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Dr Kreshnik Hoti BPharm, MPS, AACPA, PhD

Best Practice Pharmacy Dementia care

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2

Learning outcomes

Develop and understanding on medications used in dementia

 

Identify medications that can worsen cognition

 

Develop an understanding on medication related monitoring needs and outcomes in patients with dementia

 

Develop an understanding on pharmacists’ role in Dementia care

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What is dementia?

Latin word ‘demens’

Broad term

Symptoms descriptive of a range of conditions

• Brain function impairment

• Language, memory, perception, personality and cognitive skills

>65 years of age, likelihood doubles in 5 year intervals

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Definition (WHO)

“a syndrome due to disease of the brain, usually of a chronic or progressive nature, in which there is disturbance of multiple higher cortical functions, including memory, thinking, orientation, comprehension, calculation, learning capacity, language, and judgement. Consciousness is not clouded. The impairments of cognitive function are commonly accompanied, and occasionally preceded, by deterioration in emotional control, social behaviour, or motivation. This syndrome occurs in Alzheimer’s disease, in cerebrovascular disease, and in other conditions primarily or secondarily affecting the brain”

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Early signs

Ability to learn and remember new information

Difficulties with tasks which are familiar

Progression

More basic activities affected

Higher mental function impairment progress over months to years 

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Cognitive, psychiatric and behavioural symptoms

memory problems

communication difficulties

confusion, wandering, getting lost

personality changes and behaviour changes such as agitation, repetition, following

depression, delusions, apathy and withdrawal

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Dementia – national figures

Source: Alzheimer’s Australia

280.000 Australians

1600 new cases weekly

3rd leading

cause of death

Worldwide cost: US$604 billion in 2010

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Source: Alzheimer’s disease international; World Alzheimer’s report 2010. The global economic impact of dementia

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Dementia major contributor to disability

dem

entia

stro

ke

mus

culos

celet

al

card

iovas

cular

canc

er

0

2

4

6

8

10

12

years lived with disability

Source: World Health Organization. World Health Report 2003—Shaping the future. Geneva: WHO, 2003.

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Dementia predictions

35.6 million worldwide

4.6 million cases every year

People affected double every 20 years

81.1 million people affected by 2040

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Dementia predictions cont’d

Ferri et al. Global prevalence of dementia: a Delphi consensus study. Lancet 2005; 366: 2112–17

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Dementia – causes

62% (Alzheimer’s disease)

17% (vascular dementia)

10% (mixed dementia)

3% (other)

2% (fronto- temporal)

4% (lewy bodies)

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Dementia – causes

• Alzheimer’s disease causes:

• Biological• Genetics• Inflammation

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Risk factors

Modifiable:

• Obesity

• Smoking

• Physical activity and exercise

• Alcohol

• Cognitive reserve

• *head injury

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Risk factors

Treatable medical conditions:

• stroke

• diabetes

• midlife hypertension

• midlife hypercholesterolemia

• hyperhomocysteinaemia

• depression (?)

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Risk factors

Non-Modifiable:

• age

• family history

• small head size

• male gender

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Treatment

Patients and family involvement as soon as diagnosis is made

Support for daily activities

Address co-existing medical conditions

Avoid medications exacerbating cognitive function

Treat Vitamin B12 or folate deficiency if present

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Treatment

No cure

None of the available drugs prevent Alzheimer’s or modifies its pathology

Symptoms such as memory loss and confusion may be reduced (for a limited time)

Acetylcholinesterase inhibitors& memantine

Combination

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Treatment - Acetylcholinesterase inhibitors

• Donepezil

• Galantamine

• Rivastigmine

Decrease the breakdown of acetylcholine and therefore reduce the deficiency of cholinergic neurotransmitter activity

First line agents

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Treatment - Acetylcholinesterase inhibitors

25-50% of patients experience delayed deterioration of cognition by 6 months

12-20% of patients by 1 year

Benefits in cognition, function and global outcomes (MMSE gain 1.5-2 points)

Benefits assessed after 3 months

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Acetylcholinesterase inhibitors-ADVERSE EFFECTS

Incidence related to dose

Use in some patients is limited by adverse effects, especially gastrointestinal

Common: nausea, vomiting, loss of appetite, diarrhoea

Commonly increase bladder and bowel urgency and contribute to incontinence

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Treatment - memantine

AD associated with excess glutamate, therefore memantine reduces glutamate-induced neuronal degradation

Specialist initiated

Moderate to severe AD

Benefits in cognition, function, global outcome

Common adverse effects: Headache, constipation, confusion and dizziness

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Treatment summary

Generic Dosage form Dose Approved for Contraindicated

Donepezil(Aricept)

tablet 5mg up to 10mg evening

All stages GI/ureteric obstruction; Active PU

Galantamine(Reminyl, Galantyl)

CR capsule 8mg daily up to 16mg morning with food

Mild to moderate Severe hepatic impairment; CrCl <10 mL/minute; GI/ureteric obstruction; Active PU

Rivastigmine(Exelon)

Capsule, oral liquid, patch

Oral: 1.5mg BD up to 6mg BD CCPatch: 4.5mg up to 9.5mg daily

Mild to moderate Severe hepatic impairment; GI/ureteric obstruction; Active PU

Memantine(Ebixa)

Tablet 5 mg up to 20mg daily

Moderate to severe

History of seizures

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Pharmaceutical Benefits Scheme implications

Acetylcholinesterase inhibitors and memantine require authority approval

Donepezil example: • INITIAL APPLICATION FOR THE TREATMENT OF MILD TO

MODERATELY SEVERE ALZHEIMER'S DISEASE - Patients with an (S)MMSE of 10 or more

• Confirmation of diagnosis must be made by or in consultation with a specialist/consultant physician (including a psychiatrist).

• To continue treatment: patient demonstrated improvement in cognitive function

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Vitamins and supplements

Do they help?

B vitamins

Omega 3

Mediterranean diet

Vitamin E

Ginkgo Biloba

Aspirin

Brahmi

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Other agents

Statins

Testosterone

Oestrogen

Anti-inflammatory agents

Selegiline

Future therapies

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Medications negatively affecting dementia

Drugs with anticholinergic effects (Australian Medicines Handbook 2012)

amantadine, amitriptyline, atropine

belladonna alkaloids, benzhexol, benztropine, biperiden, brompheniramine

chlorpheniramine, chlorpromazine, clomipramine, clozapine, cyclizine, cyclopentolate, cyproheptadine

darifenacin, dexchlorpheniramine, dimenhydrinate, diphenhydramine, disopyramide, dothiepin, doxepin

glycopyrrolate

homatropine, hyoscine (butylbromide or hydrobromide)

imipramine, ipratropium (nebulised)

mianserin

nortriptyline

olanzapine, orphenadrine, oxybutynin

pericyazine, pheniramine, pizotifen, prochlorperazine, promethazine, propantheline

solifenacin

tiotropium, tolterodine, trimeprazine, trimipramine, triprolidine, tropicamide

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Medications negatively affecting dementia

Anticholinergic Cognitive Burden (ACB)• Score 1-3

• Definite anticholinergics score 2&3

• Every definite anticholinergic increases the risk of cognitive impairment by 46% over 6 years

• 1 point increase in ACB score = 0.33 decline in MMSE over 2 yrs

Antipsychotics

Sedatives

Tricyclic antidepressants

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Behavioural and psychological symptoms in dementia (BPSD)

Challenging & distressing

Causes: • Brain cells progressively deteriorate

• Environmental

• Medications

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BPSD

Early stages:irritability

anxiety

depression

Later stages:aggression

agitation

emotional distress

hallucinations

outbursts

delusion

sleep disturbances

restlessness

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BPSD

Review/Treat potential underlying causes:

Possible physical causes of distress or delirium• Pain, dehydration, LUTS, infection…

Medications which impair cognition

Environmental factors

Depression

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BPSD treatment

Non-drug options – first line

Antipsychotics (hallucinations, delusions or seriously disturbed behaviour)

Mood stabilizers such as carbamazepine or valproate

Antidepressants

Acetylcholinesterase inhibitors or memantine

Anxiety and agitation (oxazepam for no longer than 2 weeks)

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Antipsychotics – considerations:

Risperidone approved for BPSD

Recommended for use when symptoms cause severe distress or immediate risk of harm

Monitor if behaviour improved and adverse effects tolerated

Therapy reviewed every three months

Many troublesome symptoms do not respond

BPSD often resolves spontaneously within 12 weeks

Antipsychotics increase the risk of death in BPSD patients

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Pharmacists’ role

Refer patients with suspected cognitive impairment

Early diagnosis

Patient & family counselling and education

Promotion of risk reduction strategies

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Pharmacists’ role

Source of information• Patient,

• Family,

• Health professionals

Monitoring drug interactions

Monitoring drug contraindications

Monitor medication compliance

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Pharmacists’ role

Dose administration aids

Medication reviews• Medication usage reviews

• Home medication reviews

Identifying medications contributing/exacerbating cognitive decline

Quality use of medicines

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References Australian Medicines Handbook 2012

eTherapeutic Guidelines, Neurology

Alzheimer’s Australia; http://www.fightdementia.org.au

Alzheimer’s Association; www.alz.org

Ballard et al. Alzheimer’s disease. Lancet 2011; 377: 1019–31

Ferri et al. Global prevalence of dementia: a Delphi consensus study. Lancet 2005; 366: 2112–17

Alzheimer’s disease international; World Alzheimer’s report 2010. The global economic impact of dementia

World Health Organization. World Health Report 2003—Shaping the future. Geneva: WHO, 2003.

McCullagh CD et al. Risk factors for dementia. Advances in Psychiatric Treatment 2001; 7:24–31

Australian Institute of Health and Welfare 2007. Dementia in Australia. National data analysis and development

Archer et al. The effects of commonly prescribed drugs in patients with Alzheimer’s disease on the rate of deterioration. J Neurol Neurosurg Psychiatry 2007;78:233–239.

The Aging Brain Program at the IU Center for Aging Research. Anticholinergic Cognitive Burden List (ACB). 4/4/12

Campbell N, Boustani M, Limbil T, Ott C, et al. The cognitive impact of anticholinergics: a clinical review. Clinical Interventions in Aging. 2009;4(1):225-33