Antipsychotic medicines for behavioural and
psychological symptoms in dementia (BPSD)
This document provides clinicians with advice on the use of antipsychotic medicines in BPSD, taking into
consideration recommendations from national bodies,12,3&4 current evidence and best practice.
Symptoms of BPSD (e.g. hallucinations, delusions, anxiety, agitation, aggression, other behavioural issues:
wandering, hoarding, sexual disinhibition, apathy, shouting) can present GPs with a difficult clinical scenario.
They often occur together and recurrently,5,6&7 prevalence estimates range between 60% and 80%, with an
incidence of 90% in patients with dementia.8 Due to increased risk of death and stroke and limited
effectiveness of antipsychotics for BPSD; antipsychotic use must be time limited in most cases.9
Document target symptoms and treatment plans and discussions fully.
Non-pharmacologic interventions should be trialed before prescribing.
Only prescribe if there is severe distress or where there is immediate risk of harm to patient/others due to
Discuss the risks vs. benefits with patient/carers.
Initiate at a low dose and titrate up.
Time-limit treatment, review at least every 12 weeks.
Refer to Old Age Psychiatry where there are difficult or persistent cases
Patients treated for BPSD with antipsychotics are more difficult to care for.4 Antipsychotics may be
successfully withdrawn after 3 months of treatment and BPSDs are then less likely to redevelop.10,11,12
Patients with BPSD may successfully have their antipsychotics withdrawn without detrimental effects,
those with a neuropsychiatric inventory score of 14 or less before withdrawal are most likely to be
For people with demenatia with Lewy bodies (DLB), monitor carefully for the emergence of
severe untoward reactions, particularly antipsychotic sensitivity reactions. Which manifest as the
development or worsening of severe extrapyramidal features or acute and severe physical
deterioration for which there is no other apparent cause.
Acetylcholinesterase inhibitors (AChEIs) are recommended for some BPSD (apathy, abberant
motor behavious, anxiety, depression, delusions& hallucinations) where antipsychotics have
failed, are ineffective or inappropriate for Alzheimer’s disease, or for BPSD in DLB.3
Memantine is licensed for use in moderate (2nd line) and severe Alzheimer’s disease and has been
approved for use in South West London. However, there is a paucity of evidence supporting its use for
For people with vascular dementia AChEIs and memantine are not licensed and may even be harmful.16
Initial data shows valproate may increase mortality in BPSD and there is a paucity of evidence that it is an
effective treatment, however, association of effectiveness is more apparent at higher doses.17,18,19,20
Carbamazepine may improve hostility, aggression or agitation in BPSD, however, side-effects and drug
interactions may limit its use.21,22
Antidepressants such as SSRIs and trazodone may improve agitation, restlessness and irritability particularly
when there are signs of depression in BPSD.23,24
All health and social care staff should receive appropriate training to enable them to provide the best
possible care to patients with dementia.
Training should provide understanding of both the symptoms of dementia and the various aspects of the
person-centred approach to care of the individual.
The use of antipsychotic medicines for non-cognitive symptoms in dementia
Patient with dementia develops or already has severe non-cognitive symptoms
Non-cognitive symptoms may include: hallucinations, delusions, anxiety, agitation, aggression, behavioural
issues (e.g. shouting, sexual disinhibition, wandering).
Severe: causing severe distress or an immediate risk of harm to self or others
Refer to specialist if no pre-existing diagnosis of dementia. Patients with frontotemporal, Parkinson’s
disease or Korsakov’s dementias should be referred to a specialist.
Investigate, exclude & treat any other causes
Review: FBC, TFTs, B12, folate, infection, constipation, pain, inappropriate levels of stimulation, care
meeting needs of the patient, communication diffficulties or affective/psychotic illness
Employ non-drug interventions
Develop a person centred care plan consider: environmental and/or occupational changes, psychological
therapies, multi-sensory stimulation, exercise or massage or family involvement.
Try before considering an antipsychotic and review before attempting withdrawal.
Severe non-cognitive symptoms persist despite these interventions
Watchful waiting (wait 4 weeks)for mild to moderate symptoms
Consider antipsychotic medicine, or is one already prescribed?
o Discuss with patient &/or carer(s) risks vs. benefits ( CVA, death, side effects: up to 25% benefit)
o Identify specific target symptom(s)
o Agree criteria for assessment: rating scale(s) (e.g. NPI), 2 weekly review
o If symptoms have persisted for 3 months or more discuss with Old Age Psychiatric Team or refer to
local BPSD service (where they exist).
Record discussions and decisions & use a standard BPSD care plan (where it exists)
Prescribe an antipsychotic Withdraw antipsychotic
o Choose medicine for each individual Successful withdrawal is more likely
st in those with a neuropsychiatric
o Start at low dose (risperidone 1 line) 11,12
o Prescribe for limited period only inventory rating of 14 or less
o Continue non-drug interventions Reduce the dose slowly (if on doses
o Monitor for adverse effects higher than the following per day
o Undertake required physical monitoring e.g. risperidone 0.5mg,
o Avoid putting on ‘repeat list’ olanzapine 2.5mg, quetiapine
o Avoid antipsychotics in Parkinson’s or dementia with 50mg or aripiprazole 5mg).25
lewy bodies (refer for advice) Ensure the risk history is up to date
Prepare an action plan should
▼ symptoms reappear
o Aim to stop antipsychotic as soon as possible ▼
o Review outcomes every 12 weeks
o Record changes in target symptoms, changes in ► If severe non-cognitive symptoms
cognition and tolerability reappear on stopping antipsychotic,
return to the start of this algorithm.
o Reduce / stop antipsychotic once
(the cause of the symptoms may have
acute episode has passed or where changed)
it has had no effect on symptoms
Further information and advice:
Alzheimer’s society. http://www.alzheimers.org.uk/site/scripts/document_pdf.php?documentID=1191
Information on medicines: http://www.choiceandmedication.org/swlstg-tr
South West London Mental Health Medicines Information 020 3513 6829 or you local Old Age Mental Health Team
Medicine Initial Low Dosage Licensed for BPSD? Relative Side Effects
Sedation Extra-pyramidal Cardiac Weight
side effects gain
Amisulpride 50mg once or twice daily No ○ ● ●● ●
Aripiprazole 5mg once daily No ○ ○ ●● ●
Haloperidol 0.5mg once or twice daily No ● ●●● ●●● ●
Olanzapine 2.5mg once daily No ●● ○ ●● ●●
Quetiapine 12.5mg once or twice daily No ● ○ ● ●●
Risperidone 0.25mg once or twice daily Short-term treatment (up to 6 weeks) of ● ● ●● ●
1st line (0.5mg-2.5mg/day)26 persistent aggression in patients with
moderate-severe Alzheimer's dementia;
schizophrenia; mania in bipolar disorder
Sulpiride 100mg once or twice daily No ● ● ● ●
Key: ●●● marked effect ●● moderate effect ● mild/transient effect ○ Minimal effect
Elderly patients with dementia may have improved outcomes for globally, psychosis and agitation (pooled effect sizes 0.12-0.2) and up to 25% of patient
may benefit, however, adverse effects may outweigh any benefit in some individuals. 26&27
Elderly are more sensitive to all side-effects of antipsychotics than adults and their cognition may be worsed.16,28
NNHs for cerebrovascular events and death have been shown to be 37-53 and 77-87 respectively when antipsychotics are used for BPSD. 29&30
No antipsychotic is believed to cause these effects less than another.
Mortality may be the highest in the first 120 days of starting an antipsychotic.32
There is a three-fold increase in the risk of stroke and a two-fold increase in all-cause mortality in patients with dementia receiving atypical antipsychotics.33
Prepared by: Andy Fuller May 2009 & updated Carl Holvey Dec 2011
Medicines & Healthcare products Regulatory Authority. Assessment report. Antipsychotics and cerebrovascular accident SPC Wording for Antipsychotics in relation to: Risk of cerebrovascular accidents (CVA),
in particular when used in dementia patients as agreed following the PhVWP in September 2005
“Always a Last Resort” Inquiry into the prescription of antipsychotic drugs to people with dementia living in care homes. All-Party Parliamentary Group on Dementia April 2008
NICE Clinical Guideline 42, November 2006 (updated March 2011 to include TA 217) Dementia: supporting people with dementia and their carers in health and social care
The Royal College of Psychiatrists Faculty for the Psychiatry of Old Age. Atypical antipsychotics and behavioural and psychiatric symptoms of dementia. Prescribing update for Old Age Psychiatrists.
Lyketsos CG, Steele C, Galik E, et al. Physical aggression in dementia patients and its relationship to depression. American Journal of Psychiatry 1999;156(1):66–71.
Levy ML, Cummings JL, Fairbanks LA, et al. Longitudinal assessment of symptoms of depression, agitation, and psychosis in 181 patients with Alzheimer’s disease. American Journal of Psychiatry
Holtzer R, Tang MX, Devanand DP, et al. Psychopathological features in Alzheimer’s disease: course and relationship with cognitive status. Journal of the American Geriatrics Society 2003;51(7): 953–60.
Parnetti L, Amici S, Lanari A, Gallai V. Pharmacological treatment of non-cognitive disturbances in dementia disorders. Mechanisms of Ageing and Development, 2001;122(16): 2063–9.
Schneider et al, Clinical Antipsychotic Trials of Intervention Effectiveness- Alzheimer’s disease (CATIE-AD) trial. NEJM 2006;355:1525-1538.
Frank L, Kleinman L, Ciesla G, Rupnow MF, Brodaty H. The effect of risperidone on nursing burden associated with caring for patients with dementia. J Am Geriatr Soc. 2004;52(9):1449-55.
Ballard C, Lana MM et al “A Randomised, blinded, placebo-controlled trial in dementia patients continuing or stopping neuroleptics” PLoS Med April 1 2008, 5(4), e76 doi:10.1371/journal.pmed.0050076.
C Ballard et al. A 3-month, randomized, placebo-controlled, neuroleptic discontinuation study in 100 people with dementia: the neuropsychiatric inventory median cut off is a predictor of clinical outcome. J Clin
McShane R, Areosa Sastre A, Minakaran N. Memantine for dementia. Cochrane Database of Systematic Reviews 2006, Issue 2
Gathier S, Loftz H, Cummings J; Improvement in behavioural symptoms in patients with moderate to severe Alzheimer’s disease by memantine: a pooled data analysis; International Journal of Geriatric
Psychiatry 2008; 23: 537–545
Gathier S et al; Effects of memantine on behavioural symptoms in Alzheimer’s disease patients: an analysis of the Neuropsychiatric Inventory (NPI) data of two randomised, controlled studies; International
Journal of Geriatric Psychiatry 2005; 20: 459 - 464
Kavirajan H, Schneider LS. Efficacy and adverse effects of cholinesterase inhibitors and memantine in vascular dementia: a meta-analysis of randomised controlled trials. Lancet Neurology 2007; 7:246-255
Tariot PN et al. Treatment of Agitation, Aggression, and Behavioral Disturbances in Dementia. CurrTherRes. 2001; 62(1):51-67.
Porsteinsson AP et al. Valproate Therapy for Agitation in Dementia: Open-Label Extension of a Double-Blind Trial Am J Ger Psych. 2003;11(4):434-440;
Sival RC et al. Sodium valproate in the treatment of aggressive behavior in patients with dementia—a randomized placebo controlled clinical trial. Int J Ger Psych 2002;17(6):579-585.
Tariot PN et al. Divalproex Sodium in Nursing Home Residents With Possible or Probable Alzheimer Disease Complicated by Agitation: A Randomized, Controlled Trial Am J Ger Psych 2005;13(11):942-949
Olin et al., A Pilot Randomized Trial of Carbamazepine for Behavioral Symptoms in Treatment-Resistant Outpatients with Alzheimer Disease. Am J Ger Psych 2001:9:400-5.
Tariot PN et al. Efficacy and Tolerability of Carbamazepine for Agitation and Aggression in Dementia. Am J Psych 1998; 155(1):54-61.
A. Teri L et al. Treatment of agitation in AD: A randomized, placebo-controlled clinical trial. Neurol. 2000 55(9): 1271-1278;
Pollock BG et al. Comparison of Citalopram, Perphenazine, and Placebo for the Acute Treatment of Psychosis and Behavioral Disturbances in Hospitalized, Demented Patients. Am J Psych 2002; 159(3):460-
Alzhiemier’s Society. Optimising treatment and care for people with behavioural and psychological symptoms of dementia. July 2011
AR Maher et al., Efficacy and comparison of Atypical Antipsychotic Medications for Off-Label Uses in Adults: A Systematic Review and Analysis. JAMA. 2011; 306:1359-1369.
Schneider et al, Clinical Antipsychotic Trials of Intervention Effectiveness- Alzheimer’s disease (CATIE-AD) trial. NEJM 2006;355:1525-1538.
CLP Vigen etal., Cognitive Effects of Atypical Antipsychotic Medications in Patients With Alzheimer's Disease: Outcomes From CATIE-AD. Am J Psych, 2011:, ;:. 10.1176/appi.ajp.2011.08121844
Anon. How safe are antipsychotics in dementia? Drugs and therapeutics Bulletin 2007;45(11):81-85.
Medicines and Healthcare products Regulatory Agency, 2004. Summary of clinical trial data on cerebrovascular adverse events (CVAEs) in randomized clinical trials of risperidone conducted in patients with
dementia [online]. Available:http://www.mhra.gov.uk/home/idcplg?IdcService=GET_FILE&dDocName=con019490&RevisionSelectionMethod=Latest [Accessed 9 July 2009].
Mehta S, Johnson ML, Chen H, Aparasu RR. Risk of cerebrovascular adverse events in older Adults using antipsychotic agents. A propensity matached retrospective cohort study. J Clin Psychiatry
HC Kales et al., Risk of Mortality Among Individual Antipsychotics in Patients With Dementia. Am J Psychiatry 2011;:. 10.1176/appi.ajp.2011.11030347
PhVWP Assessment report. Antipsychotics and cerebrovascular accident SPC Wording for Antipsychotics. Risk of cerebrovascular accidents (CVA), in particular when used in dementia patients as agreed
following the PhVWP in September 2005.