Social Audit Ltd
P O Box 111 London NW1 8XG
Telephone/Fax 44 (0)171 586 7771
Dr Keith Jones
Medicines Control Agency
Market Towers, 1 Nine Elms Lane
London SW8 5NQ 4 December 1997

Dear Keith,

I tried to telephone you this afternoon, but was referred to your press office, where no-one answered the 'phone. I am therefore writing in connection with the statement the Department issued to The Times yesterday, on behalf of the MCA/CSM. I was embarrassed on your behalf to read it; it was even flimsier than I anticipated when I wrote to the Secretary of State two days ago. Surely, it would be better to withdraw it now, before questions of resignation arise?

I will not comment on the larger part of the statement which I regard either as flannel or as rather plaintive attacks on me - other than to murmur that perhaps this is related to my having taken the MCA to task on several issues in the recent past, eventually succeeding on every occasion I intervened. However, those were less urgent matters than this is. The Agency is now seeking to cover up a health problem of considerable proportions and largely of its own making. This cannot be allowed.

As part of a defence, the fact that the MCA/CSM are in step with other agencies and authorities seems neither here nor there. It is a matter of concern that other agencies have got it wrong as well, but the MCA/CSM are legally charged with protecting the public in this country. On this occasion, they have failed. These are some of the things that most concern me:

1. The MCA/CSM have been knowing and willing parties in fundamentally changing the definition of dependence. When the CSM finally determined the benzodiazepines were drugs of dependence, it was in the days when, "the diagnosis of all of the Substance Dependence categories requires only evidence of tolerance or withdrawal…". (DSM-III). That definition explains 'dependence' as the public understands it today. But now, in defending SSRI antidepressants you have, effectively in secret, adopted a fundamentally different meaning of that term, one which is miles from public understanding.

Is this not an abuse of power? To my mind it is exactly analogous to the gross massaging of, say, the unemployment statistics: the equivalent to claiming that hundreds of thousands no longer find themselves without employment, because the official definition of "unemployed" has been changed.

2. On behalf of the MCA/CSM, Dr Price has been trying to persuade me that the risk of withdrawal symptoms with SSRIs such as paroxetine are very rare, suggesting something of the order of one case per 1,000 to 10,000 in routine clinical practice. Both this estimate, and the basis on which it was adduced, are pretty much preposterous. It would probably be an underestimate to say that something of the order of 1 in 10 long-term users experience significant symptoms on withdrawal.

3. The MCA/CSM simply reveal how ill-informed they are by saying the SSRIs "have not been associated with other characteristics of dependence."

SSRIs are indeed associated with tolerance in both manifestations - diminution of drug effect over time, and dosage escalation. See my paper at section 3.4. If that doesn't worry you, there's a Lilly-sponsored study that might. It involved the analysis of 21,000 SSRI prescriptions for outpatients at a US urban teaching hospital and reported that a mean 5% of patients on fluoxetine and 15% on sertraline "had their daily dose increased with each prescription refill during the first nine prescriptions". Indeed, the mean daily dose for all 460 patients on sertraline doubled during the same period. *** (Gregor et al, 1994). This leaves the benzodiazepines standing.

4. On the question of conflicts of interest, I suggest the Committee on Standards in Public Life should adjudicate and I shall be writing to them about this. Eminent as some individual CSM members may be, it is wildly stretching a point to suggest the CSM is credible as an independent body, and that its Codes of Practice ensure it. You may be interested in the following view of the CSM's (then) leading expert on SSRIs, expressed to me this week by the President of the Royal College of Psychiatrists: "His close relationship with the industry is (also) well known, and his views are generally treated with caution for that reason".

I could go on at much length in the same vein, and shall if further provoked. In the meantime, I invite to withdraw your statement and acknowledge handsomely that there are real grounds for concern about the issues I have raised. I shall consider myself provoked if you have not issued an appropriate statement by 5.00pm on Friday 5th December. Thereafter I would feel free to release this letter to the media. In the meantime, please will you pass a copy of this letter to Professor Rawlins. Is he indisposed, by the way? I shall of course be writing to the Secretary of State.

Yours sincerely,

Charles Medawar


K.J. Gregor, J.M. Overhage, S.J. Coons, R.C. McDonald, Selective serotonin reuptake inhibitor dose titration in the naturalistic setting. Clinical Therapeutics 1994; 16(2): 306-15].


*** Correction. Please delete the words, "all 460" from this sentence: there was a very high attritrion rate in this study and only 38/460 patients completed the nine courses of sertraline treatment. Please refer to review of the paper by Gregor et al. CM, January 1998.
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List of MCA/CSM Correspondence