Analysis of paroxetine Yellow Card adverse drug reaction reports (Seroxat/Paxil)

Thu, 20 Nov 2003

A unique analysis of the British Yellow Card Reporting system for adverse drug reactions (ADR) found that the nature, the scope and severity of ADRs relating to drug dependency and suicidal behavior from the antidepressant paroxetine (Paxil / Seroxat) have been concealed and distorted under the present reporting system in the UK.

"A Comparison of Adverse Drug Reaction Reports from Professionals and Users, Relating to Risk of Dependence and Suicidal Behaviour with Paroxetine [Paxil]," by Charles Medwar and Andrew Herxheimer FRCP, has just been published in International Journal of Risk & Safety in Medicine 16 (2003/2004) 5-19 The complete article is posted at: See http://www.socialaudit.org.uk/5100what.htm#5.1

This is the first analysis of its kind: It provides compelling new information about adverse drug reaction reports that had been submitted both by patients and physicians in the UK. The focus is on risks of drug dependence and suicidal behavior linked to the antidepressant, paroxetine (Paxil / Seroxat).

The Yellow Card system is equivalent to Food and Drug Administration's MedWatch adverse drug effect reporting system. Both systems have been criticized for failing to reflect the actual scope and severity of adverse drug reactions following their approval and marketing. The important findings of this unique analysis are as relevant for the safety of US consumers as they are for those in the UK.

A similar independent analysis of FDA's MedWatch reports about antidepressants in the SSRI class is needed. The current adverse drug reaction reporting systems are failing to detect and therefore to prevent major health hazards. The public and treating physicians are being kept in the dark about drugs that pose risks of dependency, severe withdrawal symptoms and suicidal acts. Of particular significance is the discovery of a link between dose increases and suicidal behavior.

Below, Charles Medwar provides the following summary of the main findings:

1. This report is unique in two different ways:

• It is the first published critical appraisal of the role of spontaneous adverse drug reaction (ADR) reports in monitoring the safety of marketed medicines - the MHRA/CSM Yellow Card scheme is regarded "as the cornerstone of the Agency's work on medicines safety monitoring."
• This is also the first review of anonymised Yellow Card reports of suspected adverse drug reactions to paroxetine, relating to withdrawal reactions/dependence and suicidal behaviour. This report compares the value of ADR reports from drug users and health professionals.

2. This report produces new evidence of several different kinds:

• It suggests that miscoding and flawed analyses of Yellow Cards have led to under-estimation of the risk of suicidal behaviour;
• It reveals that most Yellow Cards lack important information (e.g. patient history, dosage; outcome of reaction);
• It shows that the UK regulators have systematically failed to follow up reports of suicidal behaviour, in spite of conducting several reviews;
• It suggests that poor reporting and data processing have impeded recognition of what appears to be a close relationship between suicidal behaviour and changes in drug concentration. An increased risk of suicidal behaviour during the first few days of treatment with an SSRI has long been suspected - but comparable risks seem to exist when drug dosages are either increased or lowered (during withdrawal).
• It suggests that SSRI dosages may be far too high for some users
• It gives evidence that ADR reports sent in by drug manufacturers systematically use euphemisms in describing ADRs (e.g. 'Non-accidental overdose' to describe suicide attempts) that help to obscure the true nature of risk;

3. We suggest that, although the Yellow Card is widely recognised as one of the best in the world it is, in important respects, "chaotic and misconceived". Its value is limited by the emphasis on numbers not words; the focus on rare and 'interesting' ADRs, rather than the generality of drug-induced problems; secrecy that obstructs wider access to anonymised data; and lack of input from drug users themselves.

4. Our analyses suggest that reports from patients - in their own words - communicate essential information which professional reporters can never be expected to provide. We believe that patient reports of suspected ADRs can never credibly be ignored again.

5. We have submitted this and other evidence to the on-going review of the Yellow Card Scheme, under Dr Jeremy Metters of the UK Department of Health.

The complete article is posted at: See http://www.socialaudit.org.uk/5100what.htm#5.1

I hope this is of interest.

Charles Medawar
Social Audit Ltd
P.O. Box 111
London NW1 8XG UK
TEL/FAX +44 (0)20 7586 7771
charles@socialaudit.org.uk
http://www.socialaudit.org.uk