infection or a benzodiazepine for catatonia. Appealing to the literature won’t do it, as this is largely marketing copy and the better the marketing copy the more misleading it is likely to be.

More deaths on antidepressants

The second statement that antidepressants save lives has simply got no evidence base. In 2006, the FDA in the USA got all (or most) placebo controlled antidepressant trials from companies (FDA 2006). In 2004, the MHRA in the UK got all (or most) placebo controlled trials for some antidepressants from companies (MHRA 2004). There were large discrepancies between the two datasets. But a common finding was that there were more deaths in the antidepressant arm of these trials compared to the placebo arm.

So what is happening in the case of those who tweet that an “antidepressant saved me”? There are two options. One is that they are wrong. The other is that they are right but there are a slightly greater number of voices who might have tweeted an “antidepressant killed me”. All anyone hears though are the voices saying the pills saved me.

“Antidepressants saved my life” are like the wonderful stories of people whose lives were saved when their religious medal or medal for valor deflected the bullet away from their heart. We never get to hear the stories of those who die when the medal deflects the bullet the wrong way.

It’s the same with those who swear a statin or other medical drug saved them when trials show an excess of deaths on these also. The evidence base comes back to bite us in the case of treatment induced death – Pharmacosis – which has become at least the fourth leading cause of death. Some drug must be responsible for this, but everyone – psychiatrists, cardiologists, primary care doctors and others – look the other way and say “not me”.

Why are prescriptions rising so relentlessly

If antidepressants don’t work very well, why are prescriptions rising so relentlessly? A great part of the rise stems from the fact that an ever greater number of people are stuck on these drugs permanently. There is likely no more people being put on an antidepressant for the first time each year now than there was 10 or 15 years ago, but the total on treatment continues to build because of the people who cannot stop.

Freudian slip

A year ago in the New York Review of Books Marcia Angell wrote a two-part review of recent books including Bob Whitaker’s Mad in America, Irving Kirsch’s The Emperor’s New Drugs, and Daniel Carlat’s Unhinged that, based largely on the issue of do antidepressants work and save lives, asked the question are Americans in the middle of a raging epidemic of mental illness.

A year later organized psychiatry is still fuming. The latest response is from John Krystal, the President of the American College of Neuropsychopharmacology. After the usual arguments which amount to the claim that the evidence is not what it appears to be, that only we guardians of the flame can interpret it, and that the media should stop alarming people, he comes to an extraordinary conclusion:

“By stigmatizing a field progressing toward a scientific foundation and by disparaging treatments that show signs of efficacy, Dr. Angell’s facile criticism of psychiatry could do harm.”

This is astonishing on a few levels? Herbalism and a range of other fields could be characterized as progressing toward a scientific foundation with treatments that show signs of efficacy. Put a sufficiently large number of people in a trial and choose your measures carefully and even snake oil will show efficacy. Dr. Krystal seems to have consigned psychiatry to a lower level in the pecking order than physiotherapy and other paramedical disciplines. Many in other branches of medicine will likely smile wryly.

If psychiatry is only progressing toward a scientific foundation and its treatments only show signs of efficacy, the harm lies in the fact it has sold itself as a fully scientific discipline with treatments that work and save lives. If this isn’t the case, people need to be told.