Department of Health
Market Towers 1 Nine Elms Lane London SW8 5NQ
TEL:  020 7273 0400
FAX:  020 7273 0675 .OG 02/34
13 September 2002

Dear Mr Medawar,

Paroxetine: withdrawal symptoms and dependence

I am writing further to my letter of 10 September in response to points 4, 5 and 7 that are outstanding from your letter of 2 August. I apologise for the delay in responding to these.

I attach copies of the letters to marketing authorisation holders (MAH) sent following the March 1998 meeting of the CSM to communicate the Committee’s advice and ask for amendments to the product information. I understand that the European Medicines Evaluation Agency communicated the CPMP position in relation to SSRIs and withdrawal reactions and dependence to the relevant MAH.

You ask for an explanation as to why the current PIL for paroxetine is not entirely consistent with the CSM advice of March 1998. The regulatory action on this issue took place following the finalisation of the CPMP position in 2000 and the final agreed wording was based on the principles for product information outlined in this paper rather than the initial CSM position. We will be contacting the MAH and will take the issues outstanding from the March 1998 minutes into account in our review of the Seroxat SPC and PIL at our expert meeting in November.

As mentioned in previous correspondence, we will ensure that all your correspondence is provided to the experts at this meeting.

Yours sincerely
Director, Post-Licensing Division


[We have reproduced only one letter (to SmithKline Beecham), as a specimen of the letters the MCA sent to all SSRI manufacturers - Ed]


                                                                                                            17 April 1998

Dear (SKB)

Re: Seroxat Tablets & Liquid, PL Nos. 10592/0001, 0002 & 0092

The Committee on Safety of Medicines has reviewed the evidence on withdrawal reactions and dependence associated with the SSRIs and the related antidepressants, venlafaxine and nefazodone. The Committee concluded that there was currently no evidence to suggest that these drugs were causing dependence other than physiological withdrawal reactions. The Committee also concluded that withdrawal reactions occur with all the SSRIs and related antidepressants, however the extent of the problem may differ between drugs.

It was noted that studies had not been carried out of an appropriate design to allow an estimation of frequency of withdrawal reactions. It is requested that you provide us with proposals for studies to examine the frequency, severity and natural history of withdrawal reactions with your products.

Investigation into the issue of withdrawal reactions and dependence is ongoing and an overall review of the adequacy of the SPCs for SSRIs and related antidepressants is underway. The Committee recommends the following changes to the product information with respect to withdrawal reactions at this time, although we cannot preclude the need for further changes in the future as new information emerges:

The statement ‘symptomatic treatment is seldom warranted’ should be removed from the SPC. This statement is not felt to be justified in the light of the spontaneous reporting data which suggests that a large number of patients require to restart treatment with paroxetine due to the withdrawal symptoms.

Please send in a variation application together with your SPC and PIL to room 1115 Market Towers, marking it for my attention. There will be no charge for this variation.

The issue of withdrawal reactions will be discussed at the Pharmacovigilance Working Party of the CPMP in May 1998.

Please do not hesitate to contact me should you have any queries.

Yours sincerely,

Contents page
List of correspondence with MCA/CSM