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Elizabeth L Sampson
Lecturer in Old Age Psychiatry
Royal Free and University College Medical School
Dementia does not just affect memory and orientation – many sufferers will develop “behavioural or psychiatric symptoms of dementia” (BPSD). The frequency varies according to the population studied, ranging from 20% of Alzheimer’s disease patients living in the community to up to 80% of those in institutional care.(1) BPSD are a heterogeneous range of psychological reactions, psychiatric symptoms and behaviours, ranging from depression and agitation to hallucinations and delusions. Table 1 shows the incidence and type of BPSD found in a community sample of Alzheimer’s disease patients.(2–5)
The commonest cause of dementia is Alzheimer’s disease, followed by vascular dementia secondary to cerebrovascular disease and Lewy body dementia. Patients with Lewy body dementia experience florid, detailed visual hallucinations associated with unexplained falls and parkinsonian symptoms;(6) frontotemporal dementia, a rarer cause of young-onset dementia, presents predominantly with behavioural problems such as disinhibition and personality changes.(7)
It has been estimated that there are over 3.25 million people with dementia currently living within the European Union.(8) As the elderly population of Europe increases, the incidence of dementia will rise and effective management of BPSD will become even more vital. BPSD, particularly aggression and disturbances of sleep, significantly increase the levels of burden and distress experienced by carers.(9) This leads to physical illness and depression in carers and premature hospitalisation or institutionalisation of the person with dementia. This has great economic implications for society as a whole.(10)
Elderly dementia sufferers in residential and nursing homes are frequently prescribed inappropriate neuroleptic medication, the “chemical straitjacket”, before alternative management strategies have been attempted.(11) One-third of nursing home patients in the UK are prescribed neuroleptics, and misuse continues to be a problem throughout Europe.(12) Poor prescribing practice in the USA led to the Omnibus Reconciliation Act (OBRA), which restricts the use of neuroleptics in nursing home patients and requires regular review of response.(13) Legislation varies throughout Europe, as do the regulations regarding the use of covert medication for dementia patients, and this raises many issues surrounding capacity and consent to treatment. The pharmacist is ideally placed to ensure that local and national prescribing guidelines are adhered to.
Elderly patients with neurodegenerative disease are highly sensitive to the side-effects of psychotropic medication. The antimuscarinic side-effects of tricyclic antidepressants and some neuroleptics such as thioridazine will exacerbate the cholinergic deficit that occurs in dementia and increase confusion and disorientation. Conventional neuroleptics such as haloperidol and droperidol have anti-alpha1-adrenergic activity that can cause orthostatic hypotension and falls. Oversedation, a histaminergic-mediated side-effect, leads to apathy, a loss of daily living skills and decreased social interaction. The elderly are also more likely to develop potentially fatal neuroleptic malignant syndrome.(14) Patients with Lewy body dementia are exquisitely sensitive to neuroleptic side-effects, experiencing a marked extrapyramidal syndrome with an associated hastening of cognitive decline and death.(15,16)
It is vital that patients with BPSD undergo a full medical, psychiatric and social assessment. It is important to exclude medical conditions such as pain and constipation or an underlying confusional state (delirium). These may exacerbate BPSD and can be treated with simple interventions.
A detailed description of the behaviour should be gathered from carers or staff. This enables the detection of precipitating events, such as bathing and dressing, variations in the intensity of symptoms during the day (agitation often increases at twilight – the so-called symptom of “sundowning”), and whether distraction, or altering the way in which personal care is given, is helpful. A personalised management plan can then be constructed; simple interventions such as exercise or re-establishing the sleep–wake cycle are often very effective.(17) Recently there has been an increased interest in “alternative” therapies, and small studies have shown that bright-light therapy, reality orientation and aromatherapy may be of benefit.(18,19) Carers benefit from support groups such as those run by national Alzheimer’s disease societies (see Resources). Modifying the carer’s response to difficult behaviours with cognitive therapy techniques may significantly reduce their distress and burden.(20)
Drug treatment of BPSD
When other management strategies have failed, the careful, focused and closely monitored use of medication may bring significant relief from distressing behavioural problems. Table 2 describes the most commonly used drugs and the indications for their use. The pharmacist, by carefully reviewing treatment regimens to identify potential drug-related problems, can detect improper drug selection, inappropriate dosage, adverse drug reactions and interactions. Elderly patients can be particularly sensitive to medications with antimuscarinic side-effects such as oxybutynin prescribed for the management of incontinence; the prescription of anticholinergics for extrapyramidal side-effects (EPSEs) should also be avoided.
The current mainstays of treatment of BPSD are the atypical antipsychotics risperidone and olanzapine. These should be started at low doses (ie, risperidone 0.5mg twice daily) and increased slowly with review after four weeks of treatment. There have been two placebo-controlled studies to assess the efficacy of risperidone for BPSD:(21,22) EPSEs occurred at higher doses (ie, 2mg per day) but were less frequent than with haloperidol. Psychotic and aggressive symptoms showed the greatest response to treatment. Olanzapine at 5–10mg daily reduces psychotic symptoms and aggression; the most frequent side-effects are somnolence and abnormal gait.(23) There have been no head-to-head studies comparing the efficacy of olanzapine and risperidone.
Three cholinesterase inhibitors – donepezil, rivastigmine and galantamine – are currently licensed for use in mild-to-moderate Alzheimer’s disease. There is increasing evidence from placebo-controlled trials that these may improve apathy and decrease psychotic symptoms, particularly the visual hallucinations seen in Lewy body dementia.(29,30)
Memantine, a low-affinity antagonist to n-methyl-d- aspartate (NMDA)-type receptors, may prevent excitatory amino acid neurotoxicity. This has recently been released onto the market and is licensed in the UK for use in severe Alzheimer’s disease. One study has shown significant improvement in BPSD with memantine.(31)
Despite recent advances in pharmacotherapy of dementia, few studies of cholinesterase inhibitors or memantine have used the reduction of BPSD as a primary endpoint. The development of atypical antipsychotics has allowed some symptomatic relief, but the importance of a multidisciplinary approach in managing these difficult and distressing symptoms cannot be underestimated.
Alzheimer’s Disease International
Addresses for European branches; information sheets in English and Spanish
Alzheimer’s Society Information sheets for carers and professionals
Systematic reviews of pharmacological and behavioural therapies for BPSD W:www.cochrane.org
International Psychogeriatric Association
Excellent free online educational kit on BPSD. Modules include pharmacological management and are available in English and French