Coleg Meddygaeth Prifysgol Cymru

University of Wales College of Medicine

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Adran Meddygaeth Seicolegol / Department of Psychological Medicine
Adran Cymru y Gogledd / North Wales Department
Pennaeth Adran / Head of Department
Yr Athro /Professor Michael J. Owen
Bangor
Dr. D. Healy (Cyfarwyddwr)

 

Miss Sarah Wark, Senior Scientific Assessor 28 February 2000
Post-Licensing Division, Medicines Control Agency
Market Towers, 1 Nine Elms Lane
LONDON SW8 5NQ

Dear Miss Sarah Wark,

[See previous letter]

I will be very happy in due course to send you a copy of the full study report when this is available. It may however take some weeks or even some months before I can forward this to you.

In the meantime it is my understanding that a number of the studies with various different antidepressants that have been conducted with healthy volunteers as part of a series of pre and post registration tests have noted similar reactions to the ones that I have reported in our study. So much is this the case, that there is a general understanding in the field, certainly among the older practitioners working with different pharmaceutical companies, that strange reactions of this type are almost to be expected from healthy volunteers. 20 or 30 years ago the rationale for accepting such reactions was that antidepressants would never be given to anybody who wasn't depressed and that there were clearly differences between the brains of people who were hospitalised cases of endogenous depression compared with normal volunteers.

These rationales have vanished as depression has extended to the point where cases of what were Valium are now cases of Prozac. The most commonly prescribed use for Prozac it seems to me, and many of the other SSRIs, is for anxiety and stress reactions. These are the people whom I see regularly becoming suicidal on these drugs. This is a group of patients in whom it is not clear that there are likely to be any great differences between their brain states and those of healthy volunteers.

My understanding is that there are many people in the field whom the MCA could consult who would be able to confirm this position. There is also likely to be a considerable amount of data that companies have but whether they have submitted this to you or not is less clear to me.

I think the study on Sertraline induced suicidality in healthy volunteers is directly relevant to the question of suicide in the Prozac SPC that you say you will consider in the event that new information emerges. I feel this is new information directly relevant to the Prozac SPC. I think it's highly likely that Lilly in addition to other companies will have data of the kind that I have referred to above.

As regards Legal Jeopardy I have consulted with a number of lawyers on this and all appear to agree with me.

The situation as I see it is as follows. Patients entering clinical trials have a range of adverse effects which are not at present being coded for either at all or satisfactorily. In the case of side-effects not coded for satisfactorily these include problems such as suicidal ideation, which are coded for under depression. Akathisia is not coded for. Emotional indifference or emotional blunting or disinhibition are not coded for.

This is an understandable situation. It is understandable and perhaps acceptable if in the absence of figures to support a proper incidence for these problems, marketeers for a company claim that the incidence of these side-effects is zero. Everybody knows, you included I'm sure, that side-effect data commonly marketed by companies is hopelessly inadequate and underestimates the true extent of the problems probably by a six-fold factor. The legal jeopardy arises when patients who suffer from an adverse effect on the drug to the extent that they consider a legal action are then faced with a company denying that the drug causes the problem based upon the way the side-effect data have been coded in their clinical trials. This could happen to you or me or Dr Jones. Take the side-effects that have happened on Prozac for instance, and the way Lilly have handled the data on this issue in both court cases last year and in print in academic journals within the last 18 months. It is this that constitutes a state of legal jeopardy.

I would be very grateful if you could confirm for me that our understandings coincide on this point. If they do not, and you consider that this state is not a state of legal jeopardy, I would be very grateful if you cold explain to me exactly why not. I would not want to mislead any more people than I might have already misled by including this understanding of current practices in any more articles or books that I write.

I would be very grateful therefore to hear back from you on this point specifically.

Yours sincerely,

David Healy MD FRCPsych
Director, North Wales Department of Psychological Medicine

 

Uned Hergest, Ysbyty Gwynedd, Bangor, Gwynedd LL27 2PW
Ffn: (01248) 384452 Ffacs: (01248) 371397
Hergest Unit, Gwynedd Hospital, Bangor, Gwynedd LL27 2PW
Tel: (01248) 384452 Fax: (01248) 311397

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