Selective serotonin re-uptake inhibitors (SSRIs)

The safety of SSRIs has been under continual review by the MHRA since the products were first marketed. Two areas of public concern and scientific debate have been the issues of withdrawal reactions on stopping SSRIs and whether there is an increased risk of suicidal behaviour associated with treatment with SSRIs.

The Committee on Safety of Medicines (CSM) has considered the safety of SSRIs and, in particular, the issues of suicidal behaviour and withdrawal reactions on a number of occasions.  Previous CSM considerations on SSRIs have led to harmonisation of the safety information provided for all SSRIs (2000);  updated warnings about withdrawal reactions with all SSRIs; communications to prescribers in the drug safety bulletin ‘Current Problems in Pharmacovigilance’ in 1993 and 2000; and warnings added to the patient information leaflets (PILs) that, as with all antidepressants, suicidal thoughts may occur or increase in the early stages of treatment. 

In May 2003, in response to continuing public concerns about the safety of SSRIs, an Expert Working Group of the Committee on Safety of Medicines (CSM) was convened to investigate ongoing safety concerns with these medicines, in particular around suicidal behaviour and withdrawal reactions/dependence.

The Expert Working Group issued information and key recommendations during the period of the review as data became available including:

Clear advice on the risk and benefits of the SSRIs and related antidepressants in children and adolescents was made available in June, September and December 2003:
› Safety of Seroxat (paroxetine) in children and adolescents under 18 years - contraindication in the treatment of depressive illness - message from Professor G Duff, Chairman of Committee on Safety of Medicines - June 2003
› Safety of venlafaxine in children and adolescents under 18 years in the treatment of depressive illness - message from Professor G Duff, Chairman of the Committee on Safety of Medicines - September 2003
› Selective Serotonin Reuptake Inhibitors (SSRIs) - use in children and adolescents with major depressive disorder - December 2003

An article in the September 2003 edition of the MHRA/CSM drug safety bulletin ‘Current Problems in Pharmacovigilance’, which is sent to all doctors and pharmacists in the UK, reminding prescribers of CSM advice in relation to the use of paroxetine in under 18s and reminded prescribers of the licensing status in children of other SSRIs and related antidepressants:
› Current Problems in Pharmacovigilance - September 2003 (260Kb)

A fact sheet on SSRIs to aid discussion between prescribers and patients which accompanied the September 2003 edition of ‘Current Problems in Pharmacovigilance’

Advice reminding prescribers of the recommended dose regimen for paroxetine was issued in March 2004:
› Paroxetine (Seroxat): Reminder to use the recommended dose - March 2004

A reminder of key prescribing advice for paroxetine was issued in the October 2004 edition of ‘Current Problems in Pharmacovigilance’:
› Current Problems in Pharmacovigilance - October 2004 (74Kb)

The Expert Working Group has completed its review of the large body of safety evidence from a wide range of sources – spontaneous suspected adverse drug reactions (from health professionals and patients), clinical trials, published literature and epidemiological databases. The key findings, which focus on three key areas: withdrawal reactions, dose changes and suicidal behaviour, were communicated to health professionals in the UK on 6 December 2004.  These key findings and the full report of the Expert Group are also available below:
› Selective serotonin re-uptake inhibitors (SSRIs): Findings of the Committee on Safety of Medicines - December 2004

The CSM and its Expert Working Group have concluded that SSRIs are effective medicines in the treatment of depression and anxiety conditions, and that the balance of risks and benefits of all SSRIs in adults remains positive in their licensed indications. 

The MHRA concluded its review into all the latest safety evidence relating venlafaxine (Efexor) in May 2006 and prescribing advice was updated:
› Updating prescribing advice for venlafaxine (Efexor/Efexor XL) - May 2006