Drug Safety Update

Volume 2, Issue 8 March 2009

Latest advice for medicines users

Antipsychotics: use in elderly people with dementia

Article date: March 2009
There is a clear increased risk of stroke and a small increased risk of death when antipsychotics (typical or atypical) are used in elderly people with dementia

Use of antipsychotics in dementia

Only one antipsychotic, risperidone (Risperdal ▼), is licensed for treatment of dementia-related behavioural disturbances: and then only specifically for shortterm (up to 6 weeks’) treatment of persistent aggression in Alzheimer’s dementia unresponsive to non-pharmacological approaches and where there is a risk of harm to the patient or others. Elderly people with dementia are at risk from specific serious and life-threatening side-effects when treated with antipsychotics.

Risk of stroke

In 2004 the Committee on Safety of Medicines (the predecessor to the Commission on Human Medicines) advised of a clear increase in the risk of stroke with the use of the atypical antipsychotics risperidone ▼ or olanzapine in elderly people with dementia (approximately three-times increased risk compared with placebo), and that the magnitude of risk outweighed any likely benefit of treating dementia-related behavioural problems with these drugs. A year later a Europe-wide review concluded that this risk could not be excluded for other antipsychotics (atypical or typical), and the product information for all antipsychotics was updated to include a class warning.

Increased mortality

In 2005 an analysis of 17 placebo-controlled trials found that atypical antipsychotics are associated with increased mortality when used in elderly people with dementia (about 1–2% increased risk compared with no treatment).US FDA Public Health Advisory. Deaths with antipsychotics in elderly patients with behavioural disturbances, April 11 2005 For risperidone, there is an additional increase in the risk when coprescribed with furosemide.

Subsequently in November 2008, a European assessment of published observational data concluded that a similar increased risk of death could not be excluded for the typical (conventional) antipsychotics.Schneeweiss S, et al. CAMJ 2007; 76: 627–32,Gill SS, et al. Ann Intern Med 2007; 146: 775–86

About risperidone ▼

In the case of persistent aggression in moderate to severe Alzheimer’s disease, where the patient puts themselves or others at risk of harm, short-term treatment with risperidone ▼ may be indicated if the behaviour has not responded to non-pharmacological means. A new analysis of three randomised control trialsKatz IR, et al. J Clin Psychiatry 1999; 60: 107–15De Deyn PP, et al. Neurology 1999; 53: 946–55Brodaty H, et al. J Clin Psychiatry 2003; 64: 134–43 conducted in behavioural problems in the elderly showed a clear benefit for the short-term use of risperidone ▼ when aggression only was considered. The balance of risks and benefits for risperidone ▼ use to treat behavioural disturbances in dementia is only considered to be positive within its narrow licensed indication: ie, short-term use for persistent aggression in Alzheimer’s-type dementia.

Advice for healthcare professionals:

  • There is a clear increased risk of stroke and a small increased risk of death when antipsychotics (typical or atypical) are used in elderly people with dementia
  • The balance of risks and benefits associated with risperidone ▼ treatment should be carefully assessed for every patient, taking into consideration the known increased mortality rate associated with antipsychotic treatment in the elderly. Prescribers should carefully consider the risk of cerebrovascular events before treating with risperidone ▼ any patient who has a previous history of stroke or transient ischaemic attack. Consideration should also be given to other risk factors for cerebrovascular disease including hypertension, diabetes, smoking, and atrial fibrillation

Risperidone: new Black Triangle (▼) status

The Black Triangle Scheme identifies medicines whose safety profiles are monitored intensively by MHRA and CHM. Risperidone ▼ has been added to the list of black triangle medicines after the granting of the new narrow indication in Alzheimer’s dementia as outlined above. Healthcare professionals are asked to please report via the Yellow Card Scheme all suspected side-effects to risperidone ▼ that occur when it is used to treat elderly people with dementia. You do not have to be certain of causality—if in doubt, please report.


Article citation: Drug Safety Update March 2009, vol 1 issue 8: 5.

Further information

MHRA information on antipsychotics

European Medicines Agency statement, report, and question-and-answer document

Risperdal Summary of Product Characteristics

National Dementia Strategy, published Feb 3, 2009

For further information on non-pharmacological interventions, see NICE guidance

The dementia antipsychotic withdrawal trial (DART-AD): long-term follow-up of a randomised controlled trial. Ballard C, et al. Lancet Neurol 2009; 8: 151–57.

Exposure to antipsychotics and risk of stroke: self controlled case series study. Douglas IJ and Smeeth L. BMJ 2008; 337: a1227

Royal College of Psychiatrists

Alzheimer’s Society

Alzheimer’s Research Trust





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