Document name:
Dementia prescribing:
Good practice guidance.
Portfolio
Medicines Management
Document type:
Guidelines
Staff group to whom it
applies:
All clinical staff in OPS
Distribution:
Intranet
How to access:
Intranet
Issue date:
Version 1 - August 2009
Version 1.1 – October 2010
Version 2 July 2012
April 2015
Next review:
Approved by:
Drug and Therapeutics Sub
Committee
Developed by:
Lynn Haygarth, Chief Pharmacist
Director leads:
Medical Director
Contact for advice:
Med.information@swyt.nhs.uk,
www.choiceandmedication.org/swyp
Contents
1
What is dementia? .............................................................................................. .. 1
1.1 Alzheimer’s disease ...................................................................................... .. 1
1.2 Dementia with Lewy Bodies.......................................................................... .. 2
1.3 Vascular dementia ........................................................................................ .. 2
1.4 Mini Mental State Examination (MMSE) ....................................................... .. 2
2
Prescribing for symptoms of dementia ................................................................ .. 2
2.1 Prescribing Pathways ................................................................................... .. 5
2.2 How do antidementia drugs work? ............................................................... .. 7
2.3 Side effects ................................................................................................... .. 7
2.4 Drug interactions .......................................................................................... .. 8
2.5 Cardiovascular disease ................................................................................ .. 9
2.6 Respiratory disease ...................................................................................... .. 9
3
Special considerations for prescribing in dementia ............................................. .. 10
3.1 Urinary incontinence ..................................................................................... .. 10
3.2 Sleep disorders............................................................................................. .. 11
3.3 Sexual disinhibition ....................................................................................... .. 11
4
Prescribing for management of behavioural and psychological symptoms of
dementia BPSD .................................................................................................. .. 12
4.1 Antipsychotics............................................................................................... .. 13
4.1.1 Use of antipsychotics for people with dementia ................................. .. 13
4.1.2 Choice of antipsychotic ...................................................................... .. 14
4.2 Other Choices............................................................................................... .. 15
4.2.1 Anti-dementia drugs........................................................................... .. 15
4.2.2 Antidepressants ................................................................................. .. 15
4.2.3 Benzodiazepines .............................................................................. .. 15
4.3 Polyprescribing ............................................................................................. .. 16
4.4 Summary points............................................................................................ .. 16
References ................................................................................................................ .. 17
Appendix 1: Antidementia medicines for treatment of dementia of mild to moderate
severity ................................................................................................ .. 19
Appendix 2:
Appendix 3:
Appendix 4:
Appendix 5:
Appendix 6:
Appendix 7:
Drugs with antimuscarinic (anticholinergic) effects .............................. .. 22
Use of rivastigmine patch in SWYPFT ................................................ .. 24
Example letter to GP ........................................................................... .. 25
Equality Impact Assessment Tool ....................................................... .. 26
Checklist for review and approval of procedural documents ............... .. 27
Version control sheet ........................................................................... .. 28
ii
Abbreviations used in this document
AChEIs
ACE-R
AD
BD
BP
BPSD
CNS
COPD
CYP
ECG
GP
L-dopa
LHRH
MMSE
NICE
OM
SSRI
SWYPFT
TCA
Z-drugs
Acetylcholinesterase inhibitors
Addenbrook’s Cognitive Examination
Alzheimer’s disease
Take twice a day
Blood pressure
Behavioural and psychological symptoms of dementia
Central nervous system
Chronic obstructive pulmonary disease
Cytochrome
Electrocardiogram
General Practitioner
Levodopa
Lutenising hormone releasing hormone
Mini mental state examination
National Institute for Health and Clinical Excellence
Take in the morning
Selective serotonin reuptake inhibitor
South West Yorkshire Partnership NHS Foundation Trust
Tricyclic antidepressant
Zaleplon, zopiclone, zolpidem
Trust related documents on the intranet









Antipsychotics in clinical practice: Guidelines for safe and effective use in adults with
schizophrenia (in line with NICE Guidance No 43 2002, updated 2009) version 4,
2012.
Guidelines for the pharmacological treatment of anxiety (Incorporating NICE Clinical
Guideline 22).
Antidepressants in clinical practice: Guidelines for safe and effective use of
antidepressants in adults and older people (in line with NICE Clinical Guideline 23
December 2004) Version 5.
Hypnotics in Clinical Practice Guidance on the use of hypnotics for the management
of insomnia (in line with NICE Guidance No 77 2004).
Shared Care Guidelines for anti-dementia drugs donepezil, galantamine,
rivastigmine and memantine in Barnsley.
Shared Care Guideline for memantine in Calderdale, Kirklees and Wakefield.
Patient information leaflets: hypnotics (sleeping tablets), benzodiazepines for
anxiety, antipsychotics for the treatment of schizophrenia, antidementia drugs for the
treatment of dementia of moderate severity.
Patient advice leaflets – donepezil, galantamine, memantine and rivastigmine
Medicines Code Section 17 Clinical Queries.
iii
1
What is dementia?
It is an irreversible syndrome of the brain affecting:
Memory
Orientation
Calculation
Judgement
Thinking
Comprehension
Language
Initially it starts with mild memory impairment and progresses to behavioural and
personality changes to loss of ability to carry out activities of daily living. The
prevalence of dementia increases from approximately 0.7% in those aged 60-64
years, doubling every 5 years or so to nearly 40% in those aged 90-95 years.
The most common types are:
1
2
3
Alzheimer’s Disease (pure A.D. 38% of dementias)
Dementia with Lewy Bodies (contributes about 20% of dementias)
Vascular Dementia
However 60% of dementias may be mixed.
Other diseases can manifest as dementia e.g. Huntington’s Chorea, Parkinson’s
Disease dementia, Multiple Sclerosis and AIDS dementia complex. Alcohol
abuse may be linked to dementia.
1.1
Alzheimer’s disease
This was recognised by Dr Alois Alzheimer in Germany in 1906. He found dense
deposits around the nerve cells called amyloid plaques and twisted bands of
fibres inside the nerve cells called neurofibrillary tangles. If both are present this
gives a diagnosis of Alzheimer’s. These contribute to degeneration of neurons
and shrinkage of brain volume.
Risk factors include:







Increase in age
Down’s syndrome
Gender - women greater than men
Education - if highly educated less likely
Family history
Head injury
More information at www.alzheimers.org.uk
1
1.2
Dementia with Lewy Bodies
In this type there is the intracellular inclusion of hyaline mass in the cerebral
cortex and substantia nigra. However unlike Alzheimer’s the neurofibrillary
tangles are ABSENT. It is particularly associated with fluctuating levels of
consciousness. These patients are particularly sensitive to the side effects of
antipsychotics and these should be avoided.
1.3
Vascular dementia
Onset is classically stepwise following cerebrovascular adverse events due to
occlusion of a vessel in the brain following stroke or transient ischaemic attack.
Risk factors include hypertension, diabetes and atrial fibrillation.
1.4
Mini Mental State Examination (MMSE)
(Caution the written tool is copyright)
NICE recommends a mini mental state examination is completed to determine
the severity of the dementia.
MMSE – score out of 30
21 – 26
Mild
10 – 20
Moderate
Less than 10
Severe
The symptoms and signs of dementia consist both of features attributable directly
to cognitive deficits and also to non-cognitive features some of which include
disturbed behaviours (e.g. aggression, wandering and eating disorders) and
psychiatric symptoms (e.g. hallucinations, delusions and affective disturbances).
These are sometimes referred to as Behavioural and Psychological Symptoms of
Dementia (BPSD). For more information refer to Dementia Action Alliance
(http://dementiaaction.org.uk/).
The ACE-R is also used particularly in Barnsley.
2
Prescribing for symptoms of dementia
Formulary choices for symptoms of dementia
First line
 Acetylcholinesterase inhibitors (AChEIs)
 Donepezil
 Galantamine
 If these are not suitable may consider rivastigmine particularly for
Parkinson’s patients.
 Use of rivastigmine patches is restricted.
 If AChEIs are not tolerated or contraindicated.
 Memantine
2
Acetylcholinesterase inhibitors (AChEIs) and memantine
The AChEIs are the main drugs prescribed for dementia symptoms. Memantine is only
available when the AChEIs are contraindicated or not tolerated.
These should be used in line with NICE guidance for:




People with Alzheimer’s Disease of mild and moderate severity.
Non-cognitive symptoms including hallucinations, delusions, anxiety, marked
agitation and associated aggressive behaviour.
Lewy Body Dementia and mild, moderate or severe Alzheimer’s Disease.
People with mixed dementia where Alzheimer’s Disease is considered to be
the dominant condition.
The following considerations should be taken into account:













Baseline monitoring of clinical parameters to eliminate other causes of
cognitive impairment should be taken by the GP prior to referral to local
memory service.
An ECG should be taken prior to commencing treatment.
Prescribing must take place in the approved memory service.
Consider the circumstances of the service user when choosing an AChEl. If
there are no individual considerations or contraindications choose donepezil.
Use once a day oral preparation where possible. This helps to facilitate home
care visiting once a day. Donepezil is available in an orodispersible (melt in
the mouth) tablet.
Where liquids are available these require administering twice a day. Take
care when prescribing as these are in doses per ml via a dropper.
The dose must be titrated slowly starting with the lowest available dose and
assess over four weeks for side effects.
All service users and carers should have access to the Trust information
document on antidementia medicines. (See Appendix 1)
Memantine should only be chosen for Alzheimer’s of moderate severity when
the AChEIs are not tolerated or contraindicated.
When the patient is stabilised on the treatment they may be considered
suitable for shared care.
o In the case of side effects affecting compliance and functioning, the
patients should be referred back to the local memory service.
If the MMSE goes below 10 and the diagnosis becomes one of severe
dementia the clinician should consider whether to discontinue the treatment
or whether continuation will be of benefit.
Treatment discontinuation in patients who have responded may cause
deterioration; GPs are requested to contact the local memory service for
advice.
Prescribe generically at all times as there will be cost savings coming through
in 2012 with generic products becoming available.
3
Table 1 Information on AChEIs and memantine for symptoms of dementia
Drug
When to
choose
Comments
Dose
Low
≤ £25
Medium £26 - £75
High ≥ £75 £150
Very High ≥ £150
Acetylcholinesterase inhibitors
Donepezil
Aricept®
First line for mild
to moderate
dementia.
Reversible inhibitor of
ACHE. Most commonly
prescribed.
Once a day preparation.
Galantamine
Reminyl®XL
First line and
with mixed
Alzheimer’s and
vascular
dementia.
Reversible inhibitor of
ACHE and a nicotinic
receptor agonist.
Once a day preparation.
Take care when
prescribing the liquid to
ensure dose is per ml.
More side effects
reported.
Licensed for use in
dementia related to
Parkinson’s disease.
Rivastigmine
Exelon®
Rivastigmine
patches
Exelon®
Restricted to
users not
suitable for or
tolerant of
donepezil and
galantamine.
Restricted use
Swallowing
difficulties.
Only available
via clinical
queries
mechanism.
Glutamate receptor antagonist
Memantine
For moderate
Ebixa ®
dementia only
either when
AChEIs are
Contraindicated
or not tolerated.
Cost per 28
days
5mg and 10mg
tablets to swallow
and melt in the
mouth tablets
(orodispersible)
Modified release
capsules 8mg,
16mg & 24mg,
Solution 4mg /mL
(liquid given by a
dropper)
Low
Capsules 1.5mg,
3mg, 4.5mg and
6mg.
Solution 2mg/ml
(liquid given by a
dropper)
Patches® 4.6mg
and 9.5mg.
Medium
Reduced dose in hepatic 10mg and 20mg
impairment. Do not use
tablets.
in patients with a history
of convulsions.
Oral solution
10mg/ml as a
pump spray
Medium
Medication errors and
inappropriate use of
patches has been
reported frequently due
to lack of patch removal
resulting in symptoms of
overdose including
nausea, vomiting,
diarrhoea, hypertension
and hallucinations.
Low: £120.
High
High
High
Medium
Can be used in
severe
dementia in
particular for
BPSD
Further information on the individual products is available at www.medicines.org.uk
4
2.1
Prescribing Pathways
Each locality may have a variance of the pathways to suit the needs of the
services. In Calderdale, Kirklees and Wakefield prescribing, after initiation, can
move to the GP for donepezil, galantamine and rivastigmine. In Barnsley they
are subject to a Shared Care Guidelines and can be moved to the GP after four
months.
Donepezil (Aricept®) Pathway
Decide on prescribing and obtain the patient and carer’s agreement, give drug
information leaflet and explanation about potential side effects.
Prescribing starts at 5mg once daily. Dose increase to 10 mg daily (after four to
six weeks) if no side effects.
Galantamine (Reminyl®) Pathway
Decide on prescribing and get the patient and carers agreement, give drug
information leaflet and explanation about potential side effects.
Prescribing starts at 8mg MR once daily or 4mg twice daily of liquid 4mg/ml.
Doses increases to 16mg daily for month 2 and 3 and to 24mg daily at month 4 if
no side effects.
Rivastigmine (Exelon®) Pathway
Only choose if neither donepezil nor galantamine are suitable for the
patient. It comes as both oral and patches which have different pathways.
Oral preparations-capsules and liquid
Decide on prescribing and get the patient and carer’s agreement, give drug
information leaflet and explanation about potential side effects. Consider
whether the patient can be prescribed twice a day medicines.
Prescribing starts at 1.5mg bd for 2 weeks and increases to 6mg twice daily over
4 months if no side effects.
Rivastigmine Patches
There has been a serious alert relating to inappropriate use of Exelon
patches (Ref Novartis EXE10-047 April 2010). Rivastigmine patches are not
generally available and can only be considered via the clinical queries
mechanism.

For service users with swallowing difficulties it may be suitable to consider the
rivastigmine patch. It is important to ensure there is a personal carer who is
able to apply the patch daily as per the instructions on the product
information. Home care are not able to administer the patch in many areas of
the Trust. Complete Appendix 1 – use of rivastigmine (Exelon ®) patch in
SWYPFT. A clinical queries form will also require completion.
5
Decide on prescribing and get the patient and carer’s agreement, give drug
information leaflet and explanation about potential side effects.
Initially 4.6mg applied daily to the upper part of the body for at least 4 weeks.
Increase to 9.5mg applied daily to the upper part of the body. Continue on this
dose as maintenance dose if tolerated.
The prescriber should ensure that the following issues have been
considered prior to commencing a patient on the Rivastigmine patch:
 That adequate monitoring arrangements are in place to ensure:
 the previously applied patch is removed each day.
 siting of the patch is rotated between the recommended areas of
application.
 only one patch will be worn at any time.
 patches are not removed by the patient following application.
 the skin area is clean, dry and hairless.
 the patches are changed at the same time each day.
 The person applying the patch is informed of:
 how to apply the patch
 how to remove the patch
 disposal of the patch
 action to take if the patch falls off or is removed early
 action to take if more than one patch is accidentally applied
Complete appendix 3.
NB if the patient stops treatment for more than 2 days then rivastigmine needs to
be introduced at the lowest dose and then increased gradually.
Memantine prescribing pathway
Only choose when an AChEIs is not tolerated or contraindicated. It is not
recommended in patients with severe hepatic impairment. Caution is
recommended in patients suffering from epilepsy or with a history of convulsions.
Decide on prescribing and get the patient and carer’s agreement, give drug
information leaflet and explanation about potential side effects.
The dose can be increased by 5mg weekly to 20mg daily if the patient tolerates
the memantine. There is treatment initiation pack available to support this use.
Week 1 5mg daily
Week 2 10mg daily
Week 3 15mg daily
Week 4 20mg daily
Continue on 20mg daily if this dose is tolerated.
If the patient has renal impairment with GFR between 5-29 ml/min keep dose to
10mg per day. Avoid if GFR is less than 5ml/min.
6
2.2
How do antidementia drugs work?
AChEIs



Postulated to provide a beneficial effect by augmenting cholinergic function.
Inhibit the enzyme acetylcholinesterase that is responsible for the breakdown
of acetylcholine.
When the drug inhibits this enzyme the breakdown of acetylcholine is slowed
down and therefore cholinergic neurotransmission is increased.
Each drug has a very different chemical structure:
 Donepezil – piperidine derivative.
 Galantamine – phenanthrene derivative.
 Rivastigmine – carbamate derivative.
Cross-sensitivity would not be expected. Therefore, if a patient develops an
allergic reaction such as rash an alternative can be safely tried.
Memantine



2.3
Is a NMDA ( N-Methyl-D-Aspartate) receptor antagonist.
It targets glutamate which levels are raised in dementia.
Excess glutamate leads to overexcitation on the NMDA receptor which
releases intra-cellular calcium. High levels of intracellular calcium can lead
to cell degeneration and cell death.
Side effects
AChEIs



Diarrhoea, muscle cramps, fatigue, nausea, vomiting, insomnia.
Headache, pain, common cold and runny nose abdominal disturbance,
dizziness, accident.
Urinary incontinence.
If these occur reduce the dose and titrate more slowly or change treatment.
Rare: syncope, bradycardia, sinoatrial and atrioventricular block.
If these occur consider stopping and review the treatment plan.
Memantine


Common: drug hypersensitivity, somnolence, dizziness, hypertension, dyspnoea,
constipation and headache.
Uncommon: fungal infections, confusion, hallucinations, gait abnormal, cardiac
failure, venous thrombosis/thromboembolism, vomiting and fatigue.
7
2.4
Drug interactions
Interacting
drugs
Anticholinergics
(antimuscarinics)
e.g. procyclidine,
oxybutinin
See appendix 3
for full list
Cholinomimetics
e.g.
suxamethonium
NSAIDs e.g.
ibuprofen,
diclofenac
Drugs slowing
heart rate e.g
digoxin, beta
blockers
CYP2D6 inhibitors
e.g. paroxetine,
fluoxetine
CYP3A4 inhibitors
e.g. erythromycin,
ketoconazole
Inducers of
CYP2D6 +
CYP3A4 e.g.
phenytoin,
carbamazepine
Concomitant use
of N-methyl-Daspartate
(NMDA)antagonists such
as amantadine,
ketamine or
dextromethorphan
Levodopa,
dopaminergic,
agonists
Donepezil
Galantamine
Rivastigmine
Potential antagonistic effect, monitor for reduced
efficacy of either drug.
Also may worsen the course of the illness
Memantine
May worsen
course of
illness
Effects may
be enhanced
Potential additive effect
No effect likely
Increased risk of gastric irritation and GI bleed
No effect likely
Potential additive effect, monitor for side effects (e.g.
bradycardia)
No effect likely
Donepezil
levels
possibly
increased*
Donepezil
levels
possibly
increased*
Donepezil
levels
possibly
reduced**
No effect
likely
Galantamine
levels possibly
increased*
Galantamine
levels possibly
increased*
Galantamine
levels possibly
reduced **
No effect likely
No effect likely
No effect likely
No effect likely
No effect likely
No effect likely
Increased risk
of convulsions
No effect likely
should be
avoided as
there is a risk
of CNS
toxicity
Effects may
be enhanced
*Dose reduction not necessary unless side effects occur.
** Interaction may not be clinically significant, but should be considered if lack of efficacy occurs.
NB It is unlikely that any of the antidementia drugs at therapeutic doses will affect the metabolism of other medications.
Always check SPC when prescribing
8
2.5
Cardiovascular disease
In patients with pre-existing cardiovascular disease such as sick sinus
syndrome and other supraventricular cardiac conduction conditions the
manufacturers advise caution.



May cause bradycardia due to their vagotonic effects, and arrhythmias.
May also have variable effects on BP eg raised or lowered BP.
Underlying hypotensive conditions may be exaggerated – leading to falls.
Memantine may be considered as a suitable choice however there is only
limited data in patients with recent MI, congestive heart failure or uncontrolled
hypertension. Patients should be closely monitored.
2.6
Respiratory disease
In patients with respiratory disease the manufacturers recommend that AChEIs
should be used with caution in patients with a history of asthma or COPD. This
appears to be based on the theoretical risk that cholinomimetics can cause
bronchoconstriction and bronchospasm, rather than actual reports of problems
in this patient group. If used then there must be increased monitoring of
respiratory function, especially during titration. Lower starting doses and slower
titration could be used in patients with severe or poorly controlled respiratory
disease.
9
3
Special considerations for prescribing in dementia
Polyprescribing should be minimized wherever possible and patients prescribed
more than four drugs should undergo a medication review. This can be
supported by the local pharmacy team.
Drugs with anticholinergic effects can both increase cognitive decline and
antagonize effects of the treatments. These include drugs for urinary
incontinence, antimuscarinic/anticholinergics and tricyclic antidepressants.
(Appendix 2 for further information)
3.1
Urinary incontinence
Drugs for bladder problems are often used in older patients. In addition, urinary
incontinence can be a side effect of acetylcholinesterase treatment. Those
commonly prescribed are:
•
Oxybutynin, tolterodine, and trospium
–
–
–
–
Licensed to treat urinary frequency, urgency and incontinence.
None are specific to the bladder.
All may cause constipation, tachycardia, and CNS effects.
There have still been case reports of cognitive decline in patients with
pre-existing dementia which reversed on withdrawal of the drug.
It is not an absolute contraindication to use if there is a definite clinical need.
Patients should be monitored very closely. Interaction should be considered if the
patient’s cognitive function declines or bladder symptoms worsen. There are
case reports of the combination being used successfully in patients distressed by
the symptoms of incontinence.
3.2
Sleep Disorders
In patients with dementia the sleep-wake cycle is often disturbed. It is important
to avoid benzodiazepines (even short-acting) as they can cause “hang-over” the
next morning. They also cause confusion and ataxia (increased risk of falls).
Longer acting benzodiazepines e.g nitrazepam are a particular risk.
A short course of a Z-drug may be helpful e.g. 3.75mg zopiclone. This should be
regularly reviewed and only continued if essential. Other sleep hygiene measures
should be considered. (See SWYPFT hypnotic policy)
Unfortunately many patients may already be prescribed benzodiazepines or z
drugs. It is important not to stop abruptly. If these are given there is an increased
risk of slips, trips and falls. It is most important to ensure they are only
administered when the patient is actually ready for bed.
10
Dementia may impair driving performance and the ability to use machinery. Use
of hypnotics may cause further impairment.
3.3
Sexual Disinhibition
This has a prevalence rate of 2-17% in this group of patients. It can manifest as
inappropriate nudity, public masturbation or stripping, obscene sex language, or
propositioning others. There is a significant association with severity of dementia.
There is no licensed drug for treating dementia-related sexual disinhibition.
Preparations that may be considered under the clinical queries mechanism to be
used off licence include: Anti-androgens (e.g. cyproterone), oestrogens, LHRH
analogues, serotonergics and gabapentin.
11
4
Prescribing for management of behavioural and psychological symptoms
of dementia BPSD
Many different factors may be associated with behavioural problems in patients
with dementia:
 Physical illness including:
 poorly controlled pain
 diabetes with impaired glucose metabolism
 dehydration
 hypoxia
 electrolyte disturbances
 heart failure
 delirium
 Prescribed medicines
These may cause psychotic symptoms in elderly during use or on withdrawal:
 Benzodiazepines
 Anti-Parkinson drugs - L Dopa, procyclidine
 Anti-arrhythmics – digoxin, propranolol
 Anti-inflammatories – aspirin, indomethacin
 Anticonvulsants – carbamazepine, phenytoin
 Steroids - prednisolone
 Environmental factors
 noisy and over stimulating environments
 social isolation
 visual and auditory sensory impairments
Age related neurotransmitter changes (acetylcholine, dopamine, noradrenaline
and serotonin), damage to specific brain regions responsible for emotional
activity (parahippocampal gyrus, dorsal raphe and locus coeruleus) and cortical
hypometabolism have also been proposed as possible neurobiological causes
(Lanari et al 2006).
It is also important to consider:
Does the patient have communication difficulties eg dysphasia.
Could pain control be improved?
Is it delirium or dementia? - These often exist together so treat the
delirium and often the behavioural symptoms will subside.
Is it depression which is common in dementia.
For more information about assessing symptoms please refer to:
Best practice guide: optimising treatment and care for people with BPSD toolkit
(Alzheimer’s society)
http://nww.swyt.nhs.uk/drug-therapeutics
tag/Documents/qipp/A_best_practice_guide_for_health_and_social_care_profes
sionals.pdf
Reducing the use of antipsychotic drugs toolkit
http://nww.swyt.nhs.uk/drug-therapeuticstag/Documents/qipp/Reducing_the_use_of_antipsychotic_drugs.pdf
12
4.1
Antipsychotics
There has been increasing concern over the past few years about the use of
antipsychotics in dementia.
Prior to
2000
Typical antipsychotics were common such as haloperidol,
thioridazine and promazine but older people were more sensitive
to their side-effects such as movement disorders and QT
prolongation. Atypicals became more commonly prescribed.
In 2004 The CSM reported an apparent 2 to 3 fold increase in risk of
cerebrovascular event in people with dementia prescribed
olanzapine and risperidone.
In 2005 It became apparent that no antipsychotic was safer than any
other when it was reported a 1.7 fold increase in mortality with
the typicals due to heart failure, sudden death and pneumonia.
NICE/SCIE guideline 42 Nov 2006 recommends the use of
pharmacological intervention in the first instance only if the patient is
severely distressed or there is an immediate risk of harm to the person or
others. The National Dementia Strategy advocates only the appropriate
use of antipsychotic medication for people with dementia.
Banerjee in his ‘Time for Action’ report states that across the country
180,000 people are being treated with antipsychotics of which 36,000 will
derive benefit but an additional 1,600 cerebrovascular effects (of which half
are severe) and 1,800 deaths occur than would be expected.
Antipsychotics are being use too often first line in response to behavioural
difficulty such as agitation, aggression and wandering rather than second
line after other non-pharmacological approaches have failed.
4.1.1 Use of antipsychotics for people with dementia
a.
b.
c.
d.
e.
g.
Antipsychotics should not be first line except in circumstances of extreme
risk or harm. Psychological approaches should be used in the first instance.
Identify treatable causes of BPSD (eg. delirium, pain or depression) and
prescribe accordingly.
Where antipsychotic medication is considered the client (if capacity to
consent), relative or carer should be involved in the decision after having
had the information about the potential positive and negative effects. A
patient information leaflet should be provided. The final prescription will be a
‘best interests’ decision having identified a clear target symptom
An atypical is preferred over a typical using the lowest effective dose for
shortest period of time, ideally less than 12 weeks.
Once initiated continuation should be reviewed monthly and reduction or
cessation actively considered.
A record on RiO should include the discussion about the risks and benefits
which took place with the client/relative/carer, the indication for the
prescription, alternatives considered and plans for review, reduction and
cessation.
13
h Where the use in unlicensed (see table below) an unlicensed use form (section
17 medicines code) should be completed. The responsibility for prescribing will
remain with the prescriber.
Refer to points to consider before prescribing:
Dementia Prescribing Guidance: http://nww.swyt.nhs.uk/drug-therapeuticstag/Documents/qipp/Checklist%20Guidance%20Booklet%20Print.doc
Antipsychotic in Dementia Checklist : http://nww.swyt.nhs.uk/drug-therapeuticstag/Documents/qipp/Antipsychotic%20in%20Dementia%20checklist.doc
4.1.2 Choice of antipsychotic
Antipsychotic Starting Dose
Optimal Comment
dose
ONLY USE WHEN NO OTHER STRATEGY IS AVAILABLE
Risperidone
250micrograms
1mgLicensed for use 6 weeks only
to
2mg
for treatment of persistent
500micrograms
aggression in patients with
moderate to severe Alzheimer’s
disease unresponsive to nonpharmacological approaches
and where there is a risk of
harm to self or others.
Evidence of increased risk of
stroke. May cause stiffness.
Caution in combination with
furosemide.
Amisulpride
12.5mg -25mg
50mg Unlicensed Risk of stiffness,
100mg
limited evidence of response.
Haloperidol
500micrograms
2mg- 3
Licensed only for agitation and
mg
restlessness. Risk of stiffness.
The following drugs, which are not licensed for use in dementia, have
been prescribed in the past but are no longer recommended. Service
users taking these drugs need to be reviewed.
Olanzapine
2.5mg
5mg –
Unlicensed. Evidence of
7.5mg
increased risk of stroke. Not
recommended by Trust or APC
Quetiapine
12.5mg to 25mg 100mg - Unlicensed, not recommended
no suitable
300mg
by Trust or APC – on grey list.
formulation or
Limited evidence of response.
preparation to give
12.5mg exists
In special circumstance e.g. patients with parkinsonian symptoms, or
severe EPSEs. Ensure a note is made on RiO and an unlicensed use form
completed.
14
Many patients are already prescribed antipsychotics which may be continued
inappropriately. The Trust have developed a series of tools to support the review
of antispychotics in dementia and these are available on the trust website
www.swyt.nhs.uk/ Do not hesitate to contact the Trustwide medicines
information department for support when reviewing patients prescribed
antipsychotic medication for dementia.
Tel 01924 327619 email med.information@swyt.nhs.uk
4.2
Other Choices
4.2.1 Anti-dementia drugs
There is some evidence to recommend the AChEIs. Given their mechanism of
action, these drugs would seem to be a logical choice when considering
pharmacological options for the management of behavioural disturbance in
dementia. More specifically there have been a number of studies of individual
drugs showing benefit in the management of behavioural problems in dementia
including donepezil, galantamine, rivastigmine (eg Feldman et al., 2001; Holmes
et al., 2004; Monsch et al., 2002; Gabelli, 2003; Finkel, 2004; Cummings et al
2006). Use in these circumstances is outwith the NICE guidance although the
use would be licensed. If using these drugs in particular follow the guidance in
section 2. In addition it is important to ensure the target symptoms are identified
and there is noted review and discontinuation if there is no response to
treatment.
NB: Memantine (Ebixa®) should only be prescribed for BPSD in line with
the shared care guidelines
4.2.2 Antidepressants
Although depression can be difficult to diagnose in dementia there is some
evidence of benefit particularly with SSRIs and trazodone.
Consider using antidepressants for treatment of co-morbid depressive symptoms
in dementia (e.g. citalopram or mirtazapine). As citalopram is an SSRI, monitor
for emergence of gastric symptoms.
Consider trazodone for patients with depressive symptoms and dementia
associated with agitation.
Tricyclic antidepressant use is not recommended.
See SWYPFT antidepressants in clinical practice.
4.2.3 Benzodiazepines
As a group these drugs can cause significant sedation, postural hypotension and
memory impairment so they need to be used with care. If choosing a
benzodiazepine use one with a short half life to prevent accumulation.
Lorazepam is widely used but it should only be prescribed short term
because of the risks of side-effects, especially falls and of tolerance developing.
It should only be used in low doses e.g. 500 micrograms to 1mg daily. The
15
prescription should be regularly reviewed and reduced and stopped wherever
possible.
Diazepam has also been used but this should be avoided as it has a long half life
and accumulation can occur in older people.
4.3 Polyprescribing
Many patients are already prescribed medicines for physical illness and adding in
psychotropic medicines must be done with particular care.
Consider the presentation –could it be a side effect?
 swallowing difficulties with antipsychotics
 stiffness with antipsychotics
 sedation with trazodone and lorazepam
 gastric irritation with an SSRI
Review existing treatment before prescribing other medicines.
Reviewing medication choices:
Review ideally after 4-6 weeks of commencement of acetylcholinesterase
inhibitor to check for efficacy and side effects.
Routine assessments should be repeated 3 to six monthly. (BNF, NICE)
Antipsychotic use is only advised for short term use (up to 6 weeks).
4.4
Summary points











At all times consider the circumstances of the patient.
Antipsychotics are not first line treatment.
Only prescribe antipsychotics for target symptoms, at low doses for short term
treatment.
Do not prescribe procyclidine.
Do not discharge to GP on antipsychotics without a follow up care plan.
Avoid tricyclic antidepressants.
Avoid anticholinergics.
If essential use a short course of z-drugs for sleep problems.
Only use benzodiazepines with a short half life for short term treatment.
Never use more than one benzodiazepine.
Never discharge patients on long course of z drugs and benzodiazepines.
16
References
Banerjee S (2009) The use of antipsychotic medication for people with dementia: Time
for action.
British National Formulary (BNF) Number 62 September 2011
CSM (2004) Committee on Safety of Medicines. Atypical antipsychotic drugs and
stroke.
Curran, S. and Wattis, J.P.W. (2004) Practical Management of Dementia – A MultiProfessional Approach, Radcliffe Medical, Oxford.
Drug Safety Update Volume 2, Issue 8 March 2009 from MHRA and CHM.
Food and Drug Administration – US FDA (2005) Off-label use of atypical antipsychotics
linked to increased mortality in the elderly. www.medscape.com
Knapp et al Dementia UK 2007: The full report dementia UK report. London Alzheimer’s
Society.
Lanari-Alessia, Amenta-Fncesco et al.(2006) Neurotransmitter deficits in behavioural
and psychological symptoms of Alzheimer’s disease. Mechanisms of ageing and
development, 127(2), 158-65.
MeRec Stop Press blog no 847
NICE/SCIE 2006 : Guideline to improve care of people with dementia.
NICE Donepezil, galantamine, rivastigmine and memantine for the treatment of
Alzheimer’s disease (March 2011). www.nice.org.uk
National Prescribing Centre: Key Therapeutic Topics 2010/11 Medicines management
options for local implementation.
Novartis Direct healthcare professional communication EXE10-047 March 2010
Rosler M (2002) The efficacy of cholinesterase inhibitors in treating the behavioural
symptoms of dementia. International Journal of Clinical Psychiatry127 (Suppl.), 20-36.
Series H & Degano P. Hypersexuality in dementia. Advances in psychiatric treatment
2005;11:424-431
Working Group for the Faculty of the Psychiatry of Old Age of the Royal College of
Psychiatrists, (2004) Summary guidance for the management of behavioural and
psychiatric symptoms in dementia and the treatment of psychosis in people with history
of stroke/TIA. www.rcpsych.ac.uk/college/faculty/oap
17
Antipsychotics in Dementia checklist:
http://nww.swyt.nhs.uk/drug-therapeuticstag/Documents/qipp/Antipsychotic%20in%20Dementia%20checklist.doc
Reducing Antipsychotic flowchart:
http://nww.swyt.nhs.uk/drug-therapeuticstag/Documents/qipp/Reducing%20Antipsychotic%20use%20in%20Psychiatric%2
0Illness%20Flowchart.doc
Flowchart for quetiapine liquid:
http://nww.swyt.nhs.uk/drug-therapeuticstag/Documents/qipp/Switching%20from%20Quetiapine%20Liquid.doc
18
Appendix 1
Antidementia medicines for the treatment of dementia of mild to moderate
severity
What are antidementia medicines?
These medicines are used to help improve memory and other brain functions and
prevent the deterioration caused by Alzheimer’s disease (also known as dementia) and
other similar conditions.
The ones most commonly prescribed are also known as acetylcholinesterase inhibitors
(AChEIs). Another drug, memantine, may be prescribed if the AChEIs are not suitable
for the person. They are used to help people cope with activities of daily living and help
slow down further memory loss. They may also help with other problems which may be
associated with dementia such as hallucinations (seeing or hearing things), delusions
(believing things that aren’t true), anxiety, agitation and aggressive behaviour.
They come in different forms including tablets, capsules, liquids and patches. They are
known by two names –one is the name given by the manufacturer and the other is the
“generic” name that the medicine is registered by.
Acetylcholinesterase inhibitors (AChEIs)
Generic name
Manufacturers name
Donepezil
Forms
Aricept®
5mg and 10mg tablets to swallow and
melt in the mouth tablets
(orodispersible)
Galantamine
Reminyl®XL
Modified release capsules 8mg, 16mg
& 24mg,
Solution 4mg /mL
(liquid given by a dropper)
Rivastigmine
Exelon®
Capsules 1.5mg, 3mg, 4.5mg and 6mg
and oral solution 2mg/ml (liquid given
by a dropper)
Patches® 4.6mg and 9.5mg,
Memantine is given when the AChEIs are not suitable for the patient
Memantine
Ebixa ®
5mg,10mg and 20mg tablets
Oral solution 10mg/ml
(available as a pump spray)
19
How are antidementia drugs prescribed?
These are normally prescribed by a specialist memory service. There is one in
Barnsley, Dewsbury, Halifax, Huddersfield and Wakefield. If the GP thinks you will
benefit from seeing the local memory service you will be referred. If the doctor or nurse
at the memory clinic thinks you may benefit you will be prescribed an antidementia
medicine. Also geriatricians, neurologists do start some patients on antidementia drugs.
Before starting treatment you will have a memory test. This is known a mini-mental state
examination (MMSE) or an ACE-R. This will be repeated in the future to see how you
are doing and whether you are getting any benefit from the medicine. If you are not
getting any benefit the memory service may discuss stopping the medicine.
These medicines are always prescribed at a low starting dose to try and stop side
effects occurring. The dose is normally increased after a month if you have no
troublesome side effects.
Are antidementia drugs safe to take?
You will need to have blood tests and an ECG, or heart trace, before starting to take the
medicines. This is to check that it is safe for you to take the medicine.
If you have any heart problems these medicines may not be suitable for you.
If you have asthma or respiratory problems you will monitored closely as there is a small
risk that this could be made worse.
You will also be asked what other medicines you are taking to check there will be no
risks of any interactions. You should also say if you are taking any other medicines and
health supplements that you have bought so these can be checked.
Benefits of antidementia drugs
They help slow down the rate of memory loss and allow you to continue to carry out
activities of normal daily living. They may also help with some of the distressing
symptoms of anxiety, irritability, hallucinations (seeing or hearing things) and delusions
(believing things that are not true).
How will I get my medicines?
At the beginning and for at least 2 months you will be given a prescription from the
doctor or nurse in the memory clinic to take to your local chemist. It is a good idea to
use the same chemist as they will know what other medicines you are taking.
If you are doing well then a letter will be sent to your GP asking him to prescribe for you.
If agreed, you can collect the prescription from there.
20
Side effects of antidementia drugs
These are usually mild and many wear off after a short time. Side effects include
 abdominal disturbance nausea, vomiting, diarrhoea – loose bowel movements
 muscle cramps,
 fatigue or tiredness,
 insomnia – not sleeping properly at night
 headache, pain
 common cold or runny nose
 dizziness, accident
 urinary incontinence (needing to go to the toilet a lot to empty the bladder).
If these occur the dose may be reduced or the treatment changed. Very rarely side
effects can affect the heart – if they do the treatment will be reviewed.
It is important to report any side-effects to your doctor or nurse.
Further information –
For further more detailed information please discuss with a doctor, non-medical
prescriber or pharmacist
Information leaflets on individual antidementia medicines can be found on the South
West Yorkshire Partnership NHS Foundation Trust intranet which a member of staff can
access for you.
More information can be found at www.alzheimers.org.uk and
www.choiceandmedication.org/swyp/
You may also find the information and links on NHS Direct website useful.
www.nhsdirect.nhs.uk
Do not stop or make changes to any medicines without talking to a healthcare
professional.
21
APPENDIX 2
A large population-based study, in participants with normal or mildly impaired cognition, has
shown that the use of medications with anticholinergic activity, increased the risk of cognitive
decline (as measured by the MMSE) and increased the risk of mortality over 2 years, especially
in the older adult population.
Further research is needed to confirm and extend these findings, in particular the effect on
mortality of anticholinergic burden and of different doses of medicines with anticholinergic
activity but the table below provides a useful guide to the anticholinergic burden (ACB) for a
wide range of medication.
Drugs on the Anticholinergic Burden (ACB) scale
(A total ACB scale score of three or more is considered clinically relevant)
ACB Score 1 (mild)
(severe)
Alimemazine
Alprazolam
Alverine
Atenolol
Beclometasone dipropionate
Bupropion hydrochloride
Captopril
Chlorthalidone
Cimetidine hydrochloride
Clorazepate
Codeine
Colchicine
Dextropropoxyphene
Diazepam
Digoxin
Dipyridamole
Disopyramide phosphate
Fentanyl
Fluvoxamine
Furosemide
Haloperidol
Hydralazine
Hydrocortisone
Isosorbide preparations
Loperamide
Metoprolol
Morphine
Nifedipine
Prednisone/Prednisolone
Quinidine
Ranitidine
Theophylline
Timolol maleate
Trazodone
Triamterene
Warfarin
ACB Score 2 (moderate)
ACB Score 3
Amantadine
Belladonna alkaloids
Carbamazepine
Cyclobenzaprine
Cyproheptadine
Loxapine
Meperidine
Methotrimeprazine
Molindone
Oxcarbazepine
Pethidine hydrochloride
Pimozide
Amitriptyline
Amoxapine
Atropine
Benztropine
Chlorpheniramine
Chlorpromazine
Clemastine
Clomipramine
Clozapine
Darifenacin
Desipramine
Dicyclomine
Diphenhydramine
Doxepin
Flavoxate
Hydroxyzine
Hyoscyamine
Imipramine
Meclizine
Nortriptyline
Orphenadrine
Oxybutynin
Paroxetine
Perphenazine
Procyclidine
Promazine
Promethazine
Propentheline
Pyrilamine
Scopolamine
Thioridazine (withdrawn)
Tolterodine
Trifluoperazine
Trihexyphenidyl
Trimipramine
22
Notes:
1. Certain medicines eg Risperidone (mild ACB), Quetiapine (severe ACB) and Olanzapine (severe ACB) were
licensed after 1990 and therefore not prescribed to the original CFAS cohort.
2. Brand names may conceal generic drug names.
3. Some combination medicines contain anticholinergic drugs.
4. This list is indicative and some related medicines were taken by patients in the CFAS study; if appropriate
these related medicines were given an ACB score based on the ACB of the related medicine in the Aging
Health publication
Anticholinergic Medication Use and Cognitive Impairment in the Older Population: The Medical Research
Council Cognitive Function and Ageing Study
Chris Fox,_ MD,a Kathryn Richardson,_ MSc,b Ian D. Maidment, MA,cd George M. Savva, PhD,e
Fiona E. Matthews, PhD,f David Smithard, MD,gh Simon Coulton, MSc,d Cornelius Katona, MD
23
Appendix 3
Use of rivastigmine patch in
South West Yorkshire Partnership Foundation Trust
The patch should be chosen for use when there is a carer who is able to apply the patch to the
patient every day.
The patch should be applied daily at approximately the same time of day.
Prior to prescribing the patch please ensure that there is an appropriate carer who is able to
change the patch daily in line with the instructions from Novartis – Exelon patches.
Please complete the following when prescribing rivastigmine patches.
Patient name: ___________________________________________________________________
Consultant :
___________________________________________________________________
Rio/Hospital Number:
____________________________________________________________

I have identified a carer to apply the patches.

Information on application of the patches has been issued and understood.

Information given
Rivastigmine (Exelon) patch Q & A guidance.

Exelon patch including application guidance and chart.
I confirm this information has been received and understood.
Name of memory service clinician: ____________________________________________
Signature of clinician:_______________________________________________________
Date: ____________________________________________________________________
Please fax a copy to the Chief Pharmacist’s office (01422 281568) and retain a copy in the
notes or detail on electronic record.
An electronic copy can be sent to christine.smith@swyt.nhs.uk (pharmacy secretary)
24
Appendix 4
Example letter to GPs
GP letter
Our Ref:
NHS No:
Date
PRIVATE AND CONFIDENTIAL
Dear Dr
Re:
Diagnosis: (please specify type of dementia where known and secondary diagnosis eg
depression)
Care Coordinator:
Following discussion with Dr…name and job title……….. the following medication has been
prescribed/recommended for your patient (delete as appropriate)
Medication recommended:
Reason for prescribing/target symptom: (identify nature of symptom eg agitation,
depression hallucinations etc)
Further Monitoring Arrangements:

A prescription for

Based on the current evidence in relation to prescribing antipsychotic drugs in dementia
we recommend an ongoing prescription up to 3 months only. Medication should only be
continued beyond this time if the target symptom for which medication was prescribed
recurs.
months/days has been provided.
Yours sincerely
c.c.
Dr…………………………
25
Appendix 5- Equality Impact Assessment Tool
To be completed and attached to any policy document when submitted to the Executive Management Team for
consideration and approval.
Yes/No
1.
Comments
Does the policy/guidance affect one group less or
more favourably than another on the basis of:
 Race
 Ethnic origins
travellers)
NO
(including
gypsies
and
NO
 Nationality
NO
 Gender
NO
 Culture
NO
 Religion or belief
NO
 Sexual orientation including lesbian, gay
and bisexual people
NO
 Age
NO
 Disability - learning disabilities, physical
disability, sensory impairment and mental
health problems
Recommendations are given for
treatment in older people and also
for different illness types eg lewy
body dementia which may differ
from the general
recommendations.
Currently have no patient
information leaflets in any other
media other than type face.
2.
Is there any evidence that some groups are
affected differently?
YES
3.
If you have identified potential discrimination,
are any exceptions valid, legal and/or justifiable?
YES
4.
Is the impact of the policy/guidance likely to be
negative?
NO
5.
If so can the impact be avoided?
N/A
6.
What alternatives are there to achieving the
policy/guidance without the impact?
N/A
Different patients may respond
differently to anti dementia drugs.
`
7.
Can we reduce the impact by taking different
N/A
action?
If you have identified a potential discriminatory impact of this policy, please refer it to the Director of Corporate
Development or Head of Involvement and Inclusion together with any suggestions as to the action required to
avoid/reduce this impact.
For advice in respect of answering the above questions, please contact the Director of Corporate Development or
Head of Involvement and Inclusion.
26
Appendix 6- Checklist for the Review and Approval of Procedural Document
To be completed and attached to any policy document when submitted to EMT for consideration and approval.
Title of document being reviewed:
1.
2.
Comments
Title
Is the title clear and unambiguous?
YES
Is it clear whether the document is a guideline,
policy, protocol or standard?
YES
Good practice guidance
Rationale
Are reasons for development of the document
stated?
3.
Yes/No/
Unsure
YES
Development Process
Is the method described in brief?
YES
Are people involved in the development identified?
YES
Do you feel a reasonable attempt has been made to
ensure relevant expertise has been used?
YES
Is there evidence of consultation with stakeholders
and users?
YES
D&T membership and Area
Prescribing Committee
Old age psychiatrists
4.
5.
6.
7.
Content
Is the objective of the document clear?
YES
Is the target population clear and unambiguous?
YES
Are the intended outcomes described?
YES
Are the statements clear and unambiguous?
YES
Evidence Base
Is the type of evidence to support the document
identified explicitly?
YES
Are key references cited?
YES
Are the references cited in full?
YES
Are supporting documents referenced?
YES
Approval
Does the document identify which committee/group
will approve it?
YES
If appropriate have the joint Human Resources/staff
side committee (or equivalent) approved the
document?
N/A
Dissemination and Implementation
Via trust Intranet
27
Title of document being reviewed:
8.
Is there an outline/plan to identify how this will be
done?
YES
Does the plan include the necessary training/support
to ensure compliance?
N/A
Have archiving arrangements for superseded
documents been addressed?
YES
N/
Process to Monitor Compliance and
Effectiveness
Are there measurable standards or KPIs to support
the monitoring of compliance with and
effectiveness of the document?
Is there a plan to review or audit compliance with
the document?
10.
11.
Comments
Document Control
Does the document identify where it will be held?
9.
Yes/No/
Unsure
Use of clinical queries mechanism
YES
Prescribing Observatory for
Mental Health Audit Plan
Review Date
Is the review date identified?
YES
Is the frequency of review identified? If so is it
acceptable?
YES
Overall Responsibility for the Document
Is it clear who will be responsible implementation
and review of the document?
Appendix 7- Version
YES
Control Sheet
This sheet should provide a history of previous versions of the policy and changes made
Version
Date
Author
Status
Comment / changes
1
August
2009
Lynn Haygarth
Written in line with NICE guidance
1.1
October
2010
Lynn Haygarth
Updated in line with new guidance for
rivastigmine patches
2
June
2012
Lynn Haygarth
Changes due to revised NICE guidance
and updated to include Barnsley and
use of memantine.
Drugs on the Anticholinergic Burden
(ACB) scale.
28