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Transcript
PHARMACOLOGICAL
STRATEGIES IN THE
MANAGEMENT OF ALZHEIMER’S
DISEASE
Daniel Varon, MD
Wien Center for Alzheimer’s Disease
and Memory Disorders
WHAT IS DEMENTIA?
CLASSIFICATION OF ABNORMAL
COGNITIVE STATES
SUBJECTIVE Memory Complaints
No Cognitive or Functional deficits
MILD Cognitive Impairment (MCI)
Memory complaints, some cognitive deficits but
No functional Deficits.
DEMENTIA
Cognitive + Functional Deficits
Concept of Dementia
NORMAL
SUBJECTIVE IMPAIRMENT
DECLINE
MILD COGNITIVE IMPAIRMENT
DEMENTIA
TIME
Types of dementia
Goals of Treatment in Dementia

GOALS



TARGETS



Improve or preserve ADL function
Reduce caregiver burden
Enhance quality of life
Improve or preserve cognitive function
Improve or preserve behavioral function
Slow deterioration
Manage psychiatric and behavioral symptoms
MEDICATIONS IN DEMENTIA
SYMPTOMS
- COGNITION
- Memory, language, orientation,
judgment, planning.
- BEHAVIOR
- Depression, anxiety, agitation,
hallucinations, paranoia,
aggressiveness.
- OTHER
- Weight loss, incontinence,
gait disturbances, sleep
disturbances
Treatment
NATURAL COURSE
NORMAL
SUBJECTIVE IMPAIRMENT
DECLINE
MILD COGNITIVE IMPAIRMENT
IDEAL
WITH CURRENT
TREATMENTS
DEMENTIA
TIME
MEDICATIONS IN DEMENTIA
COGNITION
Cholinesterase inhibitors
- Aricept – Donepezil
- Razadyne – Galantamine
- Exelon – Rivastigmine
Antagonist of the NMDA glutamate receptor
- Namenda – Memantina
MEDICATIONS IN DEMENTIA
Cholinesterase Inhibitors
MEDICATIONS IN DEMENTIA
ARICEPT – Donepezil
Rogers SL, et al. Neurology 1998
MEDICATIONS IN DEMENTIA
ARICEPT – Donepezil
Dose: 5mg daily for 4 weeks and then increases to
10mg. There is a 23mg formulation.
Interactions:
- Metabolized in the liver
MEDICATIONS IN DEMENTIA
RAZADYNE – Galantamine
Raskind et al. 2000
MEDICATIONS IN DEMENTIA
RAZADYNE – Galantamine
Dose:
4mg every 12h x 4 weeks
8mg q12h x 4w
12mg every12h
Galantamine ER once a day 8, 12, 24mg
Interactions:
- Metabolized in the liver
MEDICATIONS IN DEMENTIA
EXELON – Rivastigmine
Farlow et al. 2000
MEDICATIONS IN DEMENTIA
EXELON – Rivastigmine
Oral
1.5mg twice a day x 4 weeks
3mg twice a day x 4 weeks
4.5 mg twice a day x 4 weeks
6mg twice a day
Patch
4.6mg o 9.5mg
Not metabolized in the liver
MEDICATIONS IN DEMENTIA
Cholinesterase inhibitors
- Aricept – Donepezil
- Razadyne – Galantamine
- Exelon – Rivastigmine
Side effects:
- Nausea, vomiting
- Diarrhea
- Anorexia
- Slow heart rate
MEDICATIONS IN DEMENTIA
NAMENDA – Memantina
Reisberg B, et al. NEJM 2003
MEDICATIONS IN DEMENTIA
NAMENDA – Memantina
Dosis: 5mg every 7 days
5mg q12h x 7 days
5mg QAM y 10mg QPM x 7 days
10mg q/12h
Interactions:
- Not metabolized in the liver
- Excreted through the kidney mostly
unchanged (50 - 80%)
MEDICATIONS IN DEMENTIA
NAMENDA – Memantine
Behavioral and Psychological Symptoms of
Dementia (BPSD)




Symptoms of disturbed perception, thought content, mood or
behavior that frequently occur in patients with dementia.
BPSD leads to increased suffering, early institutionalization,
increased cost of care, and causes significant loss in the quality
of life for the patient’s caregivers and family.
About two-thirds of people with dementia experience some
BPSD at some point during the course of their illness.
The figure may rise to 70-80% among patients with dementia
who reside in nursing homes.
Common Psychological Changes:
Early and Middle Stages of Dementia


Depression
Anxiety


Paranoia



Fear of being alone
Delusions about “imposters”
Accusations of infidelity
Personality changes
Behavioral Disturbances:
Middles Stages


Wandering
Restlessness



Inappropriate handling of objects



Rummaging
Hoarding
Verbal agitation



Fidgeting
Pacing
Repetitious speech
Verbal aggression
Physical combativeness
Appropriate treatment of behavioral
symptoms in patients with dementia



Many factors can cause or contribute to behavioral
disturbances
Causal and contributing factors must be identified
and should inform treatment
Combination of treatment modalities is often
necessary to ensure optimal care
How does memory impairment lead to
behavioral problems?
Example
Patient is able to dress himself, but can’t remember
where his clothes are kept
Walks around naked
How does language impairment (aphasia)
lead to behavioral problems?
Example
Patient who can’t verbally communicate her dislike
of milk
Throws milk carton across the room
How does impaired recognition (agnosia)
lead to behavioral problems?
Example
Patient can maneuver to pull down his pants, but
can’t recognize that a toilet is a receptacle for
urination
Urinates on floor
How does impairment in performance of motor
tasks (apraxia) lead to behavioral problems?
Example
Patient is continent of bladder, but cannot unzip or
unbutton to pull down her pants
Wets her clothing
How does impaired executive functioning
lead to behavioral problems?

Example
Patient lacks understanding of socially appropriate
behavior and is unable to restrain impulses
(disinhibition)
Talks or behaves in a sexually inappropriate
manner in public.
Initial approach to assessment,
management, and prevention

Recognize
areas of impaired function
and
areas of preserved function


Help compensate for impairment
Support residual abilities
WHAT OTHER FACTORS MAY
CONTRIBUTE TO BEHAVIORAL
CHANGES IN PATIENTS
WITH DEMENTIA?
Management of Behavioral
Disturbances in Dementia





Address unmet physical and psychological needs
Environmental modifications
Treat medical conditions
Treat psychiatric symptoms
 Non-pharmacologic interventions
 Pharmacologic treatment
Interpersonal strategies / caregiver education
Medical conditions and somatic discomfort that
can lead to behavioral disturbances
Somatic discomfort
Medical condition
– Arthritis

Pain
– Dehydration

Constipation
– Prostatic hypertrophy

Urinary urgency
– COPD

Shortness of breath
– Cerebrovascular disease

Dizziness
– CHF

Fatigue
– Impaired vision

Heartburn
– Impaired hearing

Headache
– Urinary infection
Nonpharmacologic Strategies







Arrange regular exercise
Try to maintain social/family activities
Review photos and souvenirs
Reminisce and tell old stories
Senior centers and day centers
Engaging in tasks and familiar activities
within their capacities
Limit expectations
Communication Techniques








Use short sentences
Use simple sentence structure, and frequent reminders about
content of conversation
Keep concepts focused
Use repetition
Be patient
Be prepared to have the same conversation multiple times
Do not use leading questions if you want to find out
information (“You’re hungry, aren’t you?”)
Don’t argue. Don’t expect logic.
MEDICATIONS IN DEMENTIA
BEHAVIORAL SYMPTOMS
Sleep disturbance
Apathy
Anxiety
Depression
Agitation
Hallucinations
Delusions
0
5
10
15
20
25
30
MEDICATIONS IN DEMENTIA
DEPRESSION
SSRI’s - sertraline (Zoloft), citalopram (Celexa), escitalopram
(Lexapro).
Other antidepressants
- WELLBUTRIN – Bupropion
- EFFEXOR – Venlafaxine
- CYMBALTA – Duloxetine
- REMERON – Mirtazapina
MEDICATIONS IN DEMENTIA
DEPRESSION
Antidepressants:
- SSRIs:
Zoloft – Sertraline
Celexa – Citalopram
Lexapro – Escitalopram
Few interactions
Easy to tolerate
Paxil – Paroxetine
More interactions
More anticholinergic
Prozac – Fluoxetine
Long half life
More interactions
MEDICATIONS IN DEMENTIA
Antidepressants:
- SSRIs: Selective Serotonin Reuptake Inhibitors
Serotonin
- Side effects:
- Changes in appetite
- Nausea
- Dizziness
- SomnolenceLow sodium (less common)
-
MEDICATIONS IN DEMENTIA
Other antidepressants:
- WELLBUTRIN – Bupropion
Not used in patients with epilepsy
- EFFEXOR – Venlafaxine
Can increase BP transiently
- CYMBALTA – Duloxetine
Can cause changes in hepatic function
Can help with chronic pain
- REMERON – Mirtazapine
Increases sleep and appetite
MEDICATIONS IN DEMENTIA
PSYCHOSIS
- HALLUCINATIONS
Visual (Common in Lewy Body Disease )
Auditory
Sensory
- DELUSIONS (More common than hallucinations)
Paranoia
Confabulation
Jealousy
MEDICATIONS IN DEMENTIA
PSYCHOSIS
ATYPICAL (2nd generation)
- RISPERDAL – Risperidone
- ZYPREXA – Olanzapine
- SEROQUEL – Quetiapine
- GEODON – Ziprasidone
- ABILIFY – Aripiprazole
- (Fanapt, Invega, Latuda, Saphris)
TYPICAL (1st generation)
- HALDOL – Haloperidol
ALL ANTIPSYCHOTICS HAVE A BLACK BOX WARNING
MEDICATIONS IN DEMENTIA
SLEEP ALTERATIONS
- Sleep hygiene (initial option)
- Trazodone (second option)
- Ambien (Zolpidem)
- Lunesta (Eszopiclone)
- Sonata (Zaleplon)
- Temazepam and other benzo’s (last option)
MEDICATIONS IN DEMENTIA
Urinary incontinence
- Behavioral adjustments
- Vesicare, Enablex, Detrol, Sanctura less effects
on the CNS - anticholinergic
- Ditropan – can interfere with memory
Treatment and help are
available
Alzheimer’s disease is not yet curable, but
effective treatments are available, and
symptoms can be managed