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Karen McGee, Pharm.D. CDE
SC College of Pharmacy
USC campus
March 2008
[email protected]
Place in Therapy of SSRI’s in
Agitation of Dementia
Objectives
• Review Pathophysiology and Etiology of Dementia
• Describe Behavior Problems Associated with Dementia
• Discuss Place in Therapy of SSRI’s in Agitation of Dementia
• Decide Place in Therapy of Anti-psychotics in Agitation of Dementia
Introduction
• Types of dementia
• Alzheimers (>60%)
• Vascular (Multi Infarct)
• Mixed
• Lewy Body
Alzheimers: Etiology
• Alzheimers
• Early onset 40- 64 years
• Usual > 65 yrs
• > 50% incidence > 85 yrs
• 100,000 deaths yearly
due to
• Aspiration
• Pneumonia
• Trauma
• Nutritional
deficiency
Alzheimers: Pathophysiology
• Beta Amyloid Proteins
• Neurofibrillary Tangles
• Apo-lipo protein E
• Inflammatory Mediators
• Cholinergic system
Alzheimers: Symptoms & MMSE
• Memory Loss
• Dysphasia
• Dyspraxia
• Disorientation
• Impaired time concepts
• Cant recognize family
• Impaired calculation
• Impaired Judgment or
problem solving
• MMSE (mini mental status
exam) common test
used to evaluate
• A.k.a. Folstein
Alzheimers: Behavioral Issues
•
Depression
•
Anxiety
•
Psychotic Symptoms
•
•
•
Hallucinations
•
Delusions
•
Suspiciousness
Non-psych disturbances
•
Physical aggression
•
Verbal aggression
•
Motor hyperactivity
•
Uncooperative
•
Wandering
•
Repetitive mannerisms
Common Reason for Nursing
Home Placement
Alzheimer’s: Differential Diagnosis
• Insidious onset
• Progressive decline in
cognitive function
• Deficient in
• MMSE
• GDS
• No acute disturbance of
consciousness
• Age 40-90
• Rule out other causes:
• Hypothyroid
• B12 and folate deficient
• Syphilis
Purpose/ Controversy of this Discussion
• To support appropriate use of antipsychotic
medications for behavioral problems in dementia
• New data supports the notion that antipsychotics
should be used more sparingly
• Blackbox Warning implemented in 2007
• Warning: Increased Mortality in Elderly Patients with
Dementia Related Psychosis
Elderly patients with dementia-related psychosis treated
with atypical antipsychotic drugs are at an increased
risk of death compared to placebo. Analyses of 17
placebo controlled trials in these patients revealed a
risk of death in the drug treated patients of between 1.6
to 1.7 times that seen in placebo-treated patients. Over
the course of a typical 10 week controlled trial, the rate
of death in drug treated patients was about 4.5%
compared to 2.6% in the placebo group. Most common
cause was either cardiovascular (heart failure, sudden
death) or infectious (pneumonia).
A Pilot, Open-Label Trial of Citalopram for Restless Activity
and Abberrant motor behaviors in Alzheimer Disease
( Am J Geriatr Psych 2003;11;6:687-91)
• Study Overview
• 12 weeks
• 19 Caucasian Patients Alzheimers (14 women)
• 48-87 yrs (average 74)
• MMSE = 13 (Moderate)
• Citalopram 10 -40 mg
• Behavior review at weeks 4,8,12
• Restlessness
• Pacing
• Hyper-kinesia
• Rummaging
• Repetitions
• Put on / Take off clothes
• hoarding
A Pilot, Open-Label Trial of Citalopram for Restless Activity
and Abberrant motor behaviors in Alzheimer Disease
(Am J Geriatr Psychiatry 2003;11;6:687-91)
• Inclusion
• Stable psychotropics for 4 weeks allowed
• Sleep aids
• Quetiapine
• Valproate
• ACHE
• Memantine
• Exclusions
• Depression
• Psychotic disorders
A Pilot, Open-Label Trial of Citalopram for Restless Activity
and Aberrant motor behaviors in Alzheimer Disease
(Am J Geriatr Psych 2003;11;6:687-91)
• Primary Outcomes
• Aberrant Motor Subscale of the Neuropsychiatric
Inventory (NPI) Scale
• > 50% decrease in symptoms at week 8 and 12
• 4 pts had complete resolution of symptoms
• 2 pts were nonresponders
• 13 pts had 50-70% improvement after 8 weeks
• Secondary Outcomes
• Change in ADAS-cog ( 70 point scale)= NO Change
• Change in Caregiver stress subscales = Significant
• CG report decreased agitation, anxiety, aggression
and irritability
• Able to maintain these patients at home
A Double Blind Comparison of Citalopram and Risperidone for the
Treatment of Behavioral and Psychotic Symptoms Associated with
Dementia (Am J Geriatr Psych 2007;15:1-11)
Positive Points of the Trial
• Strongest study design to date
• Clinically useful/ valid Scale for Symptom assessment
• Duration: 12 weeks (still short)
• NNT = 103 patients to detect 15% difference with a
power of 80% and alpha = 0.05
• Pt Population was more varied & matched
• Less medication allowed
• Still allowed ACHE or Memantine in stable doses
• Also, Lorazepam up to 2 mg for acute agitation
• Study Doses (titrated)
•
Citalopram 10 -40 mg
• Risperidone 0.5 – 2 mg
A Double Blind Comparison of Citalopram and Risperidone for the
Treatment of Behavioral and Psychotic Symptoms Associated with
Dementia (Am J Geriatr Psych 2007;15:1-11)
• Inclusions
• Pts with dementia hospitalized for behavior control
• Aggression, agitation, hostility, suspiciousness, hallucinations and
delusions
• Goal: Discharge back to home, SNF or NH
• Alzheimer Dz with Moderate to severe behaviors
• > 3 on NBRS indicating moderate to severe symptoms
• Mixed or Lewy body dementia
• Exclusions
• Vascular dementia
• Schizophrenia
• Major depression
• Etoh induced dementia
• Acute or unstable physical illness
A Double Blind Comparison of Citalopram and Risperidone for the
Treatment of Behavioral and Psychotic Symptoms Associated with
Dementia (Am J Geriatr Psych 2007;15:1-11)
• Primary Outcomes:
• Change in NBRS scale
• Change in Agitation score
• Change in Psychosis score
• NBRS scale:
• 0 = No symptoms present
• 1= Very mild symptoms
• 2= Mild
• 3= Moderate
• 4= Moderate to severe
• 5= Severe
• 6= Extremely severe
A Double Blind Comparison of Citalopram and Risperidone for the
Treatment of Behavioral and Psychotic Symptoms Associated with
Dementia (Am J Geriatr Psych 2007;15:1-11)
• Results
• No significant change in Overall NBRS score
• Agitation Score: 8.2% decrease in risperidone group
and a 12.5% decrease in the citalopram group
• Psychosis Score: Both groups had a significant
decrease!
• 35.2% decrease in Risperidone group
• 32.3% decrease in Citalopram group
• Side effects
• Risperdone= more somnolence
• Risperdone and Citalopram = EPSE (rigidity and tremor)
F-Tag 329 Pharmacy Assessment &
Documentation
•
Document Target Symptoms
•
Threat to self or others
_____________________________
•
Interference with ADL’s
•
Appropriate diagnosis
•
•
Document SE monitoring
Psychosis associated with
organic brain disorders or
dementia
•
Elders should be free from
unnecessary drugs
•
AIMS, CBC, BMP, LFTs
•
•
Free of Chemical Restraint
Ongoing (quarterly
assessments)
•
Recommend tapers
•
Chemical restraint orders
•
Eliminate Poly-pharmacy
•
Trial taper in two separate
quarters with at least one
month between each taper
•
Taper annually
•
•
Should not treat the
caregivers (75% one study)
•
Unless Sx return, must
document in progress notes
Educate caregivers
Medication Classes: Place in Therapy
• 1st line- SSRI’s
•
SSRI have the latest trial data
•
Most data with Citalopram 10 mg X 3days then titrate up slowly to a
maximum of 40 mg daily
•
Paroxetine, more sedating, may offer benefit for those unable to
sleep. Dose at bedtime. Only one study in dementia
•
Monitor Baseline LFT’s and BMP and repeat to assess for
hyponatremia
• 2nd Line- Valproate
•
•
Mood Stabilizers
•
Used to treat aggressive, combative behaviors
•
Studies are lacking about place in treatment
3rd line- Antipsychotics
•
Most useful for harmful hallucinations and delusions
•
Consider last due to new blackbox warning and need for more
frequent, intensive monitoring ( Tag F329), AIMS, LFTs, CBC, BMP
Thank You!
Any Questions?