X-KENT WOODS-050429

29 April 2005

Mr Medawar,

I am writing in response to your letter of 19 April 2005 and its enclosed document criticising the MHRA’s regulation of the SSRI class of antidepressants.

Like you, I believe that there is evidence that this class of drug is over-prescribed and have said so publicly. We differ as to the reasons for that over-use and the role of regulation in rectifying it. Let me deal with the main points in your letter:

1. Having correctly pointed out that the Agency’s aims including promoting the safe use of medicines, you assert that "... the MHRA has failed to issue appropriate advice and warnings, and systematically concealed both the evidence of risks and the Agency’s failure to contain them. The Agency’s present policies expose many patients to unacceptable and unnecessary risks, allow doctors to be ill-informed, fail to contain inappropriate and excessive drug prescribing, and therefore promote medicalisation and waste. You are well aware that the Agency has accurately and repeatedly communicated the Committee on Safety of Medicine’s advice to prescribers and patients as the evidence base has been reexamined by the Expert Working Group.

The charge that the Agency has "systematically concealed" evidence of risks is absurd. The Expert Working Group’s report represents the most thorough and wide-ranging review of the evidence base for SSRIs ever carried out by any regulatory agency. You have misinterpreted or misrepresented it when you state (without citation): "First the EWG established that antidepressants in general, and SSRIs in particular, were indeed capable of precipitating suicidal behaviour". It says nothing of the sort. Moreover, you should reflect on Figures 3.1 and 3.2 of the report, showing declining or flat suicide rates by age/sex group since 1991, and Figure 7.1 showing steeply rising SSRI prescriptions over the same period.

2. Your proposed solution to the problem of over-prescription (para 3.2) is that MHRA should insert appropriate text into both the SPC and the PIL of each SSRI. You will be aware that action is being taken on PILs to ensure that they meet patients’ information needs. The SPC is of central importance for regulation but it is not a document which prescribers would often refer to in daily practice. The authoritative information source most frequently used by doctors is the British National Formulary. BNF advice is closely aligned with the content of the SPC and it is also a communication vehicle for advice from the CSM. The section in the BNF on Antidepressant Drugs (section 4.3) begins with the following statement.

"Antidepressant drugs are effective in the treatment of major depression of moderate and severe degree including major depression associated with physical illness and that following childbirth; they are also effective for dysthymia (lower grade chronic depression). Antidepressant drugs are not generally effective in milder forms of acute depression but a trial may be considered in cases refractory to psychological treatments"

This refutes your case that prescribers are not adequately informed of the need to consider severity of depression carefully before prescribing antidepressants.

On SSRIs specifically (BNF section 4.3.3), prescribers are warned of the risks of abrupt withdrawal; the CSM advice contra-indicating SSRIs for major depressive disorder in children and adolescents is prominently highlighted; and the concluding sentence reads "Suicidal ideation has been linked with SSRIs but causality has not been established".

You refer to the NICE treatment guidelines for depression: "Antidepressants are not recommended for the initial treatment of mild depression, because the risk-benefit ratio is poor" [my underlining]

What aspect of the information to prescribers would you take issue with?

3. You write "The nub of this complaint is that the MHRA has allowed and continues to allow the manufacturers to promote SSRIs for the treatment of ‘mild depression’...." As you are well aware, by law manufacturers may only advertise their products for use within the terms of the Summary of Product Characteristics. If you can produce evidence that they are doing otherwise, we have the powers to act against such promotion and we use them.

4. You emphasise that your complaint is an allegation of maladministration [your underline] but nowhere do you set out your grounds for using this term. To quote Lord Denning, maladministration covers ‘the manner in which a decision is reached or discretion is exercised; but excluding the merits of the decision itself or the discretion itself’. What specifically did you have in mind? In your title you use the less technical descriptors ‘chaotic and misconceived’ to describe the regulation of SSRI antidepressants How can you justify these?

The main thrust of your complaint is that antidepressants are over-prescribed because pharmaceutical companies are improperly promoting them and the MHRA is failing to stop companies doing so through regulation. Having spent some years researching the factors which influence prescribing practices in the UK and mainland Europe, I believe your analysis is incorrect. In the field of coronary heart disease, for example, the problem was that doctors were under-prescribing drug treatments (thrombolytics, beta blockers, ACE inhibitors for example) which had unequivocally been shown to save lives. There has been huge marketing activity by companies to promote these drugs but they remained under-used for many years after the key trials had been published. The exception was aspirin, which was rapidly and extensively adopted for cardiovascular secondary prevention despite a complete lack of pharmaceutical industry promotion. This refutes your case that aggressive marketing drives of patterns of drug use that are inconsistent with the available evidence on the risk-benefit ratio. I can point you to a rich research literature on these examples if you wish.

Your second theme (your para 3.2) is that we should be seeking to limit the prescription of anti-depressants by general practitioners (‘other than specialists in mental health’) unless certain diagnostic criteria of disease severity are met. Treatment decisions made between doctor and patient depend on individual circumstances, preferences and judgments. The ‘conspiracy of goodwill’ which you refer to in your book is a plausible factor, more amenable to information than to regulation. This has been the pattern with benzodiazepines, where overuse has been substantially reduced by professional education and patient information.

You refer to the recent report of the Health Select Committee. A formal response will be made shortly and the report is being carefully considered within MHRA.

Should you choose to post your complaint on your website, please also attach this letter; my only stipulation is that it should be included in its entirety.

Yours sincerely,

Professor Kent Woods
Chief Executive