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.
- Margallo-Lana M, Swann A, O’Brien J, et al. Prevalence and pharmacological management of behavioural and psychological symptoms amongst dementia sufferers living in care environments. Int J Geriatr Psychiatry 2001;16(1):39-44.
- Burns A, Jacoby R, Levy R. Psychiatric phenomena in Alzheimer’s disease. I: Disorders of thought content. Br J Psychiatry 1990;157:72-4.
- Burns A, Jacoby R, Levy R. Psychiatric phenomena in Alzheimer’s disease. II: Disorders of perception. Br J Psychiatry 1990;157:74-6.
- Burns A, Jacoby R, Levy R. Psychiatric phenomena in Alzheimer’s disease. III: Disorders of mood. Br J Psychiatry 1990;157:81-4.
- Burns A, Jacoby R, Levy R. Psychiatric phenomena in Alzheimer’s disease. IV: Disorders of behaviour. Br J Psychiatry 1990;157:86-94.
- McKeith IG, Galasko D, Kosaka K, et al. Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop. Neurology 1996;47(5):1113-24.
- Neary D, Snowden JS, Gustafson L, et al. Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology 1998;51(6):1546-54.
- Lobo A, Launer LJ, Fratiglioni L, et al. Prevalence of dementia and major subtypes in Europe: a collaborative study of population-based cohorts. Neurologic Diseases in the Elderly Research Group. Neurology 2000;54(11):S4-9.
- Schneider J, Murray J, Banerjee S, Mann A. EUROCARE: a cross-national study of co-resident spouse carers for people with Alzheimer’s disease: factors associated with carer burden. Int J Geriatr Psychiatry 1999;14:651-61.
- Wimo A, Ljunggren G, Winblad B. Costs of dementia and dementia care: a review. Int J Geriatr Psychiatry 1997;12:841-56.
- Thacker S, Jones R. Neuroleptic prescribing to the community elderly in Nottingham. Int J Geriatr Psychiatry 1997;12(8):833-7.
- McGrath AM, Jackson GA. Survey of neuroleptic prescribing in residents of nursing homes in Glasgow. BMJ 1996;312:611-2.
- Winograd CH, Pawlson LG. OBRA 87 – a commentary. J Am Geriatr Soc 1991;39:724-6.
- Masand PS. Side effects of antipsychotics in the elderly. J Clin Psychiatry 2000;61 Suppl 8:43-9.
- McShane R, Keene J, Gedling K, et al. Do neuroleptic drugs hasten cognitive decline in dementia? Prospective study with necropsy follow up. BMJ 1997;314:266-70.
- Byrne EJ, Burns A, Waite J. Neuroleptic sensitivity in dementia with cortical Lewy bodies. BMJ 1992;305:1158-9.
- Alessi CA, Yoon EJ, Schnelle JF, et al. A randomized trial of a combined physical activity and environmental intervention in nursing home residents: do sleep and agitation improve? J Am Geriatr Soc 1999;47:784-91.
- Ballard CG, O’Brien JT, Reichelt K, Perry EK. Aromatherapy as a safe and effective treatment for the management of agitation in severe dementia: the results of a double-blind, placebo-controlled trial with Melissa. J Clin Psychiatry 2002;63:553-8.
- Lyketsos CG, Lindell VL, Baker A, Steele C. A randomised, controlled trial of bright light therapy for agitated behaviors in dementia patients residing in long-term care. Int J Geriatr Psychiatry 1999;14:520-5.
- Marriott A, Donaldson C, Tarrier N, Burns A. Effectiveness of cognitive-behavioural family intervention in reducing the burden of care in carers of patients with Alzheimer’s disease. Br J Psychiatry 2000;176:557-62.
- Katz IR, Jeste DV, Mintzer JE, et al. Comparison of risperidone and placebo for psychosis and behavioral disturbances associated with dementia: a randomized, double-blind trial. Risperidone Study Group. J Clin Psychiatry 1999;60:107-15.
- De Deyn PP, Rabheru K, Rasmussen A, et al. A randomized trial of risperidone, placebo, and haloperidol for behavioral symptoms of dementia. Neurology 1999;53:946-55.
- Street JS, Clark WS, Gannon KS, et al. Olanzapine treatment of psychotic and behavioral symptoms in patients with Alzheimer’s disease in nursing care facilities: a double-blind, randomized, placebo-controlled trial. The HGEU Study Group. Arch Gen Psychiatry 2000;57(10):968-76.
- Katona CL, Hunter BN, Bray J. A double-blind comparison of the efficacy and safely of paroxetine and imipramine in the treatment of depression with dementia. Int J Geriatr Psychiatry 1998;13:100-8.
- Nyth AL, Gottfries CG. The clinical efficacy of citalopram in treatment of emotional disturbances in dementia disorders. A Nordic multicentre study. Br J Psychiatry 1990;157:894-901.
- Tariot PN, Erb R, Podgorski CA, et al. Efficacy and tolerability of carbamazepine for agitation and aggression in dementia. Am J Psychiatry 1998;155:54-61.
- Porsteinsson AP, Tariot PN, Erb R, et al. Placebo-controlled study of divalproex sodium for agitation in dementia. Am J Geriatr Psychiatry 2001;9:58-66.
- Howard R, Ballard C, O’Brien J, Burns A. Guidelines for the management of agitation in dementia. Int J Geriatr Psychiatry 2001;16:714-17.
- Cummings JL, Donohue JA, Brooks RL. The relationship between donepezil and behavioral disturbances in patients with Alzheimer’s disease. Am J Geriatr Psychiatry 2000;8:134-40.
- McKeith I, del Ser T, Spano P, et al. Efficacy of rivastigmine in dementia with Lewy bodies: a randomised, double-blind, placebo-controlled international study. Lancet 2000;356:2031-6.
- Pantev M, Ritter R, Goertelmeyer R. Clinical and behavioural evaluation in long-term care patients with mild to moderate dementia under memantine treatment. Zeitschrift für Gerontopsychologie & -psychiatrie 1993;6:103-7.
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