Pharmacological Management of Severe Behavioural ...

PG 14 – Pharmacological Management of BPSD Approved by Drug and Therapeutics Committee: November 2019 Review date: November 2023

of 14

Prescribing Guideline

Pharmacological Management of Severe Behavioural & Psychological

Symptoms of Dementia (BPSD)

PG14

Contents: Summary

Introduction Non-pharmacological Treatments

Pharmacological Treatments Increased Mortality

Prescribing Guidance Medication Evidence


of 14

Pharmacological Management of Severe Behavioural &

Psychological Symptoms of Dementia (BPSD)

The aim of these guidelines is to promote evidence based, cost effective prescribing and support adherence to:

o NICE Guideline NG97. Dementia: assessment, management and support for people living with dementia and their carers (2018)

o The use of antipsychotic medication for people with dementia: Time for action. (Banerjee 2009: Department of Health)

o NICE Quality Standard QS1. Dementia: support in health and social care (2018)

o Alzheimer’s Society (2011): Optimising treatment and care for people with behavioural and psychological symptoms of dementia- A best practice guide for health and social care professionals

The guidelines are NOT intended to replace prescribing information contained in the BNF or Summary of Product Characteristics.

Summary (see text for further details):

Rule out or treat differential diagnoses (Delirium, pain, constipation, infection, physical illness)

Non-pharmacological treatments

Pharmacological treatments (Treat specific functional mental health problem:

depression, anxiety, insomnia, psychosis, aggression)


of 14

Introduction

Behavioural and psychological symptoms occur in about 90% of individuals with dementia, (frequency increases with severity of dementia), causing considerable distress and/or risk of harm to the individual, increasing distress to the family/carer and potentially interfering with or preventing the provision of required care.

The presenting neuropsychiatric symptoms restlessness, wandering, agitation, aggression, sleep disturbance, sexual disinhibition and shouting are collectively referred to as ‘behavioural and psychological symptoms of dementia’ (BPSD). Each symptom needs to be treated specifically. More than one symptom can occur at the same time and the clinician needs to decide which symptoms need to be tackled first and by what approach. This range of symptoms is often reported as a single primary outcome measure in clinical trials. As a result, the efficacy of therapies for specific symptoms can be difficult to determine. Clinically, the key symptoms are aggression, agitation, psychosis, and mood disorders. Symptoms that do not usually respond to antipsychotics include wandering, social withdrawal, shouting, pacing, touching, cognitive defects and incontinence.

For people with a diagnosis of dementia, behaviours that challenge are best managed by good nursing care, the correct environment and the use of ‘ABC’ chart (antecedents, behaviours and consequences) to try and identify causes and possible triggers for the presenting behaviour. Initial steps should focus on ruling out, or treating, the differential diagnoses. Examples include delirium, constipation, pain (even without overt symptoms), infection, activity related, side-effects of mediation, or the environment Where functional mental health problems exist e.g. depression, anxiety, insomnia or psychosis these should be treated according to NICE guidance and Trust prescribing guidelines. See section of pharmacological treatments. Non-pharmacological treatments should be considered first line. Non-pharmacological and pharmacological treatments should not be seen as separate and should be used in combination where appropriate.

Non-Pharmacological Treatments Where management is not urgent or for less severe BPSD, a combination of non-pharmacological approaches are appropriate first-line treatments. Examples of non-pharmacological treatments include:

Physical presence: spending appropriate time with a person will usually help.

Recreational & social activities and therapies: These help structure the day, providing meaning and a setting for social interaction.

Behavioural interventions: identifying the nature, antecedents and consequences of the target behaviour, setting goals and devising a plan with on-going reviews.

Psychological and psychosocial interventions: tailored to the needs of the individual patients, family, carers and care staff.

Environmental interventions: design and layout of the physical environment, day/night routines.

Compensating for sensory impairments, attending to diet and general health.

Risk assessment, reduction and intervention: including appropriate placement.

Non-pharmacological approaches must always be considered first


of 14

Complementary therapies: Massage, reflexology and aromatherapy. Practitioners should be aware that no single non-pharmacological intervention (e.g. multi-sensory stimulation, bright light therapy, aromatherapy) has an evidence base that would justify its use as a direct alternative to antipsychotic medication.

Pharmacological Treatments Medication, behavioural and environmental approaches are not mutually exclusive. The appropriate initial management approach depends on the symptom, its severity, frequency and impact, and the situation in which it occurs. Pharmacological treatment is not a substitute for non-pharmacological approaches and these techniques must always be used concurrently. For all cases of agitation and aggression in dementia, pain relief, i.e. paracetamol, should be considered as an alternative to the medications below. Even without overt pain, a trial of paracetamol is worthwhile.

The expected benefits must outweigh the potential risks/side effects of medication for each individual. Pharmacological management of severe BPSD (agitation and aggression in particular) should only be considered if behaviours cause severe distress to the individual and/or there is immediate risk of harm to themselves or other patients or carers. Wandering, social withdrawal, shouting, pacing, touching, cognitive defects and incontinence do NOT respond to antipsychotic medication. Medication prescribed for the management of BPSD should be considered as an individual therapeutic trial, with the choice of medication based upon an individual risk-benefit analysis. BPSD symptoms: Aggression or severe agitation DPT approved options: Risperidone (licenced), Olanzapine, Aripiprazole, Donepezil, Memantine, Mirtazapine, SSRIs, Diazepam & Lorazepam, Lewy Bodies or Parkinson’s disease dementia: Quetiapine or Clozapine

See appendix 1 for detailed information on treatments Notes: Initial dose of risperidone 250micrograms twice a day recommended. This may be increased according to response in steps of 250micrograms twice a day on alternate days. Usual dose 500micrograms twice a day (doses up to 1mg twice a day may be beneficial for some individuals). Risperidone is the only medication with UK marketing authorisation for this indication, licensed for “the short-term treatment (up to 6 weeks) of persistent aggression in patients with moderate to severe Alzheimer's dementia unresponsive to non-pharmacological approaches and when there is a risk of harm to self or others”. All other antipsychotics are off-licence. If no response with risperidone at 1mg in divided doses, consider switching to alternative antipsychotic; optimal dosage of olanzapine & aripiprazole is 10mg. Starting dose of olanzapine 2.5mg/day, aripiprazole 5mg/d, quetiapine 12.5mg/d, clozapine – contact local pharmacist.

Always “START LOW AND GO VERY SLOW”


of 14

If patient is already on a cholinesterase inhibitor, discontinue this as it may be perpetuating agitation. Use antipsychotics in caution in Lewy Bodies or Parkinson’s disease dementia. Functional mental health problems: Functional mental health problems should be treated according to the appropriate Trust Prescribing Guideline: Depression: https://www.dpt.nhs.uk/resources/medicines-in-mental-health/for-prescribers-and-professionals/clinical-protocols-and-prescribing-guidelines Anxiety: https://www.dpt.nhs.uk/resources/medicines-in-mental-health/for-prescribers-and-professionals/clinical-protocols-and-prescribing-guidelines Notes: Use short-term benzodiazepines or antipsychotics only as a last resort. Insomnia: https://www.dpt.nhs.uk/resources/medicines-in-mental-health/for-prescribers-and-professionals/clinical-protocols-and-prescribing-guidelines Notes: Promethazine should be avoided as it increases the anticholinergic burden. Psychosis: https://www.dpt.nhs.uk/resources/medicines-in-mental-health/for-prescribers-and-professionals/clinical-protocols-and-prescribing-guidelines

Vascular dementia and Frontotemporal Dementia (FTD): There is very little evidence for the treatment of BPSD in these dementias. The cholinesterase inhibitors (donepezil, rivastigmine, galantamine) and memantine are not licensed for the treatment of vascular or frontotemportal dementia and should not be used. Refer to the Decision aid for specialist treatment strategies - Severe BPSD (Appendix 1)

Antipsychotics and increased mortality

The risk of death with second generation antipsychotics (SGA) is 1.6-1.7 times higher than with placebo, mostly due to cardiovascular causes (e.g. heart failure, sudden death) or infections (e.g.

pneumonia).

The main risks with taking antipsychotics are femur fracture (increased risk), pneumonia (60% increased risk), cerebrovascular events and an increased risk of stroke (FGA 25-72 cases/1000

patients, SGA 47/1000; without antipsychotics 12/1000).

The risk of cardiovascular adverse events is higher in the first four weeks.

The increased mortality occurs with higher doses i.e. risperidone > 1mg/day, olanzapine >2.5mg/day. This may be due to dehydration and poor mobilisation.

ENSURING ADEQUATE HYDRATION AND MOVEMENT IN THE FIRST MONTH IS ESSENTIAL.

https://www.dpt.nhs.uk/resources/medicines-in-mental-health/for-prescribers-and-professionals/clinical-protocols-and-prescribing-guidelines









of 14

Depression Do not routinely offer antidepressants to manage mild/moderate depression in those with mild/moderate dementia unless indicated for a pre-existing severe mental health problem Insomnia Do not offer melatonin to manage insomnia in Alzheimer’s disease

Prescribing Guidance

Starting medication:

Identify, quantify & document target symptoms including severity and level of distress caused to the individual (and family/carers where appropriate) and set realistic treatment goals. Suitable assessment tools include Adapted Cohen–Mansfield Agitation Inventory (Adapted CMAI) or Neuropsychiatric Inventory (NPI).

Document which non-pharmacological interventions have been used or offered to the individual and their level of effectiveness.

Complete baseline physical monitoring appropriate to the individual drug prescribed. See Practice Standard PS11 Physical Health Monitoring for more details.

Complete baseline assessment of cognition.

Clearly record rationale for treatment and choice of medication in the clinical notes, including agreed start date and initial treatment review date.

It is recognised that when medication is prescribed for the management of BPSD it will generally arise from a ‘best interest decision’. The prescriber must ensure that a formal record of capacity assessment is completed and a summary of multi-professional team discussion and rationale for treatment clearly documents in the notes (including information provided to family and/or carers where applicable).

Communication of information to family/carers:

The prescriber must discuss the possible treatment options with the individual and/or family/carers, including the anticipated benefits and potential risks of treatment (in particular, cerebrovascular risk factors should be assessed and the possible increased risk of stroke/transient ischaemic attack and possible adverse effects on cognition discussed).

Provide information in an appropriate format to support discussion about expected benefits and possible risks of treatment (see user-friendly resources).

A summary of the discussion (and note of any additional information provided) must be clearly documented in the clinical notes.

Monitoring treatment:

Regularly monitor response to treatment/changes in target symptoms & document in notes.

Assess cognition at regular intervals, and document any required action(s)/treatment plan to address any deterioration in cognition.

Monitor for side-effects associated with medication. Review treatment if side-effects intolerable or severe.

Ensure on-going physical monitoring is carried out appropriate to the medication prescribed (see Practice Standard PS11 Physical Health Monitoring for more details).

Document subsequent treatment review dates (& person responsible) in the clinical notes at each clinical review. Treatment should be time-limited and regularly reviewed.

Reviewing and stopping treatment:

Treatment should be reviewed at 6 weeks (with more frequent review considered according to clinical need).

http://daisy.exe.nhs.uk/quality-safety/medicines-optimisation/documents/practice-standards.aspx

https://daisy.dpt.nhs.uk/media/1567299/ps11-physicalhealthmonitoring.doc


of 14

Following review, unless there is severe risk or extreme distress, the recommended default management is to discontinue antipsychotic medication. Medication should only be continued for people who still have continuing BPSD, where it is felt that severe adverse consequences may occur (or have occurred) if they are discontinued or where no alternative treatment approaches are suitable. The decision to continue these drugs should be documented and the factors considered in making this decision should be recorded, as discussed above. Attempts should continually be made to reduce or stop medication.

Review doses regularly, and institute a periodic reduction in dose (eg by 10-25% every four weeks), and if no recurrence then continue the reduction every four weeks.

Acute management in an emergency situation: For individuals, receiving treatment on an in-patient ward only, where physically violent and aggressive behaviour has or may imminently result in harm to the individual and/or others, it may be appropriate to consider ‘rapid tranquillisation’ where repeated attempts at non-pharmacological interventions and oral medication has failed to produce any benefit (or has been refused). Refer to the Trust Policy for Rapid Tranquillisation (C36) and Clinical Protocol (CP11). This protocol states antipsychotic medication is not suitable for use in rapid tranquilisation in this population.

Communication of information on transfer of care:

Following a treatment review, it may be appropriate for the medication to be continued for an agreed period of time following discharge from an in-patient unit, or after review by a specialist in a community team.

Where it is appropriate for treatment to be continued in primary care, the Trust prescriber (Consultant or Associate specialist) will:

o Contact individual’s GP to request that they accept on-going responsibility for prescribing

o Where prescribing is to be continued by GP - provide them with a clear treatment plan to cover the reduction and discontinuation of medication for BPSD and who to contact if they need to seek further advice on the clinical management of the individual (i.e. original symptoms re-emerge on discontinuation of treatment).

o Include a summary of the information documented in the clinical notes regarding target symptoms, choice of medication and rationale for treatment.

https://www.dpt.nhs.uk/uploads/attachments/Medicines/For%20prescribers%20and%20professionals/Prescribing%20guidelines/antipsychoticprescribingindementia.doc is available.

User-friendly resources

Leaflets for patients/family/carers on dementia can be found on the Alzheimer’s Society website: https://www.alzheimers.org.uk/get-support/publications-factsheets-full-list)

https://www.dpt.nhs.uk/uploads/attachments/Medicines/For%20prescribers%20and%20professionals/Prescribing%20guidelines/antipsychoticprescribingindementia.doc



https://www.alzheimers.org.uk/get-support/publications-factsheets-full-list


of 14

Appendix 1

Decision aid for specialist treatment strategies: Severe BPSD

There is a lack of high quality clinical trial evidence to support the effectiveness of medication for BPSD (with evidence based on Alzheimer’s dementia rather than vascular/stroke related, fronto-temporal lobe, mixed or DLB), however increasingly there is information which questions their safety. The table below is designed to provide you with a summary of the available evidence for drugs used for the management of BPSD (specific to aggression, agitation and/or psychosis), along with a summary of possible side effects and precautions required.

ANTIPSYCHOTICS

Evidence of efficacy in BPSD, though limited, is greatest for risperidone and olanzapine, however, clinical efficacy is modest and this must be balanced against elevated risk of cerebrovascular adverse events (CVAEs), mortality, upper respiratory infections, oedema, extrapyramidal symptoms and an increase in overall mortality rate. This applies to ALL ANTIPSYCHOTICS (first and second generation) and not just risperidone and olanzapine as originally reported in the Committee of Safety of Medicines alert (2004).

A summary of the risks and benefits for treating BPSD in 1000 people over a 12 week period with an second generation antipsychotic would result in;

91-200 people with behavioural disturbance showing clinically significant improvement in symptoms

10 deaths (Evidence suggests that risk of mortality increases over time, therefore longer term treatment may result in up to 167 additional deaths over a 2 year period).

18 CVAEs of which ~50% would be severe (Evidence from observational studies suggests the increased risk of CVAE may be confined to the 2-3 month period typically encompassed in RCT follow-up studies, therefore extrapolation of data in the original CSM alert, 2004, proposing a NNH of 37 would translate to NNH of 6.3 over 1 year, resulting in an additional 159 CVAEs per 1000 people treated, may be an over-estimation).

No additional falls or fractures

58-94 people with gait disturbance

Intervention Rationale (Where stated, doses derived from published studies)

DPT use approved?

Risperidone

Licensed for the short-term treatment (up to 6 weeks) of persistent aggression in patients with moderate to severe Alzheimer's dementia unresponsive to non-pharmacological approaches and when there is a risk of harm to self or others (500micrograms - 2mg/daily).

Significant improvement in aggression & psychosis compared to placebo although additional care is needed in Lewy Body Dementia

YES

Olanzapine (Off-licence use)

Significant improvement in aggression compared to placebo (5-10mg/daily)

ONLY consider as a 2nd line option where risperidone not appropriate/not tolerated. Not well tolerated in Lewy Body Dementia.

YES

Clozapine (Licensed for psychosis in Parkinson’s Disease)

Licensed for the treatment of psychosis in Parkinson's Disease but no studies exist for BPSD. Two RCTs show a low dose 25-37.5mg/day improve psychosis without effect motor deterioration. Doses >50mg/d poorly tolerated. ONLY consider in psychosis associated with Parkinson’s Disease.

YES

Aripiprazole (Off-licence use)

Improvement in psychosis demonstrated with 2-15mg/day compared with placebo (Schneider et al 2006; NNT=13.8)

YES

Quetiapine (Off-licence use)

Reported doses prescribed: 25-200mg/day. 200mg/day reported superior to placebo for agitation where 100mg/day not superior. Has been associated with significant cognitive decline compared with placebo at 26 weeks.

YES

First Generation antipsychotics (Off-licence use)

Potential risks outweigh possible benefits: Associated with increased risk of CVE and mortality (mortality risk ≥ second generation antipsychotics)

NO


of 14

ACETYL-CHOLINESTERASE INHIBITORS (If not already prescribed for management of AD)

Intervention Rationale (Where stated, doses derived from published studies) DPT use approved?

Donepezil (Off-licence use)

Meta-analysis demonstrated a small but significant overall advantage of AChEIs over placebo with regard to the treatment of BPSD in Alzheimer’s Disease, although no short term benefit for treatment of clinically significant agitation with donepezil observed in 12 week RCT. Current evidence appears to demonstrate that AChEIs have their greatest effects on depression and dysphoria, apathy, indifference and anxiety and are probably not an effective treatment for the management of agitation or aggression in Alzheimer’s dementia. Benefit may be from slower disease progression.

YES

Galantamine (Off-licence use)

Evidence equivocal at doses of 16-24mg/day. Herrmann et al (2005) pooled analysis suggest it might improve behavioural symptoms. In placebo controlled trials, Rockwood et al (2001) reported no statistically significant difference in behavioural symptoms between groups (n=386). Cummings et al (2004) post hoc analysis reported slight improvement observed with galantamine at 16 & 24mg/day but not 8mg/d (n=978).

Not approved because available evidence equivocal and increased treatment cost cannot be justified due to lack of evidence demonstrating increased efficacy compared with donepezil.

NO

Rivastigmine (Off-licence use)

Reported doses prescribed 1.5-4.5mg bd (6-12mg/day). Evidence equivocal (most studies open-label and behaviour a secondary end-point). Meta-analysis reported rivastigmine may be tolerated and effective for BPSD (6-12mg/d) (Finkel et al, 2004)

Not approved because available evidence equivocal and increased treatment cost cannot be justified due to lack of evidence demonstrating increased efficacy compared with donepezil.

NO

NMDA ANTAGONIST

Memantine (Off-licence use)

Systemic meta- analysis suggested that memantine (10mg bd) decreases NPI scores and may have a role in BPSD (reducing agitation/aggression) but effect size small. Could be considered for management of severe symptoms of agitation/aggression and psychosis in people who have failed to respond to other medication and who are otherwise prone to a rapid decline. Maidment et al (2008). However, a randomised DB PC trial (Fox et al 2012) reported no improvement in significant agitation in people with moderate to severe AD, suggesting that memantine should not be routinely prescribed to treatment agitation in AD.

YES

ANTIDEPRESSANTS

Intervention Rationale (Where stated, doses derived from published studies) DPT use approved?

Mirtazapine (Off-licence use)

Limited evidence available. One 12 week open-label study reported mirtazapine (15-30mg/day) could be a well-tolerated treatment option for the management of agitation in people with AD. Whilst not clinically effective for the treatment of depression in people with AD, mirtazapine may act to improve general behavioural and psychological symptoms in dementia rather than depression, Banerjee (2013).

YES

SSRIs (Off-licence use)

Cochrane concludes that SSRIs are relatively well tolerated and can help with modest reductions of agitation in AD without significant cognitive deterioration or adverse reactions (Seitz et al, 2011).

YES


of 14

Citalopram was found to be effective in reducing agitation in AD by the CitAD trial, however before use consideration must be given to the cognitive and serious cardiac adverse effects also identified in the trial. (Porsteinsson et al 2014)

Trazadone (Off-licence use)

Trazadone is the most widely used antidepressant prescribed for people presenting with BPSD despite lack of robust evidence to support efficacy.

NO

BENZODIAZEPINES


DPT use approved?

Diazepam (Off-licence use)

1-2 mg up to 3 times a day (increase if necessary to max 15mg/24 in divided doses). Licensed for anxiety - short term use only for acute & severe distress and/or where sedation is required. T½ ~32 hours (21-50) longer in older adults No systemic reviews of RCTs examining the usefulness of benzodiazepines compared to placebo in the management symptoms associated with dementia (including anxiety) were identified.

NB 5mg diazepam ~ equiv to 0.5mg lorazepam.

May cause/hasten

cognitive decline.

Paradoxical disinhibition may

occur.

Contribute to falls and hip fractures.

Accumulation leading to excessive

sedation/adverse effects and/or tolerance over

time.

YES

ONLY for short

term use for acute & severe

distress and/or where sedation is

required

Lorazepam (Off-licence use)

Usual max dose = 2mg/24hours (in divided doses)

Short term use for only for acute & severe distress and/or where sedation is required Licensed for anxiety T½ ~12 hours (8-25). Similar in older adults. No systemic reviews of RCTs examining the usefulness of benzodiazepines compared to placebo in the management symptoms associated with dementia (including anxiety) were identified.

ANTI-CONVULSANTS:


DPT use approved?

Carbamazepine (Off-licence use)

Uncontrolled studies & case reports have reported improvement in presenting hostility & aggression in people with dementia who had not responded to antipsychotics as well as short term efficacy for agitation, however a review of placebo controlled RCTs to date provides equivocal information about efficacy for BPSD, and the safety and tolerability of therapeutic doses in people with dementia/older adults still needs to be established.

NO

Valproate (Off-licence use)

Cochrane concludes that valproate is ineffective in treating agitation in dementia with unacceptable adverse reactions. Further studies show it doesn’t delay emergence of agitation or slow cognitive decline. NICE evidence summary 41 suggests that valproate preparations are no more effective than placebo for treating agitation or behavioural disturbances in dementia, and that adverse effects were more common.

NO

Oxcarbazepine (Off-licence use)

No evidence to demonstrate efficacy NO

MHRA advice: In April 2018, the MHRA added warnings that valproate must not be used in pregnancy, and only

used in girls and women when there is no alternative and a pregnancy prevention plan is in place. This is because

of the risk of malformations and developmental abnormalities in the baby. See safety briefing 13-014

https://www.dpt.nhs.uk/resources/medicines-in-mental-health/for-prescribers-and-professionals/safety-briefings


of 14

Gabapentin (Off-licence use) Pregabalin (Off-licence use)

Small systematic review (Supasitthumrong 2019) found possible benefit. Small sample size and currently insufficient evidence to change approval status.

NO

Lamotrigine (Off-licence use)

Limited data reporting treatment well tolerated and effective, but evidence very weak (case reports only).

NO

Topiramate (Off-licence use)

Limited data (non-random retrospective study n=15). Reduction in Cohen-Mansfield Agitation Inventory noted but evidence very weak.

NO

References:

Alzheimer’s Society. Optimising treatment and care for people with behavioural and psychological symptoms of dementia. A best practice guide for health and social care professionals. 2011. Available at http://www.alzheimers.org.uk/site/scripts/download_info.php?fileID=1163

Ballard C.G.; Gauthier S.; Cummings J.L.; Brodaty H.; Grossberg G.T.; Robert P.; Lyketsos C.G. Management of agitation and aggression associated with Alzheimer disease. Nature reviews. Neurology, 2009, vol./is. 5/5(245-255),

Ballard C.; Corbett A.; Chitramohan R.; Aarsland D. Management of agitation and aggression associated with Alzheimer's disease: Controversies and possible solutions. Current Opinion in Psychiatry, 2009, vol./is. 22/6 (532-540),

Banerjee S, Hellier J, Romeo R et al (2013) Study of the use of antidepressants for depression in dementia: the HTA-SADD trial- a multicentre, randomised, DB, PC trial of the clinical effectiveness and cost-effectiveness of sertraline and mirtazapine. Health Technol Assess 17(7) www.alzheimers.org.uk/bpsdguide. Accessed 14 Aug 2013

Bazire S. Psychotropic Drug Directory. 2018. Warwickshire, UK

Cakir S, Kulaksizoglu I. The efficacy of mirtazapine in agitated patients with Alzheimer’s Dementia: A 12 week open label pilot study. Neuropsychiatric Disease and Treatment 2008 4(5) 963-966

Corbett A.; Smith J.; Creese B.; Ballard C. Treatment of behavioral and psychological symptoms of Alzheimer's disease Current Treatment Options in Neurology, 2012, vol./is. 14/2(113-125),

Durán JC, Greenspan A, Diago JI, Gallego R, Martinez G. Evaluation of risperidone in the treatment of behavioral and psychological symptoms. 2005; 17: 591–604 Dyer et al. An overview of systematic reviews of pharmacological and non-pharmacological interventions for the treatment of behavioural and psychological symptoms of dementia. Int psychogeriatr, 2018; vol/is 30/3(295-309)

Finkel et al. Effects of rivastigmine on behavioral and psychological symptoms of dementia in Alzheimer's disease. Clin Ther. 2004; 26: 980–90.

Fox C, Crugel M, Maidment I et al. Efficacy of memantine for agitation in Alzheimer’s Dementia: A randomised double-blind placebo controlled trial. PLoS ONE 2012 7(5): e35185 doi:10.1371/journal.pone.0035185 Herrmann N, Rabheru K, Wang J et al. Galantamine treatment of problematic behavior in Alzheimer disease: post-hoc analysis of pooled data from three large trials. Am J Geriatr Psychiatry 2005; 13: 527–34.

http://www.alzheimers.org.uk/site/scripts/download_info.php?fileID=1163

http://www.alzheimers.org.uk/bpsdguide


of 14

Herrmann N, Lanctot KL. Pharmacological management of neuropsychiatric symptoms of Alzheimer disease. Can J Psychiatry 2007; 52: 630-46. Husebo et al. Efficacy of treating pain to reduce behavioural disturbances in residents of nursing homes with dementia: cluster randomised clinical trial. BMJ 2011; 343. Kim. Y, Wilkins. K, Tampi. R,. Use of gabapentin in the treatment of behavioural and psychological symptoms of dementia: a review of the evidence. Drugs Aging. Drugs Aging. 2008;25(3):187-96

Konovalov S, Muralee S, Tampi R. Anticonvulsants for the treatment of behavioural and psychological symptoms of dementia: a literature review. International Psychogeriatrics. 2007 20:2, 293-308

Konovalov S, Muralee S, Tampi RR. Anticonvulsants for the treatment of behavioral and psychological symptoms of dementia: a literature review. Int Psychogeriatr. 2008; 20:293–308.

Lockhart et al. The Efficacy of Licensed-Indication Use of Donepezil and Memantine Monotherapies for Treating Behavioural and Psychological Symptoms of Dementia in Patients with Alzheimer's Disease: Systematic Review and Meta-Analysis. Dementia and geriatric cognitive disorders extra 07/2011; 1(1): 212-27.

Mowla A, Pani A. Comparison of topiramate and risperidone for the treatment of behavioral disturbances of patients with Alzheimer disease: a double-blind, randomized clinical trial. J Clin Psychopharmacol. 2010 Feb;30(1):40-3

Mintzer JE, Tune LE, Breder CD, Swanink R, Marcus RN, McQuade RD, Forbes A. Aripiprazole for the treatment of psychoses in institutionalized patients with Alzheimer dementia: a multicenter, randomized, double-blind, placebo-controlled assessment of three fixed doses. Am J Geriatr Psychiatry. 2007 Nov;15(11):918-31.

Pollock B.G.; Mulsant B.H.; Rosen J.; Mazumdar S.; Blakesley R.E.; Houck P.R.; Huber K.A. A double-blind comparison of citalopram and risperidone for the treatment of behavioral and psychotic symptoms associated with dementia The American journal of geriatric psychiatry, 2007 vol./is. 15/11(942-952)

Pollock B.G.; Mulsant B.H.; Rosen J.; Sweet R.A.; Mazumdar S.; Bharucha A.; Marin R.; Jacob N.J.; Huber K.A.; Kastango K.B.; Chew M.L. Comparison of citalopram, perphenazine, and placebo for the acute treatment of psychosis and behavioral disturbances in hospitalized, demented patients American Journal of Psychiatry, 2002 vol./is. 159/3(460-465) Porsteinsson AP et al. Effect of citalopram on agitation in Alzheimer disease: the CitAD randomized control trial. JAMA, 2014 vol./is. 311/7(682-691) Rodda J, Morgan S, Walker J. Are cholinesterase inhibitors effective in the management of the behavioural and psychological symptoms of dementia in Alzheimer’s disease? A systematic review of randomized, placebo-controlled trials of donepezil, rivastigmine and galantamine. Int psychogeriatr, 2009 vol/is 21/5(813-824) Sommer OH et al. Effect of oxcarbazepine in the treatment of agitation and aggression in severe dementia. Dement Geriatr Cogn Disord, 2009 vol/is 27/2(155-163)


of 14

Street JS, Clark WS, Gannon KS et al. Olanzapine treatment of psychotic and behavioral symptoms in patients with Alzheimer disease in nursing care facilities: a double-blind, randomized, placebo-controlled trial. Arch Gen Psychiatry. 2000 Oct;57(10):968-76.

National Institute for Health and Clinical Excellence. Dementia: assessment, management and support for people living with dementia and their carers (NG97). 2018 National Institute for Health and Clinical Excellence. Management of aggression, agitation and behavioural disturbance in dementia: valproate preparations. 2015 National Prescribing Service, The role of antipsychotics in managing BPSD. Prescribing Practice Review 37. 2007. Rainer M, Haushofer M, Pfolz H, Struhal C, Wick W. Quetiapine versus risperidone in elderly patients with behavioural and psychological symptoms of dementia: efficacy, safety and cognitive function. European Psychiatry 2007;22:395–403

Seitz DP, Adunuri N, Gill SS, Gruneir A, Herrmann N, Rochon P. Antidepressants for agitation and psychosis in dementia. Cochrane Database of Systematic Reviews 2011, Issue 2. Art. No.: CD008191. DOI: 10.1002/14651858.CD008191.pub2 Taylor D, Paton C, Kapur S. Maudsley Prescribing Guidelines. 2018 13th Edition. UK Supasitthumrong T et al. Gabapentin and pregabalin to treat aggressivity in dementia: a systematic review and illustrative case report. British Journal of Clinical Pharmacology. Volume 85, Issue 4, pages 690-703. April 2019


of 14

Document Control

Document History

Version Start date

End date Author History

0.1 Nov 2010 AG First draft of new Prescribing Guideline

0.2 Dec 10 CS Multiple changes post MHPF meeting Dec 10 (CS)

0.3 Feb 2011 AG/CS Changes following discussion with Denise Cope & Steven Pearson ( Consultant OPMH Psychiatrist Dorset & Devon respectively)

0.4 Feb 2011 01.03.11 AG/CS Minor corrects/typos and abbreviations. Presented to Mental Health Prescribing Forum for comment

0.5 Feb 2011 07.03.11 CS Changes made post OPMH meeting

1.0 22.03.11 KS Document signed off.

1.1 Mar 13 AG Table of treatment strategies removed and included in Appendix 1 Reference to ‘FACE’ form removed Decision aid for specialist treatment updated Link to standard GP letter added

2.0 Oct 13 KS Document ratified at DTC and signed off.

2.0 Jan 15 CS/KS Standard letter template updated

2.1 Jul 15 JL Updated to include clearer treatments and latest guidance.

3.0 Nov 15 JL Document ratified at Nov DTC and signed off

Jan 18 JBS Review date extended to June 2018

Jun 18 JBS Review date extended to December 2018

3.1 Aug 18 ER Links updated and content edited to reflect changes in NG97. Sections added on depression and insomnia. Latest guidance and trial evidence reviewed.

4.0 Sep 18 JBS Ratified at DTC and signed off

4.1 Mar 19 ER Minor update to pregabalin and gabapentin information

5.0 Apr 19 JBS Ratified at DTC and signed off

5.1 Oct 19 Oct 19 ER Gabapentin and pregabalin listed as approved. This contradicts minutes from DTC. Changed to non-approved and take to DTC for sign off on this.

6.0 Nov 19 JBS Ratified at DTC and signed off

Version Date Issued Author Name / Job Title / Email

1.0 March 2011 Amanda Gulbranson Christopher Sullivan Clinical Effectiveness Lead Lead Clinical Pharmacist [email protected] [email protected]

2.0 September 2013 Amanda Gulbranson Richard Mccollum Clinical Effectiveness Lead Consultant Psychiatrist [email protected] [email protected]

3.0 November 2015 James Lee, Senior Clinical Pharmacist [email protected]

4.0 September 2018 Emily Riddiford, Senior Clinical Pharmacist [email protected]

5.0 April 2019 Emily Riddiford, Senior Clinical Pharmacist [email protected]

6.0 November 2019 Emily Riddiford, Senior Clinical Pharmacist [email protected]

Target Audience/staff groups Clinical staff responsible for the prescribing of treatment for Behavioural and Psychological Symptoms of Dementia.

Ratifying group Drug and Therapeutics Committee

Date Ratified November 2019

Implementation date November 2019

Review date November 2023

mailto:[email protected]

mailto:%20%20%[email protected]







Pharmacological Management of Severe Behavioural ...

Documents

Transcript of Pharmacological Management of Severe Behavioural ...