formulary and clinical guideline document · mixed dementia should be managed according to what is...

Mersey Care Clinical Guideline / Formulary Document Updated: Jan 2019

Dementia Next Review: Jan 2021 1 |

Clinical Guideline / Formulary Document Pharmacy Department Medicines Management Services

DEMENTIA

Pharmacological Treatment of Alzheimer’s disease

The three acetylcholinesterase (AChE) inhibitors (donepezil, galantamine and rivastigmine) are recommended options for mild to moderate Alzheimer’s disease.

Memantine is an option for moderate Alzheimer’s disease in people who are intolerant of or have a contraindication to AChE inhibitors or for severe Alzheimer’s disease.

Prescribers should only start treatment with donepezil, galantamine, rivastigmine or memantine on the advice of a clinician who has the necessary knowledge and skills. This could include: secondary care medical specialists such as psychiatrists, geriatricians and neurologists other healthcare professionals such as GPs, nurse consultants and advanced nurse practitioners with specialist expertise in diagnosing and treating Alzheimer's disease.

Any relevant physical, sensory or learning disabilities, or communication difficulties should be considered to ensure equality of access to treatment for service users from different ethnic groups and cultural backgrounds.

Prescribers should discuss treatment options, benefits and risks with the service user and/or carer and seek carers’ views on the service user’s condition at baseline.

If prescribing an AChE inhibitor, treatment should normally be started with a drug with the lowest acquisition cost (taking into account required daily dose and the price per dose once shared care has started). However, an alternative AChE inhibitor could be prescribed if considered appropriate taking into account the adverse effect profile, expectations around adherence, medical comorbidity, the possibility of drug interactions, pharmaceutical and dosing profiles.

Do not stop AChE inhibitors in people with Alzheimer's disease because of disease severity alone.

For people with an established diagnosis of Alzheimer's disease who are already taking an AChE inhibitor:

o consider memantine in addition to an AChE inhibitor if they have moderate disease

o offer memantine in addition to an AChE inhibitor if they have severe disease When using pharmacological treatments in dementia, low initial doses and gradual dose

increments are necessary. Monitor closely for any adverse drug reactions and review treatment if side effects are

severe or intolerable (see Appendix 1). Further information on contraindications, cautions, interactions and side effects is available from manufacturer summaries of product characteristics available at: http://emc.medicines.org.uk, or the BNF.

Carer views on the service user’s condition at follow up should be considered. The decision whether to continue treatment with AChE inhibitors is highly patient-

specific. NICE advises that treatment should be continued only when it is considered to be having a worthwhile effect on cognitive, global, functional and behavioural symptoms. Carer views on the service user’s condition at follow up should be considered.

Service users who continue on pharmacological treatments for dementia should be reviewed regularly using cognitive, global, functional and behavioural assessment.

Prescribing, supply and treatment review should follow locally agreed arrangements. See Pan Mersey website for more information.

http://emc.medicines.org.uk/

http://formulary.panmerseyapc.nhs.uk/chaptersSub.asp?FormularySectionID=4



Investigations / Screening

Investigations are usually done in primary care, for suspected dementia. They include: Full blood count, ESR, urea and electrolytes, calcium, glucose, liver function tests,

thyroid function tests; serum vitamin B12/folate levels, and iron studies, if indicated Other investigations include - midstream urine culture, chest x-ray, brain imaging and

electrocardiography (ECG) —if cardiovascular problems suspected

Other Dementias

There is limited evidence on the treatment of non-Alzheimer’s dementias. There is no good evidence of efficacy of acetylcholinesterase inhibitors or memantine in

mild cognitive impairment. Mixed dementia should be managed according to what is considered the predominant

cause of the dementia. Only consider AChE inhibitors or memantine for people with vascular dementia if they

have suspected comorbid Alzheimer's disease, Parkinson's disease dementia or dementia with Lewy bodies.

In Lewy body dementia [DLB]: o Offer donepezil or rivastigmine to people with mild to moderate DLB. o Only consider galantamine for people with mild to moderate DLB if donepezil and

rivastigmine are not tolerated. o Consider donepezil or rivastigmine for people with severe DLB. o Consider memantine for people with dementia with Lewy bodies if AChE

inhibitors are not tolerated or are contraindicated. Do not offer AChE inhibitors or memantine to people with frontotemporal dementia. In Parkinson’s Disease Dementia [PDD]:

o Offer an AChE inhibitor for people with mild or moderate PDD. o Consider an AChE inhibitor for people with severe PDD. o Consider memantine for people with PDD, only if cholinesterase inhibitors are

not tolerated or are contraindicated. Avoid use of antipsychotics in people with PDD or DLB. Antipsychotics can worsen the

motor features of the condition, and in some cases cause severe antipsychotic sensitivity reactions.

Behavioural and Psychological Symptoms of Dementia (BPSD)

Behavioural and psychological symptoms of dementia include a range of non-cognitive symptoms, such as apathy, anxiety, depression, agitation, aggression, delusions and hallucinations, wandering, incontinence, altered eating habits, sexual disinhibition, shouting, hoarding, repeated questioning and sleep disturbances. Antipsychotics are sometimes prescribed for BPSD but produce only limited benefits and are associated with an increased risk of stroke and mortality, as well as other serious adverse events such as sedation, extrapyramidal side effects, dehydration, falls, chest infections and accelerated cognitive decline. Reducing inappropriate prescribing of antipsychotic medication for people with dementia is an urgent national priority. In cases of dementia associated with severe behavioural disturbance that requires urgent treatment (if violence, aggression and extreme agitation threaten the safety of the patient or others), an antipsychotic drug or a benzodiazepine may be given. The management of BPSD is discussed further below.



Driving

For advice on DRIVING and health conditions, see DVLA.

It is illegal to drive if medication impairs driving ability. See Drugs and driving: the law.

It is an offence for a person to drive with certain levels of some medications in the blood. See https://www.gov.uk/government/collections/drug-driving#table-of-drugs-and-limits for up to date information.

A guide to support medical professionals in assessing fitness to drive can be found at https://www.gov.uk/government/publications/assessing-fitness-to-drive-a-guide-for-medical-professionals

Relevant NICE Guidance

NICE guideline NG97. Dementia: assessment, management and support for people living with dementia and their carers. Published date: June 2018. https://www.nice.org.uk/guidance/ng97

NICE TA217: Donepezil, galantamine, rivastigmine and memantine for the treatment of

Alzheimer's disease. March 2011. Last updated: 20 June 2018. Available at:

http://www.nice.org.uk/guidance/ta217

NICE Dementia quality standard [QS1]. http://www.nice.org.uk/guidance/qs1. June 2010.

Related NICE quality standards http://www.nice.org.uk/guidance/qs30

http://www.nice.org.uk/guidance/qs50

Dementia Prescribing Support Documentation for Primary Care

Pan Mersey Area Prescribing Committee, DRUGS FOR DEMENTIA: INFORMATION

FOR PRIMARY CARE

https://www.panmerseyapc.nhs.uk/media/2091/dementia.pdf

Pan Mersey Area Prescribing Committee, Request by Specialist Clinician to the patient’s

GP to discharge a patient from secondary care services

https://www.panmerseyapc.nhs.uk/media/1222/dementia_discharge_201605_g31_v010

1.pdf

Pan Mersey Area Prescribing Committee, Request by Specialist Clinician to the patient’s

GP to take over the prescribing from secondary care services

https://www.panmerseyapc.nhs.uk/media/1223/dementia_prescribing_201605_g31_v01

01.pdf

https://www.gov.uk/health-conditions-and-driving

https://www.gov.uk/drug-driving-law

https://www.gov.uk/government/collections/drug-driving#table-of-drugs-and-limits

https://www.gov.uk/government/publications/assessing-fitness-to-drive-a-guide-for-medical-professionals

https://www.gov.uk/government/publications/assessing-fitness-to-drive-a-guide-for-medical-professionals

https://www.nice.org.uk/guidance/ng97

http://www.nice.org.uk/guidance/ta217







https://www.panmerseyapc.nhs.uk/media/1222/dementia_discharge_201605_g31_v0101.pdf




https://www.panmerseyapc.nhs.uk/media/1223/dementia_prescribing_201605_g31_v0101.pdf






Alzheimer’s Disease - Pharmacological Management of Cognitive Symptoms

First Line: Relative Cost Notes

Acetylcholinesterase Inhibitors (AChEIs)

£-£££

Only dementia specialists in consultation with service user/carer should initiate treatment. Appropriate AChEI should be selected following consideration of cost, adverse effects, drug interactions, other conditions, expectations around concordance, and dosing profiles. Switching between agents may considered in cases of non-response or intolerance Continue AChEI only if benefits on cognitive, global, functional and behavioural symptoms

Donepezil Tablets Brand Orodispersible tablets Oral solution

£ £££ ££-£££ ££

Both 5mg and 10mg are effective doses. Elimination half-life is long at about 70 hours

Galantamine

Tabs Brand Oral solution

££ ££-£££ ££££

Oral solution and modified release preparations are available. Reductions in dose may be necessary in hepatic or renal impairment

Rivastigmine Caps Brand Liquid Patches

£ ££ £££ ££-£££

Oral solution and patch also available; also licenced for mild to moderately severe dementia in idiopathic Parkinson's disease; Gastrointestinal side effects appear more frequent with rivastigmine. Patch may be appropriate in those unable to tolerate side effects of oral rivastigmine but application site reactions (erythema, pruritus, rash, vesicles) can occur

Second Line: Relative Cost Notes

Alternative AChEI

£-£££ If initial AChEI not tolerated or not effective, switch to another AChEI not already tried.

Memantine

Tabs Branded Liquid

£ ££ ££-£££

Recommended for moderate Alzheimer’s disease in people who are intolerant of or have a contraindication to AChEIs or in severe Alzheimer’s disease Only specialists in the care of people with dementia (in consultation with service user/carer) should initiate treatment.



Alzheimer’s Disease - Pharmacological Management of Cognitive Symptoms -Continued

Third Line: Relative Cost Notes

Memantine + AChEI £-£££ There is growing evidence of additional clinical efficacy. Consultant initiation only. Monitoring and continual review of clinical benefit essential.

Not Recommended Relative Cost Notes

Vitamin E Ginkgo biloba Souvenaid

££ Limited data available - difficult to determine evidence of clinical benefit

Antidiabetic medication Antihypertensives Statins Non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin.

£-£££ NICE advises not to offer these medication to slow the progress of Alzheimer's disease, except as part of a randomised controlled trial:



Other Dementias - Pharmacological Management of Cognitive Symptoms

Mild Cognitive Impairment

Relative Cost Notes

AChEIs Memantine

£-£££

There is no good evidence of efficacy of acetylcholinesterase inhibitors or memantine in mild cognitive impairment.

Vascular Dementia Relative Cost Notes

AChEIs Memantine

£-£££ £-£££

AChEIs and memantine are not licensed for the treatment of vascular dementia and should not be routinely prescribed for cognitive decline in vascular dementia

Specialists may consider AChE inhibitors or memantine for people with vascular dementia if they have suspected comorbid Alzheimer's disease, Parkinson's disease dementia or dementia with Lewy bodies.

DLB Relative Cost Notes

AChEIs Memantine

£-£££ £-£££

Offer donepezil or rivastigmine to people with mild to moderate DLB.

Only consider galantamine for people with mild to moderate DLB if donepezil and rivastigmine are not tolerated.

Consider donepezil or rivastigmine for people with severe DLB.

Consider memantine for people with dementia with Lewy bodies if AChE inhibitors are not tolerated or are contraindicated.

PDD Relative Cost Notes

AChEIs Memantine

£-£££ £-£££

Rivastigmine is the only AChEI licensed for symptomatic treatment of mild to moderately severe dementia in idiopathic Parkinson's disease.

Offer an AChE inhibitor for people with mild or moderate PDD.

Consider an AChE inhibitor for people with severe PDD.

Consider memantine for people with PDD, only if cholinesterase inhibitors are not tolerated or are contraindicated.

Mixed Dementia Relative Cost Notes

AChEIs Memantine

£-£££ £-£££

NICE advises that people with mixed dementia should be managed according to what is considered the predominant cause of their dementia.



Pharmacological Treatments for Alzheimer’s Disease

Drug

Dose Contraindications and Cautions Key adverse effects and Interactions

Donepezil (Aricept Eisai/Pfizer and non-proprietary formulation) - 5mg and 10mg film coated tablets - 5mg and 10mg orodispersible tablets 1mg/1ml Oral solution Licenced Indication Symptomatic treatment of mild to moderately severe Alzheimer's dementia

Initially 5mg once daily at bedtime; increased after 1 month to a maximum of 10 mg once daily, if appropriate and tolerated **Lower doses required in those with renal and hepatic disease; or Slower titration, if initial side effects, as follows: Donepezil: 5mg OD for 6weeks; then double to 10mg OD for 6 weeks.

Contra-indications - Hypersensitivity to donepezil - Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption Precautions Cardiovascular conditions – e.g. sick sinus syndrome, sinoatrial or atrioventricular block, or other conduction defects - cardiac monitoring required. Gastrointestinal – e.g ulcers, concurrent NSAIDs, undiagnosed nausea and vomiting; Genitourinary – Risk of bladder outflow obstructions. Neurological – Cerebrovascular disease; convulsions Pulmonary Conditions – e.g. asthma or chronic obstructive pulmonary disease.

Adverse effects - Very Common: nausea diarrhoea hallucinations headache. - Common: common cold, anorexia, agitation, aggressive behaviour, dizziness, syncope, insomnia, abnormal dreams and nightmares, vomiting abdominal disturbances, muscle cramps, rash, pruritus, fatigue, urinary incontinence, pain. - Uncommon: seizures, bradycardia, gastro-intestinal haemorrhage, gastric and duodenal ulcers. - Rare sinoatrial block, AV block, hepatitis, extrapyramidal symptoms; potential for bladder outflow obstruction, rhabdomyolysis and neuroleptic malignant syndrome. Pharmacokinetic Interactions -Ketoconazole, quinidine, itraconazole and erythromycin, and CYP2D6 inhibitors, such as quinidine, fluoxetine, fluvoxamine, and paroxetine could inhibit the metabolism of donepezil – Increased side effects possible - Enzyme inducers, such as rifampicin, phenytoin, carbamazepine and alcohol may reduce the levels of donepezil - Can interact with concomitant inhibitors of acetylcholinesterase, agonists or antagonists of the cholinergic system - avoid. - Beta blockers that significantly reduce the heart rate and can cause bradycardia and hypotension. - Antipsychotics, increased risk of NMS.




Drug

Dose Contraindications and Cautions Key adverse effects and Interactions

Galantamine (Reminyl, Shire and non-proprietary) - 8mg and 12mg tablets - 4mg/mL oral solution - 8mg, 16mg and 24mg modified-release capsules Licenced Indication Symptomatic treatment of mild to moderately severe dementia of the Alzheimer type.

Modified release capsules Initially 8mg once daily for 4 weeks; increased to 16mg once daily for at least 4 weeks. Maintenance treatment 16–24mg once daily according to clinical benefit and tolerability Tablet and liquid preparation Initially 4 mg twice daily for 4 weeks increased to 8 mg twice daily for 4 weeks; maintenance 8–12 mg twice daily Hepatic impairment - For immediate-release preparations in moderate impairment, initially 4 mg once daily (preferably in the morning) for at least 7 days, then 4 mg twice daily for at least 4 weeks; max. 8 mg twice daily; - For modified-release preparations in moderate impairment, initially 8 mg on alternate days (preferably in the morning) for 7 days, then 8 mg once daily for 4 weeks; max. 16 mg daily;

Contra-indications - Hypersensitivity to galantamine or to any of the excipients. - severe renal impairment - Severe hepatic impairment Precautions Genitourinary – risk of bladder outflow obstructions Cardiac disorders - 'sick sinus syndrome' or other supraventricular cardiac conduction disturbances -Use with medicinal products that significantly reduce heart rate concomitantly, such as digoxin and beta blockers -Uncorrected electrolyte disturbance. Patients with/or at risk of developing cardiovascular diseases. Gastrointestinal - peptic ulcers; concurrent non-steroidal anti-inflammatory drugs - Gastrointestinal obstruction or recovering from gastrointestinal surgery Neurological - may worsen Parkinsonian symptoms; has potential to cause seizures. Respiratory - history of severe asthma or obstructive pulmonary disease or active pulmonary infections.

Adverse effects - Very Common: vomiting and nausea. - Common: anorexia, decreased appetite (weight loss), hallucinations, depression, syncope, dizziness, tremor, headache, somnolence, lethargy, bradycardia, hypertension, abdominal pain, diarrhoea, dyspepsia, sweating, muscle spasm, asthenia and falls. - Uncommon: dehydration, visual and auditory hallucinations, paraesthesia, hypersomnia, blurred vision, tinnitus, hypotension, flushing, muscular weakness, hepatic enzymes increased, retching, first-degree AV block, sinus bradycardia, palpitations, supraventricular extrasystoles. - Rare: hepatitis, exacerbation of Parkinson’s disease, seizures and serious skin reactions (Stevens-Johnson syndrome and acute generalized exanthematous pustulosis). Interactions - Food slows the absorption rate but not extent but food reduces side effects -Ketoconazole, quinidine, itraconazole and erythromycin, and quinidine, fluoxetine, fluvoxamine, and paroxetine could inhibit the metabolism of donepezil – Increased side effects possible - Do not give with other cholinomimetics (e.g. donepezil, neostigmine, pyridostigmine, rivastigmine) - can antagonise the effect of anticholinergics - Interaction possible with drugs that significantly reduce the heart rate such as digoxin, beta-blockers, certain calcium-channel blockers and amiodarone. Caution with drugs that can cause torsades de pointes




Drug

Dose Contraindications and Cautions

Key adverse effects and Interactions

Rivastigmine (Exelon, Novartis and non-proprietary) - 1.5mg, 3mg, 4.5mg and 6mg capsules - 2mg/mL oral solution - 4.6mg/24 hours, 9.5mg/24 hours and 13.3mg/24 hours patches See BNF for dose equivalences and conversions Licenced Indications - Symptomatic treatment of mild to moderately severe Alzheimer's dementia. - Symptomatic treatment of mild to moderately severe dementia in patients with idiopathic Parkinson's disease (oral formulations).

Capsules and oral solution Initially 1.5mg twice daily, with morning and evening meals ; may be increased in steps of 1.5mg twice daily at intervals of at least 2 weeks according to tolerance up to a maximum dose of 6mg twice daily Patches Initially a 4.6mg patch per day. This can be increased to a 9.5-mg patch per day after at least 4 weeks. After a further 6 months if well tolerated and cognitive deterioration or functional decline are demonstrated, the dose can be increased to 13.3 mg/24 hours patch daily Replace patch with a new one after 24 hours If treatment is interrupted for more than several days, re-initiate with 4.6 mg/24 h patch or Slower titration, if initial side effects, as follows: Rivastigmine: 1.5 mg bd for 4 weeks, followed by 1.5mg – 3 mg for 4 weeks and finally 3 mg bd for 4 weeks

Contraindications - Hypersensitivity to the active substance, other carbamate derivatives or to any of the excipients used in the formulation, Previous allergic contact dermatitis with rivastigmine patch - Severe liver impairment. Precautions Gastrointestinal - ulcers or history of ulcers. It may cause increased gastric acid secretions. Cardiovascular - in patients with sick sinus syndrome or conduction defects (sinoatrial block, atrio-ventricular block) Respiratory - history of asthma or obstructive pulmonary disease. Genitourinary – urinary obstruction; risk of bladder outflow obstructions Neurological - cerebrovascular disease; seizures One of the excipients in Exelon oral solution is sodium benzoate. Benzoic acid is a mild irritant to the skin, eyes and mucous membrane.

Adverse effects - Very Common: anorexia, dizziness, nausea, vomiting, diarrhoea, malaise, restlessness, fatigue, - Common: confusion, agitation, headache, somnolence, tremor, abdominal pain, sweating - Uncommon: insomnia, depression, syncope, weight loss (monitor body weight) - Rare: seizures, angina pectoris, gastric and duodenal ulcers, rash, - Very rare: urinary infection, hallucinations, extrapyramidal symptoms (and worsening of Parkinson’s disease), bradycardia, atrial fibrillation, AV block, hypertension, gastro-intestinal haemorrhage, pancreatitis, Application site skin reactions with patch (e.g. erythema, application site pruritus, application site oedema, application site dermatitis, application site irritation), asthenic conditions (e.g. fatigue, asthenia), pyrexia, weight decreased Note -Adverse reactions may respond to omitting one or more doses or dose reduction -Transdermal patches may be less likely to cause gastro-intestinal disturbance Interactions - Caution is recommended when selecting anaesthetic agents. - Should not be given concomitantly with other cholinomimetic - Might interfere with the activity of anticholinergic medicinal products




Drug

Dose Contraindications and Cautions

Key adverse effects and Interactions

Memantine (Ebixa, Lundbeck and non-proprietary) 5mg, 10mg, 15mg, 20mg - Treatment initiation pack - tablets - orodispersible tablets - soluble tablets 5mg/0.5ml (10mg/mL) - oral solution Licenced Indications Treatment of patients with moderate to severe Alzheimer's disease.

Initially 5mg once daily and then increased in steps of 5mg at weekly intervals to a maximum of 20mg daily; max 20mg/day Can be taken with or without food Beware of the mechanism by which each product delivers the required dose. There is a risk of confusion between doses delivered by the pump device compared with doses delivered by the dropper

Contraindications - Hypersensitivity to the active substance or to any of the excipients Precautions -Epilepsy or history of convulsions or predisposing factors for epilepsy - Recent myocardial infarction, uncompensated congestive heart failure (NYHA III-IV), or uncontrolled hypertension. - Severe hepatic impairment - Renal impairment when eGFR less than 5 mL/minute/1.73 m

2

- Lactation and pregnancy. The oral solution contains sorbitol.

Adverse effects - Common: drug hypersensitivity, somnolence, dizziness, hypertension, constipation, dyspnoea, headache, - Uncommon: fatigue, fungal infection, confusion, hallucinations, gait abnormal, cardiac failure, Venous thrombosis / thromboembolism - Very rare: seizures, post-marketing reports of depression, suicidal ideation and suicide. Interactions ** Amantadine, ketamine, or dextromethorphan may increase both the incidence and severity of adverse effects and should be avoided. - Memantine may alter the effects of the antispasmodics baclofen and dantrolene. - The effects of L-dopa, dopaminergic agonists, and anticholinergics may be enhanced by concomitant treatment with memantine - The clearance of memantine is reduced under alkaline urine conditions. Drastic changes in diet and drugs such as carbonic anhydrase inhibitors and sodium bicarbonate should be used with caution and careful monitoring. - Possible international normalized ratio (INR) increases with warfarin

For further information on contraindications, cautions, drug interactions, and adverse effects, see the electronic Medicines Compendium (eMC) (http://emc.medicines.org.uk), or the British National Formulary (BNF) (https://www.evidence.nhs.uk/formulary/bnf/current).

http://emc.medicines.org.uk/

https://www.evidence.nhs.uk/formulary/bnf/current



Managing BPSD (in line with NICE Dementia guideline NG97)

Conduct a comprehensive assessment to identify factors that generate or aggravate BPSD. These factors can include physical health problems, infection, pain or discomfort, alcohol, constipation, depression, sleep disturbance, medication side effects, psychosocial factors, environment or personal beliefs.

Identify factors that improve BPSD e.g. music, dance, aromatherapy, cognitive stimulation, massage, multisensory stimulation, exercise, creative therapies, animal assisted therapies, environment.

Involve the person/carers/staff in developing a person-centred care plan to address individual needs. Record the plan in the case notes and review it regularly.

Challenging behaviours may be a way of communicating an unmet need.

Treat any underlying contributory problems (e.g. infection, pain, drug side effects)

Be alert for and treat any coexisting emotional disorders (e.g. depression and/or anxiety and sleep disturbances)

For mild to moderate BPSD, watchful waiting or non-pharmacological interventions (psychological, social, behavioural & environmental) should be tried first. Consider available options and tailor activities to individual preferences, skills and abilities.

The causes of any disturbed behaviour in patients with dementia should be reviewed and managed before initiating pharmacologic treatment.

Pharmacological treatment should only be initiated by dementia specialists: Consultant Psychiatrists, Neurologists, Psycho-geriatricians, Geriatricians and their Specialist Registrars, Non-Medical Prescribers and GPs with a special interest in dementia; documenting the reasons (target symptoms) for use of any pharmacological interventions and discuss risks and benefits.

Pharmacological interventions, often in conjunction with non-pharmacological interventions, should only be used in cases of severe distress or when there is immediate risk of harm to the service user and/or others.

Be aware that there is limited evidence for pharmacological management of BPSD.

Avoid prescribing medications with anticholinergic effects because they can worsen cognition.

Starting doses of medication should be low and titration gradual. The lowest possible effective dose should be used for the shortest possible time.

Dementia specialists should consider antipsychotics for BPSD only if there are severe non-cognitive symptoms (psychosis and/or agitated behaviour causing significant distress) or immediate risk of harm to the person with dementia or others.

The decision to prescribe antipsychotics should be taken on an individual basis after careful consideration of cerebrovascular risk factors and full discussion with the service user, relatives and/or carers about antipsychotic risks and benefits

Prescriptions for antipsychotics should be time limited and reviewed against target symptoms and side effects.

Monitor for benefits and side effects every 6 weeks or according to clinical need.

At each review, consider reducing or gradual withdrawal of antipsychotic treatment

Risperidone and haloperidol are licenced for the short-term treatment (up to 6 weeks) of persistent aggression with moderate to severe Alzheimer's dementia unresponsive to non-pharmacological approaches and when there is a risk of harm to self/others.



Managing BPSD (in line with NICE Dementia guideline NG97) - Continued

Avoid antipsychotics in people with Parkinson’s Disease/Lewy Body dementia wherever possible; there is a high risk of severe neuroleptic sensitivity reactions (such as severe extrapyramidal symptoms; or acute, severe physical deterioration).

Where antipsychotics are already prescribed for BPSD, all healthcare professionals should question the need for long-term use. Antipsychotics must be reviewed, and where appropriate, discontinued (gradually) in discussion with relevant colleagues, unless the service user still has severe symptoms, or previous discontinuation caused symptoms to return.

Dementia specialists should review antipsychotic treatments on transfer or discharge from hospital to another setting

Dementia specialists may consider using acetylcholinesterase inhibitors or memantine for BPSD in dementia, where appropriate (see tables below)



Dementia: Pharmacological Management of Non-Cognitive Symptoms – Managing Comorbid Conditions

Schizophrenia/Mania Relative Cost Notes

Antipsychotics

e.g. Risperidone Olanzapine Quetiapine Aripiprazole Amisulpride Haloperidol

Branded/Liquids/MR/ Orodispersible forms

£ £ £ £ £ £ ££-£££

Comorbid psychosis/mania should be managed appropriately; as per appropriate guidelines

Low doses are preferred in older adults with dementia (e.g. half of normal elderly dose)

Warning: The risk of cerebrovascular adverse events, such as stroke or transient ischaemic attack

(TIA), may be raised as much as three-fold in older adults with dementia prescribed an antipsychotic; mortality is also raised. The balance of risks and benefits associated with antipsychotics in dementia should be carefully assessed particularly where there is a previous history of stroke or TIA, hypertension, atrial fibrillation and heart valve disorders. Consideration should also be given to other risk factors for cerebrovascular disease including smoking, high BMI, immobility, diabetes and hypercholesterolaemia and dyslipidaemia.

Be aware of an increased risk of severe extrapyramidal side effects in DLB/PDD

Document all discussions about risks and benefits with the service user, relatives and/or carers

Depression+/-Anxiety Relative Cost Notes

SSRIs

Citalopram (liquid) Sertraline Mirtazapine

Tabs/orodispersible Liquid

£ (££) £ £ £££

SSRIs preferred because they are better tolerated than other antidepressants; mirtazapine is an alternative; These drugs have a low likelihood of drug interactions. Caution: QT prolongation with citalopram Avoid tricyclic antidepressants due to risk of daytime sedation, tolerance, rebound insomnia, confusion and worsened cognition, falls, disinhibition, and delirium; If a tricylic is indicated, low dose trazodone may be considered Before starting antidepressant, discuss the delayed onset of action, side effects and discontinuation reactions and the importance of adherence with the service user and/or carer.

Benzodiazepines liquids

£ £££

Short-term use only for severe cases; risk of dependence, tolerance, sedation, worsening cognition, delirium, falls, disinhibiting effects and in some cases, respiratory depression.

Sleep Disorders Price Band Notes

Zopiclone (3.75mg)

Liquid Zolpidem (5mg)

£ £££ £

Promote good sleep hygiene; Use drug treatment for a short-term only when sleep disturbances is the main problem and other approaches have failed. Do not use antihistamines or benzodiazepine due to cognitive side effects, confusion, falls or delirium



Dementia: Pharmacological Management of Non-Cognitive Symptoms – BPSD*

Antipsychotics Relative Cost Notes

Antipsychotics

e.g. Risperidone 0.5–1.0 mg/day (max 2mg) Olanzapine 2.5–5.0 mg/day (max 10mg) Quetiapine 12.5–50 mg/day (max 150mg/day) Aripiprazole 5mg/day Max 10mg/day Amisulpride 25-50mg/day Haloperidol 0.5 to 5 mg/day Branded/Liquids/MR/ Orodispersible forms

£ £ £ £ £ ££-£££

For non severe BPSD, use non-pharmacological interventions or watchful waiting

Manage factors that generate or aggravate symptoms, including any comorbid symptoms

Antipsychotics should only be used for BPSD or behaviour that challenges if there is severe distress and/or agitation OR an immediate risk of harm to the service user and others

Antipsychotics produce small reduction in neuropsychiatric symptoms of dementia (psychosis, aggression and agitation) but increase the risk of cerebrovascular adverse events and death. Other antipsychotic side effects include tardive dyskinesia, neuroleptic malignant syndrome, weight gain, hyperlipidaemia, diabetes mellitus, sedation, falls, Parkinsonism, and worsening of cognition.

Do not prescribe antipsychotics for mild-moderate BPSD – risks outweigh any benefits

Consultants or trainees after discussion with consultants may initiate antipsychotics for severe

BPSD after reviewing and managing the causes of disturbed behaviour (non-pharmacological management plus treatment of comorbidities)

Assess risk factors and discuss benefits and risks of antipsychotic fully with service user or carer

Risperidone is the only antipsychotic licenced for short term treatment (up to 6 weeks) of persistent aggression in moderate to severe Alzheimer's dementia unresponsive to non-pharmacological approaches and when there is a risk of harm to self or others. NB: Warnings regarding risks of antipsychotics in dementia also apply to risperidone.

Antipsychotic dose should be initially low and the dose gradually titrated upwards

In DLB or PDD, be aware of the risk of severe adverse effects e.g. development or worsening of extrapyramidal side effects; or acute, severe physical deterioration)

Low dose quetiapine appears to be better tolerated in DLB or PDD but monitor for side effects

Target symptoms should be clearly defined and documented and progress reviewed regularly.

Monitor for changes in cognition and antipsychotic side effects

Treatment should be time-limited and regularly reviewed (every 6 weeks or according to clinical need). More frequent monitoring may be required during titration

At each review, consider reduction of dose or gradual discontinuation of treatment

* BPSD includes symptoms such as agitation, aggression, extreme anxiety, shouting, changes in behaviour, delusions and hallucinations.




AChEIs and Memantine Relative Cost Notes

Donepezil Galantamine Rivastigmine Liquids; patches’ branded; orodispersible formulations

£ ££ £ ££-£££

AChEIs may be tried for behavioural and psychological symptoms of dementia if symptoms are causing severe distress or leading to challenging behaviour and antipsychotic drugs are inappropriate or have been ineffective

Memantine Liquid; branded

£ ££-£££

Memantine may be tried in people with behavioural and psychological symptoms of dementia if symptoms are causing severe distress or leading to challenging behaviour and antipsychotic drugs are inappropriate or have been ineffective

Antidepressants Relative Cost Notes

SSRIs

Citalopram (liquid) Sertraline

£ (££) £

SSRIs may be useful for behaviours that suggest underlying depression or anxiety. Citalopram limited evidence for agitation in people with Alzheimer’s disease. Consider also if depression+/- anxiety; use lower starting doses and small and gradual dose increases necessary; Caution – citalopram can cause dose-dependent QT prolongation Sertraline 50mg/day (max 200mg) useful if anxiety is a concern.

Mirtazapine Liquid/Orodispersible

£ ££

May be useful where depression and anxiety and sleep problems are a concern

Trazodone (liquid) ££ (£££) Trazodone may be useful when behaviour accompanied by depressive/anxiety symptoms




Other agents Relative Cost Notes

Mood stabilisers £-£££ Low doses of carbamazepine have been tried as a controlled therapeutic trial when other measures are ineffective but be aware of the risk of side effects and drug interactions. Routine use not recommended. Do not offer valproate to manage agitation or aggression in people living with dementia, unless it is indicated for another condition.

Benzodiazepines

e.g. Lorazepam; diazepam, clonazepam Liquids

£

£££

Not routinely recommended except for short-term/PRN use only in severe cases when anxiety or agitation is prominent and other approaches have failed. Adverse effects can include dependence, tolerance, sedation, worsening cognition, delirium, increased risk of falls, disinhibiting effects and in some cases, respiratory depression or worsening of breathing disorders



Dementia: Pharmacological management of violence, extreme agitation and/or aggression with risk to self and/or others

First line Relative Cost Notes

Oral agents Lorazepam or Haloperidol or Liquids, Proprietary; and orodispersible formulations

£ £ £ ££-£££

Use non-drug strategies first Follow Trust Rapid Tranquillisation procedure but be aware of the following:

Treat with lowest effective doses for the shortest possible time

Aim to reduce agitation and aggression without sedation

Monitor BP, temperature, pulse and respiratory rate NB: Be aware that Antipsychotics are associated with an increased risk of cerebrovascular

adverse events and greater mortality when used in people with dementia. No antipsychotic (with the exception of risperidone and haloperidol in some circumstances) is licensed in the UK for the treatment of BPSD; Other antipsychotics are prescribed off-label for this purpose.

Second line Relative Cost Notes

Intramuscular (IM) agents

Lorazepam Haloperidol Haloperidol and Promethazine

£ £ £££

Consider if oral treatment is refused or ineffective and severe risk or extreme distress Follow recommendations in Trust Rapid Tranquillisation Policy

A single IM agent should be used in preference to a combination.

Monitor vital signs – Blood pressure, pulse and respiratory rate should be recorded at regular intervals

Monitor for dystonia and other extrapyramidal effects. If acute dystonic reactions or distressing EPSE, consider use of anticholinergic agents

Monitor for deteriorating cognitive function

Third Line Relative Cost Notes

IM haloperidol and IM lorazepam

££ Agreed with a consultant if it is thought that there may be clinical benefit and appropriate monitoring is in place. This combination may form part of an advanced statement for an individual who has benefited from this approach in the past.

Monitor dystonia and other extrapyramidal effects, consider procyclidine.



References

1. NICE guideline NG97. Dementia: assessment, management and support for people living with dementia and their carers. Published date: June 2018. https://www.nice.org.uk/guidance/ng97

2. NICE TA217: Donepezil, galantamine, rivastigmine and memantine for the treatment of Alzheimer's disease. (2011 updated 2018) Available at:

https://www.nice.org.uk/guidance/ta217

3. NICE quality standard. Dementia: support in health and social care (QS1): June 2010 Available at: https://www.nice.org.uk/guidance/qs1

4. NICE quality Standard. Dementia: independence and wellbeing (QS30) April 2013. https://www.nice.org.uk/guidance/qs1

5. NICE advice. Key therapeutic topics. Low-dose antipsychotics in people with dementia (KTT7) January 2015. Last updated: February 2018. Available at:

https://www.nice.org.uk/advice/ktt7

6. NICE advice. Management of aggression, agitation and behavioural disturbances in dementia: carbamazepine (ESUOM40) March 2015. Available at:

https://www.nice.org.uk/advice/esuom40

7. NICE advice. Management of aggression, agitation and behavioural disturbances in dementia: valproate preparations (ESUOM41) March 2015. Available

at: https://www.nice.org.uk/advice/esuom41

8. NICE guidelines NG71. Parkinson’s Disease in Adults. July 2017. https://www.nice.org.uk/guidance/ng71

9. BAP guidelines: Clinical practice with anti-dementia drugs: a revised (second) consensus statement from British Association for Psychopharmacology.

https://www.bap.org.uk/pdfs/BAP_Guidelines-AntiDementia.pdf

10. BAP guidelines: Clinical practice with anti-dementia drugs: a revised (third) consensus statement from British Association for Psychopharmacology.


11. Banerjee S. The use of antipsychotic medication for people with dementia: Time for action. A report for the Minister of State for Care Services.

Department of Health, London, 2009. Available at:

http://webarchive.nationalarchives.gov.uk/20130107105354/http://www.dh.gov.uk/prod_consum_dh/groups/dh_digitalassets/documents/digitalasset

/dh_108302.pdf

12. Dementia Action Alliance and NHS Institute for Innovation and Improvement .The right prescription, a call to action on the use of antipsychotic drugs for

people with dementia: 2011


https://www.nice.org.uk/guidance/qs1

https://www.nice.org.uk/guidance/qs1

https://www.nice.org.uk/advice/ktt7






http://webarchive.nationalarchives.gov.uk/20130107105354/http:/www.dh.gov.uk/prod_consum_dh/groups/dh_digitalassets/documents/digitalasset/dh_108302.pdf

http://webarchive.nationalarchives.gov.uk/20130107105354/http:/www.dh.gov.uk/prod_consum_dh/groups/dh_digitalassets/documents/digitalasset/dh_108302.pdf



13. American Psychiatric Association (APA). Practice guideline for the treatment of patients with Alzheimer's disease and other dementias. Arlington (VA):

American Psychiatric Association (APA); Second Edition, October 2007.

14. Pollock et al.A double-blind comparison of citalopram and risperidone for the treatment of behavioral and psychotic symptoms associated with dementia.

Am J Geriatr Psychiatry 2007;15: 942–52.

15. Jeste et al.ACNP White Paper: update on the use of antipsychotic drugs in elderly persons with dementia. Neuropsychopharmacology 2008;33(5):957–70.

16. 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: July 2011.

17. Summary of Product Characteristics of various drugs are available at: https://www.medicines.org.uk/emc/

18. Antipsychotics: initiative to reduce prescribing to older people with dementia http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON152729

https://www.medicines.org.uk/emc/

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