PHARMACOLOGICAL STRATEGIES IN THE MANAGEMENT OF ALZHEIMER’S DISEASE Daniel Varon, MD Wien Center...
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Transcript of PHARMACOLOGICAL STRATEGIES IN THE MANAGEMENT OF ALZHEIMER’S DISEASE Daniel Varon, MD Wien Center...
PHARMACOLOGICAL STRATEGIES IN PHARMACOLOGICAL STRATEGIES IN THE MANAGEMENT OF ALZHEIMER’S THE MANAGEMENT OF ALZHEIMER’S DISEASEDISEASE
Daniel Varon, MDWien Center for Alzheimer’s Disease
and Memory Disorders
WHAT IS DEMENTIA?WHAT IS DEMENTIA?
CLASSIFICATION OF ABNORMALCLASSIFICATION OF ABNORMAL COGNITIVE STATESCOGNITIVE STATES
SUBJECTIVE Memory Complaints SUBJECTIVE Memory Complaints
No No Cognitive or Functional deficitsCognitive or Functional deficits
MILD Cognitive Impairment (MCI) MILD Cognitive Impairment (MCI)
Memory complaints, some cognitive deficits butMemory complaints, some cognitive deficits but
NoNo functional Deficits. functional Deficits.
DEMENTIADEMENTIA
Cognitive + Functional DeficitsCognitive + Functional Deficits
Concept of Dementia
NORMAL
SUBJECTIVE IMPAIRMENT
MILD COGNITIVE IMPAIRMENT
DEMENTIA
DEC
LINE
TIME
Types of dementia
Goals of Treatment in Dementia
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
GOALSGOALS
TARGETSTARGETS
MEDICATIONS IN DEMENTIAMEDICATIONS IN DEMENTIAMEDICATIONS IN DEMENTIAMEDICATIONS IN DEMENTIA
SYMPTOMSSYMPTOMS
- COGNITION- COGNITION- Memory, language, orientation, - Memory, language, orientation,
judgment, planning. judgment, planning.
- BEHAVIOR- BEHAVIOR-- Depression, anxiety, agitation, Depression, anxiety, agitation,
hallucinations, paranoia, hallucinations, paranoia, aggressiveness. aggressiveness.
- OTHER- OTHER- Weight loss, incontinence, - Weight loss, incontinence,
gait disturbances, sleep gait disturbances, sleep disturbances disturbances
Treatment
NORMAL
SUBJECTIVE IMPAIRMENT
MILD COGNITIVE IMPAIRMENT
DEMENTIA
DEC
LINE
TIME
NATURAL COURSENATURAL COURSE
WITH CURRENTWITH CURRENTTREATMENTSTREATMENTS
IDEALIDEAL
COGNITIONCOGNITION
Cholinesterase inhibitors
- Aricept – Donepezil - Razadyne – Galantamine- Exelon – Rivastigmine
Antagonist of the NMDA glutamate receptor
- Namenda – Memantina
MEDICATIONS IN DEMENTIAMEDICATIONS IN DEMENTIAMEDICATIONS IN DEMENTIAMEDICATIONS IN DEMENTIA
Cholinesterase Inhibitors
MEDICATIONS IN DEMENTIAMEDICATIONS IN DEMENTIAMEDICATIONS IN DEMENTIAMEDICATIONS IN DEMENTIA
ARICEPT – Donepezil
Rogers SL, et al. Neurology 1998
MEDICATIONS IN DEMENTIAMEDICATIONS IN DEMENTIAMEDICATIONS IN DEMENTIAMEDICATIONS IN DEMENTIA
MEDICATIONS IN DEMENTIAMEDICATIONS IN DEMENTIAMEDICATIONS IN DEMENTIAMEDICATIONS IN DEMENTIA
ARICEPT – DonepezilARICEPT – Donepezil
Dose: 5mg daily for 4 weeks and then increases to Dose: 5mg daily for 4 weeks and then increases to 10mg. There is a 23mg formulation.10mg. There is a 23mg formulation.
Interactions: Interactions: - Metabolized in the liver- Metabolized in the liver
RAZADYNE – Galantamine
Raskind et al. 2000
MEDICATIONS IN DEMENTIAMEDICATIONS IN DEMENTIAMEDICATIONS IN DEMENTIAMEDICATIONS IN DEMENTIA
RAZADYNE – GalantamineRAZADYNE – Galantamine
Dose: 4mg every 12h x 4 weeks Dose: 4mg every 12h x 4 weeks 8mg q12h x 4w8mg q12h x 4w 12mg every12h12mg every12h
Galantamine ER once a day 8, 12, 24mgGalantamine ER once a day 8, 12, 24mg
Interactions: Interactions: - Metabolized in the liver- Metabolized in the liver
MEDICATIONS IN DEMENTIAMEDICATIONS IN DEMENTIAMEDICATIONS IN DEMENTIAMEDICATIONS IN DEMENTIA
EXELON – Rivastigmine
Farlow et al. 2000
MEDICATIONS IN DEMENTIAMEDICATIONS IN DEMENTIAMEDICATIONS IN DEMENTIAMEDICATIONS IN DEMENTIA
EXELON – Rivastigmine
Oral 1.5mg twice a day x 4 weeks3mg twice a day x 4 weeks4.5 mg twice a day x 4 weeks6mg twice a day
Patch4.6mg o 9.5mg
Not metabolized in the liver
EXELON – Rivastigmine
Oral 1.5mg twice a day x 4 weeks3mg twice a day x 4 weeks4.5 mg twice a day x 4 weeks6mg twice a day
Patch4.6mg o 9.5mg
Not metabolized in the liver
MEDICATIONS IN DEMENTIAMEDICATIONS IN DEMENTIAMEDICATIONS IN DEMENTIAMEDICATIONS IN DEMENTIA
Cholinesterase inhibitorsCholinesterase inhibitors
- Aricept – Donepezil - Aricept – Donepezil - Razadyne – Galantamine- Razadyne – Galantamine- Exelon – Rivastigmine- Exelon – Rivastigmine
Side effects:Side effects:- Nausea, vomiting- Nausea, vomiting- Diarrhea- Diarrhea- Anorexia- Anorexia- Slow heart rate- Slow heart rate
MEDICATIONS IN DEMENTIAMEDICATIONS IN DEMENTIAMEDICATIONS IN DEMENTIAMEDICATIONS IN DEMENTIA
NAMENDA – Memantina
NAMENDA – Memantina
Reisberg B, et al. NEJM 2003
MEDICATIONS IN DEMENTIAMEDICATIONS IN DEMENTIAMEDICATIONS IN DEMENTIAMEDICATIONS 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%)
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 DEMENTIAMEDICATIONS IN DEMENTIAMEDICATIONS IN DEMENTIAMEDICATIONS IN DEMENTIA
NAMENDA – Memantine
NAMENDA – Memantine
MEDICATIONS IN DEMENTIAMEDICATIONS IN DEMENTIAMEDICATIONS IN DEMENTIAMEDICATIONS IN DEMENTIA
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
Fear of being alone Paranoia
Delusions about “imposters” Accusations of infidelity
Personality changes
Behavioral Disturbances:Middles Stages
Wandering Restlessness
Fidgeting Pacing
Inappropriate handling of objects Rummaging Hoarding
Verbal agitation 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?
ExamplePatient 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?
ExamplePatient who can’t verbally communicate her dislike of milk
Throws milk carton across the room
How does impaired recognition (agnosia) lead to behavioral problems?
ExamplePatient 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?
ExamplePatient 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?
ExamplePatient 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
Recognizeareas of impaired function
andareas of preserved function
Help compensate for impairment Support residual abilities
WHAT OTHER FACTORS MAY CONTRIBUTE TO BEHAVIORAL CHANGES IN PATIENTSWITH 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 Pain Constipation Urinary urgency Shortness of breath Dizziness Fatigue Heartburn Headache
Medical condition– Arthritis– Dehydration– Prostatic hypertrophy– COPD– Cerebrovascular disease– CHF– Impaired vision– Impaired hearing– 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.
BEHAVIORAL SYMPTOMSBEHAVIORAL SYMPTOMS
MEDICATIONS IN DEMENTIAMEDICATIONS IN DEMENTIAMEDICATIONS IN DEMENTIAMEDICATIONS IN DEMENTIA
0 5 10 15 20 25 30
Delusions
Hallucinations
Agitation
Depression
Anxiety
Apathy
Sleep disturbance
DEPRESSIONSSRI’s - sertraline (Zoloft), citalopram (Celexa), escitalopram (Lexapro).
Other antidepressants
- WELLBUTRIN – Bupropion
- EFFEXOR – Venlafaxine
- CYMBALTA – Duloxetine
- REMERON – Mirtazapina
MEDICATIONS IN DEMENTIAMEDICATIONS IN DEMENTIAMEDICATIONS IN DEMENTIAMEDICATIONS IN DEMENTIA
DEPRESSIONDEPRESSION
Antidepressants:Antidepressants:
- SSRIs: Zoloft – SertralineSSRIs: Zoloft – Sertraline Few interactionsFew interactions Celexa – CitalopramCelexa – Citalopram Easy to tolerateEasy to tolerate
Lexapro – Escitalopram Lexapro – Escitalopram
Paxil – ParoxetinePaxil – Paroxetine More interactions More interactions More anticholinergic More anticholinergic
Prozac – FluoxetineProzac – Fluoxetine Long half lifeLong half life More interactionsMore interactions
MEDICATIONS IN DEMENTIAMEDICATIONS IN DEMENTIAMEDICATIONS IN DEMENTIAMEDICATIONS IN DEMENTIA
Antidepressants:
- SSRIs: Selective Serotonin Reuptake Inhibitors
Serotonin
- Side effects:- Changes in appetite- Nausea - Dizziness- SomnolenceLow sodium (less common)-
Antidepressants:
- SSRIs: Selective Serotonin Reuptake Inhibitors
Serotonin
- Side effects:- Changes in appetite- Nausea - Dizziness- SomnolenceLow sodium (less common)-
MEDICATIONS IN DEMENTIAMEDICATIONS IN DEMENTIAMEDICATIONS IN DEMENTIAMEDICATIONS IN DEMENTIA
Other antidepressants:Other antidepressants:
- WELLBUTRIN – Bupropion - WELLBUTRIN – Bupropion Not used in patients with epilepsyNot used in patients with epilepsy
- EFFEXOR – Venlafaxine- EFFEXOR – VenlafaxineCan increase BP Can increase BP transiently transiently
- CYMBALTA – Duloxetine- CYMBALTA – DuloxetineCan cause changes in hepatic functionCan cause changes in hepatic functionCan help with chronic painCan help with chronic pain
- REMERON – Mirtazapine- REMERON – MirtazapineIncreases sleep and appetiteIncreases sleep and appetite
MEDICATIONS IN DEMENTIAMEDICATIONS IN DEMENTIAMEDICATIONS IN DEMENTIAMEDICATIONS IN DEMENTIA
PSYCHOSISPSYCHOSIS
- - HALLUCINATIONSHALLUCINATIONSVisual Visual (Common in Lewy Body Disease )(Common in Lewy Body Disease )AuditoryAuditorySensorySensory
- - DELUSIONSDELUSIONS (More common than hallucinations)(More common than hallucinations)ParanoiaParanoiaConfabulationConfabulationJealousy Jealousy
MEDICATIONS IN DEMENTIAMEDICATIONS IN DEMENTIAMEDICATIONS IN DEMENTIAMEDICATIONS IN DEMENTIA
PSYCHOSISPSYCHOSIS
ATYPICAL (2nd generation)ATYPICAL (2nd generation)- RISPERDAL – Risperidone- RISPERDAL – Risperidone- ZYPREXA – Olanzapine- ZYPREXA – Olanzapine- SEROQUEL – Quetiapine- SEROQUEL – Quetiapine- GEODON – Ziprasidone- GEODON – Ziprasidone- ABILIFY – Aripiprazole- ABILIFY – Aripiprazole- (Fanapt, Invega, Latuda, Saphris)- (Fanapt, Invega, Latuda, Saphris)
TYPICAL (1st generation)TYPICAL (1st generation)- HALDOL – Haloperidol- HALDOL – Haloperidol
ALL ANTIPSYCHOTICS HAVE A ALL ANTIPSYCHOTICS HAVE A BLACK BOX WARNINGBLACK BOX WARNING
MEDICATIONS IN DEMENTIAMEDICATIONS IN DEMENTIAMEDICATIONS IN DEMENTIAMEDICATIONS IN DEMENTIA
SLEEP ALTERATIONS
- Sleep hygiene (initial option)
- Trazodone (second option)- Ambien (Zolpidem) - Lunesta (Eszopiclone) - Sonata (Zaleplon) - Temazepam and other benzo’s (last option)
SLEEP ALTERATIONS
- Sleep hygiene (initial option)
- Trazodone (second option)- Ambien (Zolpidem) - Lunesta (Eszopiclone) - Sonata (Zaleplon) - Temazepam and other benzo’s (last option)
MEDICATIONS IN DEMENTIAMEDICATIONS IN DEMENTIAMEDICATIONS IN DEMENTIAMEDICATIONS IN DEMENTIA
Urinary incontinence
- Behavioral adjustments
- Vesicare, Enablex, Detrol, Sanctura less effects on the CNS - anticholinergic
- Ditropan – can interfere with memory
Urinary incontinence
- Behavioral adjustments
- Vesicare, Enablex, Detrol, Sanctura less effects on the CNS - anticholinergic
- Ditropan – can interfere with memory
MEDICATIONS IN DEMENTIAMEDICATIONS IN DEMENTIAMEDICATIONS IN DEMENTIAMEDICATIONS IN DEMENTIA
Treatment and help are available
Alzheimer’s disease is not yet curable, but effective treatments are available, and symptoms can be managed