Increasing Uptake of
Non-Pharmacologic
Approaches to Assess and
Manage the Neuropsychiatric
Symptoms of Dementia
Helen C. Kales MD
Professor of Psychiatry
Director, Section of Geriatric Psychiatry and
Program for Positive Aging
University of Michigan
Research Investigator
VA GRECC, CCMR and SMITREC
Acknowledgements
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H. Myra Kim, PhD
Claire Chiang, PhD
Janet Kavanagh, MS
Kara Zivin, PhD
Marcia Valenstein, MD
Francesca Cunningham,
PharmD
• Lon S. Schneider, MD
• Frederic C. Blow, PhD
• Laura Gitlin, PhD
• Kostas Lyketsos, MD
• NINR: R01NR014200
• NIMH: R01MH081070
• There are no conflicts to
disclose
• Discussion of off-label uses
of antipsychotics
Overview
• Neuropsychiatric symptoms of dementia (NPS)
symptom description matters
• NPS etiology matters
• Non-pharmacologic management
 The DICE approach to assessment and management
The Case of Elizabeth
• 81 year old with
dementia
• Daughter called by inhome caregiver about
“agitation”
Neuropsychiatric Symptoms of Dementia
(NPS)
• Also known as behavioral and psychiatric symptoms
of dementia (BPSD)
• Cognitive impairment is the clinical hallmark of
dementia, but it is NPS that often dominate both
presentation and course
• Present in >90% of patients with dementia at some
point in illness course
Sources: Lyketsos et al, Am J Psychiatry, 2000; Sink et al, J Am Geriatrics Soc, 2004; Steffens et al,
Am J Alzheimers Dis Other Dementias, 2005
Source: Rabheru (2004)
Miscellaneous but problematic
behaviors
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unfriendliness
poor self-care
not paying attention or caring about what is going on
repetitive verbalizations/questioning
wandering
“inappropriate” behaviors (screaming, spitting, sexual
behaviors)
• sleep problems (day-night reversal)
Elizabeth’s “agitation”:
further description would help
• Could be:
 Grumpiness
 Aggression
 Resistance
 Restlessness
 Anxiety
 Psychosis
Etiology
• Not well understood
• Likely heterogeneous
 Cognitive loss
 Preexisting psychiatric illness
 Environmental factors
 Comorbid medical conditions
 Medications
 Pain
 Delirium
• Consequence of multiple concurrent factors
Elizabeth’s “agitation”:
understanding possible etiology
would help
• Could be:
 Overstimulating environment
 Poor caregiver communication
 Pain
 Delirium
 Psychosis
How should we manage Elizabeth?
• Pharmacologic treatment:
– In real-world settings, a
patient NPS will often receive
an antipsychotic
Real-World Management
• There is no FDA-approved
pharmacotherapy for NPS
• Therefore, all use is off-label
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Antipsychotics
Benzodiazepines
Mood stabilizers
Antidepressants
Cholinesterase inhibitors and
% risk difference (CI)
Ref
NNH(CI)
Ref
Haloperidol
9.4 (7.3 - 11.5)**
11 (9 -14)
Olanzapine
5.2 (3.4 - 7.0)**
19 (14 - 29)
Quetiapine
2.3 (1.3 - 3.4)**
43 (29 -77)
Risperidone
4.5 (3.4 - 5.6)**
22 (18 - 29)
3.8 (1.5 - 6.2)**
26 (16 - 67)
Antidepressant
Table 3. Adjusted¶ absolute risk differences
between study medication users relative to
antidepressant users (N=45,669)
**p<0.01
Sources: Kales et al, Am J Psychiatry 2007; Maust et al, Under review Valproic acid
The Role of
Non-pharmacologic Management
• Recommended by multiple medical organizations and
expert groups as first-line for NPS
 *except in emergency situations when behaviors could lead to
imminent danger or compromise safety
Non-pharmacologic Management
• These interventions have not yet received widespread
uptake
• Study of new nursing home admissions
 Only 12% received a non-pharmacologic intervention
 >70% received >1 psychotropic
 15% received >4 psychotropics
Source: Molinari et al, J Gerontol B Psychol Sci Soc Sci, 2010
Why are Non-pharmacologic
Management Strategies Underutilized?
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Time
Training
Funding/reimbursement in current care systems
Lack of guidelines
Symptoms are a moving target
Why are Non-pharmacologic
Management Strategies Underutilized?
• ?Perception that they are unproven and/or unlikely to
work, especially as compared to medications
Non-pharmacologic Management
• What is it?:
 Behavioral, environmental and caregiver interventions
• Examples:
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Caregiver education and support
Activity
Communication strategies
Modifying the environment
Acupuncture
Aromatherapy
Light therapy
Massage Source: Gitlin, Kales, Lyketsos et al, JAMA2012
Non-pharmacologic Management
• Inconsistent to no evidence for:
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Reminiscence
Aromatherapy
Light Therapy
Validation Therapy
Simulated Presence Therapy
Source: Gitlin, Kales, Lyketsos et al, JAMA 2012
Non-pharmacologic Management
• Brodaty meta-analysis of 23 RCTs with family caregivers; outcomes
related to frequency/severity of NPS and caregiver well-being
 Significant treatment effect, overall effect size=0.34
 Variation among trials in dose, intensity and delivery mode
 Key features of successful trials=9-12 sessions; tailoring to patient and
caregiver; delivered in the home; multiple components
 No adverse effects for any of the trials
• REACH II (generalized approach with targeted behavioral strategy)
 Problem solving behavioral approach with significant reductions in frequency of
behavioral symptoms
• REACH VA (generalized approach with targeted behavioral strategy)
 Significant reduction in problem behaviors (p=0.04) and improvement in
caregiver burden (p=0.001) and depression (p=0.009)
Source: Brodaty et al Am J Psychiatry 2012; Belle et al Ann Int Med 2006; Nichols et al Arch Int Med 2011
Non-pharmacologic Management
• Tailored Activity Program (TAP):
 8-12 home/telephone sessions by occupational therapists;
caregiver training including customized activity
 significant reductions in problem behaviors (p=0.004) including
agitation (p=0.14) and decrease in caregiver “hours on duty”
(p=0.001)
• COPE
 Up to 12 home/telephone contacts by health professionals;
assessment for underlying medical issues; caregiver training,
significant reduction in problem behaviors (p=0.01) and
improvement in caregiver well-being (p=0.002)
Source: Gitlin et al , Am J Geriatr Psychiatry 2008; Gitlin et al, ,JAMA, 2010
Project ACT
• N=272 patients
• 11 home/telephone sessions over 4-months by health
professionals
• Identification of potential triggers of problem behaviors
 Communication
 Environment
 Patient undiagnosed medical condition
• Caregiver training to modify triggers and reduce caregiver
upset
• 3 booster contacts between 16-24 weeks
Source: Gitlin, et al, JAGS, 2010
Project ACT
• Medical test results:
 Undiagnosed illnesses detected in 34% of subjects
 Most prevalent conditions:
UTI 14.5%
Hyperglycemia 5.9%
Anemia 5.1%
Source: Gitlin, et al, JAGS, 2010
Project ACT
Source: Gitlin, et al, JAGS, 2010
Source: Gitlin, et al, JAGS, 2010
Project ACT
• At 16 weeks:
 Patient improvement in 67.5% of intervention dyads vs.
45.8% of control dyads (p=0.002)
 Reduced caregiver upset (p=0.028)
 Enhanced confidence in managing behaviors (p=0.011)
 Reduction in caregiver upset (p=0.001)
 Reduction in negative communication (p=0.17)
 Improved caregiver well-being (p=0.001)
 Improvement in ability to keep patient at home (p=0.001)
• Similar outcomes at 24 weeks
Source: Gitlin, et al, JAGS, 2010
Non-pharmacologic Management
• “If these interventions were drugs, it is hard to believe
that they would not be on the fast track to approval. The
magnitude of benefit and quality of evidence supporting
these interventions exceed those of pharmacologic
therapies…”
Covinsky , Annals of Internal Medicine 2006
Expert Consensus Panel
• Convened in Detroit Michigan,
September 7, 2011
Faculty:
• Mary G. Austrom, PhD
• Frederic C. Blow, PhD
• Kathleen C. Buckwalter, PhD
• Christopher M. Callahan, MD
• Ryan Carnahan Pharm.D., M.S.
• Laura N. Gitlin, PhD
• Helen C. Kales, MD
• Dimitris N. Kiosses, PhD
• Mark E. Kunik, MD
• Constantine G. Lyketsos, MD
• Linda O. Nichols, PhD
• Daniel Weintraub, MD
Indiana University
VA Ann Arbor/University of Michigan
University of Iowa
Indiana University
University of Iowa
Johns Hopkins University
VA Ann Arbor/University of Michigan
Weill Cornell Medical College
VA Houston/Baylor College of Medicine
Johns Hopkins University
VA Memphis / University of Tennessee
VA Philadelphia/University of Pennsylvania
Panel Results
• 1) Create an evidence-informed approach
representing best practice known to date
• 2) Construct an approach that can guide the use
of both pharmacologic and non-pharmacologic
approaches (roadmap)
• Knee-jerk prescribing of meds is not optimal
• Going through the decision-making steps to derive
the treatments tailored to the patient, caregiver,
environment is key
Panel Results
• 3) We need better and more systematic ways to
differentiate symptoms by phenomena and putative
causes.
This may improve uptake of behavioral and
environmental modification approaches
This may better direct/target medication use
This will be of critical assistance to future medication
trials
Panel Results
• 4) Behavioral and environmental modifications
should be tried first-line with three major
exceptions:
Major depression with or without suicidal ideation
Psychosis causing harm or creating potential for
harm
Aggression causing risk
Emphasis on SAFETY and ACUITY
Etiology matters!
• We don’t know what is prompting Elizabeth’s
symptoms
• Knowing the underlying cause will direct the treatment:
 Urinary tract infection
 Pain
 Issues with caregiver
 Psychosis
Panel Results
• 5) Definition of the key elements of care for NPS:
Need accurate characterization and contextualization
Examine underlying causes of NPS
Devise treatment plan
Assess intervention effectiveness
Kales
et al,
JAGS,
2014
• Describe:
Caregiver
details the
problematic
behavior
The DICE Approach
Linkage of Describe Step with
Patient/Caregiver/Environmental Considerations
Patient
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Caregiver
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Environment
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What behavior did the patient exhibit (e.g. movie in my
head)?
How did the patient perceive what occurred?
How did the patient feel about it?
Is the patient’s safety at risk?
How much distress did the behavior generate for the
caregiver?
Does the caregiver feel their safety is threatened by the
behavior?
What about the behavior is distressing to the caregiver?
What did the caregiver do during and after the behavior
occurred?
Who was there when the behavior occurred (e.g. family
members, unfamiliar people, etc.)?
When did the behavior occur (time of day) and what
relationship did this have to other events (e.g. occurring while
bathing or at dinner)?
Where did the behavior occur (e.g. home, daycare,
restaurant, etc.)?
What happened before and after the behavior occurred in the
environment?
The DICE Approach
Investigate
Examine
possible
underlying
causes of
the
problematic
behavior
Linkage of Investigate Step with
Patient/Caregiver/Environmental Considerations
Patient
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Recent changes in medications
Untreated or undertreated pain
Limitations in functional abilities
Medical conditions (e.g. urinary tract infection)
Underlying psychiatric comorbidity
Severity of cognitive impairment, executive impairment
Poor sleep hygiene
Sensory changes (vision, hearing)
Fear, sense of loss of control, boredom
Caregiver
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Caregiver’s lack of understanding of dementia (e.g. patient is
“doing this to” them “on purpose”)
Caregiver’s negative communication style (e.g. overly critical
or harsh, use of complex questions, too many choices)
Caregiver’s expectations not aligned with dementia stage
(under/over estimation of capability)
Caregiver’s own stress/depression
Family/Cultural context (e.g. not wanting to involve “outsiders”
or “air dirty laundry”, promise to keep patient at home, etc)
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Environment
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Over- (e.g. clutter, noise, people) or under- (e.g. lack of visual
cues, poor lighting) stimulating environment
Difficulty navigating or finding way in environment
Lack of predictable routines that are comforting to patient
Lack of pleasurable activities tapping into preserved
capabilities and previous interests
• Create:
Provider,
caregiver
and team
collaborate
to create
and
implement
treatment
plan
The DICE Approach
Linkage of Create Step with
Patient/Caregiver/Environmental Considerations
Patient
Respond to physical problems
• Discontinue medications causing behavioral side effects if
possible
• Manage pain
• Treat infections, dehydration, constipation, etc.
• Optimize regimen for underlying psychiatric conditions
• Sleep hygiene measures
• Deal with sensory impairments
• Prescribe psychotropics if judged necessary
Caregiver
Work collaboratively with caregiver/other team members to
institute nonpharmacologic interventions including:
• Providing caregiver education and support
• Enhancing communication with patient
• Creating meaningful activities for patient
• Simplifying tasks
Environment
Work collaboratively with caregiver/other team members to
institute nonpharmacologic interventions including:
• Ensuring the environment is safe
• Simplifying/enhancing the environment
Kales
et al,
JAGS,
2014
Kales
et al,
JAGS,
2014
• Evaluate:
Provider
assesses
whether
“Create”
interventions
have been
implemented
by the
caregiver and
are safe and
effective
The DICE Approach
Linkage of Evaluate Step with
Patient/Caregiver/Environmental Considerations
Patient
• Has the intervention(s) been effective for the
problem behavior?
• Have there been any unintended
consequences or “side effects” from the
intervention(s)?
Caregiver
• Which interventions has the caregiver
implemented?
• If the caregiver did not implement the
interventions, why?
Environment
• What changes in the environment were
made?
Using the DICE Approach with Elizabeth
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Primary symptom is aggression with a particular
caregiver around ADLs like bathing; patient
expresses that baths “hurt”; caregiver is not afraid for
her safety but feels that the patient is “doing this on
purpose”; there is no psychosis.
•
Patient does have an underlying diagnosis of
arthritis; she is currently not taking any medications
for pain. She is unable to follow multi-step
commands due to level of cognitive impairment.
Caregiver has a lack of understanding of dementia
and tone with patient when frustrated is somewhat
harsh and confrontational.
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Consider starting standing pain medication, consider
physical therapy. Educate caregiver about the
“broken brain” and behavior. Address
communication. Enhance bathing environment so
that it is soothing and calm.
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Was pain medication effective? How has it impacted
aggression around bathing? What of the
caregiver/environmental interventions were tried?
The Place for Psychotropics in the
DICE Approach
• Three first-line scenarios (major depression; psychosis or
aggression with potential for harm)
• Medications as a temporizing measure for harmful behaviors
while working up and treating the underlying causes
• Continued use may depend on symptom persistence and nonresponsiveness to other treatment strategies
• Psychotropics are unlikely to impact: unfriendliness, poor selfcare, memory problems, not paying attention or caring about
what is going on, repetitive verbalizations/questioning,
wandering
Testing and Implementing DICE
• NINR R01NR014200
• Co-PI Gitlin
• Co-I Lyketsos
• 3.5 year grant to incorporate approach into a tool
using technology
• NIA Submission
• Testing of DICE approach in primary care with team
social workers as interventionists
Summary
• NPS are ubiquitous but remain often under- or
mistreated with an
• Overreliance on medications
• Underuse of non-pharmacologic strategies with a
substantial evidence base
• Symptom description and underlying etiology matter
• The DICE approach offers an evidence-informed
structured method that is tailored, patient- and
caregiver-centered and enables clinicians to conjointly
consider pharmacologic, non-pharmacologic and
medical treatments
kales@umich.edu
http://www.programforpositiveaging.org/
www.facebook.com/ProgramforPositiveAging