I must make it clear at the outset that I am not prepared to be dragged into a long correspondence about the SSRIs and their potential for causing dependence. Your original letter of October 30th last year contained a long series of criticisms of this College's Defeat Depression Campaign and

I replied to these at some length in my letter of November 28th. Much of the content of your most recent letter is concerned with Professor Lader's memorandum to me about SSRI antidepressants. If you disagree with him or are puzzled by his views I can only suggest that you correspond with him directly.

There are only four more things I wish to say in response to your many observations, assumptions, criticisms and questions.

I must emphasise once more that the College's Defeat Depression Campaign was concerned (a) to change public attitudes to depressive illnesses, (b) to improve recognition of these illnesses by GPs and (c) to enable a higher proportion to be treated, either by psychotherapy or with antidepressants - in effective doses. It was not concerned to increase either prescribing or sales of SSRIs. Indeed, many psychiatrists, including myself, are concerned by the rapid increase of prescribing of these drugs in the last decade. Our objections are, however, largely economic. We do not regard them as having sufficient advantages over the older tricyclic drugs to justify their vastly higher cost.

I must also remind you that the College's campaign was planned several years ago. It was formally launched at the beginning of 1992 and ended early last year. Its aims and public statements, particularly about prescribing policies, can only reasonably be judged, therefore, on the basis of evidence available at that time.

There is a recurring implication in your letters to me, and in your article in the International Journal of Risk and Safety in Medicine, that the formal definition of dependence was deliberately changed either by the American Psychiatric Association and the World Health Organisation (your article in Risk and Safety in Medicine, page 111) or by this College (your letter to me of December 2nd) in order to avoid having to accept that benzodiazepines caused dependence after the publication of the APA Taskforce Report in 1990.

You misunderstand both the timing of and the reasons for the change. Those responsible for the treatment of alcoholics and drug addicts were already becoming increasingly dissatisfied with the pharmacologists' concept of dependence, and the misguided attempt to distinguish between physical and psychological dependence, in the late 1970s, long before worries about benzodiazipines began to emerge. The seminal event was probably a WHO meeting in Washington in August 1980 and a memorandum arising out of this meeting published in the Bulletin of the World Health Organisation the following year (volume 59, pages 225-242). That memorandum suggested that the misleading term physical dependence should be renamed 'neuroadaption' and dependence recognised as 'a clustering of phenomena (cognitive, behavioural and physiological)' of which 'evidence of neuroadaptation is just one' and 'not ... the most important". This statement was followed by a draft list of criteria very similar to the operational definitions that finally appeared in ICD10 in 1992 and DSM-IV in 1994.

Incidentally, you are wrong to imply (on page 82 of your article in Risk and Safety in Medicine) that ICD10 definitions were driven by those of DSM-IV. The reverse was true. I was myself closely involved, as a member of WHO's Expert Advisory Panel, in the preparation of ICD10 throughout the 1980s. I therefore know that it was in virtually its final form by 1988, two years before publication of the report of the APA Taskforce on benzodiazipine dependency and before the APA Task Force charged with producing DSM-IV even came in being. Formal publication of ICD-10 was held up by the complex bureaucracy of the WHO and its World Health Assembly, and the need to translate the entire text into all WHO's official languages.

I agree that the medical profession and the pharmaceutical industry have repeatedly hailed new sedatives, hypnotics, anxiolytics and analgesics as non-addictive only to be confronted, years later, by evidence that they did in fact lead to dependence, at least in some people. No one can say with certainty, therefore, that some of the SSRI's may not likewise prove to induce states of dependence as we now understand that term. On present evidence, however, this does not seem very likely, and the withdrawal states reported after abrupt cessation are not strong indicators that dependence is probable. Withdrawal or rebound states occur, as I pointed out in my letter of November 28th, with many drugs including beta-blockers, H2 antagonists and tricyclic antidepressants. So far as we know, SSRIs work in the same way as the original tricyclic drugs. They simply effect a more restricted range of aminergic receptors and have fewer irrelevant pharmacological actions. We are therefore justifiably reassured by the fact that no evidence that tricyclic drugs induce dependence has emerged despite widespread long term prescribing over a period of 40 years.

I am copying this letter to Professor Lader and Professor Pereira Gray.

Yours sincerely,

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	Correspondence: matters arising