Management of behavioural and psychiatric symptoms in dementia and the treatment of psychosis in people with a history of stroke/TIA

NICE guidance on dementia recommends that antipsychotics should be used only in exceptional circumstances in elderly patients with dementia (1):

• only offer antipsychotics for people living with dementia who are either:
  • at risk of harming themselves or others
  • or experiencing agitation, hallucinations or delusions that are causing them severe distress
    
    
• be aware that for people with dementia with Lewy bodies or Parkinson's disease dementia, antipsychotics can worsen the motor features of the condition, and in some cases cause severe antipsychotic sensitivity reactions
  
  
• before starting antipsychotics, discuss the benefits and harms with the person and their family members or carers (as appropriate)
  
  
• when using antipsychotics:
  • use the lowest effective dose and use them for the shortest possible time
  • reassess the person at least every 6 weeks, to check whether they still need medication
    
    
• stop treatment with antipsychotics:
  • if the person is not getting a clear ongoing benefit from taking them and
  • after discussion with the person taking them and their family members or carers (as appropriate)
    
    
• valproate should not be used to manage agitation or aggression in people living with dementia, unless it is indicated for another condition
  

Antipsychotics can be classified into two subgroups:

• typical (conventional, first-generation) and atypical (second-generation) agents
  • typical antipsychotics include haloperidol, chlorpromazine and thiothixene
  • atypical antipsychotics include risperidone, olanzapine, quetiapine, clozapine, and aripiprazole
  • the most commonly used atypical antipsychotic for agitation and psychosis in dementia
  • the US Food and Drug Administration (FDA) has not approved any antipsychotics for use in people with dementia; in the EU, only risperidone is licensed for short-term use for aggression in this patient population (2)

Mortality and use of antipsychotics (2,3,4)

• regulatory agencies issued a warning about the use of atypical antipsychotics in people with dementia in the mid-2000s due to an increased risk of death and stoke in this population
• cohort studies have also shown an association between use of typical antipsychotics and an increased risk of mortality in older people
• Luijendijk et al have postulated that this the co-occurrence of the use of typical antipsychotics and deaths might result from "confounding by indication" because many cohort studies included people with terminal illness and delirium, but did not adjust for severity of disease
  • "..conclude that terminal illness has not been adjusted for in observational studies that reported an increased risk of mortality risk in elderly users of conventional antipsychotics. As the validity of the evidence is questionable, so is the warning based on it.."
  • may be an explanation why mortality is highest during the first month of use

NICE CKS suggests either haloperidol or risperidone as antispsychotics of choice in dementia (5):

• haloperidol
  • initial dose of 0.5 mg daily
  • dose is increased gradually every 1-3 days according to response to a maximum of 5 mg daily if required (in 1–2 divided doses)
  • haloperidol treatment should be reassessed after no more than 6 weeks.
  • doses above 5 mg/day should only be considered in people who have tolerated higher doses and after reassessment of the person's individual benefit-risk profile.
• risperidone
  • initial dose of 0.25 mg twice daily
  • the dose of risperidone is adjusted by increments of 0.25 mg twice daily on alternate days according to response
  • the optimum dose is 0.5 mg twice daily, however some people may benefit from doses up to 1 mg twice daily
  • states that risperidone should not be used for more than 6 weeks in people with persistent aggression in Alzheimer's dementia
  • whilst on treatment with resperidone then, evaluate people frequently and regularly to reassess the need for continuing treatment
  • MHRA advises that monitoring blood concentration of risperidone may be helpful in certain circumstances, such as presenting symptoms suggestive of toxicity, or when concomitant medicines may interact to increase blood concentration of risperidone

Risperidone in the treatment of neuropsychiatric symptoms of dementia:

• Huang et al undertook a meta-analysis and concluded (6):
  • risperidone is probably the best pharmacological option to consider for alleviating neuropsychiatric symptoms in people with dementia in short-term treatment when considering the risk-benefit profile of drugs

A previous guideline suggested (7):

1. Assessment

• Any changes in environment, relationships or physical health?
• To whom is the symptom a problem and why?
• Do family carers and care staff need additional training to improve therapeutic interactions?

2. Non-pharmacological management: have these approaches been tried?

• Psychosocial, behavioural and environmental interventions
• Aromatherapy

3. Treatment of new cases, or if severe symptoms arise on withdrawal of medication

Considering postponing treatment for a few days or using 'as required' medication initially, particularly if carers report symptoms on withdrawal of existing medication.

Depression: Commonly missed. Assess for this and consider a therapeutic trial of SSRI.

Dementia with Lewy Bodies (DLB): Beware traditional antipsychotics. Cholinesterase inhibitors are often used first line by specialists. Newer antipsychotics are also used but with increasing evidence of risk.

Any drug used should be commenced at the lowest possible dose, monitored and titrated carefully with regular reviews, aimed at short-term use only, for the treatment of severe psychosis, severe emotional distress or behaviour that is dangerous to the individual or others.

• Cholinesterase inhibitors are licensed for mild to moderate severity AD, with some evidence of benefit in behavioural and psychiatric symptoms and in other dementias
• Memantine is licensed for moderate to severe AD, though evidence of benefit in behavioural disturbance and psychiatric symptoms is very limited
• Newer antipsychotics are felt to have a favourable side effect profile compared to older antipsychotics, though may still cause cerebrovascular events, sedation, extrapyramidal side effects (EPSE), and agitation. Total daily dose quetiapine 25-150mg, sulpiride 100-1200mg and amisulpride 50-400mg.
• Other medications (Limited evidence of benefit and all prescribing is off licence) Traditional antipsychotics and other commonly used sedatives have potentially serious adverse effects which include sedation, confusion, accelerated cognitive decline, falls, urinary symptoms, hypotension, cardiac side effects, EPSE and tardive dyskinesia (TD). Consult the BNF for use in individual patients.

Reference:

1. NICE (June 2018). Dementia
2. Muhlbauer V et al. Antipsychotics for agitation and psychosis in people with Alzheimer's disease and vascular dementia. Cochrane Database of Systematic Reviews 2021, Issue 12. Art. No.: CD013304. DOI: 10.1002/14651858.CD013304.pub2.
3. Rochon PA et al. Antipsychotic therapy and short-term serious events in older adults with dementia. Arch Intern Med. 2008 May 26;168(10):1090-6
4. Luijendijk HJ, de Bruin NC, Hulshof TA, Koolman X. Terminal illness and the increased mortality risk of conventional antipsychotics in observational studies: a systematic review. Pharmacoepidemiology and Drug Safety 2016;25(2):113-22.
5. NICE CKS. Dementia: antipsychotics (Accessed 14th July 2023)
6. Huang Y and others, Pharmacological treatment of neuropsychiatric symptoms of dementia: a network meta-analysis, Age and Ageing, Volume 52, Issue 6, June 2023, afad091, https://doi.org/10.1093/ageing/afad091
7. Summary - Guidance for the management of behavioural and psychiatric symptoms in dementia and the treatment of psychosis in people with history of stroke/TIA. Working group for the Faculty of Old Age Psychiatry RCPsych, RCGP, BGS, and Alzheimer's Society, following CSM restriction on risperidone and olanzapine. April 2004.