bnf 4.6 management of non-cognitive symptoms associated

114 | DTB | Vol 52 | No 10 | October 2014 dtbbmjcom

DTB | Management of non-cognitive symptoms associated with dementia

BNF 46

DTB CMECPD

DTB CMECPD A CMECPD module based on this article is available for completion online via BMJ Learning (learningbmjcom) by subscribers to the online version of DTB If prompted subscribers must sign into DTB with their username and password All users must also complete a one-time registration on BMJ Learning and subsequently log in (with a BMJ Learning username and password) on every visit The answers to the multiple choice questions will be freely available on dtbbmjcom on publication of the next issue of DTB

Management of non-cognitive symptoms associated with dementiaUp to 75 of patients with dementia will experience non-cognitive symptoms1 These often present as psychotic symptoms behavioural disturbances and changes in mood1 Such symptoms provide a significant challenge for patients and their carers and are often difficult to manage Antipsychotic drugs have been widely used to treat non-cognitive symptoms of dementia However in 2004 data emerged linking the use of some antipsychotic drugs with an increased risk of stroke and death in patients with dementia2 Since then there has been a national drive to ensure that antipsychotic drugs are used appropriately In 2007 we reviewed the safety of antipsychotics in people with dementia3 Here we provide an update on the evidence for the efficacy and safety of interventions used to manage non-cognitive symptoms of dementia

BackgroundNon-cognitive symptoms of dementia are referred to as the behavioural and psychological symptoms of dementia (BPSD) or neuropsychiatric symptoms and often present as agitation aggression abnormal vocalisations delusions hallucinations wandering and disinhibition Management of such symptoms remains extremely challenging and for over a decade there has been particular concern over the high use of antipsychotic drugs in patients with dementia Data emerged in 2004 that led to warnings against the use of risperidone and olanzapine in dementia due to an increased risk of cerebrovascular events and mortality2 These safety concerns are thought to apply to all antipsychotic drugs45 In 2009 an independent review commissioned by the Department of Health in England noted that widespread use of antipsychotics in patients with dementia meant that the potential benefit of their use in specific individuals was likely to be ldquooutweighed by their risks overallrdquo6 The report recommended a reduction in the rate of antipsychotic prescribing in dementia to a third of the 2009 level over a 3-year period This triggered a national drive to reduce the use of antipsychotics in patients with dementia The only antipsychotic drug currently licensed for use in people with dementia is risperidone78 However it is only indicated for short-term treatment (up to 6 weeks) of persistent aggression in patients with moderate to severe Alzheimerrsquos disease who are unresponsive to non-pharmacological interventions and are at risk of harm to themselves or others8

Assessing non-cognitive symptomsIdentifying and characterising behavioural change in people with dementia is difficult yet important and the use of validated scales to assess non-cognitive symptoms of dementia can be helpful (see Box)

Contributing factorsInvestigation and appropriate management of underlying causes of behavioural symptoms should be considered and include a review of the patientrsquos medication Behavioural problems can be worsened by some drugs with anticholinergic properties (eg tricyclic antidepressants phenothiazine antipsychotics) benzodiazepines and some analgesics (eg tramadol)13

The exclusion of physical causes or delirium is also important in patients with dementia Constipation untreated pain and infections (including urinary tract and pulmonary infections) can cause or worsen behavioural

DTB CMECPD

Box Assessing non-cognitive symptoms

Behavioural Pathology in Alzheimerrsquos Disease Rating Scale (BEHAVE-AD)9

bull 25 items rated from 0 to 3 maximum score 75 (most severe)

bull Assessment uses 7 categories paranoia and delusions hallucinations activity disturbances aggressiveness diurnal rhythm disturbance affective disturbances anxiety and phobias

Cohen-Mansfield Agitation Inventory (CMAI)10

bull 29 items rated for frequency (never to several times an hour 1ndash7) maximum score 203 (most severe)

bull Specifically focuses on agitated behaviour (verbal and physical)

bull Examples include hitting kicking grabbing onto people pushing spitting pacing cursing making strange noises screaming making verbal sexual advances eatingdrinking inappropriate items

Clinical Global Impression of Change (CGI-C)11

bull 7-point scale (1mdashvery much improved 7mdashvery much worse)

bull Global rating of all aspects of a patientrsquos condition compared with baseline using direct observation and information from others

The Functional Assessment Staging Scale (FAST)12

bull Measures the level of basic activities such as bathing dressing and toileting through 7 stages ranging from independent to totally dependent

dtbbmjcom Vol 52 | No 10| October 2014 | DTB | 115


disturbances agitation and aggression in dementia1415 A study in 352 care-home residents concluded that systematic management of pain significantly reduced agitation associated with moderate to severe dementia (plt0001)16

Treatment optionsNon-drug interventions are widely advocated as the first-line treatment options1

Non-pharmacological interventionsA variety of non-pharmacological interventions have been suggested for managing BPSD These include115

bull aromatherapy

bull multisensory stimulation

bull reminiscence therapy

bull cognitive stimulation

bull psychomotor and exercise interventions

bull therapeutic use of music andor dance

bull animal assisted therapy

bull massage

Systematic reviews of trials of psychological approaches concluded that behavioural management techniques could be beneficial16 and both these and education intended to change carersrsquo behaviour have been shown to be successful with effects that can last for several months1718 A more recent systematic review found that supervised person-centred care communication skills or modified care mapping (an observational process used to evaluate quality of care from the perspective of the person living with dementia) with implementation plans were clinically beneficial although there was little evidence of cost-effectiveness19 Evidence from the small number of studies available suggests that helping patients relive past experiences through reminiscence therapy can lead to improvements in mood behaviour well-being social interaction and self-care17-2021 Music therapy and sensory stimulation may have short-term effects on behaviour1722 Whilst previous reports showed short-term benefits of an environment that provides multi-sensory stimulation (lsquosnoezelenrsquo) a Cochrane review did not find any significant effects on behaviour and mood in people with dementia23 Positive results have been reported from some controlled trials of aromatherapy commonly using extracts of lavender and melissa with significant reduction in agitation21 However when assessed under rigorous randomised clinical trial conditions there was no evidence that melissa oil aromatherapy is superior to placebo or donepezil24 A systematic review identified seven studies of aromatherapy in dementia and concluded that the results were equivocal25

A systematic review found evidence to suggest that training care-staff to understand and manage these symptoms can lead to significant symptom reduction (in 12 of the 20 studies included) and has a positive impact on the way staff behave towards patients26

Other strategies for improving behaviour include ensuring that the patientrsquos environment is safe calm and predictable identifying and removing environmental stressors and avoiding situations that may agitate or frighten the patient Since the effectiveness of long-term behavioural management is largely dependent on the care-giver it is important to assess the role and needs of the care-giver27

Pharmacological interventionsClinical efficacy of antipsychotic drugs

The CATIE-AD multi-centre double-blind placebo-controlled trial compared the use of olanzapine (mean dose 55mgday) quetiapine

(mean dose 565mgday) or risperidone (mean dose 10mgday) in 421 outpatients with Alzheimerrsquos disease and psychosis aggression or agitation28 The main outcome measures were the time to discontinuation of treatment and the number of patients with at least minimal improvement on the Clinical Global Impression of Change (CGI-C) scale at 12 weeks This study showed no significant differences among treatments in terms of time to discontinuation (p=052) or CGIC score (p=022) All drugs were poorly tolerated because of sedation confusion and extrapyramidal effects A descriptive analysis of the study reported that olanzapine and risperidone but not quetiapine showed some improvements on certain neuropsychiatric rating scales compared with placebo29

A meta-analysis of trials of second-generation (atypical) antipsychotics for aggression and psychosis in Alzheimerrsquos disease included nine placebo-controlled trials of which only five had been published in full30 Outcome assessments included measures of agitation and aggression (Cohen-Mansfield Agitation Inventory [CMAI] Behavioural Pathology in Alzheimerrsquos Disease Rating Scale [BEHAVE-AD]) global change (CGI-C Functional Assessment Staging Scale [FAST]) and adverse effects assessed using an extrapyramidal symptom rating scale The reviewers concluded that risperidone and olanzapine are useful in reducing aggression and risperidone in reducing psychosis but that both drugs are associated with serious adverse effects The authors commented that due to modest efficacy and significant increase in adverse effects neither risperidone nor olanzapine should be routinely used in dementia unless there is severe distress or a serious risk of physical harm to those living or working with the patient

Increased harms with antipsychotic drugs

The independent review of the use of antipsychotics in people with dementia reported that a meta-analysis of 15 randomised placebo-controlled trials of second-generation antipsychotics showed an increased risk of cerebrovascular events with a pooled relative risk of 257 (95 CI 141 to 466) and an absolute risk difference of 17 (95 CI 09 to 25)6 Pooled analysis of 15 randomised controlled trials reported an odds ratio for death of 154 (95 CI 106 to 223 p=002) with second-generation antipsychotic use compared with placebo in patients with dementia31

Based on these risks the authors calculated that treating 180000 people with dementia with a second-generation antipsychotic drug (assuming an average treatment period of around 6ndash12 weeks) would result in an additional 1620 cerebrovascular events (around half of which may be severe) and an additional 1800 deaths per year6

Two studies have investigated whether the risk of mortality differs between antipsychotic drugs One was a population-based study of 75445 new users of antipsychotics in nursing homes in the USA32 and the other was a retrospective cohort study using USA national data for 33604 dementia patients beginning outpatient treatment with an antipsychotic or valproate derivative (as a non-antipsychotic comparison)33 The outcome measure was the 180-day mortality rate Both studies found that when compared with risperidone haloperidol users had an increased risk of mortality (hazard ratio [HR] 207 95 CI 189 to 226 and HR 154 95 CI 138 to 173 respectively) whereas quetiapine users had a decreased risk (HR 081 95 CI 075 to 088 and HR 073 CI 067 to 070 respectively) No significant differences were observed for olanzapine aripiprazole and ziprasidone32 The effects were strongest shortly after the start of treatment and remained after adjustment for dose There was a dose-dependent relationship with mortality for all drugs except quetiapine32

Initiatives for reducing the use of antipsychotics in dementia

Recommendations resulting from the review commissioned by the Department of Health6 have led to a national drive to reduce the rate of antipsychotic prescribing for people with dementia Strategies included improving systems for initiation maintenance and cessation of antipsychotic drugs in primary care mental health services for older people and general hospitals regular audits of antipsychotic



prescribing with feedback to prescribers and setting realistic goals for reducing antipsychotic use A national audit carried out in primary care in England recorded a decrease in the number of people with dementia receiving prescriptions for antipsychotics from 17 in 2006 to 7 in 201134

Alternative pharmacological options

Alternative effective pharmacological options for the management of BPSD are scarce There is limited evidence with anticonvulsants A review of trials of carbamazepine valproic acid gabapentin lamotrigine and topiramate in the treatment of BPSD concluded that these drugs could not be recommended for routine use although some patients may benefit35 A review of trials of levetiracetam oxcarbazepine topiramate and zonisamide found that there was no good quality evidence for their use in BPSD and all were associated with problematic adverse effects36

A meta-analysis of trials of antidepressants concluded that the selective serotonin re-uptake inhibitors (SSRIs) sertraline and citalopram were associated with a reduction in symptoms of agitation when compared with placebo in two studies Both SSRIs and trazodone appear to be tolerated reasonably well when compared with placebo and with antipsychotics but further studies are needed to determine whether they are safe and effective in this patient group37

Anticholinesterase inhibitors (eg donepezil galantamine rivastigmine) are used to enhance cognitive function in dementia7 They have also been tried in BPSD but the evidence is inconsistent Despite some positive results on behavioural symptoms in earlier studies a large independent study found no apparent benefit for donepezil in agitation associated with dementia compared with placebo38 A Cochrane review of memantine found that slightly fewer patients with moderate to severe Alzheimerrsquos disease taking memantine develop agitation but found no evidence of an effect on agitation that is already present39

Benzodiazepines should be avoided in patients with dementia as their use is associated with cognitive decline40 and increased risk of falls and hip fractures41 Promethazine a sedating antihistamine has been used for short-term use on a lsquowhen requiredrsquo basis but long-term use should be avoided as it has high anticholinergic activity that is associated with cognitive decline42

Guidelines for the management of non-cognitive symptomsIn the UK guidelines have been produced by the National Institute for Health and Care Excellence (NICE)1 and the Scottish Intercollegiate Guidelines Network (SIGN)43 More recently NHS Wales has produced guidelines for the pharmacological management of BPSD14 A briefing paper by the British Psychological Society outlines the current stepped care approach to managing BPSD with a focus on non-pharmacological interventions15 In general UK guidelines recommend a stepped care approach to managing BPSD These are based on identifying and addressing potential precipitating factors and the use of non-pharmacological interventions before the use of antipsychotic drugs is considered

Guidance produced by the European Federation of Neurological Societies and the European Neurological Society states that antipsychotic medications may be used for aggression psychosis and agitation but acknowledges that there is little evidence to guide practice44

In the USA guidelines for the management of BPSD produced for family practitioners recommend the use of non-pharmacological interventions as the most appropriate initial strategy for managing problematic behaviour27 If behavioural disturbances persist a psychotropic drug may be necessary

The stepped care model

The stepped care approach to assessment and intervention is based on the presumption that distresseddistressing behaviour represents an unmet need15 The model is not intended as a rigid pathway and may be modified to the needs of the individual although step 1 should be undertaken first Non-pharmacological interventions may be introduced at any step as appropriate

Step 1mdashidentification and treatment of physical causes address needs of carers

Step 2mdashunderstanding the person in more detail and getting the care environment right

Step 3mdashhigh-intensity interventions tailored to specific presentations and needs delivered by experienced practitioners and care staff

Step 4mdashspecialist interventions identified for more complex presentations

Prescribing antipsychotic drugs

In general antipsychotic medication should only be considered where there is extreme distress or immediate risk of harm to the patient or others114 People with Alzheimerrsquos disease vascular dementia Lewy body dementia or mixed dementias with mild-to-moderate non-cognitive symptoms should not be prescribed antipsychotic drugs1 Treatment with antipsychotic drugs may be considered for patients with severe non-cognitive symptoms under certain circumstances Specific symptoms should be targeted as antipsychotics are not effective in some behavioural disturbances associated with dementia (eg mood disturbances or disinhibition) and have only been found to be effective for psychotic symptoms or agitation and aggression Before prescribing an antipsychotic a risk-benefit analysis should be carried out and the potential benefits and harms associated with antipsychotic drug therapy discussed with the patient (if possible) and relatives or carers114

Risperidone is indicated for short term treatment (up to 6 weeks) of persistent aggression in patients with moderate to severe Alzheimerrsquos disease who are unresponsive to non-pharmacological interventions and are at risk of harm to themselves or others7 The starting dose for risperidone is 250microg twice daily increasing if necessary in steps of 250microg twice daily not more frequently than every other day8 The usual dose is 500microg twice daily although some patients may require up to 1mg twice daily714 Patients must be evaluated frequently and regularly and the need for continuing treatment reassessed8

Other antipsychotic drugs that have been used if risperidone is contraindicated or not tolerated include olanzapine1430 and aripiprazole14

Patients who respond to treatment should have the drug withdrawn after 6ndash12 weeks14 The dose should be halved for 2 weeks and if there is no recurrence of symptoms stopped after a further 2 weeks If symptoms recur the drug may be restarted at the initial dose

Ongoing challengesThe management of the behavioural symptoms of dementia remains problematic It is not always clear who is responsible for reviewing patients who are already on antipsychotic drugs or for monitoring their physical health Communication between primary and secondary care needs to improve in order to ensure appropriate management and follow-up of patients6 Without clear and specific shared care protocols in place patients may be left on treatment for many months or sometimes even years without a review6 Similarly staff in care homes should be mindful of patients prescribed antipsychotic medication and alert prescribers to ensure that physical health monitoring and medication reviews are undertaken Commissioners of health and social care services should ensure that appropriate evidence-based non-drug interventions are made available to minimise the need for antipsychotic drug treatment



ConclusionHelping to support people with behavioural change associated with dementia can represent a significant challenge to carers and healthcare professionals Physical causes of behavioural symptoms must be investigated and treated including any iatrogenic problems Non-pharmacological approaches should be tried where possible but many of the interventions are time consuming and may not be routinely available Antipsychotics are not indicated in the majority of patients with dementia although in a small proportion of patients the benefits may outweigh the risks involved The reported reduction in prescribing of antipsychotic drugs for patients with dementia is encouraging

Short-term use of risperidone may be considered for persistent aggression in patients with moderate to severe Alzheimerrsquos dementia unresponsive to non-pharmacological interventions and who are at risk of harm to themselves or others Risperidone should be prescribed at the lowest effective dose and for the shortest period of time Responsibility for monitoring the outcomes from treatment must be clearly defined and regular reviews carried out to assess its clinical benefit and tolerability

Patients and carers should be made aware of the risks involved with antipsychotic use and may have concerns that will need to be addressed Healthcare services must ensure that a risk benefit analysis is carried out for each patient with dementia when considering the use of an antipsychotic They should involve the patient (where possible) family and carers and explain the potential risks attributed to these drugs document all discussions and treatment choices and ensure regular reviews are carried out Clear communication between primary and secondary care is essential to ensure reviews are carried out appropriately

[R=randomised controlled trial M=meta-analysis] 1 National Collaborating Centre for Mental Health 2007 Dementia the NICE-SCIE

guideline on supporting people with dementia and their carers in health and social care [online] Available httpwwwscieorgukpublicationsmiscdementiadementia-fullguidelinepdf [Accessed 17 September 2014]

2 Medicines and Healthcare products Regulatory Agency 2004 Atypical antipsychotic drugs and stroke [online] Available httpwwwmhragovukSafetyinformationSafetywarningsalertsandrecallsSafetywarningsandmessagesformedicinesCON1004298 [Accessed 17 September 2014]

3 How safe are antipsychotics in dementia DTB 2007 45 81-5 4 European Medicines Agency 2008 CHMP Assessment Report on conventional

antipsychotics [online] Available httpwwwemaeuropaeudocsen_GBdocument_libraryReport201001WC500054057pdf [Accessed 17 September 2014]

5 Sacchetti E et al Risk of stroke with typical and atypical anti-psychotics a retrospective cohort study including unexposed subjects J Psychopharmacol 2008 22 39-46

6 Banerjee S 2009 The use of antipsychotic medication for people with dementia time for action [online] London Institute of Psychiatry Kingrsquos College London Available httpwebarchivenationalarchivesgovuk20130107105354httpwwwdhgovukprod_consum_dhgroupsdh_digitalassetsdocumentsdigitalassetdh_108302pdf [Accessed 17 September 2014]

7 Joint Formulary Committee British National Formulary Edition 67 London Royal Pharmaceutical Society and British Medical Association March 2014

8 Risperdal Tablets Liquid amp Quicklet Summary of product characteristics UK Janssen-Cilag November 2013

9 Reisberg B et al The BEHAVE-AD assessment system a perspective a commentary on new findings and a historical review Dement Geriatr Cogn Disord 2014 38 89-146

10 Cohen-Mansfield J 1991 Instruction manual for the Cohen-Mansfield Agitation Inventory (CMAI) [online] Available httpwwwdementia-assessmentcomausymptomsCMAI_Manualpdf [Accessed 17 September 2014]

11 Schneider LS et al Validity and reliability of the Alzheimerrsquos Disease Cooperative Study-Clinical Global Impression of Change the Alzheimerrsquos Disease Cooperative Study Alzheimer Dis Assoc Disord 1997 11 (suppl 2) S22-32

12 Sclan SG Reisberg B Functional assessment staging (FAST) in Alzheimerrsquos disease reliability validity and ordinality Int Psychogeriatr 1992 4 (suppl 1) 55-69

13 Byrne G et al Pharmacological treatment of behavioural problems in dementia Aust Prescr 2005 28 67-70

14 NHS Wales 2013 Pharmacological management of behavior problems in patients with dementia (BPSD) [online] Available httpwwwwalesnhsuksites3documents814bpsd-abhbguidelinesfinal[10june2013]pdf [Accessed 17 September 2014]

15 Brechin D et al Alternatives to antipsychotic medication psychological approaches in managing psychological and behavioural distress in people with dementia Leicester British Psychological Society 2013

R 16 Husebo BS et al Efficacy of treating pain to reduce behavioural disturbances in residents of nursing homes with dementia cluster randomised clinical trial BMJ 2011 343 d4065

M 17 Moniz Cook ED et al Functional analysis-based interventions for challenging behaviour in dementia Cochrane Database Syst Rev 2012 2 CD006929 DOI10100214651858CD006929pub2 [Last assessed as up-to-date 21 July 2012]

18 Livingston G et al Systematic review of psychological approaches to the management of neuropsychiatric symptoms of dementia Am J Psychiatry 2005 162 1996-2021

19 Livingston G et al A systematic review of the clinical effectiveness and cost-effectiveness of sensory psychological and behavioural interventions for managing agitation in older adults with dementia Health Technol Assess 2014 18 1-226 v-vi

20 Cotelli M et al Reminiscence therapy in dementia a review Maturitas 2012 72 203-5

21 Douglas S et al Non-pharmacological interventions in dementia Adv Psychiatr Treat 2005 10 171-7

22 Chaudhury H et al The role of physical environment in supporting person-centered dining in long-term care a review of the literature Am J Alzheimers Dis Other Demen 2013 28 491-500

23 Chung JCC Lai CKY Snoezelen for dementia Cochrane Database Syst Rev 2002 4 CD003152 DOI10100214651858CD003152 [Last assessed as up-to-date 21 April 2008]

R 24 Burns A et al A double-blind placebo-controlled randomized trial of Melissa officinalis oil and donepezil for the treatment of agitation in Alzheimerrsquos disease Dement Geriatr Cogn Disord 2011 31 158-64

M 25 Forrester LT et al Aromatherapy for dementia Cochrane Database Syst Rev 2014 2 CD003150 DOI10100214651858CD003150pub2 [Last assessed as up-to-date 20 January 2014]

26 Spector A et al 2013 A systematic review of staff training interventions to reduce the behavioural and psychological symptoms of dementia Ageing Res Rev 2013 12 354-64

27 Sadowsky CH Galvin JE Guidelines for the management of cognitive and behavioral problems in dementia J Am Board Fam Med 2012 25 350-66

28 Schneider LS et al Effectiveness of atypical antipsychotic drugs in patients with Alzheimerrsquos disease N Engl J Med 2006 355 1525-38

R 29 Sultzer DL et al Clinical symptom responses to atypical antipsychotic medications in Alzheimerrsquos disease phase 1 outcomes from the CATIE-AD effectiveness trial Am J Psychiatry 2008 165 844-54

M 30 Ballard C et al Atypical antipsychotics for aggression and psychosis in Alzheimerrsquos disease (review) Cochrane Database Syst Rev 2006 1 CD003476 DOI10100214651858pub2 [Last assessed as up-to-date 21 February 2006]

M 31 Schneider LS et al Risk of death with atypical antipsychotic drug treatment for dementia meta-analysis of randomized placebo-controlled trials JAMA 2005 294 1934-43

32 Huybrechts KF et al Differential risk of death in older residents in nursing homes prescribed specific antipsychotic drugs population based cohort study BMJ 2012 344 e977

33 Kales HC et al Risk of mortality among individual antipsychotics in patients with dementia Am J Psychiatry 2012 169 71-9

34 Health and Social Care Information Centre 2012 National Dementia amp Antipsychotic Prescribing Audit 2012 [online] Available httpwwwrcpsychacukpdfnati-deme-anti-pres-audi-summ-reppdf [Accessed 17 September 2014]



35 Konovalov S et al Anticonvulsants for the treatment of behavioral and psychological symptoms of dementia a literature review Int Psychogeriatr 2008 20 293-308

36 Dolder CR Nealy KL The efficacy and safety of newer anticonvulsants in patients with dementia Drugs Aging 2012 29 627-37

M 37 Seitz DP et al Antidepressants for agitation and psychosis in dementia Cochrane Database Syst Rev 2011 2 CD008191 DOI10100214651858CD008191pub2 [Last assessed as up-to-date 17 August 2010]

38 Howard RJ et al Donepezil for the treatment of agitation in Alzheimerrsquos disease N Engl J Med 2007 357 1382-92

39 McShane R et al Memantine for dementia Cochrane Database Syst Rev 2006 2 CD003154 DOI10100214651858CD003154pub5 [Last assessed as up-to-date 21 February 2006]

40 Verdoux H et al Is benzodiazepine use a risk factor for cognitive decline and dementia A literature review of epidemiological studies Psychol Med 2005 35 307-15

41 Chang CM et al Benzodiazepine and risk of hip fractures in older people a nested case-control study in Taiwan Am J Geriatr Psychiatry 2008 16 686-92

42 Carriere et al Drugs with anticholinergic properties cognitive decline and dementia in an elderly general population the 3-city study Arch Intern Med 2009 169 1317-24

43 Scottish Intercollegiate Guidelines Network 2006 Management of patients with dementia a national clinical guideline [online] Available httpwwwsignacukguidelinesfulltext86indexhtml [Accessed 17 September 2014]

44 Sorbi S et al EFNS-ENS Guidelines on the diagnosis and management of disorders associated with dementia Eur J Neurol 2012 19 1159-79

DOI 101136dtb2014100282



disturbances agitation and aggression in dementia1415 A study in 352 care-home residents concluded that systematic management of pain significantly reduced agitation associated with moderate to severe dementia (plt0001)16

Treatment optionsNon-drug interventions are widely advocated as the first-line treatment options1

Non-pharmacological interventionsA variety of non-pharmacological interventions have been suggested for managing BPSD These include115

bull aromatherapy

bull multisensory stimulation

bull reminiscence therapy

bull cognitive stimulation

bull psychomotor and exercise interventions

bull therapeutic use of music andor dance

bull animal assisted therapy

bull massage

Systematic reviews of trials of psychological approaches concluded that behavioural management techniques could be beneficial16 and both these and education intended to change carersrsquo behaviour have been shown to be successful with effects that can last for several months1718 A more recent systematic review found that supervised person-centred care communication skills or modified care mapping (an observational process used to evaluate quality of care from the perspective of the person living with dementia) with implementation plans were clinically beneficial although there was little evidence of cost-effectiveness19 Evidence from the small number of studies available suggests that helping patients relive past experiences through reminiscence therapy can lead to improvements in mood behaviour well-being social interaction and self-care17-2021 Music therapy and sensory stimulation may have short-term effects on behaviour1722 Whilst previous reports showed short-term benefits of an environment that provides multi-sensory stimulation (lsquosnoezelenrsquo) a Cochrane review did not find any significant effects on behaviour and mood in people with dementia23 Positive results have been reported from some controlled trials of aromatherapy commonly using extracts of lavender and melissa with significant reduction in agitation21 However when assessed under rigorous randomised clinical trial conditions there was no evidence that melissa oil aromatherapy is superior to placebo or donepezil24 A systematic review identified seven studies of aromatherapy in dementia and concluded that the results were equivocal25

A systematic review found evidence to suggest that training care-staff to understand and manage these symptoms can lead to significant symptom reduction (in 12 of the 20 studies included) and has a positive impact on the way staff behave towards patients26

Other strategies for improving behaviour include ensuring that the patientrsquos environment is safe calm and predictable identifying and removing environmental stressors and avoiding situations that may agitate or frighten the patient Since the effectiveness of long-term behavioural management is largely dependent on the care-giver it is important to assess the role and needs of the care-giver27

Pharmacological interventionsClinical efficacy of antipsychotic drugs

The CATIE-AD multi-centre double-blind placebo-controlled trial compared the use of olanzapine (mean dose 55mgday) quetiapine

(mean dose 565mgday) or risperidone (mean dose 10mgday) in 421 outpatients with Alzheimerrsquos disease and psychosis aggression or agitation28 The main outcome measures were the time to discontinuation of treatment and the number of patients with at least minimal improvement on the Clinical Global Impression of Change (CGI-C) scale at 12 weeks This study showed no significant differences among treatments in terms of time to discontinuation (p=052) or CGIC score (p=022) All drugs were poorly tolerated because of sedation confusion and extrapyramidal effects A descriptive analysis of the study reported that olanzapine and risperidone but not quetiapine showed some improvements on certain neuropsychiatric rating scales compared with placebo29

A meta-analysis of trials of second-generation (atypical) antipsychotics for aggression and psychosis in Alzheimerrsquos disease included nine placebo-controlled trials of which only five had been published in full30 Outcome assessments included measures of agitation and aggression (Cohen-Mansfield Agitation Inventory [CMAI] Behavioural Pathology in Alzheimerrsquos Disease Rating Scale [BEHAVE-AD]) global change (CGI-C Functional Assessment Staging Scale [FAST]) and adverse effects assessed using an extrapyramidal symptom rating scale The reviewers concluded that risperidone and olanzapine are useful in reducing aggression and risperidone in reducing psychosis but that both drugs are associated with serious adverse effects The authors commented that due to modest efficacy and significant increase in adverse effects neither risperidone nor olanzapine should be routinely used in dementia unless there is severe distress or a serious risk of physical harm to those living or working with the patient

Increased harms with antipsychotic drugs

The independent review of the use of antipsychotics in people with dementia reported that a meta-analysis of 15 randomised placebo-controlled trials of second-generation antipsychotics showed an increased risk of cerebrovascular events with a pooled relative risk of 257 (95 CI 141 to 466) and an absolute risk difference of 17 (95 CI 09 to 25)6 Pooled analysis of 15 randomised controlled trials reported an odds ratio for death of 154 (95 CI 106 to 223 p=002) with second-generation antipsychotic use compared with placebo in patients with dementia31

Based on these risks the authors calculated that treating 180000 people with dementia with a second-generation antipsychotic drug (assuming an average treatment period of around 6ndash12 weeks) would result in an additional 1620 cerebrovascular events (around half of which may be severe) and an additional 1800 deaths per year6

Two studies have investigated whether the risk of mortality differs between antipsychotic drugs One was a population-based study of 75445 new users of antipsychotics in nursing homes in the USA32 and the other was a retrospective cohort study using USA national data for 33604 dementia patients beginning outpatient treatment with an antipsychotic or valproate derivative (as a non-antipsychotic comparison)33 The outcome measure was the 180-day mortality rate Both studies found that when compared with risperidone haloperidol users had an increased risk of mortality (hazard ratio [HR] 207 95 CI 189 to 226 and HR 154 95 CI 138 to 173 respectively) whereas quetiapine users had a decreased risk (HR 081 95 CI 075 to 088 and HR 073 CI 067 to 070 respectively) No significant differences were observed for olanzapine aripiprazole and ziprasidone32 The effects were strongest shortly after the start of treatment and remained after adjustment for dose There was a dose-dependent relationship with mortality for all drugs except quetiapine32

Initiatives for reducing the use of antipsychotics in dementia

Recommendations resulting from the review commissioned by the Department of Health6 have led to a national drive to reduce the rate of antipsychotic prescribing for people with dementia Strategies included improving systems for initiation maintenance and cessation of antipsychotic drugs in primary care mental health services for older people and general hospitals regular audits of antipsychotic












































































DOI 101136dtb2014100282












































































DOI 101136dtb2014100282

bnf 4.6 management of non-cognitive symptoms associated

Documents