Introduction   A discussion paper by Medawar on the treatment of depression called 'The Antidepressant Web' has been published in International Journal of Risk & Safety in Medicine (Annex 1). In this paper Medawar questions the efficacy of antidepressant drugs and claims that selective serotonin reuptake inhibitors (SSRIs) are drugs of dependence. To support these claims, Medawar makes comparisons between the number of spontaneous reports of withdrawal reactions and dependence associated with benzodiazepines and SSRI's on the UK ADROIT database.

Background  There have been a large number of reports of withdrawal reactions in the UK associated with the SSRIs, in particular with paroxetine. A comparison of withdrawal reactions associated with the SSRIs was carried out using the ADROIT database and an article was published by staff in the MCA and a member of the CSM in 1996 (Annex 2). Assessment of the UK spontaneous reporting data at that time did not identify other features of dependence associated with reports of withdrawal reactions with SSRIs.

UK spontaneous reporting has recently begun to indicate that withdrawal reactions may be a particular problem with venlafaxine.

Despite the known extent of benzodiazepine dependence this was poorly identified by spontaneous reporting, and few spontaneous reports of this phenomenon have been submitted. In contrast, the scheme has identified symptoms occurring on withdrawal of SSRIs which were not associated with other features of dependence. Therefore the use of spontaneous reporting data to compare these two groups of drugs is inappropriate.

Action   Medawar's paper is currently being reviewed along with all other available evidence relating to withdrawal reactions and dependence associated with SSRIs and related antidepressants. The aim of this review is to clarify the issue of withdrawal reactions associated with SSRIs and to ensure that the information contained in the product information for doctors and patients is adequate.

Post-Licensing Division
UK Medicines Control Agency
19 December 1997