Reducing Harmful Use of Antipsychotics in People with Dementia
Submitting Institution
King's College LondonUnit of Assessment
Biological SciencesSummary Impact Type
HealthResearch Subject Area(s)
Medical and Health Sciences: Clinical Sciences, Public Health and Health Services
Summary of the impact
King's College London researchers have had a major widespread impact on
medical care for people with dementia. They have demonstrated the limited
benefit and considerable harm done by the use of antipsychotics in
dementia patients. Their follow-on campaigning and policy work brought
this major health issue to the forefront of the political agenda and led
them to work with the Department of Health to create a best practice
guide, now widely used nationally and internationally. In addition, they
have worked with the BMJ to develop an e- learning package for General
Practitioners. The combined impact of this work has made a major
contribution to a 60% reduction in the use of antipsychotic drugs in
people with dementia in the UK and major changes in practice
internationally, preventing 1000's of unnecessary deaths.
Underpinning research
In the UK there are around 800,000 people with dementia. Up to 90% of
these individuals will experience behavioural and psychological symptoms
(BPSD) such as aggression, agitation and psychosis with huge personal cost
to the patient and their carers. Work at King's College London (KCL) on
treatment for BPSD has been carried out by Prof Clive Ballard
(2003-present, Professor of Age Related Diseases), Prof Robert Howard
(1998-present, Professor of Old Age Psychiatry) and Prof Sube Banerjee
(1992 -2012, Professor of Mental Health and Ageing).
In the mid 2000's it was estimated that up to 25% of people with
dementia, and more than 45% of those with dementia living in care homes,
were being prescribed antipsychotics for BPSD. However, KCL researchers
questioned both the efficacy and safety of such medications in these
patients. One KCL-led randomised, controlled trial (RCT) involving 93
patients (in collaboration with colleagues at Oxford and Newcastle
Universities) demonstrated that the atypical antipsychotic (AA) quetiapine
was ineffective in the treatment of aggression and psychosis in people
with Alzheimer's disease (1). A KCL led meta-analysis showed that many
other AAs, including risperidone, olanzapine and aripiprazole, conferred
only very modest benefits (2). The DART-AD trial was a KCL-led RCT
involved dementia patients continuing typical or atypical antipsychotic
treatment (n = 51) or switching to a placebo (n = 51). For most, there was
no overall detrimental effect on BPSD and some benefits were seen in
functional and cognitive status over 6-12 months following antipsychotic
withdrawal (3). Of particular importance, there was, however, a
significantly increased long term risk of mortality for patients
continuing antipsychotic treatment versus those on placebo. Cumulative
survival at 24 months was 46% vs 71%; at 36-months it was 30% vs 59% (4).
Overall, these studies highlighted significant associations between AAs
and greater cognitive decline, stroke and a very substantial and
accumulating increase in mortality over time.
A key barrier for clinicians discontinuing or withholding antipsychotic
drugs is the fear that BPSD cannot be effectively treated with alternative
approaches. The DART-AD trial (3,4) demonstrated that antipsychotics can
be withdrawn without significant worsening of BPSD and following on from
this, KCL led a trial of person-centred care training for staff in 12 care
homes (focused intervention training and support: FITS). Over 9 months,
antipsychotic use was reduced by 50% in the intervention care homes but
was unchanged in the facilities not receiving the FITS intervention,
without any worsening of BPSD (5). KCL work including clinical trials and
meta- analyses have also highlighted the limited utility of anti-dementia
drugs and anticonvulsants in treating BPSD (6, 7) but highlighted the
potential value of the anti-depressant mirtrazapine as a therapy for
agitation (8). The development of evidence to support alternative
treatment approaches and to highlight pharmacological treatments that are
not efficacious has contributed to enabling the reduction in antipsychotic
drugs to be achieved without a major increase in the prescription of
alternative non-evidence based pharmacological therapies.
References to the research
1. Ballard C et al Quetiapine and rivastigmine and cognitive decline in
Alzheimer's disease: randomised double blind placebo controlled trial. BMJ
2005;330(7496):874. Doi: 10.1136/bmj.38369.459988.8F (145 Scopus
citations)
2. Ballard C, Howard H. Neuroleptic drugs in dementia: benefits and harm.
Nat Rev Neurosci 2006; 7(6):492-500. Doi: 10.1038/nrn1926 (83 Scopus
citations)
3. Ballard C, et al Investigators DART AD. A randomised, blinded,
placebo-controlled trial in dementia patients continuing or stopping
neuroleptics (the DART-AD trial). PLoS Med 2008;5(4):e76. Doi:
10.1371/journal.pmed.0050076 (70 Scopus citations)
4. Ballard C, et al DART-AD investigators. The dementia antipsychotic
withdrawal trial (DART- AD): long-term follow-up of a randomised
placebo-controlled trial. Lancet Neurology 2009a;8(2):151-57. Doi:
10.1016/S1474-4422(08)70295-3 (184 Scopus citations)
6. Howard RJ, et al. Donepezil for the treatment of agitation in
Alzheimer's Disease. NEJM 2007; 357:1382-92. Doi: 10.1056/NEJMoa066583
(119 Scopus citations)
7. Ballard CG, et al. Management of agitation and aggression associated
with Alzheimer disease. Nature Reviews Neurosci 2009; 5:245-55. Doi:
10.1038/nrneurol.2009.39 (85 Scopus citations)
8. Banerjee S, et al. Sertraline or mirtazapine for depression in
dementia (HTA-SADD): a randomised, multicentre, double-blind,
placebo-controlled trial. Lancet 2011; 378(9789):403- 11. Doi:
10.1016/S0140-6736(11)60830-1 (75 Scopus citations)
Grants: This work has been enabled by the support of numerous
funders, including MRC, NIHR, HTA, Lottery fund and other charities, with
a total related grant income of >£5.5m.
Details of the impact
KCL research guides government policy: In the late 2000's, a
number of government documents arose highlighting the issues surrounding
the prescription of antipsychotic medication to people with dementia. A
report on improving services for people with dementia from the House of
Commons Public Accounts Committee, to which Prof Banerjee gave evidence,
specifically discussed the work of KCL when questioning antipsychotic
prescribing practices (1a). This report is cited in the Department of
Health's (DoH) consultation on the National Dementia Strategy, which,
mirroring conclusions of KCL research, posits that two ways care for
residents in care homes could be improved is by "deployment of
non-pharmacological management strategies for behavioural disorders in
dementia" and by "specialist input into decision making
concerning the initiation, review and cessation of antipsychotic
medication for people with dementia" (1b). Prof Clive Ballard was a
key advisor for reports published in 2008 by Paul Burstow, MP and the All
Party Parliamentary Group on Dementia. Burstow uses the findings of Fossey
2006 to support that "promotion of person-centred care...in the
management of patients with dementia with behavioural symptoms provides
an effective alternative to antipsychotic drugs" (1c). The latter,
an enquiry into the use of antipsychotic drugs in people with dementia in
care homes, also uses Fossey to say that "training and support for care
home staff reduces the need to use antipsychotics in residents with
dementia and can be a viable alternative for managing challenging
behaviour" (1d).
Following these, in 2009, the DoH produced a report led by Prof Banerjee
that details how unnecessary antipsychotic prescribing in people with
dementia in the UK is estimated to lead to 1800 deaths and 1600
cerebrovascular adverse events every year (2e). The report cites a number
of KCL led studies including Fossey 2006 when discussing prevalence of
antipsychotic prescribing in nursing homes and how behavioural
interventions can help reduce the need for antipsychotics. For instance,
when stating that "there is a clear emerging consensus about the
positive and negative effects of antipsychotic drugs," the report
cites Ballard 2006 and a 2009 review by Prof Ballard containing this
paper, along with Ballard 2005, 2009a and 2009b (2f). It also cites the
DART-AD trial (Ballard 2008, 2009b) when saying how "continuation
compared with cessation of antipsychotic medication was associated with
increased mortality." The government response to this report
included that it needed to "ensure that antipsychotic drugs are only
prescribed to people with dementia when necessary and are not used when
non-pharmaceutical approaches can be equally effective" (2g).
KCL research guides practice: This body of policy work led to the
development of the 2011 Best Practice Guide on optimising treatment and
care for BPSD, written by KCL researchers in partnership with the DoH and
supported by the Dementia Alliance, provides clear guidance on appropriate
use of antipsychotics and safer alternatives. It also provides a toolkit
following a basic stepped care model and includes clinical checklists and
guidance on symptom assessment, treatment and monitoring. It cites Ballard
2008 and 2009b as two of only 10 key references and Ballard's 2009 paper
(1f) as a key review (2a). The guide has been accessed online more than
100,000 times and been distributed to over 15,000 UK clinicians. It is
available in six languages, with wide international dissemination. In
parallel, KCL, the Alzheimer's Society and the BMJ developed an e-learning
package for GPs (2b). The guide is referenced in many government websites
such as the NHS's Clinical Knowledge Summary on Dementia (that also cites
Ballard 2005) (2c) and is as a key resource in the DoH's Dementia
Commissioning Pack (2d).
Current National Institute for Health and Care Excellence (NICE)
guidelines on `Supporting people with dementia and their carers' state
that "people with...dementias with mild-to-moderate non-cognitive
symptoms should not be prescribed antipsychotic drugs because of the
possible increased risk of cerebrovascular adverse events and death."
They back this with studies including Ballard 2005 and they use Fossey
2006 when discussing the utility of training and support when aiming to
reduce drug use and agitation in nursing homes (2e). Banerjee's 2009
report is also cited in the 2010 NICE `Dementia quality standard'
discussing challenging behaviour (2f).
Regulatory Impact: KCL research has also contributed to two
Medicines and Healthcare products Regulatory Agency's (MHRA) working
groups in 2009 (3a, with Ballard 2009a as a resource) and 2012 (3b, citing
Ballard 2006 and Banerjee's report). These highlight the increased risk of
stroke and death with antipsychotics in people with dementia and led to
warning letters circulated to all doctors in the UK. The MHRA also
produced an `Antipsychotics Learning Module' that cites NICE guidance and
Prof Banerjee's 2009 report (3c).
Overall Impact in Reducing Antipsychotic use in people with dementia:
The combination of these efforts has led to a massive reduction in
antipsychotic prescribing to people with dementia. Part of the government
response to Prof Banerjee's report on antipsychotic prescribing was to
appoint a National Clinical Director for Dementia. One of their
responsibilities was to provide the 2012 NHS audit of English primary care
GP practices that encompassed almost 200,000 people with dementia. This
showed a 60% reduction in antipsychotic use from 2006 to 2011 (4a). With
permission from KCL, the FITS intervention is being implemented by the
Alzheimer's Society, the DoH, the University of Worcester and HC-One care
homes into a person- centred care training package that is being trialled
in 150 UK care homes, involving more than 5,000 people (4b).
KCL research making an impact across the globe and raising public
awareness: KCL researchers serve as members of the US Alzheimer's
Association and Ballard's 2009 review (1f) is cited in their report
`Challenging Behaviors' (5a). They have also worked with the US nursing
home regulator Centers for Medicare & Medicaid Services, who in 2012
launched a national initiative to improve behavioural health and minimise
medication use in people with dementia (5b). The `Time for action' report
is also cited in the WHO `Dementia: a public health priority,' jointly
developed with Alzheimer's Disease International, when highlighting issues
in the use of antipsychotic medication for people with dementia (5c). The
contribution of KCL to raise public awareness includes extensive
communication through the lay media, including over 250 national
television and radio interviews and a key role in developing a 2010 BBC1
Panorama episode addressing antipsychotic use in people with dementia
(5d). They are also involved in development of information packages to
empower carers of people with dementia to have more informed discussions
regarding prescribing decisions, such as those produced by the Alzheimer's
Society (5e).
Sources to corroborate the impact
1. KCL research guides government policy
a. House of Commons Committee of Public Accounts. Improving services and
support for people with dementia. 2008. (pg 34, Ev14). http://www.publications.parliament.uk/pa/cm200708/cmselect/cmpubacc/228/228.pdf
b. DoH. Transforming the quality of dementia care: consultation on a
national dementia strategy. 2008(pgs47/48):http://webarchive.nationalarchives.gov.uk/20130107105354/http://www.dh.gov.uk/prod_consum_dh/groups/dh_digitalassets/documents/digitalasset/dh_085567.pdf
c. Paul Burstow MP: Keep
Taking the Medicine 4. 2008. paulburstow.org.uk/en/document/keep-
taking-the-medicine-4.pdf
d. All-Party Parliamentary Group on Dementia: `Always a Last Resort.'
April 2008. http://www.alzheimers.org.uk/site/scripts/download_info.php?fileID=322
e. The use of antipsychotic medication for people with dementia: Time for
action. Nov 2009. http://www.rcpsych.ac.uk/pdf/Antipsychotic%20Bannerjee%20Report.pdf
f. Ballard CG, et al. Management of agitation and aggression associated
with Alzheimer disease. Nat Rev Neurol 2009;5(5):245-55. Doi:
10.1038/nrneurol.2009.39
g. Government response to Professor Sube Banerjee's Report on the
prescribing of anti-psychotic drugstopeoplewithdementia:12Nov2009:http://webarchive.nationalarchives.gov.uk/2013010710
5354/http://www.dh.gov.uk/prod_consum_dh/groups/dh_digitalassets/documents/digitalasset/dh
_108363.pdf
2. KCL research guides practice
a. Alzheimer's Society/Department of Health (UK): Optimising treatment
and care for behavioural and psychological symptoms of dementia. A best
practice guide for health and social care practitioners. 2011. http://www.alzheimers.org.uk/site/scripts/download_info.php?fileID=1163;
References: http://www.alzheimers.org.uk/site/scripts/documents_info.php?documentID=1675
b. BMJ Learning. Management of dementia in primary care. March 2012. http://learning.bmj.com/learning/module-intro/dementia-primary-care.html?moduleId=10032231&searchTerm="dementia"&page=1&locale=en_GB
c. NHS's Clinical Knowledge Summary: Dementia. May 2012 http://www.cks.nhs.uk/dementia/management/scenario_ongoing_management#-406488
d. Commissioning Pack resources: Reduce inappropriate prescribing of
antipsychotics: http://webarchive.nationalarchives.gov.uk/20130107105354/http://dementia.dh.gov.uk/dementia
-commissioning-pack/commissioning-pack-resources-antipsychotics/
e. NICE-SCIE guideline on supporting people with dementia and their
carers in health and social care: http://www.nice.org.uk/nicemedia/live/10998/30320/30320.pdf
f. NICE Dementia quality standard QS1. June 2010. Non-cognitive symptoms
and behaviour that challenges. http://publications.nice.org.uk/dementia-quality-standard-qs1/quality-statement-7-non-cognitive-symptoms-and-behaviour-that-challenges
3. Regulatory Impact
a. Antipsychotic use in elderly people with dementia. Drug Safety Update
March 2009, vol 1 issue 8: http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON088116
b. Antipsychotics: initiative to reduce prescribing to people with
dementia. Drug Safety update May2012,5(10):http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON152729
c. MHRA: Antipsychotics Learning Module. 2009. http://www.mhra.gov.uk/ConferencesLearningCentre/LearningCentre/Medicineslearningmodules/Antipsychoticslearningmodule/CON155606?useSecondary=&showpage=33
4. Overall Impact in Reducing Antipsychotic use in people with
dementia
a. Focused Intervention Training and Support (FITS):
http://alzheimers.org.uk/FITS
b. National Dementia & Antipsychotic Prescribing Audit 2012. Clinical
Audit Support Unit: https://catalogue.ic.nhs.uk/publications/clinical/dementia/nati-deme-anti-pres-audi-summ-
rep/nati-deme-anti-pres-audi-summ-rep.pdf
5. KCL research making an impact across the globe and raising public
awareness
a. Alzheimer's Association - Challenging Behaviors.http://www.alz.org/documents_custom/statements/challenging_behaviors.pdf
b. Centers for Medicare & Medicaid Services website:
http://www.nhqualitycampaign.org/star_index.aspx?controls=dementiaCare;
resource by Prof Ballard: http://www.nhqualitycampaign.org/files/CliveBallardPresentation.pdf
c. World Health Organisation: `Dementia: a public health priority.' 2012:
http://whqlibdoc.who.int/publications/2012/9789241564458_eng.pdf
d. BBC TV Panorama. What Have the Drugs Done to Dad? Aired 1.11.2010. http://www.bbc.co.uk/programmes/b00vz22h
e. Alzheimer's Society 2011. Reducing the use of antipsychotic drugs: http://www.alzheimers.org.uk/site/scripts/download_info.php?fileID=1133