Medicines and Healthcare Products Regulatory Agency (Hansard, 19 April 2004)

§ Ms Rosie Winterton

Since paroxetine (Seroxat) was authorised in 1990, its safety has been closely monitored by the Medicines and Healthcare products Regulatory Agency (MHRA) and the Government's independent expert advisory committee, the Committee on Safety of Medicines (CSM). The CSM has considered the safety of Seroxat on a number of occasions in response to the receipt of new data in relation to the issues of suicidal behaviour and withdrawal reactions.

The CSM's expert working group on the safety of selective serotonin reuptake inhibitors (SSRIs) was established in May 2003 to review the current available evidence relating to the safety of SSRIs, including paroxetine. The CSM's expert working group comprises the following members whose areas of expertise include psychiatry, child and adolescent psychiatry, epidemiology, statistics and general practice:

Professor Ian V. D. Weller
Professor Deborah Ashby
Mr. Richard Brook (resigned in March 2004)
Professor Mary G. A. Chambers
Dr. Jonathan D. Chick
Professor Colin Drummond
Professor David J. Gunnell
Professor Klaus Ebmeier
Dr. Elizabeta Mukaetova-Ladinska
Mr. Eamonn O'Tierney
Dr. Ross J. Taylor
Dr. Ann York
Dr. Morris Zwi

Members of the Medicines Act advisory committees such as the CSM and its working groups are required to follow a code of practice relating to declarations of interests in the pharmaceutical industry. The code is rigorously followed at each meeting to ensure the integrity of the advice given to the Licensing Authority by those committees. None of the members of the CSM's expert working group have a personal interest in GlaxoSmithKline or any of the other companies which hold marketing authorisations for SSRIs.

To date the expert group has met nine times and has completed the most comprehensive review yet undertaken of the safety of SSRIs in paediatric use. An interim report, which provides information on the key evidence considered by the group up to July 2003 and the action that has been taken as a result of the group's advice, was published on the MHRA/CSM website in September 2003. The expert group is now focused on completing its task of reviewing all the data related to the use of paroxetine and the related drugs in adults, specifically focusing on suicidal behaviour, withdrawal reactions and the dosage recommendations.

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As part of the ongoing in-depth review, the expert group has recently re-evaluated the original dose finding studies carried out for the licensing of paroxetine. The expert group initially reviewed one of the dose finding studies for paroxetine in October 2003. On the advice of the expert group, the manufacturer was then asked to provide data to justify the current dosing recommendations for all indications as part of the European review of the risks and benefits of paroxetine. The expert group reviewed the completed data set at their meeting on 27 February 2004.

This review confirmed that, as stated in the product information provided to prescribers, the recommended daily dose is 20mg, with the exception of obsessive compulsive disorder and panic disorder, for which the recommended daily dose is 40gm.

On 10 March 2004, the CSM confirmed the advice of its expert group and advised that public communication was necessary on the basis of the re-evaluation of clinical trial data and the evidence of prescribing outside of the recommendations in the summary of product characteristics. Ministers accepted the CSM's advice and a communication underlining the recommended daily doses for paroxetine was issued to health professionals on 11 March 2004.

The CSM's current advise is that the balance of risks and benefits of this medicine in the licensed indications is favourable and, on this basis. there are no plans to restrict its use in new patients.