La Reine Margot: Data Access, Ghostwriting, Suicide and Mad Reviewers

Another study giving a first hint of the findings in our 2012 Mortality in Schizophrenia paper (See The Madness of Psychiatry) was published in the British Journal of Psychiatry in 2006 – Lifetime Rates of Suicide in Schizophrenia. It took several years and some smuggling to get it into print. In the course of exploring the issues, it seemed useful to touch base with Herb Meltzer who had links to the InterSePT study, a widely marketed study which looked at suicide on clozapine and olanzapine.

Failing to get the InterSePT Data

From: David Healy [mailto:[email protected]]
Sent: Wed 1/22/2003 3:51 AM
To: Meltzer, Herbert; Tom Ban; tom ban
Subject: InterSePT

Dear Herb

Along with I suspect many others, I’ve been poring over the InterSePT results published in Archives. This is a study that will almost certainly open up the question of suicide in schizophrenia as a live issue for years to come.  Congratulations.

The Archives paper suggests that you should have the number of patient exposure years to both clozapine and olanzapine, but this is not actually presented. I wonder whether I could ask you for these details? I have access to other FDA data and a further unpublished dataset on suicide in schizophrenia and these details would enable comparability between datasets.

Regards

David Healy

22/01/03

Dear David:

Thanks for the congratulations. I will try to obtain the exposure information for you from Novartis. The drop out rate was the same in percentage and I believe in time so there  probably will be no significant difference. Forty percent was the approximate rate for both. This is given in the paper.

Should you find any significant issues with regard to the study, I would encourage you to bring them to light.

If I can be of further help to you in your interest in suicide in schizophrenia, please do not hesitate to write. It remains a keen interest of mine.

With best regards

Herb
Herbert Y. Meltzer, MD

From: David Healy [mailto:[email protected]]

Sent: Wed 2/5/2003 7:37 AM

To: Meltzer, Herbert; Tom Ban; tom ban
Subject: Suicides in Schizophrenia

Dear Herb and Tom

Please find attached a draft M/s on suicide in schizophrenia. This has gone nowhere at this point. I would greatly appreciate any comments on methodology, or conclusions or on the overall characterisation of these sensitive clinical issues.

The InterSePT paper offers sufficient detail to include the probably correct patient exposure years for the whole group. Clearly a confirmation of the figures would be great. There is no way to distinguish between clozapine and olanzapine without specific figures for each drug.

If there are no insuperable methodological or conceptual issues here I would envisage presenting some of the figures in Geneva in April, so a relatively rapid response would be appreciated.

David

2/6/03

David:

I have looked over the draft you sent me. In my judgement, it is very, very premature for you to think of presenting or sending it anywhere. You get yourself into all kinds of problems by trying to do too much and not concentrating on the good ideas. (Now where have I said that before?).

The data from Wales is interesting in its own right. Stick to it. Explore it. Ask the tough questions about that data set in as rigorous a way as you can. Don’t try, in this paper, at least, to use it as the platform to launch the idea that antipsychotics increase the risk of suicide attempts and completions. If you take a step back, you will realize that differences in time, place, diagnosis, psychosocial support (family structure in particular), substance abuse, longevity, availability of hospitalization or its equivalent, to name the most obvious, make this an extremely weak way to explore your hypothesis about antipsychotic drugs increasing the rate of suicide.

You could do a real service to the field and your reputation by a solid bit of historical epidemiology here. From there, take on the Khan data. Your interpretation of what it says about suicide and antipsychotic drugs should be confined to what you can glean from the paper itself, not this historical comparison which in no way can be used as the reference point for the effect of drugs in the Khan study. The reference point is the placebo group in that study, and there is no hint that the drugs increased the rate as I recall. In discussing the Khan study in InterSept and talks, we have been cautious in making comparisons in the rates between the two studies because there are so many differences between them. After taking the Khan paper on, take on InterSept and have a go at its methodology, conclusions, whatever. Or go after it first, if that is your wont. You have, in trying to do much, produced a very weak argument so your good points get overlooked, a repetition of the strategic error in your last book, in my judgement.

I wish I had the time to be of more help to you but I really don’t. There are very many, many pressing things I have to do. My advice is to find a colleague who you respect and plead with him to deconstruct your logic and approach, to make you justify every line, every inference. You really need that. You do not need the adulation of an unusually beneficient Max Fink whose affection for you is equalled only by your affection for him. You are a gifted person. I have thought of you as the person who could someday write a splendid history of some particular aspect of psychopharmacology. Don’t squander those gifts. Don’t worry about tilting at windmills. Build the edifice first.

One last thing. I just read Amos Elon’s The PIty of It All. It is a recently published story of the German Jews from the 18th century to 1933. It is the most magnificent piece of history I have ever read. It is filled with intimate details gleaned from years of scholarship. When he reaches a conclusion, you feel its inevitability given what he has presented you with. You finish the book and you feel great lessons have been learned. You get inside the people he has written about.

I hope someday to see writing from you of that quality. Tom Ban knows how much I revere good history. That is why my response to your recent book was so strong. You can do so much better than you are doing. Why rush to present something before its time? If you have gotten yourself into a situation where every time you give a talk you have to have some very provocative view point that causes your audience to get their adrenals and pituitaries secreting at full blast, you are in deep trouble. Forgive me for being so blunt and harsh here. I come at this out of genuine desire to be of help. If you interpret this that I have any desire to suppress evidence that antipsychotic drugs increase the risk of suicide, you could not be more wrong.

I asked the Novartis people to send you the data when you first asked me. I am not sure they are willing to.

I will try again.

Herb

Reading Herb:

First even Herb appears to agree that antipsychotics “cause” suicide. But his line, like that of so many others, is that patients can’t be told this – the media can’t be told – no-one can be told.

Herb refers to his hostile review of one of my books The Creation of Psychopharmacology which had appeared in 2002 – in contrast to a positive review of it by Max Fink. It is now widely accepted that second generation antipsychotics are no better than first generation drugs. Creation stated this clearly in 2002, and stated that the field was being fooled by marketing. The ability to make a call like this shows that you don’t need clinical trials to tell when something is evident – there is evident based medicine that tells anyone looking that the second generation drugs weren’t all that good.  Then there is evidence based medicine like InterSePT, and doctors are keen to be fooled by evidence-based medicine. (See False Friends)

Creation was written in 2000. It was the book behind the talk – Psychopharmacology & the Government of the Self – at which Charlie Nemeroff was present and after which he put pressure on the University of Toronto to let Healy go.

Second, it is clear Herb doesn’t have the InterSePT data, and possibly never had. The paper was probably “ghostwritten”.

Herb is linked to the reintroduction of clozapine and second generation antipsychotics to the US market. InterSePT did a great deal to boost the sales of clozapine – with its PR message that patients are much more likely to die from suicide than from the effects of clozapine on their white blood counts – and the marketing material produced by Novartis exhorting doctors to give clozapine early the only drug shown to reduce the risk of suicide.

But in InterSePT there were in fact more suicides on clozapine than on olanzapine – the drug with the highest suicide and suicidal act rate in clinical trial history. A convenient choice of comparator for clozapine.

This email to Herb came relatively soon after his hostile review of Creation, and after the email sequence between Herb and Bruce Chartton below. So what’s with the friendly tone? 

In Alexandre Dumas’ novel La Reine Margot, made into an extraordinary movie by Patrice Chéreau, Margot returns to a Ball in the Palace being held by the King her brother. She is returning from the morgue where she has just kissed the head of her lover guillotined by the King. A drop of his blood has ended up on her sleeve. The King comments on the blood. What matter she says provided we all keep smiling.

A colleague Bruce Charlton was surprised by HM’s review of Creation and tackled him on some issues leading the following email sequence.

From:     Self <Single-user mode>
To: “Meltzer, Herbert”
Subject: Science Healy review
Date: Mon, 26 Aug 2002 13:41:39

Dear Dr Meltzer,

I am writing about your Science review of David Healy’s ‘The creation of psychopharmacology’. While I appreciate that you did your best to provide a balanced evaluation of a book with whose perspective you apparently fundamentally disagree, I was nonetheless puzzled by the fact that you focused and framed the review with statements about Healy having advocated free availability of drugs – eg:

‘What many will find most provocative about this book and its predecessor, The Antidepressant Era (2), is the recommendation that powerful psychotropic drugs, including neuroleptics such as chlorpromazine, could or should be available without prescription.’

and

‘he believes  that people should be allowed to purchase these drugs without medical supervision’

Having read the book with some care, I don’t recall Healy having made such statements, at least not explicitly – could you direct me to the places where he does so? Or were you perhaps drawing upon other background information concerning the author’s views?

Sincerely yours, Bruce Charlton

Bruce G Charlton  MD

Subject:          RE: Science Healy review
Date sent:        Mon, 26 Aug 2002 11:25:51 -0500

From:             “Meltzer, Herbert”

Ask yourself why you think what he has written is not so straight forward and read on. In the next few pages, he makes his case against requiring prescription for psychotropic drugs in general very clear. On  p 264 he writes,

“Should the conspiracy against the public that is prescribing rights be extended to nonmedical health professionals such as clinical psychologists.”

You will find many, many passages in the book I reviewed where his intent is very clear but he writes to give himself some “wriggle room” if he is called to justify his position. I believe he is attempting to convince the uninformed but to give himself “an out” with people like me.

I have high regard for David Healy as an interviewer.

Are you a colleague of his?

Herb Meltzer

From:     Self <Single-user mode>
To: “Meltzer, Herbert”
Subject: RE: Science Healy review
Date: Mon, 26 Aug 2002 16:48:29

Thanks for this clarification – I see the passage you mean. However, I wouldn’t really call this straightforward advocacy, especially since the section is clearly framed as a ‘thought experiment’. Rather, I think the passage makes a specific argument concerning  the way the neuroleptics have been used (especially in terms of dosage), compared with how they might have been used.

Anyway, thanks again.

Sincerely yours, Bruce Charlton

Subject:          RE: Science Healy review
Date sent:        Mon, 26 Aug 2002 09:47:42 -0500
From:             “Meltzer, Herbert”
To:               “Charlton, Bruce”

Dr Charlton:

David Healy makes the case that chlorpromazine should have been an over the counter drug from the start and that medical use of the drug produced adverse events that might not have occurred if it was over the counter  in “the Antidepressants” on pgs 258-259.  As you indicate, he did not reiterate this in the book I reviewed. I assume that if he had changed his view on such an important matter he would have stated so. You will have to ask him why he made such an important point in a book mainly on depression and makes no mention of it in a book that deals with chlorpromazine.

Herb Meltzer

From: Charlton, Bruce”
Sent: Wed 8/28/2002 9:40 AM

To: Meltzer, Herbert

Subject: Science Review

Dear Dr Meltzer,

I know David Healy (although I am not a colleague) and rate his work very highly. As you suggested, I checked with him, and he says that he has never advocated OTC availability of chlorpromazine etc. in print, and that the examples you cited from the Antidepressant Era were indeed intended as a thought experiment, as I had assumed.

I don’t actually know what his private views are on the topic, but – whatever they are – it seems rather strange that Healy’s assumed but unstated opinions should have formed the main thrust and focus of your Science review.

Anyway, thank for clarifying this point for me.

Sincerely yours, Bruce Charlton

Subject:          RE: Science Review
Date sent:        Wed, 28 Aug 2002 10:58:06 -0500
From:             “Meltzer, Herbert”
To:               ” Charlton, Bruce”

Whatever you and Healy mean by a thought experiment, there is a clear advocacy that this is what Healy believes would have been in the best interest of people who need chlorpromazine. I take that as advocacy for changes in public policy which he then goes on to explicitly ask for. His statement, in the second book,  that ‘any future Rousseau’s should be able to try the interventions of twenty-first century psychiatry in a setting that will enable him to decide freely whether they have anything to offer him” and the continued attack on the concept of having to receive a prescription for psychotropic drugs from physicians is advocacy.

If he is just venting spleen for all the attention he devotes to the issue, that is rather pathetic in my view. I and others read his views as a call for a change in policy. Read again the last two pages of the postscript of the Antidepressants, which followed the section on chlorpromazine. He is clearly advocating the end of prescription medicine. Whatever ambiguity there is is more likely deliberate than accidental.

Space limitation really prevented me from describing many of the things in the book, which profoundly disturbed me. Sentences like; “The current thinking is that there is little or no scientific knowledge about the latest generation of compounds other than what is provided by pharmaceutical companies.” offend me deeply. Firstly, they are untrue. I and my colleagues have done extensive research with no support from industry, studies which have had a big impact on the field. Secondly, even if there has been industry support, I have NEVER changed my views one iota on what I wrote or said to please any of them. Thirdly, this type of exaggerated prose,  is very misleading to the lay leader who does not know better.

I believe the review covered much more than that single issue.

Herb Meltzer

Patients as cannon-fodder

For the record, my position about prescription only is that it confers an extraordinary privilege on the prescriber but brings an extraordinary responsibility – to go way beyond the extra mile to keep the person in your care safe.

All too often prescription only privileges puts doctors in the position of the generals in the Crimea or Great War who sent the troops over the top in a doomed Charge of the Light Brigade. We want generals that we the infantry can trust, generals with a proven track record of keeping their troops safe to fight another day – Chiefs like Joseph of the Nez Perce, perhaps.

3 COMMENTS

  1. I am glad somebody is at last writing about how olanzapine and clozapine are actually pushing people to commit suicide. I have first hand experience of this. My son was force-fed olanzapine. When he came home from hospital he developed deep depression and suicidal thoughts. He tried to get off the drug but just could not. He developed severe akathisia and could not stop walking day and night. He developed also a strange sleeping pattern; he could only sleep 10 minutes at a time. Doctors did not believe what we were telling them and refused to help. After 6 weeks of this he could not take it any longer and tried to kill himself. It was pure luck that I found him in time and the emergency services saved his life. When I told his psychiatrist what had happened, he looked at me incredulously and told me to leave it to the specialists. My son had entered the hospital with a severly infected toe and delirium, he came out diagnosed “severly mentally ill” and traumatised by his experience.He came off all antipsychotic medication behind doctors’ backs. He had been put on risperidone. He hasn’t had a suicidal thought since and is actually enjoying life. The daughter of a friend has had a similar experience on clozpine.

  2. If I am interpreting this correctly, 1) Dr. Metzler put his name on a paper without having access to all the data, 2) he is not sure if he is allowed to even see the data, or to tell you, or anyone else, about it if he does see it, 3) in review of your book he finds fault with an argument that you didn’t make in print, but that he knew that you secretly believed in, and 4) to top it all off, he is lecturing you about interpreting data. Am I missing something?

  3. Meltzer speaks of being offended, why would anyone think it an insult for a researcher to be asked for raw data, to in effect, “show his work”? It should be customary. This is not the dark ages when knowledge is hidden from the masses, let alone other professionals in the same field. It is trust, but verify in science; and one who is unwilling to verify, should not be trusted…The fact that he is evasive and insulting does nothing to detract from his juvenile implication that it’s an insult to have been asked for raw data. Why would any professional think it an insult to be asked for data that should be openly shared with other medical professionals as a matter of course?

    I for one have a bad feeling about this drug and not only because my son takes it. If one looks at what is available–it is patently obvious there has been a consistent effort to declare this drug better than EVERY other drug for at least a decade—articles stating it treats addiction, aggression, and a handful of other common “off label” marketing targets we are all now familiar with. Rarely will one find an article which does not decry the need to use Clozpine more often for schizophrenia and/or for more diagnoses. Clozapine is used less frequently in real world practice that any other neuroleptic drug, yet the number of deaths attributed to Clozapine in the AERS data makes it the number three killer out of all the FDA approved drugs. Seeing what it is doing to my son makes me biased, however, there is something seriously wrong when there is such a disparity between the claims of superiority being made, and the number of patients with fatal outcomes…So I have something to say for any person claims what a wonder drug it is–prove it SHOW ME the DATA. I’m just a mother and what I see is Clozapine robbing my son of his abilities while his health declines.

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