Connecticut school shooting… an antidepressant connection or not? We need to know the answer

Sadly it’s happened again. This time in an elementary school in Connecticut.

We need to understand the cause and we need to go beyond the usual US gun laws discussion…

I’ve said it before and I’ll say it again – I wonder if antidepressant medication is involved?

I’m not saying antidepressants are the cause, I’m asking for you to consider if an adverse reaction to  medication might be the catalyst for extreme, violent episodes in some patients

Why not check  medical records? Why not collect data? Why not ask the question?

Big pharma has done no research (that we know of, at least), but I know of one study and I’ve made mention of it in a previously, but given recent events in Connecticut, I think it’s worth bringing up once more.

Published on September 12, 2006, this study by David Healy, Andrew Herxheimer and David B. Menkes deals with an issue that cannot be ignored.

“Recent regulatory warnings about adverse behavioural effects of antidepressants in susceptible individuals have raised the profile of these issues with clinicians, patients, and the public. We review available clinical trial data on paroxetine and sertraline and pharmacovigilance studies of paroxetine and fluoxetine, and outline a series of medico-legal cases involving antidepressants and violence.

Both clinical trial and pharmacovigilance data point to possible links between these drugs and violent behaviours. The legal cases outlined returned a variety of verdicts that may in part have stemmed from different judicial processes. Many jurisdictions appear not to have considered the possibility that a prescription drug may induce violence.

The association of antidepressant treatment with aggression and violence reported here calls for more clinical trial and epidemiological data to be made available and for good clinical descriptions of the adverse outcomes of treatment”.

The link to the paper is here and I suggest you scroll down to the end and read the 9 cases listed in the annex.

Also worth a look is SSRI stories.

And there’s a video here, in which film maker Michael Moore discusses possible causes in another school shooting – Columbine.

Professor David Healy meets with the MHRA to talk SSRI withdrawal reactions

Notes of the 26 June 2009 meeting – thanks to Bob Fiddaman at Seroxat Sufferers.

I find it unbelievable that all too many GPs still know next to nothing about withdrawal reactions from SSRIs.

Prof Healy considered that there was little evidence available on how to manage patients who had difficulty withdrawing from SSRIs. All agreed that this was a very difficult area to study as the management of the patient would differ depending on the patient.” Maybe if the drug companies would start by admitting there is a problem we could begin to look for some answers.

Unfortunately all the drug companies take the same stance that Glaxo has with Seroxat/Paxil – problem, what problem??

Still, we should get some answers in the Autumn of 2010 – that’s when the High Court in London is scheduled to hear the start of the UK class action against Glaxo and Seroxat. I, for one, cannot wait to follow this trial and see all the secret documents that have been hidden from the public for so long by Glaxo.

Open Court – that’s what we want – let’s have everything out in the full glare of the world’s press.

Anyway – here are the notes from Prof Healy’s meeting with the MHRA:

Meeting to discuss awareness and management of withdrawal reactions with SSRIs and related antidepressants
Professor David Healy
Mrs Sarah Morgan
Dr Julie Williams
Ms Diane Leakey

1. Introductions and background
MHRA explained that the background to this meeting was a meeting held with Mr Fiddaman in September 2008. Mr Fiddaman had raised concerns about a lack of awareness on the part of health professionals of withdrawal reactions with SSRIs and related antidepressants. Prof Healy explained that he had had a long term involvement with the safety of SSRIs and that he received a large number of e-mails directly from people withdrawing from SSRIs asking for advice on management of withdrawal symptoms. Before the meeting Prof Healy had provided documents that he had produced relating to the management of withdrawal from SSRIs.

2. Existing advice on management of withdrawal reactions with SSRIs/SNRIs
All agreed that most health professionals get their information from guidelines issued by the National Institute for Health and Clinical Excellence (NICE) and the British National Formulary (BNF) rather than directly from the Summaries of Product Characteristics (SPC), although it was noted that the SPC was very important as it dictated the information that would be available to the patient through the Patient Information Leaflet. MHRA informed Prof Healy that they had provided input to the recent consultation for revision of the NICE depression guideline and that the revised guideline would be available towards the end of the year. MHRA had also informed the BNF that they were looking at the area of withdrawal reactions and would contact them in the future regarding proposals for updates to the relevant sections of the BNF. MHRA also raised the important role played by Prescribing Advisors in the Primary Care Trusts in influencing prescribing practice. Prof Healy said that a key point not included in the guidance currently available was the existence of liquid formulations of SSRIs which could be useful in the management of withdrawal to allow slow tapering. Prof Healy also stated that before treatment started there should be a discussion between the prescriber and the patient about the possibility of withdrawal reactions.

3. Awareness of withdrawal reactions in clinical community
Prof Healy expressed the view that general practitioners (GPs) were not aware that withdrawal reactions on stopping SSRIs could be prolonged in some patients and were not aware of how to manage withdrawal reactions in these patients. Prof Healy was concerned that GPs may instinctively advise patients to withdraw by taking tablets on alternate days and this was not an appropriate approach.

4. New evidence relevant to management of withdrawal reactions
Prof Healy was not aware of any new evidence relevant to the management of withdrawal reactions. When asked if he had a view on the size of the problem of serious and prolonged withdrawal reactions with SSRIs, Prof Healy said that this was not possible to measure. Prof Healy said that while the propensity of an SSRI to cause withdrawal reactions was often thought to be only related to the half-life of the
drug, this seemed unlikely to be the case – it could also be related to the potency of the different drugs at the serotonin reuptake site. The lack of understanding of the problem contributes to a lack of effective solutions.
MHRA asked whether in his view there was any way that patients who were more at risk of prolonged withdrawal reactions could be identified. Prof Healy said that he felt that from his experience women seemed to be more at risk than men but it was unknown whether this was because more women than men were treated with SSRIs. MHRA said that their review of the issue had not identified any link between the risk of withdrawal reactions and the gender of the patient. Prof Healy considered that there was little evidence available on how to manage patients who had difficulty withdrawing from SSRIs. All agreed that this was a very difficult area to study as the management of the patient would differ depending on the patient.

5. Dependence/withdrawal for women of child-bearing years
Prof Healy had asked for the issue of use of SSRIs in pregnancy to be included in the agenda. He said that it was an important issue and the subject of upcoming court cases in the USA. Prof Healy said that it was important that women of childbearing years were appropriately informed of the risk of withdrawal reactions with SSRIs before beginning treatment and stated that in his view doctors may be liable under the Congenital Disabilities Act 1976 if they did not adequately inform patients of the risks of treatment during pregnancy.
MHRA said there had been communications about a small risk of congenital malformations associated with paroxetine and this issue was under further discussion at EU level. Prof Healy highlighted a recent publication describing an animal study looking at reproductive toxicity of a variety of SSRIs. MHRA asked for the reference and to be kept informed of any further new evidence of relevance to this issue.
MHRA noted that NICE had published its antenatal and postnatal mental health: clinical management and service guidance and that it was important that NICE was kept informed of any new evidence or advice in this area. MHRA agreed to find out whether review of the guideline was planned and to let Prof Healy know the best contact point for communication on this issue. Post meeting note: Prof Healy confirmed post-meeting that he had contacted NICE on this issue.

6. Opportunities for better communication with health professionals
Prof Healy said that the focus should be on highlighting to GPs that withdrawal reactions could be serious and prolonged in some patients and agreed that NICE and the BNF would be reasonable routes.

7. AOB
MHRA thanked Prof Healy for attending the meeting and agreed that it would be important to keep in contact on important new evidence in this area.

How drug companies re-engineer illness to keep making money

In this interview with Christopher Lane (from Psychology Today), David Healy outlines just a few of the ways way drug companies market their pills…

David Healy, a former secretary of the British Association for Psychopharmacology, is the author of over 120 articles and 14 books, including The Antidepressant Era, The Creation of Psychopharmacology, and Mania, a fascinating new book on the history of bipolar disorder. His criticism of drug-company practices has put him at odds with colleagues in psychiatry and pharmacology. At the same time, his undisputed expertise as a leading academic, researcher, and clinician gives him a unique perspective on patterns and problems in Anglo-American psychiatry. He recently agreed to answer a number of questions about the growing prevalence and expanded definition of bipolar disorder.

Part of what you describe in your new book Mania: A Short History of Bipolar Disorder is a fair amount of “biomythology” about the illness. What aspects in particular do you have in mind?

Biomythology links to biobabble, a term I coined in 1999 to correspond to the widely-used expression psychobabble. Biobabble refers to things like the supposed lowering of serotonin levels and the chemical imbalance that are said to lie at the heart of mood disorders, ADHD, and anxiety disorders. This is as mythical as the supposed alterations of libido that Freudian theory says are at the heart of psychodynamic disorders.

While libido and serotonin are real things, the way these terms were once used by psychoanalysts and by psychopharmacologists now—especially in the way they have seeped into popular culture—bears no relationship to any underlying serotonin level or measurable chemical imbalance or disorder of libido. What’s astonishing is how quickly these terms were taken up by popular culture, and how widely, with so many people now routinely referring their serotonin levels being out of whack when they are feeling wrong or unwell.

In the case of bipolar disorder the biomyths center on ideas of mood stabilization. But there is no evidence that the drugs stabilize moods. In fact, it is not even clear that it makes sense to talk about a mood center in the brain. A further piece of mythology aimed at keeping people on the drugs is that these are supposedly neuroprotective—but there’s no evidence that this is the case and in fact these drugs can lead to brain damage.

How does our understanding of “mania” differ today from earlier conceptions of the phenomenon?

Bipolar disorder itself is a somewhat mythical entity. As used now the term bears little relation to classic manic-depressive illness, which required people to be hospitalized with an episode of illness, either depression or mania. The problems that currently are grouped under the heading “bipolar disorder” are akin to problems that, in the 1960s and 1970s, would have been called “anxiety” and treated with tranquilizers or, during the 1990s, would have been labeled “depression” and treated with antidepressants.

How did we move so rapidly in the 1990s from a psychotherapeutic treatment model for children to a largely drug-related one?

I think a key factor in this shift has been the availability of operational criteria. These were introduced in 1980 in DSM-III, the 3rd edition of the Diagnostic and Statistical Manual of Mental Disorders. The idea was to bridge the gap between the psychotherapists, on the one hand, and the neuroscientists on the other. It was hoped that if both camps could ensure that patients met 5 of 9 criteria for depression, for instance, then at least the patient groups would be homogenous, even if the views on what had led to the problems weren’t.

It was still assumed, however, that there was a place for clinical judgment, so that a patient who met 5 of the 9 criteria for depression but had ‘flu or was pregnant would be diagnosed as being pregnant rather than depressed. But in the face of company marketing, and with the advent of the Internet, clinical judgment has been eroded. Patients going on the Internet or faced with drug company materials now all too easily find that they meet criteria for a disorder and there is often nothing or no-one to tell them this is not equivalent to having the disorder.

In the extreme, I have had patients with highly social careers come to me and say they think they have Asperger’s Syndrome because they’ve been on the Internet and find that they meet the criteria for this when, in fact, almost by definition, such a person cannot have Asperger’s Syndrome. In the absence of clinical judgment there is a default towards a biological option and a drug solution. Criteria create a problem for which a drug is all too often the answer, in just the same way that measurements of your lipid levels create a problem that a statin is the answer to.

Operational criteria are interacting here with a certain loss of medical authority. It is not possible for a doctor today to say to a patient, “Based on my 15 to 20 years experience, you do not have PTSD,” or whatever. She cannot say, “We do not need to continue this conversation; come back when you’ve had a medical training and 15 years of clinical experience.”

The doctor has to engage with the patient on the level of the material that’s out there in popular culture, and when she tries to do this she will find that she’s up against an extraordinarily skilful deployment of those materials by pharmaceutical company marketing departments who are masters at populating the wider culture to suit their interests.

In the mid-1990s, you note, roughly half of all mood disorders were redefined as bipolar disorder rather than depression. What do you think accounts for that dramatic shift in perspective?

The key event in the mid-1990s that led to the change in perspective was the marketing of Depakote by Abbott as a mood stabilizer. Before that, the concept of mood stabilization didn’t exist. And while in a popular TV series we can accept that Buffy the Vampire Slayer gets a new sister in Season Five that she had all the time but we didn’t know about, we don’t expect this to happen in academia.

The introduction of mood stabilization by Abbott and other companies who jumped on the bandwagon to market anticonvulsants and antipsychotics was in fact quite comparable to Buffy getting a new sister. Mood stabilization didn’t exist before the mid-1990s. It can’t be found in any of the earlier reference books and journals. Since then, however, we now have sections for mood stabilizers in all the books on psychotropic drugs, and over a hundred articles per year featuring mood stabilization in their titles.

In the same way, Abbott and other companies such as Lilly marketing Zyprexa for bipolar disorder have re-engineered manic-depressive illness. While the term bipolar disorder was there since 1980, manic-depression was the term that was still more commonly used until the mid-1990s when it vanishes and is replaced by bipolar disorder. Nowadays, over 500 articles per year feature bipolar disorder in their titles.

You just have to look at Lilly’s marketing of Donna from the Zyprexa documents on the Internet to see what is going on here: “Donna is a single mom, in her mid-30s, appearing in your office in drab clothing and seeming somewhat ill at ease. Her chief complaint is ‘I feel so anxious and irritable lately.’ Today she says she has been sleeping more than usual and has trouble concentrating at work and at home. However, several appointments earlier she was talkative, elated, and reported little need for sleep. You have treated her with various medications including antidepressants with little success. . . You will be able to assure Donna that Zyprexa is safe and that it will help relieve the symptoms she is struggling with.”

Donna could have featured in ads for tranquilizers from the 1960s to the 80s, or for antidepressants in the 1990s, and would have probably been more likely to respond to either of these treatment groups than to an antipsychotic, and less likely to be harmed by them than by an antipsychotic. What company marketers are so good at doing is framing the common symptoms people have—we almost all have—in a manner most likely to lead to a prescription for the remedy of the day. It flies in the face of a century of psychiatric thinking to see conditions that patients like Donna have as bipolar disorder. But while a century of psychiatric thinking used to count for something, it doesn’t any longer.

Between 1996-2001, you explain, there was a fivefold increase in the use of antipsychotics (Zyprexa, Risperdal, Abilify, Seroquel, and others) in preschoolers and preteens. What role did DSM-IV play in that, with its introduction of the still-controversial category Bipolar II disorder?

The concept of juvenile bipolar disorder flies even more in the face of traditional wisdom in psychiatry than does calling Donna bipolar. As of 2008, upwards of a million children in the United States—in many cases preschoolers—are on “mood-stabilizers” for bipolar disorder, even though the condition remains unrecognized in the rest of the world.

I am not sure how much DSM-IV played a role in this switch. I think the companies would have found a way to engineer the switch even without the introduction of Bipolar II disorder in DSM-IV.

So then how much of that shift is attributable to SSRI antidepressants coming off patent while the antipsychotics were still major revenue earners?

I think this was in fact central to what happened. The antidepressants were due to come off patent whereas the anticonvulsants were older drugs that could be repatented for this purpose, and the antipsychotics—which also could be (and were) marketed as mood stabilizers—were early in their patent life.

A related point that’s worth bringing out is that the switch happened because companies weren’t able to make new and more effective antidepressants. Had they been able to do so, I think they would have probably stuck with the depression model rather than made the switch to bipolar disorder.

In terms of what is happening in the US, I think we have to look at how skillfully the drug companies have exploited doctors. Doctors have wanted to help. While the drugs are available on prescription only, doctors tend to see giving a medicine as the way to go, where previously they had been much more skeptical about the benefits of drug treatments.

The drug companies have engineered a situation in which academics have become the primary spokespeople for the drugs. We see the sales rep in the corner and think we can easily resist his or her charms—but we still let them pick up the drinks tab. But it’s the academics who sell the drugs. Doctors who think they are uninfluenced by company marketing listen to the voices of academic psychiatrists when these, in the case of the antidepressants or antipsychotics given to children, have talked about the data from controlled trials, and by doing so have been witting or unwitting mouthpieces for company marketing departments.

In your opinion, did the FDA’s 2004 decision to add black-box warnings to SSRIs over pediatric use lead to greater off-label prescriptions and even the move toward antipsychotics, on the presumption that the latter are safer to use on children?

I think this had very little effect on the switch from depression to bipolar disorder, but what was quite striking was how quickly companies were able to use the views of the few bipolar-ologists who argued that when children become suicidal on antidepressants it’s not the fault of the drug. The problem, they said, stems from a mistaken diagnosis and if we could just get the diagnosis right and put the child on mood stabilizers then there wouldn’t be a problem.

There is no evidence for this viewpoint, but it was interesting to see how company support could put wind in the sails of such a perspective.

It was also interesting to see how close to delusional people could get about an idea like this. Faced with details such as even healthy volunteers becoming suicidal on an antidepressant, committed bipolar-ologists were quite ready to say that this just shows that these normal people are latently bipolar.

In this case, I think most people will see that “latent bipolarity,” as a concept, is functioning a little bit  like the way latent homosexuality once functioned for the Freudians. Most people will also see that the first concept is impossible. What the companies have done is hand a megaphone to the proponents of that view on bipolar disorder, which was until very recently a distinctly minority one.

And are the antipsychotics in fact safer than antidepressants?

No, they are not. The antipsychotics are as dangerous as the antidepressants. Before the introduction of the antipsychotics, the rates of suicide in schizophrenia were extremely low—they were hard to differentiate from the rest of the population. Since the introduction of the antipsychotics the rates of suicide have risen 10- or 20-fold.

Long before the antidepressants were linked with akathisia, the antipsychotics were universally recognized as causing this problem. It was also universally accepted that the akathisia they induce risked precipitating the patient into suicidality or violence.

They also cause a physical dependence. Zyprexa is among the drugs most likely to cause people to become physically dependent on it. As far as I am concerned, Zyprexa’s license for supposed maintenance treatment in bipolar disorder stems from data that is in fact excellent evidence for the physical dependence it causes and the problems that can arise when the treatment is stopped.

In addition, of course, these drugs are known to cause a range of neurological syndromes, diabetes, cardiovascular problems, and other problems. It’s hard to understand how blind clinicians can get to problems like these, especially in youngsters who grow obese and become diabetic right before their eyes.

But we have a field which, when faced with the obvious, instead chose to listen to Eli Lilly voices saying, “Oh no, there is no problem with Zyprexa. The psychosis is what causes diabetes—Henry Maudsley recognized that 130 years ago.” Well Henry Maudsley hated patients, and saw very few of them at a time when diabetes was rare. We recently looked at admissions to the North Wales Hospital from 1875-1924, years spanning his career, and among the more than 1,200 cases admitted for serious mental illness, not one had diabetes and none went on to develop it.

We also looked at admissions to the local mental-health unit between 1994 and 2007, and in over 400 first admissions none had type 2 diabetes, but the group as a whole went on to develop diabetes at twice the national rate.

This is not surprising. What is is how the entire field swallowed the Lilly line, especially when it was so implausible to begin with. We had great difficulties getting this article published—one journal refused even to have it reviewed.

One way of raising the profile of bipolar disorder in children, you note, was to argue that they’d been misdiagnosed with ADHD. What were the implications and effects of that claim?

In the case of children with ADHD, I think what one needs to appreciate is that in most of the world until very recently (and in countries like India still), ADHD is a very rare disorder where children, usually boys, are physically very overactive. This is a condition they grow out of in their teens. Treatment with a stimulant can make a difference in cases like this. Whether treatment is always called for, however, may depend on the circumstances of the child as opposed to the nature of any supposed condition.

It is only in a world where schooling or adherence to a particular set of social norms is compulsory that a condition like ADHD becomes a disorder. There was greater scope over a century ago than there is now for children to do other things in childhood and wait until they settled down in adolescence without being treated for their condition.

What we have today is not ADHD as it was classically understood, but rather a state of affairs we have had for centuries, which is “the problem child.” Today the problem child is labeled as having ADHD. But having just one label is very limiting. Child psychiatry needed another disorder—and for this reason bipolar disorder was welcome.

Not all children find stimulants suitable, and just as with the SSRIs and bipolar disorder it has become very convenient to say that the stimulants weren’t causing the problem the child was experiencing; the child in fact had a different disorder and if we could just get the diagnosis correct, then everything else would fall into place.

One fascinating phenomena at the moment is a clear looping effect with adult ADHD. Quite recently Britain’s NICE [National Institute for Health and Clinical Excellence] guidelines for ADHD came out and stated that adult ADHD is a valid clinical disorder. I am quite sure that a few years ago, 85 to 90 percent of physicians in the UK would not have thought adult ADHD was a valid clinical disorder. One might expect guidelines to be somewhat conservative, but in this case what we appear to be seeing is the guideline process getting out ahead of the field, leading clinicians in a direction that seems to be quite surprising.

Drug companies understand all too well that those constructing guidelines are supposed to be value-neutral and to follow the data. This means they can readily engineer trials that may show minimal benefit for their drug for a condition they have called “adult ADHD.” The makers of the guidelines have little option but to suspend judgment and to accept that the condition named must be real. So, for instance, as Lilly grasped, they end up endorsing the use of the agent like Strattera.

What’s astonishing about the current situation is that there seems to be almost no way to get the guideline makers—who are sitting in the middle of the road, immobilized by the oncoming headlights—out of the way of the pharmaceutical juggernaut. You can point out how they are being manipulated but they shrug and ask, “What can we do?”

We have recently begun a survey, here in North Wales, looking at aspects of this situation. In response to questions, clinicians here have indicated that three years ago they were quite certain they would not have used adult ADHD as a valid condition, but that three years from now they anticipate that they probably will. I think this shows a realistic appreciation of company abilities to change the climate in which clinical practice takes place, and the relative futility of attempting to stand up to such changes.

You have to treat real patients. What do you tell them about these conditions and their treatment options?

Many clinicians, scientists, and patients have heard about postmodernism. They might have heard company criticism of someone like me along such lines as “Pay no heed to him, he’s just a postmodernist.” The implication is that postmodernism is all-but a psychiatric disorder in its own right, in which academics like me refuse to concede that there’s any reality to human behaviors—or the physical underpinnings of disorders of human behavior. By contrast, the story goes, there are the hard scientists who work in or with drug companies who deal only with facts and hard data, and the proof is that they bring new and helpful drugs to the market.

Well, I think what Donna’s story above illustrates is that pharmaceutical marketing departments are actually the postmodernists par excellence. They treat the human body (including its disorders and complaints) as texts to be interpreted one way this year and in just the opposite way a year or two later.

In contrast, when it comes to the hazards of these drugs—just like the tobacco companies before them—the motto of Pharma has become “doubt is our product”—they simply refuse to concede that their drugs are linked to any hazard at all . . . until the drug goes off patent. You cannot get a better definition of postmodernism than “doubt is our product.”

So, to the matter of whose treatments are better: I’m quite happy that the patients coming to see me would in general get more effective and safer treatment for their problems than they’d get from physicians adhering to the latest guidelines. Trouble is, I only have to slip up once to have a big problem, whereas atrocities can be committed on the other side without anyone likely to be affected by blowback.

David Healy is the author of 14 books, including The Antidepressant Era, The Creation of Psychopharmacology, Let Them Eat Prozac: The Unhealthy Relationship between the Pharmaceutical Industry and Depression, and, most recently, Mania: A Short History of Bipolar Disorder. Christopher Lane is the author most recently of Shyness: How Normal Behavior Became a Sickness.

Panorama interactive forums

The links below will take you to three Panorama interactive web forums that took place after broadcasts of the Seroxat programmes.

They’re worth watching to see our good friend Alastair Benbow in full flow defending Seroxat as only he can… you also get to see Charles Medawar, David Healy and Andrew Herxheimer.

14 October 2002

11 May 2003

11 July 2003

Manufacturing Consensus – Adult ADHD in the UK

The excerpt below is from David Healy’s Marketing Drugs and Changing Lives in the US… you can read more here.


Consensus conferences aimed at producing guidelines for clinical practice came into existence in the late 1980s (Sheldon and Smith 1993). A range of bodies took up this apparently academic development. Within psychiatry, groups such as the British Association of Psychopharmacology and the European College of Neuropsychopharmacology, for example, produced guidelines on the treatment of a range of conditions from depression through to schizophrenia. This may have happened in part in an effort to establish a political profile. In a number of the organizations that produced guidelines, the influence of key individuals with links to pharmaceutical companies is apparent.

At the same time pharmaceutical companies began to sponsor meetings aimed at producing expert consensus on issues such as the appropriate use of medication in schizophrenia. These company sponsored meetings have often resulted in products that may appear almost indistinguishable from non-company sponsored guidelines or algorithms. While this might be thought as an exercise designed to confound the recommendations of independent committees, in fact committees that should be independent have come up with recommendations that barely differ from explicitly company-sponsored exercises.

And my point is…?

A couple of posts ago I wrote about a news item that I saw last week – Adult ADHD Marketing Reaches the UK. I wondered where the story had come from – what the “strong evidence” and “research” is…

It is only in the last few years that strong evidence has emerged about the extent of ADHD in the adult population. It is thought up to 8% of children may be affected, and research suggests that half or more may have symptoms past adolescence into their twenties, thirties or even forties.

Yet the condition is barely recognised by the health service beyond 18 years of age.

Professor Anthony Hale, professor of psychiatry at the University of Kent, said patients are being failed by the system. “There are huge numbers of people across the country who are on waiting lists to see adult psychiatrists who don’t have the expertise to deal with them. The 4% of the adult population figure is very real.”

…Dr Marios Adamou, whose clinic is due to close in October due to lack of funding, said poor access to treatment is a real problem.

“For some people it may mean catastrophe, because some people without the medicine are prone to offending behaviour, and prone to aggression. So a few people may end up being arrested, being imprisoned. Others may fail in their courses, others may fail in their occupation.”

Dr Adamou says Britain is years behind most other European countries in dealing with this problem.

Most of the medication is licensed for use only in children, and many of the treatments are controlled drugs, so GPs – and many adult psychiatrists – are often reluctant to prescribe them.

The “strong evidence” and “research” mentioned, comes from a consensus meeting of 2006 (ADHD in transition from child to adult), organised by the British Association for Psychopharmacology (BAP) and funded by Cephalon, Janssen, Lilly, Shire UK and Shire US – all drug companies that manufacture ADHD drugs – Adderall, Modafinil, Concerta and Strattera. All of the drug companies also supplied ‘observers’ who attended the meeting to… ‘observe’, I suppose.

The Consensus Group was headed by Professor David J Nutt – would this be a good time to mention the Professor’s links, I wonder? Professor Nutt has acted as a consultant to Pfizer, GSK, MSD, Novartis, Asahi, Organon, Cypress, Lilly, Janssen, Lundbeck, Wyeth. He has speaking honoraria (in addition to above) with Reckitt-Benkiser and Cephalon. Grants or clinical trial payments from MSD, GSK, Novartis, Servier, Janssen, Yamanouchi, Lundbeck, Pfizer, Wyeth, Organon. He has 300 shares with GSK (ex-Wellcome). Professor Nutt also promoted Seroxat at Glaxo’s launch of Seroxat for “social anxiety disorder”.

Also at the consensus meeting were Professor Anthony Hale and Dr Marios Adamou, who work together in Kent. In 2003 in a letter they co-wrote to the BMJ they signed off: Competing interests: M. Adamou is a co-investigator to pharmaceutical companies producing or developing neurotropics. A.S. Hale is an investigator and advisor to pharmaceutical companies producing or developing neurotropics.

I just can’t help thinking that maybe things might not be quite so clear cut as they seemed when this story was first published.

Adult ADHD – coming to a UK GP near you ASAP.

Panorama interactive forums – watch here

I’ve just been prompted by an email from a friend to post up these links to three Panorama interactive web forums that took place after broadcasts of the Seroxat programmes.

They’re worth watching to see our good friend Alastair Benbow in full flow defending Seroxat as only he can… you also get to see Charles Medawar, David Healy and Andrew Herxheimer.

14 October 2002

11 May 2003

11 July 2003

Antidepressants and Violence: Problems at the Interface of Medicine and Law

I’ve made mention of this study in a previous post, but given recent events at Virginia Tech, I think it’s worth bringing up once more.

Published on September 12, 2006, this study by David Healy, Andrew Herxheimer and David B. Menkes deals with an issue that cannot be ignored.

“Recent regulatory warnings about adverse behavioural effects of antidepressants in susceptible individuals have raised the profile of these issues with clinicians, patients, and the public. We review available clinical trial data on paroxetine and sertraline and pharmacovigilance studies of paroxetine and fluoxetine, and outline a series of medico-legal cases involving antidepressants and violence.

Both clinical trial and pharmacovigilance data point to possible links between these drugs and violent behaviours. The legal cases outlined returned a variety of verdicts that may in part have stemmed from different judicial processes. Many jurisdictions appear not to have considered the possibility that a prescription drug may induce violence.

The association of antidepressant treatment with aggression and violence reported here calls for more clinical trial and epidemiological data to be made available and for good clinical descriptions of the adverse outcomes of treatment”.

The link to the paper is here and I suggest you scroll down to the end and read the 9 cases listed in the annex.

Dr June Raine at the MHRA was warned about Seroxat 7 years ago

My good friend Bob Fiddaman, over at Seroxat sufferers writes:

Dr June Raine is the Director of the Post-Licensing Division at the Medicines and Healthcare Products Regulatory Agency (MHRA) and her responsibilities include all the issues that relate to medicines once they are authorised for use on the market.

Now, you have to ask yourself two fundamental questions here. Firstly, Dr June Raine is still the Director of the Post-Licensing Division at the MHRA – Why?

And secondly… Why have no criminal charges been brought against her?

Bob’s post Dr June Raine, MHRA knew 7 years ago tells the story of David Healy’s letter to her on the 7 June 2000. He wrote the day after the Court case in “Cheyenne, Wyoming… found GlaxoSmithKline guilty on several accounts including the count that Paroxetine can cause suicidality, that it specifically did so and contributed to the wrongful death of Don and Rita Schell as well as Deborah and Alyssa Tobin and that the company had been responsible for a failure to test and a failure to warn”.

David Healy wrote his letter in order to try and save lives.

As an expert witness in the Schell/Tobin case, Professor Healy had been granted access to Glaxo’s archives and had made shocking discoveries:

“What I found was that approximately 25% of the volunteers in the studies that I reviewed which were all of the healthy volunteer studies done prior to the filing of this drug for registration in the US and in the UK – 34 studies approximately in all. These yielded a 25% agitation, nervousness/akathisia rate. Some of the multiple does studies in healthy volunteers lasting 2-3 weeks yielded an up to 85% withdrawal rate in the volunteers.

All of their healthy volunteer studies were supposed to have been made available to me but not all were. Of the ones that were missing there was trace correspondence left in once indicating that the investigator had never witnessed such a level of problems in a study with healthy volunteers. Another study was a single dose study which in a dose dependent fashion yielded a 75% rate of severe adverse events most of which involved the central nervous system. There were other disturbing indications from one of the other missing studies.

Volunteers who had participated in the programme went on to suicidal acts. The relationship between their intake of paroxetine and later suicidal acts is a matter about which neither you nor SmithKline Beecham should be sanguine.

These studies were for the most part done on company employees. None of the studies bar the missing ones were done by investigators with a background in psychiatry. The investigators were general physicians with a primary interest in gastrointestinal problems who could not have been expected to detect mental problems of this sort that have concerned me and I would have thought should concern you”.

Professor Healy carried on:

“My testimony in this case also bore witness to sealed studies and other unreported data. It commented on the Montgomery Baldwin Study which yielded a projected rate of 45 suicide attempts in a group of recurrent brief depressive disordered patients on paroxetine per annum versus 12 on placebo. The figures were not statistically significant in great part one has to suggest because the company had terminated the study early. This termination and subsequent non-publication I would imagine the jury will have found and others will find significant.

Dr Hudson, currently of the MCA, was a witness for SmithKline in this case. He may well be able to give you further details on some of the issues involved. His testimony involved repeated reference to the fact that SmithKline Beecham cannot decide whether their drug had caused problems such as the wrongful death of Don and Rita Schell or Deborah and Alyssa Tobin or the wrongful deaths of many other people whose deaths have been reported to SmithKline even when these reports have been accompanied by the opinions of their treating physicians that the drug had indeed contributed to the problem. Dr Hudson’s testimony was that until controlled trials or other similar studies had proven in general that paroxetine could cause such problems that the company could not make decisions on any specific case”.

In conclusion he wrote:

“I think what will also be clear is that SmithKline Beecham recognised the presence of withdrawal syndromes in their volunteers from the early to mid 1980s. That withdrawal syndromes occurred at a much higher rate than occur on benzodiazepines. Nevertheless they applied for and have received from you and other regulators a licence to claim that their drug is effective in the prophylaxis of depression and these claims have been based on designs which almost certainly are designs better suited to show the presence of a withdrawal syndrome than designs suited to demonstrate prophylaxis in depressive disorders. A great number of people have in recent years been told that when they begin to feel ill on discontinuing treatment that this is the recrudescence of their mood disorder rather than a discontinuation syndrome from their drug. I would imagine that a great many such people and others on their behalf will feel extraordinarily let down and angry when faced with the evidence that I’ve been faced with”.

I think we all have to ask why June Raine and the MHRA did nothing in 2000 and still today they do nothing.

David Healy – SSRIs & withdrawal/dependence 2003

Another PDF for download here – David Healy briefing paper – this is from 2003 and is an overview of SSRI withdrawal and dependence, written in as thorough and rational a way as you could ever wish for:

“Dependence on and withdrawal from anitdepressants has been recognised since the early 1960s.

The withdrawal syndrome complicates the evaluation of patients after drug discontinuation since both patients and physicians often interpret the onset of symptoms as an upsurge of “anxiety” related to incipient relapse, and resume treatment with the gratifying subsidence of the “anxiety”. This may cause both patients and physicians to overvalue the importance of the medication to the patient’s stability” (Kramer et al 1961).

Therapeutic drug dependence or normal dose dependence needs to be distinguished from drug dependence of the sort caused by opiates and amphetamines.

Companies have not been required to test their drugs for therapeutic drug dependence prior to marketing.

In the case of the SSRIs it would seem that therapeutic drug dependence has been used as a means to claim prophylactic efficacy for these drugs”.

You really must download this one.

3 years on and the FDA have done nothing

David Healy made a submission to the FDA in February 2004. The Executive summary is below and the full paper can be read here:

The enclosed document arose from a direct invitation from Dr. Robert Temple, Director of the Office of Drug Evaluation I, of the Food and Drug Administrion, in the course of a meeting organised at FDA on February 3rd 2004. The meeting was focussed primarily on the issue of suicidality in children taking SSRIs. But this issue does not stand alone. It would appear that we have reached a crisis point in both the regulation of psychotropic drugs and perhaps all drugs and a crisis point in psychiatry and perhaps all of medicine. It will become clear from the material laid out here that most if not all of the supposedly scientific literature on giving SSRIs to children may be ghost-written. It also seems clear that FDA do not know basic things about the use of these drugs such as how many people are on the drugs.

This paper offers a model that for the first time gives an estimate as to likely numbers of people who have taken Prozac, Paxil and Zoloft since their launch in the US. From this it is possible to derive an estimate of the numbers of people who have committed suicide over and above the numbers who would have committed suicide had SSRI drugs never been marketed. This points to a figure of 21,000 excess suicides. It seems quite likely that when this model is in due course fed real figures from actually dead people, that this estimated figure will appear conservative.

One way out of the problem is outlined in this paper, namely to adopt a system that encourages consumer reporting of adverse events. The current crisis makes it clear that consumer reports are often considerably more accurate than physician reports.

The material laid out here gives rise to a series of questions for FDA:

In the light of Traci Johnson’s death on February 7th 2004, will FDA obtain Pfizer’s entire folder on the 1982 Hindmarch study in which healthy volunteers were given Zoloft, and make a statement as to whether data of this kind can indicate whether SSRIs can induce suicidality?

Will FDA undertake to obtain all of Glaxo SmithKline’s trials in children and make available an analysis of all the data in regard to suicidality and aggressive behavior?

In the light of the details below, will FDA comment on their characterization of the British approach to the question of the risk benefit ratio for SSRIs in pediatric populations as superficial?

Will FDA confirm that companies have inappropriately coded suicidal acts under the heading of placebo in trials of Prozac, Zoloft and Paxil in adults, and will the agency give a true set of figures for the suicidal acts on both active treatment and placebo in registration trials for adults?

Given that Paxil/Seroxat shows the greatest number of withdrawal syndrome reports to WHO for any psychotropic drug ever, and given that the full dimensions of this problem remain unknown, with the company changing its estimates as to the frequency and severity of the problem at regular intervals, will FDA outline exactly how a randomized withdrawal design could demonstrate these drugs work for either children or adults?

Given the abundance of evidence that physicians commonly increase the dose of SSRIs when faced with a patient not doing well on treatment, particularly during the early phases of treatment, what advice will FDA offer to doctors to minimize the risk of this happening inappropriately?

What will FDA do to remedy the incredible fact that Americans track the fate of parcels through the post 100 times more accurately than they track the death of children and adults on these drugs?

Specifically, in the light of the failures of physicians to report adverse events, will FDA consider an initiative begun by the mental health charity, MIND (UK) to foster consumer reporting of drug induced adverse events?

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