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Dear Sir Kenneth,

I am enclosing a copy of my paper, The Antidepressant Web, to be published this week in the International Journal of Risk and Safety in Medicine. This describes a situation which may well concern you, not least because of its relevance to the question of perceptions of benefit and risk to which you referred in your report, On the State of the Public Health, 1995. To my mind, it also suggests it might be useful to include in future editions of your report some commentary on the significance of iatrogenic disease and the effectiveness of measures used to control it.

Briefly, the presenting problem is that there is now overwhelming evidence that (in particular) SSRI antidepressants are as much drugs of dependence as benzodiazepines - though they fall outside current definitions of 'dependence' in ICD-10 and DSM-IV, as indeed the benzodiazepines arguably do too. The BDZs were classified as drugs of dependence essentially on the strength of evidence of normal dose dependence, especially after long-term use - and pretty much in the days when DSM-III ruled, when "The diagnosis of all of the Substance Dependence categories requires only evidence of tolerance or withdrawal...." The same point is underlined in the 1990 report of the American Psychiatric Association's Task Force report on Benzodiazepine Dependency: "The presence of a predictable abstinence syndrome following abrupt discontinuance of benzodiazepines is evidence of the development of physiological dependence... "

The enormous scope for confusion is also underlined by data in the following table which is based on Yellow Card reports of suspected adverse reactions submitted to the UK Medicines Control Agency/Committee on Safety of Medicines:

REPORTS TO MCA/CSM OF SUSPECTED ADVERSE REACTIONS, TO MARCH 1997

	Introduced	Ballpark No.	Yellow Card	reports of:
		of NHS scripts in England only	withdrawal reactions	dependence- all forms
Temazepam	1977	50m	5	3
Diazepam	1963	180m	20	16
Fluoxetine	1989	9m	59	10
Paroxetine	1991	6m	802	9

On the face of it, it seems absurd to classify benzodiazepines as drugs of dependence but SSRIs not: either they both are or neither is. In the meantime, the public is receiving extremely confusing advice and I also fear that sweepingly optimistic, but quite mistaken, assumptions have been made about the long term effectiveness of antidepressants, as a result.

The picture today seems to be alarmingly reminiscent of the position around 15 years ago, when the conventional wisdom was that barbiturates were drugs of dependence but benzodiazepines not. Indeed, similar patterns of behaviour go back to the last century: see Power and Dependence, enclosed. However, the present problem may be more serious, because of bullish statements, notably from the Royal College of Psychiatrists, about the lack of any dependence risk with SSRIs, together with advice about the need for long-term, if not indefinite treatment. The Medicines Control Agency and Committee on Safety of Medicines clearly share this view.

I should be grateful if you would let me know if any of the matters discussed in this paper fall within your remit - including the wider issue of ill-health caused by drug use in therapeutic settings. My best guess would be that the cost of iatrogenic disease to the NHS approximates the total cost of the national drug bill, but does your own department have any more reliable estimate I might refer to? I would welcome information on this, together with any comments on this paper you might feel able to make. I should add that I intend shortly to post on the Internet both the paper I am sending you, and correspondence on relevant matters arising. I hope this will encourage rather than deter any response from you because of the opportunity it will provide to all concerned to consider all points of view.

Many thanks for your attention and I shall look forward to hearing from you.

 Yours sincerely,

 Charles Medawar

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