Transcript Treatment options for the management of Depression in the

Dementia
Stephen Bleakley, Deputy Chief Pharmacist
Southern Health NHS Foundation Trust
October 2013
Director: The College of Mental Health Pharmacy
Outline
Facts and figures
 Symptoms
 Types of dementia and pathology
 Diagnosis
 Management
 Behavioural & psychological
symptoms of dementia (BPSD)

What is dementia?
A progressive degenerative
neurological disease
• Affects 800,000Dementia
people in the UK
– 5% of those aged over 65
– 20% over 80s
• Figure expected to double over the next
30 yrs
• Predominant features are
– cognitive decline
– loss of functional ability
• Accompanying behavioural symptoms in
about 90% of patients
Cognition
A group of mental processes that include:
•
•
•
•
•
Attention and memory
Learning and retaining new information
Reasoning, problem solving
Decision making
Understanding and producing language
i.e being able to receive information, comprehend
it, store it, retrieve it and use it
Functional ability
Able to perform Activities of Daily Living (ADL)
• Basic ADL skills:
• Personal hygiene, grooming
• Dressing/undressing, self-feeding
• Functional transfers (on/off bed or toilet)
• Bowel and bladder management
• To be able to live independently (higher level):
• Housework
• Taking medication
• Shopping/ groceries
• Managing money
Risk factors for dementia
 Age


Gender (women > men)
Genetic



About 1 in 4 cases are familial
1st degree relatives have 2.5 fold increased risk
Downs syndrome
 High BP, high cholesterol, smoking,
alcohol
 Other: Low IQ/ education level,
head injury, toxins e.g. aluminium (?)
Types of dementia

Alzheimer’s disease

Vascular Dementia

Dementia with Lewy Bodies (DLB)

Mixed dementia

Others
Alzheimer’s disease
Most common type (60%)
 Insidious onset, gradual deterioration
 First sign is failing memory
 Cognition, language, behaviour and
ADL all affected
 Women > men
 Profound cholinergic loss

Cholinergic Hypothesis
 Degeneration
of cholinergic neurones
 A reduction
in levels of acetylcholine
released at the cholinergic synapse
 Cognitive
deterioration results
Vascular Dementia
 Caused
by ischaemic damage to the brain

Usually follows a stroke or multi-infarct

Abrupt onset, stepwise deterioration

Depression can be common

No licensed treatment
Dementia with Lewy Bodies (DLB)

Presence of abnormal protein deposits inside
nerve cells
Clinical Features
 Dementia
 Parkinsonism (rigidity, tremor)
 Visual hallucinations
 Fluctuation in severity
 Extreme sensitivity to antipsychotic drugs
 No licensed treatment

Diagnosis
• Exclude physical causes
• Cognitive Assessments eg Mini Mental
State Examination (Psychiatrist/
psychologist)
• ADL functioning (Occupational Therapist)
• Involve relatives and carers
Physical Causes
• Confusion, delirium, cognitive impairment
can also be caused by:
– Hyponatraemia
– Hypoglycaemia
– Hypothyroidism
– Alcohol related disease
– Low vitamin B12 and folate levels
– Urinary Tract or chest infections
– Medicines eg antipsychotics,
anticholinergics
Mini Mental State Examination
 What
is the year, season, date?
 Where are we? country, city, floor?
 Name 3 objects: table, apple, penny
 Serial of 7s
 Spell “WORLD” backwards
 “No ifs ands or buts”
 Follow a command: Take a paper in your right
hand, fold it in half & put it on the floor
 Read and obey: (close your eyes)
 Copy this diagram
Acetylcholinesterase Inhibitors
Donepezil
(Aricept)
Mech. of Inhibits
action
AChE
Rivastigmine
(Exelon)
Galantamine
(Reminyl)
Inhibits
Inhibits
AChE and AChE and
BuChE
nicotinic
agonist

AChE = Acetylcholinesterase

BuChE = Butyrylcholinesterase
Acetylcholinesterase Inhibitors
They all essentially work in the same way
 They inhibit the enzyme(s) which is responsible
for the breakdown of Acetylcholine
 Leading to increase in Acetylcholine in the brain
 They are not a cure but stabilise memory for a
few months/ years
 They don’t work for everyone (NNT 4-12)
 NICE recommend them for mild to moderate
Alzheimer’s Disease only (not in vascular or LBD
although sometimes used off-license)

Comparisons of AChEIs
Drug
Advantages
Disadvantages
Donepezil
Once
daily dose
Not affected by food
Interactions
Rivastigmine
Patch
Twice
Galantamine
Liquid
and liquid
available
Interactions with
other drugs unlikely
occur
No liquid
can
daily dose
for capsules.
Reduced
absorption if taken
with food
available
Interactions can
occur
Modified release once
daily capsules available Food slows down
absorption of drug
Cholinergic Side Effects
 GI
disturbance
 nausea, vomiting, diarrhoea (take with/after
food)
 Weight Loss
 Headache / Dizziness
 Fatigue
 Muscle Cramps
 Sweating
 Disturbed sleep and nightmares
 Bradycardia (caution in sick sinus syndrome)
Interactions with AChEIs
Drug
Metabolism
Levels
increased by
Donepezil
(Aricept®)
Substrate at
Ketoconazole
CYP 3A4 and Itraconazole
2D6
Erythromycin
Quinidine
Fluoxetine
Rivastigmine
(Exelon)
Non-hepatic
metabolism
Galantamine
(Reminyl)
Substrate at
Ketoconazole
CYP 3A4 and Ritonavir
2D6
Erythromycin
Quinidine
Fluoxetine
Paroxetine
Amitriptyline
Levels
decreased by
PD interactions
Rifampicin
Phenytoin
CBZ
Alcohol
Anticholinergic
Cholinergic agonist
Muscle relaxants
(succinylcholine)
Beta blockers
PK interactions unlikely
(May inhibit metabolism of substances
mediated by BuChE eg cocaine,
heroin)
None reported
The Maudsley Prescribing Guidelines – 11th Edition
Anticholinergic
Cholinergic agonist
Muscle relaxants
Anticholinergic
Cholinergic agonist
Muscle relaxants
Beta/ Ca-channel
blockers, digoxin,
amiodarone
AChEI + Anticholinergics
• Avoid combination where possible.
• Inefficient use of AChEIs- not cost-effective
• Anticholinergics can also cause delirium,
confusion, disorientation etc..
• If a bladder anticholinergic drug is required then
best to chose:
• a more (bladder) selective drug eg
Darifenacin (less impairment of cognitive
function) or
• one with reduced penetration through the BBB
eg Trospium (reduced CNS effects)
Australian Prescriber | VO L UME 2 9 | N UMB E R 1 | F E B R UA RY 2 0 0 6
Memantine (Ebixa®)
NMDA (N-methyl-D-aspartate) antagonist
 Glutamate binds to NMDA receptors allowing
calcium into the brain nerve cell- cell
degeneration
 Memantine prevents this destruction by blocking
the NMDA receptor site
 For Moderate to Severe Alzheimer’s disease
 5mg daily increased by 5mg weekly to 20mg daily
 S/Es: constipation, headache, dizziness,
hypertension, drowsiness

Drug interactions of Memantine
Drug
Metabolism
Levels
increased by
Levels
decreased by
Pharmaco-dynamic
interactions
Memantin
e
Primarily
non-hepatic
Cimetidine
Ranitidine
Procainamide
Quinidine
Quinine
Nicotine
None known
Effects of L-dopa,
dopaminergic agonists
and anticholinergics may
be enhanced
Renally
eliminated
Carbonic
anhydrase
inhibitors,
sodium
bicarbonate
Isolated cases
of INR
increases with
warfarin
Effects of barbiturates
and neuroleptics may be
reduced
Avoid combination with
amantadine, ketamine,
dextromethorphan
Dose adjustments for
antispasmodics,
dantrolene or baclofen
Taylor D, Paton C, Kapur S. Maudsley Prescribing Guidelines in Psychiatry - 11th Edition. Oxford, UK: Wiley-Blackwell; 2012.
Stopping Treatment

Lack of clinical benefit
 difficult to assess

Worsening of condition

Side effects

Reduce dose gradually to withdrawal
NICE Guidance (Updated March 2011)
• AChEIs recommended in mild-moderate AD
• Memantine recommended in:
– Moderate AD in pts intolerant to AChEIs
– Severe AD (MMSE < 10)
• When assessing severity, do not rely solely on cognition scores
– Consider linguistic difficulties, level of education, cultural
background
– Hearing, vision, learning disability, communication problems
• Except in clinical trials, do not use:
– AChEIs or memantine in vascular dementia
– AChEIs in Mild Cognitive Impairment (MCI)
Quiz- Dementia
• Name the 3 most common types of
Dementia.
• Which type may occur after a stroke?
• In which type must you always avoid
antipsychotics?
• How does the main class of
medication for AD work?
• What are some of the side effects of
AChEIs?
• When should you use Memantine?
Behavioural & Psychological Symptoms
of Dementia (BPSD)
• Anxiety
• Agitation & aggression
• Insomnia
• Hallucinations, delusions
• Depression
• Wandering, disinhibition
• Vocalisations
Triggering factors
• BPSD may be caused by:
–Pain
–Constipation
–Infections (eg. UTI, chest infection)
• Eliminate these potential causes
first
• Symptoms may resolve
BPSD Leads to:
– Considerable carer burden
– Care home admissions
– Hospital admissions
– Increased cost of care
• Causes still unknown
• Various neurotransmitters
implicated
– Acetylcholine, dopamine,
serotonin
Non-pharmacological Management
 Psychological
therapies
 Aromatherapy
(evidence for lavender & Melissa balm)
 Snoezelen
rooms (specially designed rooms with
soothing and stimulating environment)
 Pet
therapy
 Music
therapy
 Massage
therapy
 Reflexology
 Homeopathy
The best non-drug approaches
Individualised
Engaging
care
activities
Compassion
and empathy
Chemical Cosh’ for dementia kills 1,800 Britons a year
1,800 a year die from dementia ‘cosh’ pills
Adverse effects of antipsychotics
in dementia

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Stroke risk-3-fold increase risk of stroke
Mortality rate 1.6 to 1.7 times higher
Hastening of cognitive decline
DLB extreme sensitivity to antipsychotics
EPSEs
Sedation, increased agitation
Metabolic side effects
Warnings with ALL typical and atypical
antipsychotic drugs
ONLY Risperidone licenced for BPSD:
-“Up to 6 weeks’ treatment of persistent
aggression in patients with moderate to
severe Alzheimer’s dementia who have
not responded to non-pharmacological
approaches and where there is a risk of
harm to themselves or others”
When prescribing antipsychotics in Dementia
•
•
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•
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•
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Exclude physical illness eg pain, infection
Target the symptom requiring treatment
Consider non-pharmacological methods first
Carry out risk/benefit analysis
Discuss options and risks to patient and
relatives/carers
Maintain lowest possible dose for shortest period
Review appropriateness of treatment (every 3
months)
Monitor for side effects
Document clearly treatment choices and
discussions with patient, family or carers
Other Pharmacological Management
• Benzodiazepines
• Antidepressants (SSRIs, trazodone)
• Mood stabilisers
(carbamazepine,valproate)
• Acetylcholinesterase inhibitors/
Memantine
• Paracetamol
• Antipsychotics
How can pharmacists help?
Role of the pharmacist

Help identify those in need of referral

To provide up to date information on efficacy and
safety of drugs to patients, carers & prescribers
 Help to ensure national guidance is followed
 Encourage regular review / audit of medication in BPSD
 Efficacy benefits
 Adverse effects

THUS: Improve clinical outcomes & quality of life in pts
and decrease burden to family and carers
Web resources
• www.choiceandmedication.org/southernhealth
• www.southernhealth.nhs.uk
– Shared care guidelines on AChEIs and
memantine
•
•
•
•
http://www.alzheimers.org.uk/
http://www.dementiauk.org/
http://www.marc.soton.ac.uk/
http://www.dendron.nihr.ac.uk/
THANK YOU
[email protected]
www.southernhealth.nhs.uk
www.cmhp.org.uk
References
• Oxford Textbook of Psychiatry- Part 4- Dementias
• Taylor D, Paton C, Kapur S. The Maudsley
Prescribing Guidelines 11th Ed
• Bishara D. The Pharmacological Management of
Alzheimer’s Disease. Progress in Neurology and
Psychiatry. 2010; 14: 16-22
• Mini Mental State Examination -adapted from
Folstein et al
• NICE Clinical guideline 42. Dementia. Revised
March 2011