JAMDA xxx (2019) 1e6

JAMDA
journal homepage: www.jamda.com

Controversies in Care

When Less is More, but Still Not Enough: Why Focusing on

Limiting Antipsychotics in People With Dementia Is the
Wrong Policy Imperative
Helen C. Kales MD a, b, *, Laura N. Gitlin PhD, FGSA, FAAN c,
Constantine G. Lyketsos MD, MHS d
a
Program for Positive Aging, Department of Psychiatry and Behavioral Sciences, University of California Davis, Sacramento, CA
b
Department of Psychiatry, University of Michigan, Ann Arbor, MI
c
College of Nursing and Health Professions, Drexel University, Philadelphia, PA
d
Department of Psychiatry and Behavioral Sciences, Johns Hopkins Bayview and Johns Hopkins University, Baltimore, MD

a b s t r a c t

Antipsychotic reductions have been the primary focus of efforts to improve dementia care in nursing
homes by the Centers for Medicare & Medicaid Services National Partnership. Although significant
antipsychotic reductions have been achieved, this policy focus is myopic in 2 ways; there is no evidence
for any increases in use of nonpharmacologic interventions, and there are indications for compensatory
increases in the use of other (unmeasured) sedating psychotropics. This increased use of other sedating
psychotropics is more concerning than the antipsychotics that they replaced, as there is even less sup-
port of efficacy for behavioral and psychological symptoms of dementia (BPSD) and ample proof of
harms, including mortality. The current paradigm of “assessment” and “treatment” for BPSD is largely
cursory and reflexive, with little effort put forth to understand possible underlying causes. This contrasts
with the methodical, evidence-based way the field handles other symptoms considered “medical” (eg,
shortness of breath). To move beyond this nonmedical approach to BPSD, we suggest a conceptual model
that includes putative causal contributors. Although at their core BPSD are caused by brain circuitry
disruptions, such disruptions are theorized to increase the person with dementia’s vulnerability to 3
categories of triggers: those related to the (1) patient (eg, pain, hunger, and infection), (2) caregivers (eg,
competing priorities, unrealistic expectations, and negative communications), and (3) environment (eg,
overstimulation and limited light exposure). Assessing modifiable triggers is inherently person-centered
as it enables clinicians to select specific nonpharmacologic strategies to mitigate identified triggers.
Assessing triggers and selecting strategies, however, is time-intensive and reflects a paradigm shift
necessitating a reorganization of dementia care including compensation for time spent elucidating and
addressing modifiable triggers, vs unintendedly incentivizing the use of potentially harmful psychotro-
pics. This paradigm shift should also include the measurement and restriction of any sedating medica-
tions for BPSD, particularly without assessment of underlying causes.
Published by Elsevier Inc. on behalf of AMDA e The Society for Post-Acute and Long-Term Care Medicine.
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-
nc-nd/4.0/).

This work was supported by the Department of Defense (grant W81XWH-16-1-
0551; H.C.K., L.N.G, C.G.L.) and VA Health Services Research and Development
(grant IIR 15-330; H.C.K.).
H.C.K. has authored a manual and created a training website for caregivers
based on the DICE Approach. L.N.G. and C.G.L. are coauthors of the DICE manual and
training website.
The authors have received grant support (research or Continuing Medical Ed-
ucation) in the past from the National Institute of Mental Health, National Institute
of Aging, Associated Jewish Federation of Baltimore, Weinberg Foundation, Forest,
Glaxo-Smith-Kline, Eisai, Pfizer, Astra-Zeneca, Lilly, Ortho-McNeil, Bristol-Myers,
Novartis, National Football League (NFL), Elan, Functional Neuromodulation, and
Bright Focus Foundation. They also disclose receipt of payment as consultant or
advisor from Astra-Zeneca, Glaxo-Smith Kline, Eisai, Novartis, Forest, Supernus,
Adlyfe, Takeda, Wyeth, Lundbeck, Merz, Lilly, Pfizer, Genentech, Elan, NFL Players
Association, NFL Benefits Office, Avanir, Zinfandel, BMS, Abvie, Janssen, Orion,
Otsuka, Servier, and Astellas. In addition, honorarium or travel support was
received from Pfizer, Forest, Glaxo-SmithKline, and Health Monitor.
* Address correspondence to Helen C. Kales, MD, Program for Positive Aging,
Department of Psychiatry and Behavioral Sciences, University of California Davis,
2230 Stockton Boulevard, Sacramento CA, 95817.
E-mail address: kales@umich.edu (H.C. Kales).

https://doi.org/10.1016/j.jamda.2019.05.022
1525-8610/Published by Elsevier Inc. on behalf of AMDA e The Society for Post-Acute and Long-Term Care Medicine. This is an open access article under the CC BY-NC-ND
license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
2 H.C. Kales et al. / JAMDA xxx (2019) 1e6
Mr Johnson is an 88-year-old man with moderate Alzheimer’s
disease residing in a long-term care (LTC) facility. He also has
arthritis, hypertension, diabetes, and a history of falls. A nurse
contacts the on-call physician one weekend stating that Mr
Johnson is “agitated,” and that they need her to “add something
to calm him down . . . maybe risperidone.” However, the physi-
cian is concerned about the facility’s CMS rating (impacted by
the rate of antipsychotic use). Instead, she prescribes gabapentin
100 mg twice daily, with the rationale that it is sedating, not
tracked by CMS, and that she read about its usefulness in de-
mentia in a nonepeer-reviewed medical journal. Two weeks
later, nurses report that Mr Johnson is still having episodes of
agitation, and a different consulting physician increases the dose
to 200 mg twice daily. One month later, dayshift notes that Mr
Johnson is still agitated with some ADLs and seems more
confused. In the next team meeting, staff assert that Mr Johnson’s
dementia is “just progressing” and that social work should talk
to family about moving him to a higher level of care (locked
dementia care unit).
Behavioral and psychological symptoms of dementia (BPSD;
although we note this is an imperfect term, so too are the alternatives,
and BPSD is the most widely used term internationally) are defined as
signs and symptoms of disturbed perception, thought content, mood,
or behavior, and include agitation, depression, apathy, repetitive
questions, psychosis, aggression, wandering, sleep problems, and a
variety of socially inappropriate behaviors.1 Although cognitive
symptoms are thought of as the hallmark of dementias, BPSD are
nearly universal, with 1 or more symptoms affecting nearly all people
with dementia over the illness course.2 Symptoms co-occur (eg,
depression with anxiety or wandering with sleep problems), further
increasing their impact. As opposed to cognitive decline, BPSD are
among the most complex, stressful, and costly aspects of dementia
care and lead to a panoply of poor health outcomes, including
morbidity, mortality, hospital stays, and early placement in nursing
homes.3,4 For family caregivers, BPSD are strongly associated with
stress and depression, reduced income from missing work, and
worsened quality of life.5,6 For long-term care staff, BPSD are associ-
ated with decreased quality of care, injury, increased workload, lost
days of work, burnout, and staff turnover.7,8
Antipsychotics (APs) have been used to treat BPSD since the 1950s.
Although modestly efficacious, partly due to sedation, they carry sig-
nificant risks including accelerated mortality,9 resulting in FDA “black
box” warnings for atypical and typical APs in 2005 and 2008 respec-
tively.10,11 To address the high use of APs in persons living with de-
mentia in LTC settings, the Centers for Medicare & Medicaid Services
(CMS) launched the National Partnership to Improve Dementia Care in
Nursing Homes (hereafter referred to as the CMSNP) in 2012 to
“improve the quality of care” for nursing home residents with de-
mentia, primarily by achieving reductions in APs.12 Also in 2012, the
American Board of Internal Medicine initiated “Choosing Wisely,”13
targeting “low-value care,” including the first-line use of APs for
BPSD. The Choosing Wisely guideline concerning APs was endorsed by
the American Psychiatric Association and the American Geriatrics
Society. Since the establishment of the CMSNP, and other AP reduction
efforts, AP use has been significantly reduced from 24% of LTC resi-
dents in 2009 to 15% in 2018.14
Since the launch of the National Partnership, significant reductions
in the prevalence of antipsychotic medication use in long-stay
nursing home residents have been documented. CMS and its
partners are committed to finding new ways to implement prac-
tices that enhance the quality of life for people with dementia,
protect them from substandard care and promote goal-directed,
person-centered care for every nursing home resident. (CMSNP
Website, 201914)
In the wake of these policy efforts and national campaigns, Mr
Johnson’s case highlights several important questions surrounding
LTC residents with BPSD:
1. Have AP use declines resulted in compensatory upshifts in the
use of nonpharmacologic strategies, which are widely recom-
mended as first-line by expert bodies and considered integral
to “person-centered care”?
2. Have AP use declines resulted in compensatory increases in the
use of other sedating psychotropics?
3. Are “popular opinion,” personal beliefs, and drug company
detailing regarding psychotropics and other sedating drugs
relied upon by clinicians more than the evidence base?
4. How can clinicians assess and manage BPSD in an evidence-
based manner?
5. What is the role of policy-making bodies in engendering a
reorganization of long-term dementia care to truly “promote
goal-directed, person-centered care for every nursing home
resident”?
Have AP Use Declines Resulted in Compensatory Upshifts in
the Use of Nonpharmacologic Strategies?
As noted, AP use has been significantly reduced. So, what is
the problem? CMS developed a training program and care plans to
promote “person-centered high quality care” and the use of non-
pharmacologic treatment alternatives to APs.12,15 More recent regu-
lations attempt to address “unnecessary medication use.”16 However,
the CMSNP’s only quality measure related to dementia is the fre-
quency of AP use, which CMS reports publicly through the Nursing
Home Compare website and the Five-Star Quality Rating System for
nursing homes.17
Although both the CMSNP and the Choosing Wisely Initiative
recommend nonpharmacologic interventions as first-line, there is no
evidence for significant compensatory increases in the use of non-
pharmacologic strategies. Less than 2% of LTC facilities consistently
implement the person-centered care approaches embodied by the use
of behavioral or environmental strategies for BPSD.18 Why? A myriad
of nonpharmacologic approaches are available, but supportive evi-
dence for efficacy for any 1 strategy is heterogeneous (eg, aroma-
therapy or acupuncture or reminiscence), and, thus, cherry-picking a
single strategy to use a priori for BPSD is not likely to be helpful nor
measurable in current LTC settings.2
Most LTC staff lack the knowledge, skills, or experience to effec-
tively implement nonpharmacologic approaches.19,20 Somewhat
unsurprising then are data indicating that the nonpharmacologic
approach with the strongest evidence base is the comprehensive
training of caregivers, including education and support, stress reduc-
tion/cognitive reframing techniques, and specific skills in problem
solving. Individual nonpharmacologic approaches (eg, music or
physical activity) may be used within such comprehensive programs
as tailored activities.2,21 Expert opinion also endorses the assessment
of underlying causes (eg, pain, unmet needs) as the critical first step in
any approach to BPSD.22
However, such programs are tough to implement in LTC without
adequate (1) training of staff, (2) reimbursement (eg, for time spent in
assessment and management), or (3) buy-in throughout a given fa-
cility from the administration to front-line staff. In the current para-
digm, front-line staff are trained and incentivized to complete tasks,23
rather than to problem-solve or think “outside the box” and, therefore,
lack motivation to use nonpharmacologic strategies. There is no
incentive to implement comprehensive staff caregiver support pro-
grams or nonpharmacologic strategies, from either the administration
or staff perspective, within the current zeitgeist.
 H.C. Kales et al. / JAMDA xxx (2019) 1e6
Have AP Use Declines Resulted in Compensatory Increases in
the Use of Other Sedating Psychotropics?
Although their use declined slightly over the study period, atypical
antipsychotics continue to be used at a high rate . . . an increased
use of sedative and non-sedative antidepressants suggests that the
latter class of drugs is being substituted for the former in the
management of neuropsychiatric symptoms. (Vasudev et al24)
The use of mood stabilizers, possibly as a substitute for antipsy-
chotics, increased and accelerated after initiation of the partner-
ship in both LTC residents overall and in those with dementia.
Measuring use of antipsychotics alone may be an inadequate proxy
for quality of care and may have contributed to a shift in
prescribing to alternatives. (Maust et al25)
There are several studies now showing evidence of substitution, 2
from the United States25,26 and 1 from Canada.24 The Maust et al study
found that AP use reductions have resulted in compensatory increases
in use of other sedating psychotropics in LTC residents with dementia,
such as mood stabilizers25dincreasing from 16% in 2009 to 20% in
2014, despite evidence for the lack of efficacy and elevated mortality
rates.27,28 The Vasudev et al study found evidence for substitution
with sedative and nonsedative antidepressants.24 Benzodiazepine
increases are harder to measure (not covered under Medicare Part D
until 2013); however, use remains high (22% of LTC residents with
dementia) despite evidence of a plethora of harms and lack of effi-
cacy.25 Thus, despite CMS press releases reporting success in achieving
AP reductions, the evidence shows that LTC providers are finding
alternative sedating agents to prescribe to residents with
BPSDdhardly person-centered care.
As a result, almost 70% of LTC residents with dementia are pre-
scribed psychotropics with little understanding of underlying causes
of BPSD, or increases in the application of evidence-based non-
pharmacologic strategies.25 In many cases, the alternative (eg, valproic
acid) is worse than the AP it replaceddfraught with side effects and
proven not to be efficacious.2 As noted by a recent international panel
of experts in geriatric psychiatry, APs like risperidone are the most
efficacious (albeit modestly) agents we have for BPSD such as psy-
chosis and agitation/aggression.22 In some cases, the use of an AP like
risperidone might be appropriate (eg, psychosis or agitation/aggres-
sion with risk of harm).
With APs set up as the primary CMSNP focus, we have created a
state of affairs where the knee-jerk use of sedating medications con-
tinuesdsame modus operandi, different names. As with Mr Johnson,
staff observes a symptom described vaguely as “agitation,” calls a
physician, and obtains a prescription for a sedating medication typi-
cally with no assessment of an underlying cause (eg, pain, infection,
unmet needs, and ineffective staff communication). Contrast this
scenario with a medical symptom such as shortness of breath. Does a
physician assume pneumonia and prescribe antibiotics? No, she or he
works algorithmically, starts with a thorough history and careful
physical, selects laboratory work based on the clinical picture, and
then uses these data to derive a targeted treatment.
Do “Popular Opinion,” Personal Beliefs, and Drug Company
Detailing Regarding Psychotropics and Other Sedating Drugs
Tend to be Relied Upon More Than the Evidence Base?
In a Los Angeles nursing home last year, regulators found that more
than a quarter of its residents had been placed on Nuedexta, noting
that a facility psychiatrist had given a talk about the drug to em-
ployees. This psychiatrist was a paid speaker for Avanir. At another
facility in 2015, also in Southern California, an employee admitted
to inspectors that a resident had been given a diagnosis of pseudo-
3
bulbar affect to “somehow justify the use” of Nuedexta, even
though its intended purpose was to control the resident’s “mood
disturbances” and yelling out.
(“The Little Red Pill Being Pushed on the Elderly,” CNN report
201829)
In the case of dextromethorphan-quinidine, our findings show that
this medication was quickly used after approval primarily in
elderly patients with dementia and/or PD. (Fralick et al30)
Despite the preponderance of evidence from randomized
controlled trials and systematic reviews indicating that APs are the
only group of medications with some evidence for efficacy in
BPSD,22,31 a wide variety of sedating medications are being used for
BPSD in LTC facilities in the wake of the black-box warnings, the
CMSNP, and Choosing Wisely. These include medications with no
scientific evidence for efficacy for BPSDdor in some instances evi-
dence for lack of efficacy, such as valproic acid,26 gabapentin, benzo-
diazepines, dextromethorphan hydrobromide quinidine sulfate
(Nuedexta),30 and hydroxyzine hydrochloride (Atarax). Thus, instead
of solid scientific evidence, clinicians appear to be relying on other
sources of information. In the case of gabapentin, information sources
include case series32,33 and articles in nonepeer-reviewed jour-
nals34,35 (medical magazines for health professionals sent free of
charge or by nonpaid subscription). For dextromethorphan hydro-
bromide/quinidine sulfate, “off label” detailing has been widely
implemented to apparent success. There is evidence that the medi-
cation’s manufacturer has targeted facilities with high rates of AP use
who would see dextromethorphan-quinidine “as an attractive alter-
native,” given the close monitoring of AP prescribing.29 As long as
AP prescribing is the only CMS quality measure related to BPSD,
substitutions to bypass surveillance will continue, regardless of the
evidence base.
At a staff level, there are ample data that, despite evidence to the
contrary, staff continue to believe that psychotropic medications are
both effective for BPSD and more effective than behavioral in-
terventions.36 Education is not sufficient to change staff’s behavior,
and yet it remains the primary strategy used to decrease psychotropic
use and increase the use of behavioral or environmental ap-
proaches.37,38 Instead, active engagement strategies empowering
stakeholders (including front-line staff) to identify barriers to person-
centered care and ways to integrate evidence into practice is much
more effective, but little used or incentivized in current care
systems.36
How Can LTC Clinicians and Staff Assess and Manage
Behavioral and Psychological Symptoms of Dementia (BPSD)
in an Evidence-Based Manner?
How do we move beyond reflexive “sedative” approaches to
address BPSD? We propose a conceptual model for understanding
causal contributors, developed by the authors2 and expanded on at a
recent National Institute of Mental Health/National Institute on Aging
Expert Workshop on BPSD (Figure 1).39 This model suggests that at
their core, BPSD are caused by brain circuitry disruptions; in turn,
these disruptions increase a person’s vulnerability to 3 categories of
“triggers”: (1) patient (pain, hunger, and infection), (2) caregiver
(depression, unrealistic expectations, and negative communications),
and (3) environment (overstimulation and limited light exposure). This
model encourages clinicians to consider BPSD in their complexity and
to assess for and modify triggers. Optimally, this model decreases the
need for psychotropic medications, or delays their use until non-
pharmacologic strategies have been deployed and evaluated for their
success in mitigating or eliminating triggers and, then, targets the
safest medications for the clinical phenotypes for which they are
proven to workdfor example, APs for psychosis22 and augmentation
4 H.C. Kales et al. / JAMDA xxx (2019) 1e6

Behavioral Effect
¾ Loss of executive/inhibitory control
¾ Impaired threat assessment
¾ Mood instability
¾ Sensory impairment
Modifiers* ¾ Sleep-wake disruption
¾ Stimulus-bound/goal-directed behavior
¾ Genes ¾ Impaired information processing
¾ Reserve ¾ Other
¾ Resilience
¾ Comorbidities
Disruption in brain
¾ Other
*Some of these are circuitry
Circuits Involved
also potentially
¾ Monoamines
modifiable ¾ Salience network Behavioral and
¾ Limbic system Psychological
¾ Circadian system
¾ Other Symptoms (BPSD)
¾ Agitation
¾ Psychosis
Neurodegeneration ¾ Depression
¾ Apathy
¾ Sleep disruption
Vulnerability to
¾ Other
POTENTIALLY
stressors/triggers MODIFIABLE

Patient Factors Caregiver Factors Environmental Factors

¾ Acute medical illness
¾ Pain threshold/expression
¾ Premorbid personality
¾ Premorbid psychiatric
disorder
¾ Unmet needs: fatigue, poor
sleep, hunger, fear, boredom
¾ Other
¾ Emotional state (distress, ¾ Over-or under-stimulation
depression, fatigue) ¾ Safety issues
¾ Loss of mastery/stress ¾ Lack of activity or structure
¾ Communication challenges ¾ Limited light exposure
¾ Unrealistic expectations ¾ Residence and
¾ Caregiving style neighborhood
¾ Limited resources (human, ¾ Other
financial)
¾ Other

Fig. 1. Proposed model of causal contributors to BPSD in persons with Alzheimer’s and related dementias.

of antidepressants. Other medications may hold promise, for example,
citalopram for agitation,40 but further research is necessary.
What is the optimal way to embed this approach in clinical
care? We have operationalized this model in an algorithmic
approachd“DICE” (Describe-Investigate-Create-Evaluate)2,41 (Figure 2).
DICE provides a systematic way of assessing and responding to trig-
gers leading to heuristic treatment planning. Unlike other approaches
that pit nonpharmacologic approaches against the pharmacologic,
DICE integrates both treatment approaches and provides guidelines
for first-line medication use. These include (1) significant clinical
symptoms of depression with or without suicidal ideation, (2) psy-
chosis with concern for harm or risk to self or others, and (3)
aggression with concern for harm or risk to self or others. Impor-
tantly, DICE goes beyond “staff education” strategies and empowers,
motivates, and engages staff as key stakeholders in problem-solving,
brainstorming, identifying triggers, and implementing person-
centered care strategies tailored to potentially underlying contribu-
tors to BPSD.
understanding about BPSD; and environmentaldlack of structure
with varied bathing schedule. In the Create phase, strategies are
developed collaboratively with key staff members to respond to
triggers. Staff set up a care routine to ensure hearing aid use during
activities like bathing. The shoulder signs and symptoms trigger a
physician assessment for a possible rotator cuff tear and trial of a
standing dose of pain medication (Mr Johnson might not remember
to ask for a “prn”). Staff learn about BPSD emanating from neu-
rodegeneration as opposed to being intentional “bad” behavior,
potential triggers, and the utility of strategies like routinizing
bathing times, calm communication, and “relaxing the rules” (eg,
daily baths are not necessary). They may also try having a male
staff member bathe Mr Johnson. Staff work on regular structure so
that baths do not occur unexpectedly. In the Evaluate phase, the
team assesses for the consistent implementation and efficacy of
strategies, prioritizing staff observations, after a trial period (eg,
1 week). Also evaluated are any “side effects” (eg, unexpected
increased resistance with a male staff member).

Applying the DICE Approach to the Case of Mr Johnson
Staff say that Mr Johnson is “agitated.” In the Describe phase, the
physician obtains a nuanced behavioral description and context
and discovers that episodes are better characterized as resistance to
care during daily baths with female staff. In the Investigate phase,
the physician learns that Mr Johnson has hearing loss and often
forgets to wear hearing aids. Mr Johnson rubs his right shoulder
during the examination and has reduced range of motion there. The
primary caregiver working with Mr. Johnson appears exasperated
and says, “he does this stuff to make me upset.” She gives Mr
Johnson baths at different times on any given day. Potential triggers
from the conceptual model found in the Investigate phase include
the following: patientdpoor hearing and possible shoulder injury
pain; caregiverdfrustrated staff member with a lack of
What is the Role of Policy-Making Bodies in Engendering a
Reorganization of Long-Term Dementia Care to Truly
“Promote Goal-Directed, Person-Centered Care for Every
Nursing Home Resident”?
To promote person-centered dementia care, policy bodies should
focus their efforts in 2 ways. First, the measurement of quality de-
mentia care in LTC facilities must go beyond the focus on measure-
ment of percentage of residents on APs and anecdotes about
individual cases of “successful” use of nonpharmacologic strategies
that are not objectively measured. Quality in this area must include
measurement of and restrictions on use of all sedating medications
(eg, benzodiazepines, mood stabilizers, dextromethorphan hydro-
bromide quinidine sulfate, and hydroxyzine). Facilities should be
given credit for the implementation of structured, evidence-based
 H.C. Kales et al. / JAMDA xxx (2019) 1e6
Fig. 2. The DICE approach for assessment and management of BPSD.
approaches to assess and manage BPSD, moving nonpharmacologic
strategies beyond anecdotal and unmeasured efforts and providing an
integrated methodology for addressing BPSD.
Second, because structured, evidence-based approaches like DICE
are more time-intensive than knee-jerk prescribing, this paradigm
shift in assessing and treating BPSD must be linked with policy
changes to engender a reorganization of dementia care where clini-
cians are fairly compensated for time spent elucidating and addressing
modifiable triggers, and not unintendedly provided incentives to
sedate people with dementia.
Implications for Practice and Policy
Lowering AP Use is Not Enough
Approaches like DICE improve precision and prevent reflexive use
of psychotropics in response to vague symptoms like “agitation,”
while being inherently person and caregiver centered. Providers can
then “choose wisely” from behavioral and environmental in-
terventions based on knowledge of the person with dementia and
potentially modifiable triggers. Training health providers in struc-
tured, evidence-based approaches like DICE and embedding and
reimbursing them in care contexts is the right policy imperative,
leading to greater efficiency, precision, and effective quality care.
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