Transcript Pharmacological treatments for Alzheimer`s

Treatment for Behavioral
and Psychological
Symptoms of Alzheimer’s
Disease
Mindy Wasson
April 12, 2007
Mr. Powdrill
Alzheimer’s Disease (AD)

Definition: “ a progressive neurodegenerative disease
characterized by a loss of function and death of nerve
cells in several areas of the brain.”
Statistics in the U.S.

Prevalence:
affects 4.5 million people
 accounts for 90% of all cases of neurodegenerative
diseases.
 Expected to affect as many as 16 million by 2050
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Mortality:
over 100,000 die each year
 4th leading cause of death in adults
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Symptoms of AD

Cognitive:

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Functional:
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memory loss, language
disturbances
difficulty dressing, difficulty
eating, incontinence
Behavioral/Psychological:

agitation, aggression, delusions,
hallucinations
Behavioral and Psychological
Symptoms of AD (BPSD)
Psychosis
Agitation
Altered Circadian
Rhythms
Anxiety
Depression
BPSD are very common
Cumulative prevalence:
since onset of illness
Point prevalence:
over the last month
Community sample of 362
people with dementia
___________________
80%
62%
Why are BPSD important?

Excess disability

Increased hospitalization
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Premature institutionalization
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Suffering for patient and caregiver
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Substantial increase in financial
costs

Increased risk for abuse
Overview of Treatment Strategy
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Address underlying medical/medication-related
factors
Caregiver education/training
Non-pharmacological interventions

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Always 1st choice
Pharmacological interventions
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ONLY if non-pharmacological behavioral
interventions fail
Medical and Medication-related
factors
Medical factors:
 Vision/hearing loss
 Acute/chronic pain
 Malnutrition
 Dehydration
 Urinary retention
 Urinary incontinence
 Constipation
 Infection
Medications:
 Anticholinergics
 Opiates
 Sedative-hypnotics
 Antidepressants
 Beta-blockers
 Antipsychotics
 Benadryl
 Quinolones
Caregiver Education and Support
3 R’s:
 Repeat
 Reassure
 Redirect


Used to stress the importance
of patience and coolness
during interactions and
redirection
Also to remind the difficulty
of patient’s situation and the
need to be supportive and not
demanding
ABC’s
 Antecedent
 Must assess multitude of
potential causes of BPSD
 Behavior

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Assess reactions of patient to
causes found and develop a
theme and appropriate plan of
action
Consequences

Assess the severity of
behavior; positive/negative
reinforcement
Non-pharmacological Interventions

Careful evaluation of environment may be a clue
to underlying cause of BPSD:

Consistent and pleasant environment:

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Speak slowly, keep commands simple, use gestures
Gentle touch, soft lighting, music, calm colors, orientation clues,
plants
Consistent schedule:
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Stable routine; change must be gradual
Promote sleep: increase daytime activity with supervised walks;
spend time outside; gardening; molding clay
Pharmacological Interventions

In general, modest benefits with significant potential for side
effects
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Categories
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Atypical antipsychotics- best evidence
Antidepressants- some evidence
Cognitive Enhancers- some evidence
Anticonvulsants- mixed results
Typical antipsychotics- not used
Sedative-hypnotics- serious side effects
 All choices are off-label usages
Efficacy of Atypical Antipsychotics
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Primary off-label treatment choice
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Up to 45% people with dementia are taking antipsychotics
small effect on behavioral symptoms
NNT=6 patients must be treated for 1 to
respond
Response usually in first 2-4 weeks
Effects can be variable; high rates of
discontinuation
Atypical Antipsychotics: SAFETY
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Extrapyramidal symptoms
Diabetes and dyslipidemia*
Cerebrovascular adverse
events (CVAEs)*
Mortality*
Cognitive Impairment
Fails
Sedation
QT prolongation
FDA Warnings: Atypical
Antipsychotics

CVAEs (Apr. 2003, Jan. 2004):

Risperidone:
Meta-analysis of elderly patients with AD (n=1779)
 significantly higher incidence of CVAEs with risperidone
versus placebo
 Overall odds ratio was 3.32
 45% of events were considered serious/life-threatening

FDA Warnings: Atypical
Antipsychotics
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Mortality (April 2005):
Meta-analysis of 17 placebo-controlled clinical trials
(n=5106) among elderly patients with dementia
 assessed incidence of mortality for aripiprazole,
olanzapine, risperidone, quetiapine
 Pooled 4.5% incidence of mortality for atypical
antipsychotics compared to 2.6% for placebo
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FDA Warnings
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FDA concluded that atypical antipsychotics
should no longer be used among elderly patients
with dementia
So what should be used?
Very few well designed clinical trials; mostly
retrospective and contradictory:
 Antidepressants: modest benefits, but safer
 Anticonvulsants: questions about efficacy, tolerability,
and drug-drug interactions
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Cognitive enhancers:
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Sedative-hypnotics:
modest benefits, patient should
probably already be on these anyway
risks generally outweigh benefits
Conclusions
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AD is prevalent, deadly, and on the rise
BPSD has been seen up in to 80% patients with AD

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Major negative impact on patients, families, and caregivers
Non-pharmacological: Evidence-based interventions
can be very effective even in extreme situations of
distress
ALWAYS 1st choice; requires persistence and training to be
fully effective
 Continue interventions even when pharmacological treatment
is indicated
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Conclusions
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Pharmacological:
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Antipsychotics have been primary treatment choice
for over a decade
Are unsafe and only modestly effective
 Should only be used when immediate harm to patient or
others exists; NEVER as 1st line
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Best treatment option is now unclear
 Need well-designed clinical trials assessing
effectiveness and safety of non-antipsychotic choices
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References
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