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 October 2012

The Madness of Psychiatry


One hundred years ago patients with psychosis were 4 times more likely than the rest of their contemporaries to be dead at the end of their first 5 years of treatment. The main cause of death was tuberculosis. The asylum was a place where if you had the wrong genetic makeup you were at great risk of catching tuberculosis, particularly if you were a young woman.

The advent of the antipsychotics

In 1954, chlorpromazine, the first of the antipsychotics, was introduced. It seemed extremely safe. In the early days chlorpromazine was given in doses of 50 mg three times a day. Twenty years later antipsychotics in some cases were being given in doses equivalent to 50,000 mg of chlorpromazine per day and the fact that patients still walked around fairly normally seemed to confirm the essential safety of the drugs.

Even if there was evidence the drugs shortened lives, in the 1960s a few years of life lost seemed a reasonable trade to many for the chance to get out of the asylums. But you can’t depend on people to be grateful for ever – and while losing a year or two of life might be a reasonable trade off, losing 10 or maybe 20 years is another matter.

15-20 years of life lost

Shockingly, over the last 5 years, a series of large studies, some looking at national databases, have shown that patients with psychosis are 2 to 3 times more likely to die in any one year than the rest of us. Death is primarily by heart attack or stroke. Being two or three times more likely to be dead may not sound much but other studies point to 15-20 years of lost life. The results have been consistent and have raised concerns about the contribution from the antipsychotics especially the second generation drugs which have bad cardiac profiles.

Even more shockingly, almost no-one knows what happens to patients with psychosis 5 and 10 years after they are first admitted – they do not know in New York, London, Berlin or Paris. No one in North Wales knew until this year. The studies that have already been done survey cross sections of patients and don’t answer this question. No doctor can in fact tell patients or their families how likely they are to be alive or dead 1, 5 or 10 years after first admission. If there are risks they cannot tell them what the risks are. This is important because if we know what the risks are we know what to look out for in order to minimize those risks.

What does happen in the first five years?

The bad news

Patients with psychosis, just as they were 100 years ago, are now 4 times more likely to be dead after 5 years of treatment than the rest of us. Patients with schizophrenia are 11 times more likely to be dead – this is much worse than 100 years ago.

Patients with schizophrenia are 10 times more likely to be dead at the end of the first year of treatment than they were 100 years ago. There is no other illness in medicine where such a statement could be made.

Death in the early years of schizophrenia does not come from heart attacks or strokes – it comes from suicide. In their first year of treatment, patients with schizophrenia are over a hundred times more likely to commit suicide than the rest of us.

Heart attacks and strokes do happen but they happen in patients over the age of 65 with delusional disorders or acute and transient psychoses.

See Healy et al (2012) Mortality in Schizophrenia.

Some questions

Some of the reviewers of this article went into orbit – they did not want to see it published. Among the points raised were that of course we know schizophrenia causes suicide – if you didn’t find it one hundred years ago it’s because the hospital hid it well or patients were straitjacketed – anything except accept that we are doing worse.

Does schizophrenia cause suicide?

No, it doesn’t. The historical data show that the suicides do not come from the illness. Patients 100 years ago did not commit suicide – there does not seem to be a significant risk inherent in the illness.

Did patients 100 years ago have an opportunity to commit suicide?

Yes they did. They spent 99% of their time working on farms or in kitchens or sewing rooms.

Did the hospital hide the suicides?

No. The staff were under a legal obligation to report suicides to the authorities. When patients with mood disorders committed suicide, the records make it very clear what happened and that these reports were submitted.

Does de-institionalization cause these suicides?

No it doesn’t. If patients today were dying 5-10 years into their illness, when they have lost their social networks, jobs, and hopes, the idea that deinstitutionalization might be contributing would seem more likely but in fact they are dying before they lose their families, networks and hopes. One possibility though is that the institution was more of a protective factor for patients 100 years ago than we have appreciated. However it did not protect patients 100 years ago with mood disorders who went on to commit suicide in hospital.

The good news

So what causes the suicides? The evidence points to the antipsychotics. In placebo controlled double blind trials these drugs show an excess of suicides and suicidal acts with drugs like Zyprexa having the highest suicide and suicidal act rate in clinical trial history.

This is good news because if most deaths in young people with schizophrenia come from suicide and the antipsychotics make a contribution to this, there is an opportunity to correct the problem. The problem almost certainly stems from drug induced dysphoria. Patients are not on the right drug for them. A simple question – do you like the effect of this drug and do you find this effect useful, along with a willingness to switch from a drug that isn’t suiting someone to one that does, could eliminate the problem.

This is worth trying to make part of the culture of clinical practice because if we can eliminate suicides in year one of treatment we could go very close to restoring the life expectancy of patients with schizophrenia or other young people with psychosis to normal.

There may be no other measure in medicine that for such little cost could make such a difference to life expectancy.

There may be nothing else quite as good as this that psychiatrists could do to save their own skins. They have lost antidepressant prescribing to family doctors, clinical psychologists, nurses or pharmacists. But they cannot blame anyone else if things go wrong in the schizophrenia and psychosis domain. If they cannot ensure their patients safety, what brand value is there left in psychiatry?

There is good news on the heart attack front also. The increased risk of heart attacks and strokes lies in people over the age of 65 with acute and transient psychoses or delusional disorders. These patients are at prior risk of heart attacks or strokes, and in many cases we can detect this. The antipsychotics work on dopamine which has significant effects on the cardiovascular system, and in this way the drugs may tip these patients over the edge.

The antipsychotics already come with black box warnings for patients over the age of 65 – who have dementia. These warnings need to be extended to anyone over 65.

These are the patients who need to be screened before being put on treatment and monitored after they start. But it is a much smaller and more manageable group than all patients with psychosis. The acute and transient patients are also a group who do not need in any case to remain on antipsychotics in the longer term. This puts a premium on stopping treatment where possible.

But who cares about patients with psychosis?

Owing to the hostility of reviewers in order to get published we “toned down” the findings in an article just out in the BMJ Open – Healy et al 2012, so that the abstract of the article points only to the relatively benign tip of an iceberg that lies beneath. The fact that we toned things down may have meant BMJ didn’t press release the article in the way they have done recently for articles pointing to minor elevations in risk of Alzheimer’s in patients taking benzodiazepines. Getting journalists interested has proven difficult. Schizophrenia is not sexy. Young people dying unnecessarily lights no-one’s fire it seems – at least not these young people.

But that’s not all there is as the next posts La Reine Margot and the St Bartholomew’s Day Massacre may bring out.

RxISK Stories: Listening to Parents



When you lose a child or a partner from a rare illness, everyone is supportive, no-one denies you. They listen. But if a child dies from suicide or a complication of treatment with a drug especially a psychotropic drug no-one listens. Our culture has no place for this kind of death. They say maybe it’s for the best. He’d never have been able to face the life he’d have had – something they would never say this about a child with cancer.

The system tells you that your child had a serious mental illness, when in fact he might have started on drugs for ADHD or anxiety. It tells you his diabetes was a complication of his schizophrenia when it was caused by Zyprexa or Quetiapine. If you are like me, you assume no doctor would give your child a drug that wouldn’t benefit him. You see the deterioration but unless you keep a record and can show that each time things got worse the change coincided with treatment, you do not think it could be the drugs. It’s easier to live with the idea that the problems come from an illness rather than from the treatment. I told my son he had to take the treatment when he begged me to let him stop.

If he fails to get better the dose will go up – in other areas of medicine a failure to respond leads to a change of strategy. But in this case drugs are added to drugs. If he becomes edgy or paranoid or can’t sleep these are all excuses to add more drugs rather than stop the treatment. Cold turkey from one drug might be thrown into the mix of other drugs.

If you later figure out somehow that what happened was drug related – you get angry. You phone the doctor – you want to talk to them. They tell you no it’s not the drug – your son was mentally ill. They’re in denial. Their vested interest lies in not believing the treatment they gave might have caused the problem.

You meet other people who introduce you to all that was known about the problem before you ended up locked in it – because they have been there before you. You may get in contact with the few experts who seem to accept there is a problem. You cannot believe that others new about this but still nothing was done.

You want to correct things and you try to use the system. You’ve discovered this problem and you think if people hear the issues they will be as horrified as you and will say we mustn’t let this happen again. You might look for an inquest, get in touch with the Department of Health, the body responsible for licensing the doctor, the regulator, local politicians.

The regulator will refer you to the Department of Health, who will refer you to the licensing body for doctors, who will refer you to the professional body, who will refer you back to the regulator. We have all written to the regulator and the minister for health and we all get the stock letters back (Ed: See Margaret’s Story).

I went through the thing of doing suicide statistics to show there is a problem but got nowhere. The data are in fact corrupt and useless but not even the media want to know about this newsworthy story. The government is going broke because of its spending on drugs and you think it could use this as an opportunity to cut back on drug spending – but no. The professional body will decide that at least some fraction of other doctors would have done the same.

If an inquest implicates the drugs, you think that the next set of practice guidelines which you have heard are in development will reflect this but they never do.

You lose your faith and become a zombie. On TV there is always a good guy to put things right but here there isn’t. You will never be the same person again.

You’re alone with each other – husband and wife. First you blame yourself – then the other. It’s very hard to not blame each other. Husbands and wives break up. You need to be able to give to keep any relationship going, but you’ve got nothing left to give. You can’t make love anymore because love was all about children. You’re doing things because you know you have to, not out of any sense of fun. You can’t stand the memories even though you don’t want to lose them. You may be told you are depressed and your doctor is highly likely to suggest you need a pill.

You meet others who have lost children who have become advocates for more treatment. Other members of your family think you are deluded and family meetings become difficult. After time you find that the parents who see things the same way as you stop getting in touch, not because they have changed their mind but in an effort to get on with their lives. It just isn’t possible to grieve to a conclusion.

I was once you. I was middle class too. I believed in the system. I totally believed in the medical system. I used to pass the wastelands and see the disenfranchised, smoking dope or taking drugs, who rejected the system and were rejected by it – and thought can they not see if you just approach the world trustingly you bump into people whom you can in fact trust. Now I know no certainty. I have no choices. I have a wonderful GP but even there I have to be suspicious. I have become one of the disenfranchised.


You want to forgive but you can’t forgive people who don’t ask for forgiveness. The doctor thinks he is doing a good job – all doctors think they are doing well. Maybe they couldn’t function if they thought otherwise.

I have – many of us have – fantasies about getting a hired gun – Clint Eastwood in Unforgiven. He might set up as a sniper near a pharmaceutical company, bomb its premises or lock up the doctor and force feed him the pills he put our loved one on.

The system needs to stop Listening to Prozac and start Listening to Parents and Partners. We need to be acknowledged. This will not be through an adversarial forum which has to rule one way or the other. It should have the power to acknowledge that drugs come with unavoidable risks and perhaps offer a 60-40 judgment that your husband or son was caught in a spiral that is easier to see in hindsight than at the time.

Doctors need a forum like this because if the drugs are not poisons that need expert input, they may end up being administered by nurses and pharmacists. At present treatment would often be safer if it were dispensed by a machine – the machine could be programmed not to keep you on treatments that don’t suit.

Doctors might have a more interesting and rewarding job if they recognized the problems treatment can cause. This is the moment when they could engage in genuine team work with patients or with parents or partners. Instead their default is – come back when you have had 10 years of medical training. They are fundamentally not team players.

We are the second hand sufferers of adverse events – the ones who get driven to suicide or premature death from heart attacks by the effects of prescription drugs on our children or partners. A grisly inversion of the DES story, where the daughters of mothers who had taken diethylstilbestrol developed cancer of the vagina in their teenage years. Rather than DES Daughters we are DSE Parents. Where are the doctors who want to recognize this side effect of treatment and bring healing?

RxISK prize

I would like to establish an annual prize for a piece of work covering the adverse effects of treatment – the wider impacts these can have and the ways people or families may have found to overcome them. I cannot afford to fund this on my own. I would like to call for donations through to help fund this. RxISK has foundations in the US, Canada and the UK.

Report drug side effects

Help us make medicines safer for all of us by reporting drug side effects at Less than 5% of serious drug side effects are reported. Our mission is to capture this missing data directly from patients through’s free drug side effect reporting tool and use this data to help make medicines safer for all of us.

When you report your drug side effect on, you also receive a free RxISK Report to take to your doctor or pharmacist. This report serves as a means to initiate a more detailed discussion of your treatment and the option to send a report to your country’s health authority — beginning with the FDA in the United States and Health Canada in Canada (more countries will be added soon).

Adverse events are known to be the 4th leading cause of death. Our goal is to knock these off the top 10 list. We can only accomplish this with your help.

Tell us your story today at

The Madness of Young People

In 1861 Benedikt Morel, a physician in France, described a terrifying new illness. It involved young people in their late teens or early twenties about to enter what should have been the prime of their lives who instead sank into a profound and seemingly incurable state of what he termed precocious dementia. Morel painted a picture of a terrifying and seemingly close to incurable loss of cognitive function.

In short order all around Europe, there were similar reports of the new illness. Some called it adolescent insanity, others hebephrenia, and later dementia praecox.

An epidemic of insanity

A short while before, the English, French and Germans had begun to build the first specialist hospitals for any set of medical disorders. They were designed to promote recovery from mental illness by offering a focus on hygiene and a behavioral approach that would build up the morale of the affected person.

Very soon after opening however the beds filled so that fresh wards had to be built which in turned filled rapidly. Asylum superintendents in their annual reports asked whether insanity was increasing. Those who thought it was, put the changes down to urbanization or industrialization and the increasing pace of modern life.

In mid-nineteenth century, the patients who came into the asylums mostly had melancholia or acute and transient disorders. Very few patients had dementia praecox. But by the end of the century, dementia praecox accounted for by far the largest number of admission.

From recovering to warehousing

The early asylums were geared for patients who were expected to recover but few recovered from dementia praecox. Some of these new young mad patients only stayed in hospital for a short time. Three to five years after admission, the women in particular caught tuberculosis and died from it. But among those who did not die from tuberculosis, some were there 10, 20, 30 and in some cases 60 years later. The mission of the asylums changed from recovery to warehousing. The reputation grew that you only ever came out in a box.

Briefly around 1920 soon after its name switched to schizophrenia, the illness became popular. Artists, and others like Carl Jung who thought creatively might be allied to madness were happy to brand their struggles as schizophrenic.

But it is almost impossible to interest the media in schizophrenia now. Nobody wants to have anything to do with this graveyard of hope.

Don’t be ridiculous schizophrenia didn’t just start in the 19th century

In 1980 a controversy blew up in the ivory towers. Some argued that schizophrenia had only appeared in the nineteenth century and if so we should redouble our efforts to pinpoint a cause – especially as the antipsychotics were definitely not the cure. Indeed worryingly, dementia paralytica (tertiary syphilis – General Paralysis of the Insane/GPI) looked very similar to dementia praecox. If we had had the antipsychotics when patients with GPI came into hospitals they would have controlled these patients just as much as they control schizophrenia making it harder to recognize that penicillin rather than antipsychotics were the cure for GPI.

Most of psychiatry dismissed this idea, as did I. The increase in insanity was apparent rather than real – most argued. We were warehousing awkward patients. Doctors had a conflict of interest – the more patients the more powerful they were.

Then the data on admissions to the North Wales asylum fell into my hands. Yes there was an increase in first admissions for insanity in line with increases in the population. But beyond this there was a tripling of first admission rates for schizophrenia between 1875 and 1905 over and above the increases linked to population change, while the rates of admission for other disorders remained constant.

These findings cannot be explained by industrialization, urbanization, or culture change as North West Wales did not urbanize, or industrialize and had no shift in ethnic mix.

All the old textbooks from 1900 say schizophrenia affected men and women equally. All the textbooks from 2000 say it affects 2 or more men for every woman. In our records the figures for 1875-1924 show almost exactly the same number of women and men but the figures for 1994 to 2010 show 2 men for every woman. (See Healy et al, 2012).

Schizophrenia disappearing – are you joking?

But even more surprising, starting in 2005, perhaps a good deal earlier for women, first admission rates for schizophrenia have plummeted. Other surveys which look at admission rates for schizophrenia will miss this as first admissions only account for 15% of admissions. The figures have dropped from 15-20 new cases per year to 5 per year – figures not seen in North Wales since 1876.

A ward has closed. This is the kind of thing that speaks louder than academic articles.

What’s going on? The drop cannot be explained by early intervention services or home treatment teams or any other change in service because there has been no change of service in North Wales during this time.

What made psychoses chronic?

The North Wales nineteenth century figures nail down for the first time a specific increase in schizophrenia reinforcing calls to pinpoint what might have caused it. The modern data add to the urgency of these calls. While the factors that led to this increase in schizophrenia may not be the same as those leading to its decrease now, it would be very satisfying to find something that might both account for some of the increase and some of the decrease.

Two strong candidates come to mind. In the nineteenth century we began to use lead for more and more purposes. Lead pipes carried our water. Lead solder closed the tin cans in which food was increasingly put. Lead was added to food and even to the medicines we took. The paint we coated our houses in had high concentrations of lead. The paint on bars of cots that teething babies gnawed on were impregnated with lead. Our children wrote with lead pencils in school. When the automobile arrived, we put lead in gasoline and concentrations of lead in urban air grew rapidly.

Lead is neurotoxic to children in particular. If the brain damage it can cause is what made some psychoses chronic in later life, then to see a drop in admission rates around 2005 in North Wales, where lead was once mined, we would want to see a fall in lead concentrations around 1980. And in 1980 lead was being removed from water-pipes, paint, gasoline, and had already been removed from food and medicines. The soil concentration of lead in North Wales began falling fast at this time. Elsewhere in the USA in particular, rates of admission for schizophrenia track lead levels and those admitted have higher levels of lead than controls.

Another possibility lies in changing childbirth practices. In mid-nineteenth century we introduced anesthesia and this led male obstetricians to ever greater feats of heroism with forceps and other instruments, delivering blue and sometimes close to black babies from “mid-cavity”. Around 1980 there were major changes in practice with increased rates of Caesarean Sections and the active management of labor aimed at delivering pink babies.

From chronicity to recovery

It would be wonderful to pinpoint a cause. We are probably though looking for a cause for chronicity rather than a cause for schizophrenia. What may be happening is that what might have been acute and transient psychoses against a background of subtle brain insults turn into chronic psychoses. The question then will be what the original conditions look like – are they in fact acute and transient psychoses?

Some reviewers of our findings have been intensely hostile. They seem to hear a message that mental illness is disappearing. It isn’t. In same way that we will have respiratory illnesses as long as we have respiratory systems, but respiratory disorders like tuberculosis rise and fall – this is what happens to real medical disorders, so also as long as we have brains we will have mental disorders but specific disorders like dementia paralytica and dementia praecox can come and go.

There is good news here for anyone interested in recovery in mental disorders. The patients we see in future may be much more likely to recover. This opens up the possibility of reconfiguring services. But if something like lead poisoning once made some psychoses chronic we need to keep an eye out for other things that might do this in future. For example we should track what the outcomes are when we save intensely premature babies – in so doing do we cause the kind of damage that might lead on to chronic psychosis.

There is a message for anyone treating chronic psychoses. The patients are right when they say the drugs don’t cure. The antipsychotics can be helpful if used judiciously but realizing that a cure is not going to appear if we just hammer the dopamine system a little bit harder might let us devise more sensitive and nuanced treatment approaches.

We need more sensitive and nuanced approaches because at present more patients are dying earlier than they should and these deaths are linked to the way we are using antipsychotics.

The Madness of Carl Jung: A Dangerous Method

Carl Jung was one of Freud’s earliest supporters and in many respects rivaled him in terms of influence. Some of their interactions provide the basis for the story behind the book and recent movie – A Dangerous Method. Just as Freud did, he famously analyzed himself and while doing so apparently became psychotic. His psychosis was however seen as a way to sanity – a forerunner of 1960s thinking about psychosis. It was also viewed in semi-spiritual terms.

This was all of interest when we came to explore another condition we found in the North Wales hospital records, a condition that made us keenly aware we were playing with fire. Against the background of a major strike in the quarries and mines of North Wales, in the autumn of 1904 and through to the summer of 1905, a preacher called Evan Roberts toured Wales stimulating the Great Revival – and stimulating into madness some of those who gathered in North Wales to hear him preach. There was a spike of admissions to the Asylum for psychoses that looked like schizophrenia or bipolar disorder (see Linden et al 2010).

Fire from Heaven

There is a well-known condition – Jerusalem syndrome, which affects Christians who go to the Holy Land. They go mad, but no-one knows what happens to them because they are sent home to the 4 corners of the globe. But we know what happened in 1905 because our patients had nowhere else to go. What happened was that they recovered and did not become unwell again. Today if recognized, these conditions can be called acute and transient psychoses in Europe and brief reactive psychoses in North America.

If recognized. Today a schizophreniform psychosis is likely to lead to a diagnosis of schizophrenia and treatment with antipsychotics for life. Or if the admission has a manic flavor, North American clinicians are obliged by DSM to diagnose a bipolar disorder, which is a sentence to a life of “mood-stabilizers”.

We ran into trouble with our article on religious psychoses – there were many in North Wales who read the research as critical of religion. Stay away we were warned darkly. This caught us completely by surprise. At the time the paper was being written, Lehman’s Brothers was collapsing and the threat of a Great Depression was very real. We saw the religious fervor of 1905, allied to the stress of a general strike, as producing the kind of conditions that any society can throw up from time to time, and that any of us can generate in our personal lives.

These are the patients who recover

One of currently fashionable ideas is Recovery. We are all supposed to have a recovery orientation. And of course it is helpful always to see the person rather than just the illness, but repeating this mantra is often aspirational rather than useful. These are the patients with psychoses who recover – who need to be recognized.

An important message from the historical record is that these patients recover without drug treatment. The worry today is that they will be slapped on medication and will be unable to get off it because of physical dependence or unhelpful advice from the mental health services that they have schizophrenia or bipolar disorder and need to remain on treatment for life.

These are the patients who now often give clinicians the impression that treatments work well, when in fact they were likely to recover anyway, and the real risk is they will be kept on treatments they don’t need. Is there any harm in staying on an antipsychotic just in case? Well in our data, older patients with acute and transient psychoses are particularly prone to heart attacks and strokes – much more so than younger patients with schizophrenia.

A second message from the modern records is these patients make every effort to have no further contact with the mental health services. If they escape physical dependence on drugs, their clinicians are never likely to see them again. This means that most doctors end up with a misleading impression as to how many patients with psychoses actually recover fully – they underestimate the possibility of recovery.

The once and future psychoses

When the asylums opened in the early nineteenth century, there were few if any cases of schizophrenia. Patients with psychoses who were admitted recovered and asylums were institutions geared toward recovery by giving patients a structured daily routine and opportunities for work on the farm and other activities. They were not the warehouses they later became when schizophrenia emerged. If schizophrenia – chronic psychosis – were to vanish, these brief reactive psychoses would be psychoses that are left. But these schizophreniform psychoses are a disorder that we barely understand. There are vanishingly few case series published to give us even the average age of onset or gender ratio of the patients affected. The biggest studies there are have 40 or so patients. Our databases contain hundreds of cases.

In this mix there may be psychogenic psychoses – mental rather than physical disorders. This may be something like the condition Jung induced in himself that many see he portrayed as a semi-spiritual state or stage of growth. There may be other personality based conditions. Yet other brief psychoses may be more physical in nature but still open to recovery.

These are conditions we need to learn more about because as we shall see in our records it looks like schizophrenia or at least chronicity is vanishing, and we are going to have to re-orient our services much more toward recovery than before.

The Madness of Childbirth

The North Wales asylum made its way into my life by accident. The history department at Bangor University secured a grant to look at the social impact of the asylum. Looking at the records they collected, it was striking how people declared their madness a century ago – they tore off their clothes and escaped through windows, which they never do now.

A quixotic database

But when we set about entering North West Wales records from the asylum in 1896 to compare with admissions in 1996, something more startling became apparent – we admit 15 times more people with serious mental illness now, and compulsorily detain 3 times more people (Healy et al 2001). This prompted a quixotic adventure – why not enter all records from North West Wales between 1875 and 1924 and build a modern database covering admissions from 1994 to 2010?

This was quixotic because no-one wanted to fund us. Grant-giving bodies in history were not able to see the value in quantifying records or in having modern data. Modern epidemiologists could not see the value in historical records. So over 15 years and without support we put together easily the largest body of historical epidemiology in existence – we had no competition, no-one else thought this made sense.

Made by God – or maybe Tolkien

North West Wales is uniquely suited to what we did. It’s surrounded by the sea on 3 sides and the mountains on the fourth. The population remained almost exactly the same between 1896 and 1996. It was then and is still now almost exclusively Welsh. It was rural and never urbanized. The people are poor and so there is no private care. There was then and is now only one place to go for a hospital admission. In the case of the few people who left the area, through the National Health Service we have been able to track everyone down so not a single person is lost to follow-up.

Almost God-given for our purposes. This is where Tolkien set Middle Earth. To the South East looms Mordor which casts a long shadow – suggesting a Pharmageddon to come.

The response from some experts to our findings has not been unlike the dismissive attitude of Orcs or Black Riders to Hobbits. They sneeringly fall back on the fact that we have made diagnoses based on century old records. One hostile reviewer argued that when black men in America in the 1960s could be detained compulsorily and diagnosed as having schizophrenia, what chance is there our records have it right. Others are sure women with unwanted pregnancies were incarcerated in mental asylums and diagnosed as schizophrenic.

The ultimate proof that out methods are right lie in a set of  bricks and mortar developments, as will become clear.

The madness of childbirth

Postpartum (or puerperal) psychosis was one of the severest mental illnesses ever. It accounted for the admissions of one in ten of the women of child-bearing years admitted to the old asylums between 1875 and 1924. It came in two forms. The most dramatic form happened in women who had never had a hint of mental illness before, who were stably married and well-placed who within a week or two of giving birth to their first or fourth or other child went floridly mad. These women with de novo onset postpartum psychoses accounted for 4 out of every 5 cases. Their psychosis looked completely different to either schizophrenia or manic-depressive illness.

The second group were women who had had a previous mental illness who after giving birth might have a further episode of essentially the same illness they had before. Their illness typically looked like a further episode of manic-depressive illness.

When the asylum closed it was replaced by 3 district general hospital units, across North Wales, the Hergest Unit in the West, Ablett and Llyn-y-Groes in the middle and East. All 3 had mother and baby units. This units were opened up because of the rates of admission for both kinds of postpartum psychosis in our asylum records – these map directly onto what was in 1993 the accepted rate for the occurrence of post-partum psychoses.

A vanishing disorder

Hergest was the first of these general hospital units to open but within 3 years of opening, the mother-and-baby unit closed. There were no cases. The Ablett mother and baby unit had just opened up and this is where Cora went (see Cora’s Story)– and going there may have partly caused her loss of life. All 3 mother-and-baby units have now closed.

Our historical and contemporary databases bring this out perfectly. De novo onset postpartum psychoses have vanished – the manic-depressive type remains (see Tschinkel et al 2007). These are not disorders you can treat in the community. They are the most high risk in all psychiatry.

But when we came to report the findings we were in for a surprise. No-one it seems wanted to hear about a disorder vanishing – not the postpartum experts whose careers depend on it and are still busy portraying it as commoner than ever. Not the health service managers whom one might have thought would have an interest because of the budgetary implications. Nor the researchers you might have thought would be interested in the implications for theories of mental illness. Not the historians specializing in postpartum psychoses or women’s mental health. It was difficult to get published.

Abuse of psychiatry – a twentieth century phenomenon?

What our critics fail to realize is that we are not going on historical or contemporary records. Doctors in the nineteenth century made diagnoses based on how the patient looked when they walked in the door but we have had the entire lifetime medical record of these patients available to us and could base our diagnoses on these.

Doctors today don’t make diagnoses on the patient as they walk in the door. When the patient is discharged, the ward clerk or someone with no medical training typically enters the diagnostic code into an administrative database. This can work very well in medicine, but doesn’t make sense in psychiatry. A great deal of modern psychiatric epidemiology is based on diagnoses like these – close to useless. Other studies are based on diagnostic interviews instead, which are also close to useless. Almost 50% of cases of schizophrenia, as clear cut a condition as psychiatry has, get a different diagnosis during their first year or two of admission. It takes time for the nature of the illness to become clear. And this is where our approach scores for both historical and modern cases – we make our assessments based on the full clinical record with input from everyone who knows the patient.

There has been extensive work by others on historical records at this point. These have revealed several famous examples of individuals who may not have been made and who have protested against their incarcerations. But these are exactly the cases that we do not diagnose as having a psychosis. If a Black or Irish man had been inappropriately incarcerated in North West Wales in 1896 we would have spotted it. In fact the asylum records show clinicians sensitive to issues of whether this patient was “a knave or a fool”. They were very reluctant to admit and quick to discharge knaves. There was not a single admission for unwanted pregnancy or ethnic factors, and in cases where there was domestic or other abuse, these issues were clearly flagged up, making it possible for us to take this into account retrospectively.

The abuse of the asylum by doctors was a mid-twentieth century phenomenon – a telling example of how medicine can turn to the dark side rather than sustain progress. But just because the Nazis exterminated mental patients and psychiatry acted like an agent of the State in both the Soviet Union and the West in mid-century doesn’t mean it was always this way. Life in the Shire, if not perfect, was once good enough. The challenge has always been to keep it that way – although a case can be made that things are getting even worse now.

Where did postpartum psychoses go?

So what happened postpartum psychoses? We have no idea. This is in complete contrast to catatonia which has also vanished and we are certain we can explain this. It’s also in contrast to schizophrenia, where we have some good ideas.

What could have happened? The postpartum psychoses look more like steroid psychoses than schizophrenia. Perhaps their disappearance stems from the active management of labor now which means few women get as fatigued as once happened, or the use of pain relief like Heroin (see Tschinkel et al 2007). If post-partum psychoses are related to catatonia, the availability of benzodiazepines might be expected to make a big difference.Whatever the reason, our best guess is this condition began to disappear somewhere between the late 1970s and the 1980s. We want any suggestions anyone can offer.

RxISK Stories: Cora’s Story – A Benzodiazepine Story

This blog post has first been published on the website and can be viewed here.

In RxISK Stories, we regularly take you to dark places where few would wish to go. We have perhaps become too used to the horrific consequences of medicines going wrong that we fail to appreciate how off-putting this sequence of posts can be. It is like a doctor taking a friend into an operating theater just when the surgeon is sawing through the breastbone failing to appreciate that the friend is likely to faint away.

We want you to give us some good news stories – about new uses for drugs, or discoveries about how to manage side effects. The supporters of drugs classically say that critics fail to take into account all the lives that would be lost if the drug were not used – nowhere more so than in the case of the antidepressants where warnings they argue will deter people from seeking and getting the benefits of treatment. But the efforts to persuade doctors to prescribe and the rest of us to take antidepressants went hand in hand with efforts to persuade doctors to stop prescribing and the rest of us to stop taking benzodiazepines. And this gives rise to deaths also.

Cora’s story

Cora was 18 and beautiful. Slim, with long blond hair, about average height. She had just finished high school, where she had been the homecoming queen. She was set to attend college, though she wasn’t certain what direction to take there. She had a boyfriend but was worried he might want to leave her, while at the same time knowing her parents didn’t approve of him.

At a rock festival with her boyfriend, she got lost and, trying to find him, had taken a fall and injured her arm. She was admitted to a local hospital for treatment and sent home from there. Several days later, in a state of perplexity she was brought to the psychiatric unit where I have inpatient beds.

Had she been traumatized or abused in some way? Had she been taking drugs and had a trip gone awry? Had her boyfriend left her? Her mental state was quite unstable, but despite having input from the many people involved in looking after someone in hospital I couldn’t make a diagnosis. Cora was not hearing voices, did not have delusional beliefs, and was not consistently depressed, elated or anxious. But she was volatile. At times in the ensuing weeks, apparently improved, I gave her leave to go out with her parents, but she was typically brought back severely confused again – sometimes only minutes after having walked out through the hospital doors. At other times she was almost completely unresponsive and inaccessible. I could see no reason to give her an antidepressant or an antipsychotic. On occasion when she seemed particularly agitated I wrote her up for a minor tranquilizer – a benzodiazepine.

Finally after about 6 weeks she went on weekend leave with her parents, held her own, and did not come back. I was happy to file her case as diagnosis unknown. I heard she was doing well at college and was still dating the same boyfriend.

I saw her again a year later – 8½ months pregnant. She was clearly too unwell to be managed at home. But where she had been mute and inaccessible previously, now she was over-active, manipulative, and attention-seeking while still seeming confused; her actions did not seem fully under her own control. She looked as though she might go into labor at any moment, so I held off medication.

After the birth, I sent her to a hospital that had a mother and baby facility. The psychiatric team that took over her care there, I learned, thought she had schizophrenia. She was put on regular antipsychotics, but apparently was not making much progress and the baby was taken from her. Some months later, I heard she had been given weekend leave; one evening of that weekend, having told her parents she was going out for a walk, she laid her neck on the track in the face of an oncoming express train.

Looking back at Cora’s confusion, emotional lability, and switches between immobility and overactivity, I came to see that she had a textbook case of uncomplicated catatonia. Few readers of this blog will know what catatonia is, as it has supposedly vanished, even though 50 years ago up to 15% of patients in asylums were estimated to suffer from it, and it was one of the most horrifying mental illnesses, with a much greater fatality rate than any other disorder except General Paralysis of the Insane (tertiary syphilis). While mental health professionals are aware catatonia is listed in the DSM, few would spot a case if faced with it.

If Cora had a rare condition that doctors do not now need to recognize, if she was the exception that proves the rule of medical progress, she would have been unfortunate. But in fact up to 10% of patients going through mental health units in America and worldwide still have the features of catatonia – if they are looked for (Chalasani et al). Sometimes the only condition they have is catatonia; other times catatonic features complicate another disorder and resolving the catatonia may make it easier to clear whatever other problem is present. But almost no-one thinks of catatonia and so, like me, they miss the diagnosis. Cora was given antipsychotics, which are liable to make a catatonia worse. She died when a few days’ consistent treatment with a benzodiazepine would almost certainly have restored her to normal, making her death scandalous rather than accidental.

But the benzodiazepines are a group of drugs that are no longer on patent, and no company has thus any incentive to help doctors see what might be in front of their eyes when it comes to a disease like catatonia. Instead, all of the pharmaceutical exhortations are to attend to diseases for which on-patent drugs are designed, even if this means conjuring diseases out of thin air—disease mongering—such as  fibromyalgia, to market  on-patent medications such as Pfizer’s Lyrica, or restless legs syndrome, a disorder conjured up as a target for GlaxoSmithKline’s Requip (ropinirole).

Catatonia and other vanishing diseases are part of the “opportunity cost” of disease mongering, lost in the chatter about disorders that match up with on-patent drugs.

No one has any idea how many versions of Cora’s story play out in daily clinical practice — versions in which the diagnosis of a treatable disease goes unnoticed by doctors pleased with themselves for making a fashionable diagnosis like fibromyalgia and who, even in the face of treatment failure, will add ever more on-patent drugs to a patient’s treatment regimen rather than go back to the drawing board and look more closely at the patient in front of them. Once upon a time the height of medical art lay in being able to go back and look at cases afresh and match the profile of symptoms against less fashionable or apparently uncommon disorders – no longer.

The dark side

Studies this week in BMJ and BMJ Open linked benzodiazepines to an increased risk of developing dementia and early death. For many the benzodiazepines like Valium remain much darker drugs than Prozac, Cymbalta, Pristiq and other drugs. The risks of getting diagnosed with dementia are quite likely to turn out to be much higher in those given an antidepressant than in those given benzodiazepines and the risks of suicide and premature death are certainly greater on antidepressants. The antidepressants are in many ways much darker drugs than the benzodiazepines. We need to find a way to bear this in mind while still holding on to the idea that for the right person either of these drug groups could be life-saving.

Cora’s story can be found in Pharmageddon which was written as a tribute to many who have died like her and especially to the people, mostly women, who have campaigned to make treatment safer for all of us.

The Madness of North Wales

Influenced like many of my generation by the writings of Laing, Szasz, Illich, Jung and Freud, I studied medicine to do psychiatry. At the time research was becoming mandatory for anyone hoping to engage with the field. I chose to work on the serotonin system. But this was working on the mind as much as the brain; this was the serotonin system brought into view by LSD rather than the one that Prozac would later usher in. This was biology as a source of variation and individuality rather than standardization. This background made me acutely aware of an emerging biobabble, biomythologies, and the rhetoric in claims made by what later came to be called biological psychiatry.

Where did schizophrenia come from – or is this a stupid question?

I was newly perched at a laboratory bench in 1980, when the controversy blew up about whether schizophrenia increased in frequency in the nineteenth century. Faced with a clear increase in hospitalizations for insanity, Fuller Torrey in 1980 and Edward Hare in 1983 argued that an infectious or other trigger must have been at work. I instinctively took the opposite side – schizophrenia didn’t suddenly appear in the nineteenth century; surely we have always had it. German Berrios’ cautionary note about the changing meaning of mania rang true and I’ve spent a great deal of my career since dealing with the shifting meanings of terms like neurosis, psychosis, depression and mania (See Mania).

I have spent even more time supporting an argument put forward by Andrew Scull in 1984 in response to Torrey and Hare to account for the increase in hospitalizations, namely that health systems attend to our ailments to secure their own health.

But even the biological psychiatrists who displaced social psychiatry in the 1980s were inclined to see schizophrenia as emblematic of the human condition rather than a disease that might rise and fall. Tim Crowe argued the genes responsible for language gave rise to schizophrenia. Geneticists and neuroscientists have not been inclined to think schizophrenia could have recently appeared and might as soon disappear.

But for doctors and historians the rise and fall of diseases is almost central to the definition of a disease – or should be. When it comes to mental illnesses the rules seem to change.

An English experiment on the Irish

In the 1980s, prior to working on the history of psychopharmacology, I looked at annual reports from the superintendents of Irish asylums who, facing a tide of insanity that rose higher in Ireland than anywhere else in the world, for the most part dismissed claims that there was a real increase in insanity. Asylums were an experiment invented by the English. They thought it a prudent idea to try it out on the Irish first, and built the first asylums in Ireland and more there than anywhere else. Never a people to miss a chance, the Irish at least in part took to wintering in facilities put in place by the British. This all made sense to me. There had to be a mundane explanation like this to account for the fact that in the face of the highest rates of incarceration ever recorded, mental illness never featured in Irish literature, one of the richest in the world. Against this background it was clear there was no true increase in insanity or no way to tell if there was a true increase or not.

The madness of North Wales

In 1996 in North Wales we began working on a project that has turned all my ideas upside down. This research led to a series of articles demonstrating a disappearance of classic postpartum psychosis, showing that severe social dislocation can trigger schizophrenia like psychoses that in general have a very good outcome, that hospitalizations for severe mood disorders (melancholia) are declining in frequency and then the findings for schizophrenia. We hope to feature the research on a forthcoming website – The Madness of North Wales – along hundreds of records, music, literature, art and other material aimed at making North Wales live and allowing us to outline a series of dramatic and universal accounts of madness in all its varieties through some intensely dramatic personal and local stories. (See The North Wales Mental Health Research Project).

Get your hands off schizophrenia – it’s mine

All was going well with our research and publications, until we attempted to publish papers on schizophrenia. Over the same two decades I have published articles on the hazards of psychotropics drugs, with journals scared to publish for legal reasons, and companies possibly finding other ways to sabotage publication, but I have never had reviews as vituperative as some of the reviews for these schizophrenia articles.

The first of two papers offer the best figures yet on the issue of whether schizophrenia did in fact rise in frequency during the nineteenth century or not. The message in the paper is very much a good news message – as I will lay out in the next post – but one of the reviewers, a medical historian, was adamant that nothing we could do would permit him to recommend publication. The paper would have been rejected had the editor not suggested disregarding this review  – something that no editor had ever done for an article of mine before.

We sent a second paper to another of medicine’s most prestigious journals which usually has an open review system but in this case the reviewers chose to remain anonymous. One of the reviewers argued that because some black males were incarcerated in US hospitals in the 1960s, we could never be sure any historical diagnoses from case records were correct. This might sound reasonable but was in fact lunatic in that we were not relying on the diagnoses in the records to make our diagnoses as the paper made clear. But the editor sided with the reviewers.

The question is whether the reviewers and editor were exceedingly twitched because of the paper’s findings which make it clear that compared to any other medical disease, uniquely patients with schizophrenia in many ways fare far worse now than a century ago. Faced with an absence of suicide in schizophrenia a century ago, an absence we can be very confident about, one reviewer suggested that this could have only come about because patients were permanently strait-jacketed and secluded. This self-evidently was not the case – the patients demonstrably spent 99% of their time on hospital farms or in sewing rooms or kitchens. But this cut no ice with editors or reviewers.

Why these findings count

Such has been the resistance to the findings that like them or not, it would seem that the responses to the findings must be telling us something important. There is resistance to any undermining of the idea of progress. There is a fundamental disagreement about the nature of disease and in particular mental disease. When many hear the message that schizophrenia is rapidly declining in frequency it seems they in fact hear that insanity is vanishing. It is as though the message that tuberculosis is declining in frequency were heard as respiratory disorders are vanishing, when the only way respiratory disorders will ever vanish is if we no longer have respiratory systems. Even though schizophrenia may have risen and might now be falling, as long as we have brains we are almost certain to create new and perhaps equally as bad mental diseases in the future.

The rise and fall of schizophrenia that will be outlined in the next post may give some clues as to how we produce insanities – and some of the steps we can take to prevent them. As long as we refuse to concede a disorder like this might rise and fall in frequency, we are never going to look for the things we could change that might make a difference. This is why the issue counts.