A recent editorial1 stated that 20-50 per cent of patients with dementia in institutional care are prescribed atypical anti-psychotics off-licence to treat symptoms such as agitation, aggression and depression. These symptoms are referred to as behavioural and psychological or neuropsychiatric symptoms.
The widespread use of atypical antipsychotics is surprising, given the evidence of their adverse effects in patients with dementia.
Typical and atypical antipsychotics show evidence of adverse effects |
In 2004, the DoH's Committee on Safety of Medicines warned all GPs that neither risperidone nor olanzapine should be used for treatment of behavioural symptoms in dementia because of an increased risk of cerebro-vascular diseases.
In April 2005, the US Food and Drug Administration reported an increased risk of death in people with dementia taking atypical antipsychotics. At that time, an independent meta-analysis of published data identified an increased risk of death with antipsychotics of odds ratios 1.54 (95 per cent CI 1.06-2.23).2
This analysis was updated a year later and showed similar results.3 Data suggested excessive drowsiness was common, with a number needed to harm for one such adverse event as low as 10.
Moreover, drowsiness coupled with extrapyramidal side-effects and worsening cognitive function from antipsychotic therapy could result in more time being spent in bed, an increased risk of UTI or urinary incontinence and death from infectious, pulmonary and cardiovascular causes. This was supported by estimates of one death for 100 patients treated with these drugs.3
Typical antipsychotics
These findings question the use of atypical antipsychotics in patients with dementia. So what is the position with typical antipsychotics like chlorpromazine?
The data on these drugs are not promising. Older adults with dementia prescribed typical antipsychotics have a similar risk of ischaemic stroke to those taking atypical antipsychotics.4
More recent evidence backs up these findings, suggesting a higher than three times risk of stroke in people with dementia prescribed any antipsychotic drugs.
In fact, all antipsychotics were associated with increased risk of stroke in any patient, irrespective of existing dementia.5
Alternatives
So what are the alternatives for GPs asked by personal carers or care home workers to help deal with aggressive outbursts or other such psychological symptoms?
Non-drug approaches are a suitable alternative.1 This would initially involve a careful examination to rule out any treatable physical factors, such as pain from any cause, side-effect of medication or physical environmental factor.
Psychological assessments to rule out depression should also be carried out. If this is difficult to conduct on a patient with severe dementia, the opinion of an old-age psychiatrist should be sought.
A recent systematic review of non-drug treatments for the management of neuropsychiatric symptoms in dementia highlighted the lack of good evidence. The best quality evidence was reported from three trials that evaluated focused training of carers in managing behavioural symptoms and other unmet needs of patients with dementia.6
Additionally, the recently published NICE guidelines on dementia7 recommend use of aromatherapy, based on the positive effects observed in two randomised trials.
Although early research on music therapy, light therapy, multi-sensory stimulation and bright light therapy show promising trends for the effects of these treatments, further evidence is essential before they are widely recommended.
NICE guidance
NICE guidance on dementia suggests drug therapy may be considered if the person is severely distressed or there is immediate risk of harm to the person or to others.
This should be done only after full discussion of the benefits and risks of treatment with the patient, their family and/or carers, and an assessment of the cerebrovascular risk factors.
The dosage should be low initially, then titrated upwards. After administering the drug, changes in patients' cognition should be assessed and recorded at regular intervals and alternative medication considered if necessary.
Target symptoms that need to be treated should be identified, quantified and documented, and changes in these symptoms should be assessed and recorded at regular intervals. Treatment should be time limited and regularly reviewed - every three months or according to clinical need.
NICE further recommends that patients with Alzheimer's disease who present with challenging behaviour symptoms causing significant distress or potential harm to the patient or to people around them may be offered an acetylcholinesterase inhibitor only if nonpharmacological and antipsychotic therapy have been tried and have proved not to be appropriate or effective.
Patients with dementia with Lewy bodies who have distressing symptoms may be offered an acetylcholinesterase inhibitor as a first option.
In conclusion, patients with dementia in general practice on antipsychotic therapy need to be identified and carefully assessed for withdrawal of treatment.
Special attention must be given to the education of carers and staff in care homes on management of these symptoms.
Antipsychotic therapy may still be reserved for the management of severe and challenging symptoms of dementia that do not respond to nonpharmacological treatments and, if this fails to control the symptoms, acetylcholinesterase inhibitor therapy may be considered in patients with Alzheimer's disease or dementia with Lewy bodies.
- Professor Nazareth is professor of primary care and population sciences at University College London References
1. O'Brien J. Antipsychotics for people with dementia. BMJ 2008; 337: a602 doi:101136/bmj.a602
2. Schneider LS, Dagerman KS, Insel PS. Risk of death with atypical antipsychotic drug treatment for dementia: meta-analysis of randomized, placebo-controlled trials. JAMA 2005: 294: 1,934-43.
3. Schneider LS, Dagerman KS, Insel PS. Efficacy and adverse effects of atypical antipsychotics for dementia: meta-analysis of randomized, placebo-controlled trials. Am J Geriatr Psychiatry 2006: 14: 191-210.
4. Gill S, Rochon P, Herrmann N et al. Atypical antipsychotic drugs and risk of ischaemic stroke population based retrospective cohort study. BMJ 2005; 330: 445 doi:10.1136/bmj.38330.470486.8F
5. Douglas I, Smeeth L. Exposure to antipsychotics and risk of stroke: self controlled case series study. BMJ 2008; 337: a1,227.
6. Ayalon L, Gum AM, Feliciano L, Arean PA. Effectiveness of nonpharmacological interventions for management of neuropsychiatric symptoms in patients with dementia: a systematic review. Arch Intern Med 2006: 166: 2,182-8.
7. NICE. Dementia: Supporting people with dementia and their carers in health and social care. London: NICE and SCIE, November 2006.
