PAROXETINE (SEROXAT) - RISK OF SUICIDAL BEHAVIOUR IN ADULTS

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To:	MHRA Drug Alerts NHS Trust Chief Executives NHS Trusts - Medical Directors (England) NHST/FT/007 - NHS FOUNDATION TRUSTS (ENGLAND) - MEDICAL DIRECTOR Primary Care Trusts - Directors of Public Health Primary Care Trusts - Medical Directors Public Health Link
Cc (Groups):	Chairman - Professional Executive Committee of PCT Regional Directors of Public Health Strategic Health Authorities (England) - Directors of Public Health Territorial CMOs
Fax To:

From:	Professor Gordon Duff - Chairman of the Commission on Human Medicines
Date:	8 May 2006

Reference	CEM/CMO/2006/6
Category:	NON URGENT (cascade within 48 hours)

Title:	PAROXETINE (SEROXAT) - RISK OF SUICIDAL BEHAVIOUR IN ADULTS

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Directors of Public Health of PCTs to forward to:
- All GENERAL PRACTITIONERS - please ensure this message is seen by all prescribing nurses, practice nurses and non-principals working in your practice and retain a copy in your `locum information pack'.
- Deputising services
- Project manager/Nurse lead in Walk in Centres
- Lead nurses in PCTs
- Leads at nurse-led PMS Pilots
- PCT Mental Health Services
- PCT Pharmaceutical Advisers to forward to community pharmacists
- PCT Prescribing Advisers

To: Medical Directors of NHS Trusts to forward to:
- Consultants in Psychiatry
- Nurse Executive Directors of NHS Trusts & Mental Health Trusts,& NHS Trusts with Mental Health Services
- Trust Chief Pharmacists to forward to Medicines Information Pharmacists

Cc:
- Regional Directors of Public Health
- Directors of Public Health of Strategic Health Authorities to forward to: SHA pharmaceutical advisers and SHA lead nurses
- Mental Health Leads in SHAs
- UK CMOs
- Chairmen of Professional Executive Committee

MESSAGE FROM PROFESSOR G DUFF, CHAIRMAN, COMMISSION ON HUMAN MEDICINES.

8th May 2006 CEM/CMO/2006/6

Dear Colleague,

Paroxetine (Seroxat) – risk of suicidal behaviour in adults

I am writing to inform you about the new analyses of paroxetine clinical trials that are being published by the manufacturer of Seroxat, GlaxoSmithKline.

These new analyses examine the risk of suicidal behaviour in clinical trials in the adult population, and were conducted as part of a review by the US FDA. The new analyses highlight the importance of monitoring all patients treated with SSRIs for worsening of their symptoms or mood changes but do not alter the prescribing advice for SSRIs issued in December 2004 following the review by the CSM Expert Working Group on the Safety of SSRIs.

The new analyses are being evaluated by the Commission on Human Medicines (CHM) and the Medicines and Healthcare products Regulatory Agency (MHRA). Following our further investigations and discussions with other European regulatory agencies the Seroxat product information for prescribers and patients will be updated as needed. In the meantime, this letter reminds you of the previous advice that has been issued.

Reminder of current advice to prescribers:

Careful and frequent patient monitoring by healthcare professionals and, where appropriate, other carers, is important in the early stages of treatment with paroxetine, especially if a patient experiences worsening of symptoms or if new symptoms arise after starting treatment.

Young adults (18-29 years of age) are at a higher background risk of suicidal behaviour than older adults and therefore should be monitored particularly closely.

The key findings and recommendations of the CSM Expert Working Group on the Safety of SSRIs in relation to the risk of suicidal behaviour in adults can be found at Annex 1. The Group’s full report can be found on the MHRA website (http://www.mhra.gov.uk).

Further information on the use of SSRIs, including paroxetine, in the treatment of depression and anxiety can be found in the NICE guideline on the management of depression in primary and secondary care (http://www.nice.org.uk).

Please report any suspected adverse reactions to paroxetine via the Yellow Card Reporting Scheme to the CHM/MHRA (http://www.yellowcard.gov.uk)

For further information please call the Medicines and Healthcare products Regulatory Agency on 020 7084 2000 or visit the website (http://www.mhra.gov.uk)

Yours sincerely

Professor Gordon Duff
Chairman, Commission on Human Medicines

Annex 1

Key findings of CSM’s Expert Working Group on the Safety of SSRIs

Use of SSRIs in adults – suicidal behaviour

The conclusions of the Group on this issue can be summarised as follows:

There is epidemiological evidence that the risk of self-harm in depressed patients is greatest around the time of presentation to medical services. It is general clinical experience that the risk of suicide may increase in the early stages of treatment for depressive illness.

Careful and frequent patient monitoring by healthcare professionals and, where appropriate, other carers, is important in the early stages of treatment, particularly if a patient experiences worsening of symptoms or new symptoms after starting treatment.

Studies indicate that increases in the prescribing of SSRIs have not been associated with an increase in population suicide rates, although interpretation of these findings is difficult as a range of factors influence population trends in suicide.

From the available clinical trial data, both published and unpublished, a modest increase in the risk of suicidal thoughts and self-harm for SSRIs compared with placebo cannot be ruled out. There is insufficient evidence from clinical trial data to conclude that there is any marked difference between members of the class of SSRIs, or between SSRIs and other antidepressants, with respect to their influence on suicidal behaviour.

Evidence from non-experimental studies based on the General Practice Research Database indicates that there is no increased risk of suicidal behaviour with SSRIs compared with tricyclic antidepressants (TCAs).

There is no clear evidence that there is an increased risk of self-harm or suicidal thoughts when SSRIs are discontinued.

Evidence of a relationship between suicidal behaviour and increasing/decreasing dose is not robust; however, patients should be monitored around the time of dose changes for any new symptoms or worsening of disease.

Young adults

The increased risk of suicidal behaviour seen in children and adolescents with depressive illness treated with SSRIs raised the question as to whether there was a similar increased risk in young adults. The clinical trial data for each product was reviewed in relation to a possible effect in young adults, and the GPRD study looked specifically at this age group. From these analyses, the Group concluded that there is no clear evidence of an increased risk of self-harm and suicidal thoughts in young adults of 18 years or over. However, given that individuals mature at different rates and that young adults are at a higher background risk of suicidal behaviour than older adults, as a precautionary measure young adults treated with SSRIs should be closely monitored. The Group also recommended that in further research on the safety and efficacy of SSRIs, young adults should be assessed separately.

Additional Information: