Prescribing Guideline

Pharmacological Management of Severe Behavioural & Psychological Symptoms of Dementia (BPSD) PG14

Document Control Version

Date Issued

Brief summary of change

1.0

New Prescribing Guideline

Author(s) name/job title/email

Amanda Gulbranson Christopher Sullivan Clinical Effectiveness Lead Lead Clinical Pharmacist [email protected] [email protected] Clinical staff responsible for the prescribing of treatment for Behavioural and Psychological Symptoms of Dementia. 1st March 2011

Target Audience/staff groups Date Approved by Mental Health Prescribing forum Ratifying group Date Ratified Implementation date Review date

Medicines Management Governance Group th 17 March 2011 nd 22 March 2011 March 2013

Document History Version

Start date

End date

Author

History

Nov 2010

AG CS AG/CS

First draft of new Prescribing Guideline Multiple changes post MHPF meeting Dec 10 (CS) Changes following discussion with Denise Cope & Steven Pearson ( Consultant OPMH Psychiatrist Dorset & Devon respectively) Minor corrects/ typos and abbreviations. Presented to Mental Health Prescribing Forum for comment Changes made post OPMH meeting Document signed off.

0.1 0.2 0.3

Dec 10 Feb 2011

0.4

Feb 2011

01.03.11

AG/CS

0.5 1.0

Feb 2011

07.03.11 22.03.11

CS KS

PG 14 – Pharmacological Management of BPSD Approved by Medicines Management Governance Group: March 2011 Review date: March 2013 Page 1 of 11

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: • NICE CG42: Dementia (Nov 2006) • The use of antipsychotic medication for people with dementia: Time for action. (Banerjee 2009: Department of Health)

•

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

Treatment choice and duration 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/ preventing the provision of required care. The presenting neuropsychiatric symptoms include psychosis, agitation, aggression, mood disorder and wandering and are collectively referred to as ‘behavioural and psychological symptoms of dementia’ (BPSD). For people with a diagnosis of dementia, behaviours that challenge are best ‘managed’ by good nursing care, the correct environment and use of ‘ABC’ (antecedents, behaviours and consequences) to try and identify causes and possible triggers for the presenting behaviour (e.g. hunger, pain).

Non-pharmacological approaches must always be considered first (but are beyond the scope of this guideline)

Pharmacological treatment is not a substitute for non-pharmacological approaches and these techniques must always be used concurrently. Where non-pharmacological interventions have failed or are inappropriate, other possible causes (i.e. physical illness) should be eliminated prior to considering an individual trial of medication for the management of BPSD using the Pharmacological treatment Algorithm below.

PG 14 – Pharmacological Management of BPSD Approved by Medicines Management Governance Group: March 2011 Review date: March 2013 Page 2 of 11

Could presenting symptoms be a result of underlying physical cause (including pain)?

YES

YES

Assess, diagnose and provide appropriate treatment

Symptoms resolved? NO

NO Could presenting symptoms be sideeffects of concurrently prescribed medication?

YES

Complete a medication review and rationalise treatment

YES Symptoms resolved?

NO

NO

Could presenting symptoms be caused by underlying depressive illness and/ or anxiety disorder?

YES

Assess, diagnose and provide appropriate treatment (refer to local prescribing guidelines)

Symptoms resolved?

NO NO Consider and implement appropriate nonpharmacological interventions (e.g. environmental changes, psychological therapies, multisensory stimulation, massage, aromatherapy)

YES

Symptoms resolved?

NO

Consider, discuss and provide appropriate pharmacotherapy in accordance with this prescribing guidance (PG14)

YES Symptoms resolved?

NO

YES

No further intervention needed at this time. Continue to provide care for individual in accordance with current care-plan

Individual presents with behaviours that challenge (e.g. agitation, wandering, aggression, tearfulness, sexual disinhibition shouting, hallucinations, delirium) Identify and document target symptoms, severity and level of distress caused to individual (Use suitable assessment tool i.e. Cohen–Mansfield Scale or Neuropsychiatric Inventory )

Review prescribed medication regularly. After a period of 3 months, aim to reduce and stop medication when presenting behaviour has settled. Advise GP of plan to reduce and stop medication if still prescribed medication (after a trial of reduction) on discharge from in-patient unit or community team

Where a medication has been ineffective, always stop it before introducing a subsequent treatment

PG 14 – Pharmacological Management of BPSD Approved by Medicines Management Governance Group: March 2011 Review date: March 2013 Page 3 of 11

Pharmacological Management: The expected benefits must out-weigh the potential risks/side effects of medication for each individual. Pharmacological management of severe BPSD should only be considered if behaviours cause severe distress to the individual and/ or there is immediate risk of harm to other patients or carers. Once a decision has been reached to start medication for the management of BPSD, the available evidence base is insufficient to support specific recommendations on the preferred choice of medication or indeed the order in which different medicines/ different classes of medication should be prescribed. Medication prescribed for the management of BPSD should be considered as an individual therapeutic trail, with the choice of medication based upon an individual risk-benefit analysis. Always “START LOW AND GO SLOW”. Pharmacological treatment strategies for BPSD (must be used in conjunction with Appendix 1): (X= Not recommended √= May be considered) Medication

People with mild, moderate or severe Alzheimer’s disease, mixed dementias or Dementia with Lewy Bodies (DLB) with severe non-cognitive symptoms (psychosis and/ or agitated behaviour causing significant distress and/ or risk of physical harm/ violence to self and/ or others)

People with vascular dementia with severe noncognitive symptoms (psychosis and/ or agitated behaviour causing significant distress and/ or risk of physical harm/ violence to self and/ or others)

NB Wandering behaviour does NOT respond to medication Antipsychotic (Risperidone licensed for 6 weeks treatment of aggression)

√ (AChEI recommended first line option for people with DLB)

√

Acetyl cholinesterase inhibitor (AChEIs)

√ Preferred treatment for DLB √ Consider when antipsychotic drugs inappropriate or have been ineffective

X

Memantine

√ Consider when AChEIs inappropriate or have been ineffective

Benzodiazepines

Antidepressants Mood stablisers (Carbamazepine & Valproate)

X (Insufficient evidence to recommend)

√ For acute short term use only.

Caution: Increase risk of falls Prescribe if an underlying depressive illness and/or anxiety disorder is suspected or confirmed ONLY consider when antipsychotic/ AChEIs /drugs/ memantine inappropriate or have been ineffective

X

PG 14 – Pharmacological Management of BPSD Approved by Medicines Management Governance Group: March 2011 Review date: March 2013 Page 4 of 11

Initiation of medication for BPSD (by, or on the recommendation from, a specialist): • 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 and/ or offered to the individual (as appropriate) and level of effectiveness. • Complete baseline physical monitoring, appropriate to the individual drug prescribed. • 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 (& person responsible for completion). Where necessary complete a FACE form documenting all relevant discussions around choice of treatment. • It is recognised that prescribing for BPSD will generally arise from a ‘best interest decision’. The prescriber must ensure that appropriate assessment and discussion to support this is documented in the notes. 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. During 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 in the notes • Monitor for emergence of side effects associated with mediation. Discuss with individual and/ or carer and review treatment if side effects intolerable or severe. (NB people with DLB have increased sensitivity to antipsychotic side effects, including acute & severe physical deterioration- monitor carefully). • Ensure on-going physical monitoring is carried out appropriate to the medication prescribed. • 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: • Attempt to reduce and stop medication as soon as possible after presenting target symptoms have settled for a period of 3 months (treatment should be regularly reviewed; at least every 3 months or according to clinical need) • Reduce & stop medication after 4 weeks if no positive response to treatment observed (or if presentation deteriorates) 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 PG 14 – Pharmacological Management of BPSD Approved by Medicines Management Governance Group: March 2011 Review date: March 2013 Page 5 of 11

the DPT Policy for Rapid Tranquillisation and DPT Clinical Protocol 11. This protocol states antipsychotic medication is not suitable for use in rapid tranquilisation in this population. Communication of information on transfer of care: • After presenting symptoms have settled for a period of 3 months, an attempt should be made to reduce and stop the medication prescribed BPSD. • In some circumstances 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 DPT prescriber (Consultant or Associate specialist) will: • Contact individual’s GP to request that they accept on-going responsibility for prescribing • 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). • Include a summary of the information documented in the clinical notes regarding target symptoms and choice of medication and rationale for treatment. User-friendly resources Patient decision aid (intended to assist healthcare professionals in consultations with people with dementia and their family/carers) when treatment with antipsychotic drugs is being considered for BPSD: http://www.npci.org.uk/therapeutics/cns/dementia/resources/pda_dementia_antipsychotics.pdf Leaflets for patients/family/carers on dementia can be found on the Alzheimer’s Society website: www.alzheimers.org.uk/Facts_about_dementia/factsheets.htm)

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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 base generally based on Alzheimer’s dementia rather than vascular/ stroke related, frontotemporal lobe, mixed or DLB), however increasingly there is information which questions their safety. The table below is designed to provide you with a summary 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. Please refer to the BNF and product data sheet for more detailed prescribing and administration advice. Place in therapy:

I

Strong evidence from at least one published systematic review of multiple well-designed randomised controlled trials

II

Strong evidence from at least one published properly designed randomised controlled trial of appropriate size and in an appropriate clinical setting

III

Evidence from published well-designed trials without randomisation, single group pre-post, cohort, time series or matched case-controlled studies

IV

Evidence from well-designed non-experimental studies from more than one centre or research group

V

Opinions of respected authorities, based on clinical evidence, descriptive studies or reports of expert consensus committees

EVIDENCE

Safe/ W ell tolerated Less w ell to lerate d / Safety con cern

T O LER AB IL IT Y/ SAF ET Y

Weak (III-V)

Strong (I &II)

C

D

A

B

Intervention

Rationale Place in therapy Approved for (Doses stated from published studies) use in DPT? ANTIPSYCHOTICS Evidence of efficacy in BPSD, though limited, is greatest for risperidone and olanzapine, however, clinical efficacy is at best only modest and this must be balanced against elevated risk of cerebrovascular adverse events, mortality, upper respiratory infections, oedema, extrapyramidal symptoms and an increase in overall mortality rate which 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). Summary of risks and benefits for treating1000 people with dementia for BPSD over a 12 week period with an atypical 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 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 that 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 (Doses stated from published studies)

Place in therapy

Approved for use in

PG 14 – Pharmacological Management of BPSD Approved by Medicines Management Governance Group: March 2011 Review date: March 2013 Page 7 of 11

Risperidone

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

B

DPT? YES

Significant improvement in aggression & psychosis compared to placebo Olanzapine

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

B

(Off-license use if prescribed for dementia/ BPSD) Amisulpride

D

200mg/ daily Preliminary observation suggests that amisulpride may be useful to control agitation and disruptive behaviours. RCT (open prospective) demonstrated equivalent efficacy to risperidone. Only small open-label studies available. Evidence weak. (Off-license use if prescribed for dementia/ BPSD)

Aripiprazole

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

D

(Off-license use if prescribed for dementia/ BPSD)

Quetiapine

50-200mg/ day 200mg/ day reported superior to placebo for agitation where 100mg/ day not superior to placebo

D

Showed harm compared with placebo at 26 weeks for severe impairment battery (SIB) (Off-license use if prescribed for dementia/ BPSD) First Generation antipsychotics (i.e. chlorpromazine, haloperidol & promazine)

Possible improvement in psychosis and psychomotor agitation, but increased frequency of side effects such as extra-pyramidal side effects ( with high-potency drugs) and postural hypotension and anticholinergic side effects ( with low potency drugs) in addition to increased risk of CVE and increased mortality associated with antipsychotics results in potential risks out-weighting benefits. (Off-license use if prescribed for dementia/ BPSD)

ACETYL-CHOLINESTERASE INHIBITORS Intervention Rationale (Doses stated from published studies)

D Increased mortality risk ≥ atypical (second generation) antipsychotics

Place in therapy

YES 2nd line option if risperidone not appropriate/ not tolerated YES Treatment option if risperidone/ olanzapine not appropriate/ not tolerated YES Treatment option if risperidone/ olanzapine not appropriate/ not tolerated YES Treatment option if risperidone/ olanzapine not appropriate/ not tolerated NOT FOR BPSD

Approved for use in DPT?

PG 14 – Pharmacological Management of BPSD Approved by Medicines Management Governance Group: March 2011 Review date: March 2013 Page 8 of 11

Rivastigmine

C

YES

10mg/ day Evidence equivocal. Feldham et al (2001) reported statistically significant improvement with donepezil, whereas several other studies have reported no significant difference between treatment arms. Only 2 studies methodologically adequate & designed to evaluation impact on behavioural symptoms; (1)Holmes et al reported deterioration in placebo group and improvement in donepezil group (NPI)- statistically significant difference (p=0.02) with ITT analysis but not in observed case studies. (2)Tariot et al reported improvement in both groups (NPI) relative to baseline, but no clinical/ statistical difference between donepezil & placebo groups. (Off-license use if prescribed for BPSD)

C

YES

16-24mg/ day Evidence equivocal 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 of Tariot et al (2000) reported slight improvement (NPI) observed with galantamine (p=0.04) at 16 & 24mg/ day but not 8mg/d (n=978) (Off-license use if prescribed for BPSD)

C

YES

C

YES (NOT FIRST LINE)

Place in therapy

Approved for use in DPT? ONLY

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) (Off-license use if prescribed for BPSD)

Donepezil

Donepezil cont.

Galantamine

NMDA ANTAGONIST Memantine 10mg bd Systemic meta- analysis suggested that memantine decreases NPI scores and may have a role in BPSD (reducing agitation/ aggression) but effect size small Maidment et al (2008). 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. (Off-license use if prescribed for BPSD)

ANTIDEPRESSANTS Intervention Rationale (Doses stated from published studies) Mirtazapine Consider where co-morbid depression present and

Treatment of

PG 14 – Pharmacological Management of BPSD Approved by Medicines Management Governance Group: March 2011 Review date: March 2013 Page 9 of 11

SSRI ineffective or not tolerated. Consider as first line where increased sedative effect may be therapeutically beneficial. 15-45mg nocte Lack of evidence to demonstrate efficacy in BPSD

depression onlyrefer to Clinical Guidelines for Unipolar depression

(Off-license use if prescribed for dementia/ BPSD) Citalopram (SSRI)

Consider where co-morbid depression +/- anxiety spectrum disorders present. 10-20mg daily

Treatment of depression/ anxiety disorders onlyrefer to Clinical Guidelines for Unipolar depression/ anxiety

Lack of evidence to demonstrate efficacy of SSRIs in BPSD (Off-license use if prescribed for dementia/ BPSD) Trazadone

Consider where co-morbid depression present and SSRI/ mirtazapine ineffective or not tolerated. Consider where increased sedative effect may be therapeutically beneficial. Limited evidence for efficacy of antidepressants for BPSD (as opposed to treatment of co-morbid depression). Trazadone most widely used antidepressant prescribed for people presenting with BPSD despite lack of robust evidence to support efficacy.

(Off-license use if prescribed for dementia/ BPSD) BENZODIAZEPINES Diazepam 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 T1/2 ~32 hours (21-50) longer in older adults No systemic reviews of RCTs examining the usefulness of benzodiazepines in the management symptoms associated with dementia (including anxiety) were identified. NB 5mg diazepam ~equiv to 0.5mg lorazepam (Off-license use if prescribed for dementia/ BPSD) Lorazepam 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 T1/2 ~12 hours (8-25) Similar in older adults No systemic reviews of RCTs examining the usefulness of benzodiazepines in the management symptoms associated with dementia (including anxiety) were identified (Off-license use if prescribed for dementia/ BPSD) ANTI-CONVULSANTS: Intervention Rationale (Doses stated from published studies) Valproate Despite positive treatment responses documented in case reports, retrospective chart reviews and open-label studies, the existing d/b, p/c, RCTs do

Treatment of depression onlyrefer to Clinical Guidelines for Unipolar depression

IF BPSD THOUGHT TO BE PART OF DEPRESSIVE ILLNESS ONLY IF BPSD THOUGHT TO BE PART OF DEPRESSIVE ILLNESS

ONLY IF BPSD THOUGHT TO BE PART OF DEPRESSIVE ILLNESS

D

Paradoxical disinhibition may occur May cause/ hasten cognitive decline Contribute to falls and hip fractures Accumulation leading to excessive sedation/ adverse effects and/ or tolerance over time

Place in therapy D GI side effects

YES ONLY for short term use only for acute & severe distress and/ or where sedation is required

Approved for use in DPT? YES (NOT FIRST LINE)

PG 14 – Pharmacological Management of BPSD Approved by Medicines Management Governance Group: March 2011 Review date: March 2013 Page 10 of 11

not support the proposal that valproate is effective in the management of agitation, aggression or other BPSD in people with dementia.

Carbamazepine

(Off-license use if prescribed for dementia/ BPSD) 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. (Off-license use if prescribed for dementia/ BPSD)

Impaired cognition Hepatotoxicitymonitor liver function before & during treatment D Impairment of balance & increased risk of falls Drug interactions Impaired cognition Blood dyscraisias Hyponatraemia Hepatic dysfunction Serious skin reactions

YES (NOT FIRST LINE)

The Trust supports the use of Maudsley Prescribing Guidelines (current edition) as an evidenced based prescribing resource for mental health specialists, however clinicians must be aware that these guidelines contain prescribing recommendations not supported by local healthcare community. (Link with Athens password: http://lib.myilibrary.com/Browse/open.asp?ID=231236)

PG 14 – Pharmacological Management of BPSD Approved by Medicines Management Governance Group: March 2011 Review date: March 2013 Page 11 of 11