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Management of BPSD
Shahla Baharlou, MD and Christine Chang, MD
Brookdale Dept of Geriatrics and Adult Development
March 5, 2008
Objectives
Participants will be able to:
1. Define BPSD
2. Evaluate BPSD
3. Discuss the Guidelines for Management
of BPSD
•
•
Nonpharmacologic Interventions
Pharmacologic Interventions
What Is BPSD?
What Is BPSD?
Behavioral and Psychological
Symptoms of Dementia
What Is BPSD?
Non-cognitive manifestations of dementia
Behavioral Symptoms
Psychological Symptoms
What Is BPSD?
Behavioral Symptoms
“Agitation”
Related to resistiveness to care
Physical vs Verbal
Aggressive vs Nonaggressive
What Is BPSD?
Psychological Symptoms
Mood Symptoms
Psychotic Symptoms
Sleep Disturbances
Why Is BPSD Important?
• Lifetime risk is nearly 100%
• Associated with increased morbidity
and nursing home placement
• Potentially treatable
Case: Part 1A
1. What Do You Do Next?
a. Start haloperidol 0.5 mg at night
b. Start risperidone 1 mg at night
c. Increase donepezil to 10 mg
d. Increase oxybutynin to 10 mg twice a day
e. Increase acetaminophen to 1000 mg
twice a day
f. Clarify the history and perform a careful
physical and neurologic exam
Evaluation of BPSD
1. Obtain a History - clear description of
the behavior from the patient & others
• Temporal onset, course
• Associated circumstances
• Relationship to key environmental
factors
• In context of the patient’s medical,
family and social history
Evaluation of BPSD
2. Careful Physical & Neurologic Exam
Assess Mental Status
Pay attention to:
• Appearance and Behavior
• Speech
• Mood
• Thoughts and Perceptions
• Cognitive Function
• Attention
Evaluation of BPSD
3. Lab Studies
•
CBC and metabolic panel in all cases of
new onset BPSD
•
Brain imaging, EKG, CXR, and urinalysis
based on the history and exam
Evaluation of BPSD
R/O Delirium
• Acute Conditions such as acute
infection like pneumonia and UTI, pain,
angina, constipation, endocrine
abnormality, electrolyte imbalance
• Medication Toxicity or adverse effects
of medications due to new or existing
medications
Evaluation of BPSD
R/O Environmental Causes
1. Make sure pt’s basic physical needs are met
2. Environmental Precipitant
• Disruptions in routine
• Over Stimulation
• Under Stimulation
Evaluation of BPSD
After medical, environmental, and
care giving causes are excluded, it
can be concluded that the primary
cause is progression of the dementia
Case: Part 1B
Case: Part 2
2. What Do You Do Next?
a.
b.
c.
d.
e.
f.
g.
Start haloperidol 0.5 mg at night
Start risperidone 1 mg at night
Increase donepezil to 10 mg
Start citalopram 10 mg daily
Start valproate 250 mg daily
Start carbamazepine 100 mg daily
Review nonpharmacologic, patientcentered interventions
Guidelines for Management of BPSD
1997 Consensus statement from the American
Psychiatric Association
2003 Consensus statement from the American
Geriatrics Society and American Association
for Geriatric Psychiatry
Guidelines for Management of BPSD
Nonpharmacologic Interventions First
• 40% of BPSD symptoms spontaneously
resolve; “they come and go”
• Placebo response can be quite substantial
• No FDA approved medications for psychosis
in AD
Nonpharmacologic Strategies:
To Minimize Development of BPSD
• Maintain a structured daily routine
• Environmental modifications
• Utilize good communication skills
• Encourage independence in ADLs
Nonpharmacologic Strategies:
To Minimize Development of BPSD
Person-Centered
Showers and Towel Baths
• Create environment based on patient
comfort and preference
• Cover with towels to maintain
warmth and modesty
• Use no-rinse soap and warm water
• Use gentle massage to cleanse
• Modify shower spray
www.bathingwithoutabattle.unc.edu
Nonpharmacologic Strategies:
Agitation/Aggression (<1/wk)
1. Identify the precipitating factor and avoid
the triggers
2. Distraction Techniques
3. Behavior Modification
• Positive reinforcement of desirable
behavior
Nonpharmacologic Strategies:
Agitation/Aggression (<1/wk)
4. Environmental Modifications
•
•
•
Preferred music
Aromatherapy-lavender
Light and pet therapy
5. Exercise and structured activity
therapies
***Physical restraints should be avoided
Case: Part 3
3. What Do You Do Next?
a.
b.
c.
d.
e.
f.
Prescribe zolpidem 5 mg
Recommend melatonin 0.3 mg
Prescribe triazolam 0.125 mg
Prescribe trazodone 25 mg
Prescribe mirtazapine 7.5 mg
Counsel about nonpharmacologic
interventions to promote sleep
Matching Target Symptoms
Sleep-wake Cycle Disturbance >1 Month
After R/O depression + other psychiatric
conditions:
Consider: Nonpharmacologic Interventions
•
•
•
Only Guidelines for patients with primary sleep disorders
exist
No RCT of newer agents tested in this population
McCurry SM et al. Nighttime insomnia treatment and
education for Alzheimer's disease: a RCT. JAGS. 2005
Matching Target Symptoms
Sleep-wake Cycle Disturbance >1 Month
Nonpharmacologic Interventions
•
Follow Structured sleep and rising times that
were not to deviate no more than 30 minutes
from the selected times
•
Encouraged patients not to nap after 1 PM and
limit naps to 30 minutes or less
•
Walk for 30 minutes, exercise daily
•
Reduce light/noise levels in their sleeping areas
Matching Target Symptoms
Sleep-wake Cycle Disturbance >1 Month
Nonpharmacologic Interventions
•
Switch to decaffeinated drinks and reduce
evening fluid consumption
•
If nocturia affected sleep, encourage toileting
schedules at night, use of incontinence pads,
exclude urinary tract infections
•
Eliminate triggers for nighttime awakenings ie
control night time pain, give nightly snack,
take activating meds in the AM
Case: Part 4
4. Which Is the Most Appropriate
Pharmacologic Treatment?
a.
b.
c.
d.
e.
f.
Prescribe diphenhydramine 25 mg
Prescribe zolpidem 5 mg
Prescribe melatonin 0.3 mg
Increase donepezil to 10 mg
Prescribe trazodone 25 mg
Prescribe mirtazapine 7.5 mg
Matching Target Symptoms
Sleep-wake Cycle Disturbance >1 Month
APPROVED Hypnotics for
INSOMNIA
1.
2.
BZO R Agonists
a. BZO
Temezepam, Triazolam
b. Non-BZO
Zolpidem
Zaleplon
Eszopiclone
Melatonin R Agonist
Ramelteon
NON-APPROVED for INSOMNIA
1.
2.
3.
Sedating Antidepressant
Trazodone
Mirtazapine
Antipsychotics
Anticonvulsants
NONPRESCRIPTION AGENTS
1.
2.
Sedating Antihistamines
Melatonin
Matching Target Symptoms
Sleep-wake Cycle Disturbance >1 Month
GRS 6 Recommends:
• Trazodone
• Mirtazapine
• Zolpidem and zaleplon
Avoid:
• Benzodiazepines
• Antihistamines especially diphenhydramine
Associated with high risk for falls, hip fractures, disinhibition, and
cognitive disturbance when prescribed for patients with dementia
Matching Target Symptoms
Sleep-wake Cycle Disturbance >1 Month
Pharmacologic Therapy for primary sleep disturbances
when nonpharmacologics fail
• Benzodiazepine receptor agonists
• Atypical Antipsychotics
• Cholinesterase inhibitors
• Melatonin as a hypnotic in this population appears
equivocal
Pandi-Perumal SR, et al. Melatonin and sleep in aging population. Exp Gerontol. 2005
Case: Part 5
5. What Is the Most Effective Initial
Management Strategy for This Patient?
a. Enrollment in Adult Day Health Care Center
b. Caregiver education and training in coping
skills
c. Prescribe nortriptyline 25 mg
d. Prescribe sertraline 25 mg
e. ECT (Electroconvulsive Therapy)
Matching Target Symptoms
Mood Symptoms: Depression
Depression of 2 weeks’ duration resulting in
significant distress or sustained depressive
features lasting more than 2 months
Consider Antidepressants –1st line: SSRIs
• Citalopram
• Sertraline (improved depressive symptoms
and ADLS w/o improving cognition)
• Avoid fluoxetine and paroxetine
Case: Part 6
6. What Would You Do Next?
a.
b.
c.
d.
Switch to another agent in same class
Switch to another agent in another class
Titrate dose of initial medication
Add methylphenidate 5 mg
Matching Target Symptoms
Mood Symptoms: Depression
If a first agent has failed an adequate
therapeutic dose for 8 to 12 weeks,
consider alternatives:
•
•
•
•
Bupropion
Mirtazapine
Venlafaxine
Tricyclic agents
(desipramine and nortriptyline)
Matching Target Symptoms
Mood Symptoms: Depression
For partial responders to an antidepressant,
consider augmentation strategies
Methylphenidate ????
Matching Target Symptoms
Mood Symptoms: Depression
If depression remains and patient is in
danger of serious weight loss or suicidal
ideas despite several antidepressant trials,
consider ElectroConvulsive Therapy
*No RCT in BPSD or geriatric pts
Case: Part 7
7. What Is Your Recommendation?
a.
b.
c.
d.
e.
Refer for nursing home placement
Do a time-limited trial of haloperidol 0.5 mg
Do a time-limited trial of risperidone 0.5 mg
Do a time-limited trial of olanzapine 5 mg
Do a time-limited trial of valproate 250 mg
Guidelines for Management of BPSD
1997 Consensus statement from the American
Psychiatric Association endorse:
– Matching target symptoms to relevant drug class
2003 Consensus statement from the American
Geriatrics Society and American Association for
Geriatric Psychiatry recommends:
– Atypical antipsychotic: 1st line for psychotic features
– SSRI’s : 1st line for depression
Systematic reviews, Meta analysis, Randomized
controlled trials 2004+
Psychosis in Dementia
Clinical criteria for diagnosis of AD with
psychosis:
Presence of intermittent delusions or
hallucinations occur for at least 1 month
and must cause distress
Pharmacologic Interventions
• If nonpharmacologic interventions fails or
if “agitated” behaviors are too harmful to
patient or others, consider pharmacologic
agents
• What to prescribe?
Matching Target Symptoms
Psychosis in Dementia
1. Antipsychotics
Atypical (Risperidone, Aripiprazole, Olanzapine) vs
Conventional (Haloperidol)
2. Memory Enhancers
Cholinesterase Inhibitors (ie. Donepezil)
NMDA receptor antagonists (Memantine)
3. Anticonvulsants/Mood Stabilizers
4. Antidepressants
SSRI, Trazodone
Conventional Antipsychotics
Haloperidol
• Might be effective in treating aggression in
patients with dementia but side effects limits
its use; extrapyramidal symptoms
• Risk for neuroleptic malignant syndrome,
tardive dyskinesia, orthostasis, and prolong
QTc
Cochrane Database of Systematic Reviews. 4, 2007
Atypical Antipsychotics
• Significant improvement in aggression with
risperidone and olanzapine and psychosis
with risperidone
• Significantly higher risk of serious
cardiovascular effects including stroke and
extrapyramidal symptoms outweighs the
benefit
Cochrane Database of Systematic Reviews 2006
Atypical Antipsychotics
• Large multi-center (42 sites), double-blind, placebo
controlled trial
• 421 pts with Alzheimer dementia with BPSD and MMSE
between 5-26 (outpatient/assisted living)
• Comparing olanzapine (5.5 mg/d), risperidone (1 mg/d) and
quetiapine (56.5 mg/d) with placebo
• Duration: 36 weeks
• Modest trends or no significant effects on symptoms in
comparison to placebo. Effect on symptoms was offset by
adverse effects
NEJM 2006; 355: 1525-38
Blackbox Warning
for Atypical Antipsychotics
• Increased risk of mortality. Rate of death
was 1.6 to 1.7 times that of placebo
• Death appeared to be heart related or from
infections (eg, pneumonia)
• Diabetes mellitus, hyperglycemia,
ketoacidosis, and hyperosmolar states
http://www.fda.gov/cder/drug/infopage/antipsychotics/default.htm
Cholinesterase Inhibitors
Donepezil
• Multicenter, blinded, randomized, parallel trial
• 285 pts with severe Alzheimer dementia-mostly
nursing home
• 12 weeks trial
• Not a significant advantage over placebo for
treatment of agitation in patients with severe
dementia
• A modest benefit from donepezil on cognitive
measures compare to placebo
N Engl J Med 2007; 357; 14 (1382-1392)
Cholinesterase Inhibitors
Galantamine
• Improves of behavioral symptoms in patients
with mild to moderate dementia
• Effective dose 16 mg daily titrated over 4 weeks
• The higher dose likely to  adverse effect
without any added benefit
Cochrane Database Systematic Reviews. 2006
NMDA Receptor Antagonists
Memantine
• Two out of three RCT showed that patients with
moderate and severe Alzheimer dementia
displayed less agitation on Memantine 20 mg/day
at 6 months
• Unpublished data shows no clinically detectable
effect in patients with mild to moderate dementia
Cochrane Database of Systematic Reviews 2007 Issue 4
Anticonvulsants
Valproate
• Low dose (<480 mg/d) is ineffective and high dose
(1000mg/d) is associated with increased rate of
adverse effects
• Side effects: somnolence, thrombocytopenia,
infection
• Not recommended for Rx of BPSD based on existing
trials
Cochrane Database of Systematic Reviews 2007 Issue 4
Anticonvulsants
Gabapentin
• No RCT
• Generally well tolerated but has reported
alarming side effects including case reports
of abrupt aggravation in patients with Lewy
body dementia
International psychogeriatrics; Nov 2007
Anticonvulsants
Carbamazepine
• Equivocal information on efficacy of carbamazepine
based on limited RCT trials. Additionally safety and
tolerability are other concerns
• Another concern is drug-drug interaction
International psychogeriatrics; Nov 2007
Antidepressants
SSRI
• Limited studies. No Cochrane review
• In one RCT double blind trial-85 pts in acute inpatient setting
• Citalopram comparing to Perphenazine and placebo in pts
with BPSD (mean MMSE 6.4-9.9)
• Significant improvement in agitation, aggression, psychosis,
lability, tension factor with short course of both Citalopram and
Perphenazine
• Improved cognition and retardation significantly in Citalopram
group
• No difference in side effect profile among 3 groups
Am J Psychiatry 2002; 159:460-465
Antidepressants
Trazodone
• Limited trial indicates no significant difference
between Trazodone (dose of 50-300 mg
daily) and placebo in treatment of behavioral
and psychologic manifestation of dementia
Cochrane Database of Systematic Reviews. 4, 2007
Take Home Points
• Always obtain a thorough hx about the “disturbance”
• Rule out delirium and other environmental factors
contributing to the disturbance
• Use nonpharmacologic interventions for BPSD first
• Consider “targeted,” time-limited pharmacologic
trials for severe or persistent BPSD symptoms given
modest evidence of efficacy and moderate potential
for harm
Thank you