7.1 Members declared interests as follows:

The Committee noted that DELETED had been approached recently by a representative of one of the manufacturers regarding the issue, but that DELETED had declined to enter into any discussion

7.2 The Committee were informed that a review of data on withdrawal reactions associated with the SSRIs and the related antidepressants nefazodone and venlafaxine had been carried out to investigate the nature of withdrawal reactions and to assess any evidence that these drugs are associated with features of dependence. This was done in the light of the publication of 'The Antidepressant Web' by Charles Medawar in which the author likens these drugs to benzodiazepines in their ability to cause dependence.

7.2.1 The conclusions of the review were that withdrawal reactions occur with all SSRIs and related antidepressants, although to different extents for each drug. In the main these reactions are mild and self-limiting, although more severe reactions have been reported. No strong evidence from any source, had been identified to suggest that the SSRIs and related antidepressants cause features of dependence other than withdrawal symptoms.

7.2.2 The Committee's attention was drawn to the assessor's conclusions, the first 4 points of which relate to specific changes to product information. The Committee were informed that DELETED had expressed concern at the use of the term 'withdrawal reaction' when referring to symptoms occurring on withdrawal of treatment due to the fact that the term 'withdrawal' has a specific meaning and implies that the drug is addictive. DELETED had suggested the use of the term 'discontinuation reactions'.

7.2.3  The Committee were informed that the paper had been reviewed by the Sub-Committee on Pharmacovigilance who agreed with the listed conclusions adding that the CSM and further experts should be consulted prior to publication of an article in 'Current Problems in Pharmacovigilance'.

7.3 The Committee agreed that the review had revealed no evidence of dependence associated with the SSRIs and related antidepressants. They agreed that withdrawal reactions with the SSRIs and related antidepressants appear to be a class effect, however it was clear that different drugs caused these reactions to different extents.

7.3.1 The Committee commented that withdrawal reactions did not appear to be restricted to a particular group of patients but occurred in patients treated for any indication. They noted that to date, studies had not been carried out of an appropriate design to allow an estimation of frequency of withdrawal reactions.

7.3.2 The Committee were asked whether they though that withdrawal reactions with these drugs had public health implications. The Committee considered that there was no evidence to suggest that this was so.

7.3.3 The Committee were asked whether they thought that a change in terminology from withdrawal reactions to 'discontinuation reactions' would be appropriate DELETED. It was agreed that it would be inappropriate to change medical terminology in this way.

7.3.4 The Committee were asked whether they thought that there were similarities between withdrawal reactions with the SSRIs and the situation with benzodiazepines. They commented that dose escalation and drug seeking behaviour were evident in association with benzodiazepines but that these features were not evident in patients taking SSRIs. .

7.4 The Committee recommended the following:

7.4.1 The product information for fluoxetine, citalopram and nefazodone should contain a general statement about the risk of symptoms on withdrawal such as the following:

'Withdrawal reactions have been reported in association with selective serotonin reuptake inhibitors (SSR[s). Common symptoms include dizziness and nausea. Abrupt discontinuation of treatment with SSRIs should be avoided.'

This general statement should be tailored to take into account different classes and properties of each drug.

7.4.2 A reassuring statement should be added to the SPC and PIL along the lines of the following:

'The majority of symptoms experienced on withdrawal of SSRIs are non-serious and self-limiting

The PIL should contain the following additional advice:

"If you experience severe symptoms, contact your doctor"

7.4.3 The current warning in the product information for sertraline should be expanded to include information on the symptoms to be expected on withdrawal.

7.4.4 The statement 'symptomatic treatment is seldom warranted' should be removed from the paroxetine SPC.

7.4.5 Reference to withdrawal reactions being 'rare' should be removed from the product information for fluvoxamine and sertraline.

7.4.6 Reports of withdrawal reactions associated with the SSRIs and related antidepressants should continue to be carefully monitored for signs of dependence and the follow up procedure for Yellow Card reports for all SSRIs and related antidepressants should be continued.

7.4.7 An article in 'Current Problems in Pharmacovigilance' should be published summarising this review and reminding doctors about the risk of withdrawal reactions with SSRIs and other antidepressants.

7.4.8 The possibility for specific targeted investigation of the frequency and severity of withdrawal reactions, and of dependence should be discussed with the MA holders,

7.5 The Committee complimented the assessors on a very good report. 

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