|
I am writing to inform you of an important concern about the safety of
atypical antipsychotic drugs and provide new prescribing recommendations.
Evidence reviewed by the Committee on Safety of Medicines (CSM) indicates an
increased risk of stroke which particularly applies when these drugs are
used by elderly patients with dementia.
Background
Although no atypical antipsychotic drug is licensed for the treatment of
behavioural disturbance in dementia, they are quite frequently used for this
purpose and manufacturers have conducted clinical trials in this indication.
The Committee has reviewed the available data from trials of risperidone and
olanzapine and considered other relevant evidence.
Relevant evidence
Risperidone is the most extensively studied drug in this context and a
meta-analysis of randomized placebo-controlled clinical trials in elderly
patients with dementia has shown that, compared with placebo, the risk of
stroke with risperidone was approximately three times higher.
A pooled analysis of randomized placebo-controlled clinical trials of
olanzapine in elderly patients with dementia has shown a similar increased
risk of stroke and a 2-fold increase in all-cause mortality.
The mechanism by which these drugs are associated with stroke is unclear.
Although some patients with dementia may have underlying vascular disease,
the risk is not confined to this group. Although most of the evidence
causing concern comes from patients with dementia, the risk may not be
confined to use in this indication and should be considered relevant to any
patient with a history of cerebrovascular disease or relevant risk factors
(see below).
CSM advice on balance of risks and benefits
The CSM has advised that there is clear evidence of an increased risk of
stroke in elderly patients with dementia who are treated with risperidone or
olanzapine. The magnitude of this risk is sufficient to outweigh likely
benefits in the treatment of behavioural disturbances associated with
dementia and is a cause for concern in any patient with a high baseline risk
of stroke.
Prescribing advice
- CSM has advised that risperidone or olanzapine should not be used for
the treatment of behavioural symptoms of dementia.
- Use of risperidone for the management of acute psychotic conditions in
elderly patients who also have dementia should be limited to short-term and
should be under specialist advice (olanzapine is not licensed for management
of acute psychoses).
- Prescribers should consider carefully the risk of cerebrovascular
events before treating any patient with a previous history of stroke or
transient ischaemic attack. Consideration should also be given to other risk
factors for cerebrovascular disease including hypertension, diabetes,
current smoking and atrial fibrillation.
Although there is presently insufficient evidence to include other
antipsychotics in these recommendations, prescribers should bear in mind
that a risk of stroke cannot be excluded, pending the availability of
further evidence. Studies to investigate this are being initiated.
Patients with dementia who are currently treated with an atypical
antipsychotic drug should have their treatment reviewed. Many patients with
dementia who are disturbed may be managed without medicines. Treatment
guidelines are available at websites listed below.
Product information
Prescribing information for risperidone and olanzapine are being amended to
reflect the advice given above.
Further information
(available from 1pm Tuesday 9 March)
Treatment guidelines are available at the following websites:
Information for patients and carers is available at the following website:
Further information about the CSM advice can be found on the Medicines and
Healthcare products Regulatory Agency (MHRA) website:
For any additional information please phone the MHRA on 020 7084 2000.
Professor Gordon Duff
Chairman, Committee on Safety of Medicines
|
