The goal of this webinar was to help physicians and healthcare professionals differentiate delirium, terminal restlessness, and dementia-related agitation and aggression in patients near the end of life.

1. A Change in Behavior:
A Pragmatic Clinical Guide
to Delirium, Terminal
Restlessness, and Dementia
The information in the pages that follow is considered by VITAS® Healthcare Corporation to be confidential.

2. CME
Provider
Information
Satisfactory Completion
Learners must complete an evaluation form to receive a certificate
of completion. You must participate in the entire activity as partial
credit is not available. If you are seeking continuing education
credit for a specialty not listed below, it is your responsibility to
contact your licensing/certification board to determine course
eligibility for your licensing/certification requirement.
Physicians
In support of improving patient care, this activity has been
planned and implemented by Amedco LLC and VITAS®
Healthcare. Amedco LLC is jointly accredited by the
Accreditation Council for Continuing Medical Education
(ACCME), the Accreditation Council for Pharmacy Education
(ACPE), and the American Nurses Credentialing Center
(ANCC), to provide continuing education for the healthcare
team. Credit Designation Statement – Amedco LLC designates
this live activity for a maximum of 1 AMA PRA Category 1
CreditTM. Physicians should claim only the credit commensurate
with the extent of their participation in the activity.

3. CE Provider
Information
VITAS Healthcare programs are provided CE credits for their Nurses/Social
Workers and Nursing Home Administrators through: VITAS Healthcare
Corporation of Florida, Inc. CE Broker Number: 50-2135. Approved By:
Florida Board of Nursing/Florida Board of Nursing Home Administrators/
Florida Board of Clinical Social Workers, Marriage and Family Therapy &
Mental Health Counseling.
VITAS Healthcare programs in Illinois are provided CE credit for their Nursing
Home Administrators and Respiratory Therapists through: VITAS Healthcare
Corporation of Illinois, Inc. 8525 West 183 Street, Tinley Park, IL 60487/NHA
CE Provider Number: 139000207/RT CE Provider Number: 195000028/
Approved By the Illinois Division of Profession Regulation for: Licensed
Nursing Home Administrators and Illinois Respiratory Care Practitioner.
VITAS Healthcare, #1222, is approved to offer social work continuing
education by the Association of Social Work Boards (ASWB) Approved
Continuing Education (ACE) program. Organizations, not individual courses,
are approved as ACE providers. State and provincial regulatory boards have
the final authority to determine whether an individual course may be accepted
for continuing education credit. VITAS Healthcare maintains responsibility for
this course. ACE provider approval period: 06/06/2021 – 06/06/2024. Social
workers completing this course receive 1.0 ethics continuing education credits.
VITAS Healthcare Corporation of California, 310 Commerce, Suite 200, Irvine,
CA 92602. Provider approved by the California Board of Registered Nursing,
Provider Number 10517, expiring 01/31/2023.
Exceptions to the above are as follows: AL: No NHAs, DE: No NHAs, DC:
No NHAs, GA: No NHAs, KS: No NHAs, NJ: No NHAs, OH: No NHAs, PA:
No NHAs, TX: No NHAs, VA: No NHAs, WI: No NHAs and Nurses are not
required – RT only receive CE Credit in Illinois

4. Objectives
By the end of this presentation, you
will be able to:
• Differentiate among delirium, terminal
restlessness, and dementia-related
agitation and aggression
• Identify and treat contributors to
behaviors in dementia
• Implement effective non-pharmacologic
management approaches to behaviors
in dementia
• Incorporate pharmacologic treatment
strategies to manage behaviors
in dementia

5. Background: Dementia Epidemiology
Alzheimer's Association. (2021). 2021 Alzheimer's Disease Facts and Figures. Available at: https://www.alz.org/media/Documents/alzheimers-facts-and-figures.pdf
• 2021 US Alzheimer’s estimate:
6.2 million
– 72% are ages 75+
– 2/3 are women
• Dementia cases projected for
2050: 12.7 million Americans
• Estimated lifetime risk for
Alzheimer’s dementia at age
65+ is 21.1% for women and
11.6% for men
• One in 9 Americans aged
65+ has Alzheimer's dementia
• Between 2000-2019,
Alzheimer’s-related deaths
increased 145%

6. Background:
Dementia
Near the
End of Life
• 1 in 3 older adults who die each
year have a diagnosis of dementia
• Alzheimer’s kills more Americans
than breast cancer and prostate
cancer combined
• Dementia is the fifth-leading cause
of death in persons over 65
• > 500,000 deaths a year in US
are attributed to dementia
Alzheimer's Association. (2021). 2021 Alzheimer's Disease Facts and Figures. Available at:
https://www.alz.org/media/Documents/alzheimers-facts-and-figures.pdf

7. Effect of COVID-19 Pandemic on Deaths
from Alzheimer’s Disease
Alzheimer's Association. (2021). 2021 Alzheimer's Disease Facts and Figures. Available at: https://www.alz.org/media/Documents/alzheimers-facts-and-figures.pdf

8. Hospice Use by Primary Diagnosis
0
200,000
400,000
600,000
800,000
1,000,000
1,200,000
1,400,000
1,600,000
1,800,000
1992 1998 2005 2014
Other
Kidney disease
Stroke
Chronic lower respiratory disease
Alzheimer's disease
Heart disease
Cancer
Aldridge, M., et al. E. (2017). Epidemiology and patterns of care at the end of life: Rising complexity,
shifts in care patterns and sites of death. Health Affairs, 36(7), 1175-1183.

9. Mitchell, S., et al. (2009). The clinical course of advanced dementia. New England Journal of Medicine (361), 1529-1538.
Symptoms of End-Stage Dementia
0
5
10
15
20
25
30
35
40
Dyspnea Pain Pressure ulcers Aspiration Agitation
Residents
With
Symptoms
(%)
Distressing Symptoms
Months Before Death (no. of residents alive during interval)
> 9-12 > 6-9 > 3-6 0-3

10. 4.3%
11.2% 15.2%
44.3%
38.2%
13.3%
32.6%
30.3%
30.0%
31.4%
82.3%
56.0% 54.5%
25.7%
30.4%
Normal cognition Mild cognitive
impairment
Mild dementia Moderate
dementia
Severe dementia
No symptoms
1-2 symptoms
3+ symptoms
Neuropsychiatric Symptoms (NPS)
by Stage of Cognitive Impairment
Radue, R., et al. (2019). Neuropsychiatric symptoms in dementia. In Handbook of Clinical Neurology (Vol. 167, pp. 437-454). Elsevier.

11. Case 1
• 61-year-old with Huntington’s disease who
presents to the hospice inpatient unit (IPU)
with impulsivity and agitation
– Has not slept in 2 days; is more confused,
pacing, eating food out of garbage
• Patient recently admitted to hospice with
functional decline, falls, weight loss,
dysphagia, and worsening behaviors
• Interventions to date: Haldol 5mg every
6 hours and every 2 hours as needed,
mirtazapine 30mg at night, sertraline 50mg
daily, lorazepam 1mg every 6 hours and
1 hour as needed, amantadine 200mg daily
• Urinalysis and bloodwork were unremarkable;
patient was transferred to the IPU for further
management of impulsivity and agitation

12. Case 2
• 86-year-old with cerebral atherosclerosis and
recent functional decline
– In the past 2 weeks: bedbound, fall, stage II
sacrum, poor appetite, weight loss, and
increased agitation/aggression
• Daughter took patient out of ALF after patient
hit and tried to bite several staff
– Patient spends most of the day yelling,
swearing, kicking; is very restless in bed
• Comorbidities: hard of hearing, poor vision,
arthritis, peripheral vascular disease, history
of stroke, hypertension, depression, and
heart failure
• Bloodwork and urinalysis were unremarkable;
patient admitted to hospice and transferred to
the IPU for management of vocalizations and
agitation/aggression
• Medications: sertraline 100mg daily

13. Guiding
Principles
• Identify dementia etiology as symptoms
and treatments vary
• Differentiate delirium, terminal restlessness,
and dementia-related behavior
• Evaluate and manage all contributors
• Identify the target symptoms to be treated
and characterize impact on
patient/caregiver
• Non-pharmacologic interventions
– Person-centered
– Caregiver
– Environment
• Pharmacologic treatment

14. Most Common Etiologies of Dementia
Alzheimer’s Association. Differentiating dementias. In Brief for Healthcare Professionals, (7). Retrieved from: https://www.alz.org/media/Documents/inbrief-differentiating-dementias.pdf
Karantzoulis, S., & Galvin, J. (2011). Distinguishing Alzheimer's disease from other major forms of dementia. Expert Review of Neurotherapeutics, 11(11), 1579–91.
Pathophysiology
Amyloid plaques and
neurofibrillary tangles
Pathophysiology
Combination of
Alzheimer’s disease and
vascular disease
Pathophysiology
Alpha-synuclein
protein
Pathophysiology
Tau protein
Mixed Dementia = > 1 Neuropathology – Prevalence Unknown

15. Dementia
Etiology
Considerations
• Depression is more common in
vascular dementia
• Hallucinations are seen more
often in Lewy body dementia
– Special consideration ACEI
and antipsychotics
• Frontotemporal dementia often
exhibits executive control loss
– Disinhibition
– Wandering
– Social inappropriateness
– Apathy
• Behaviors increase in frequency with
all conditions as disease progresses
Ringman, J., & Schneider, L. (2019). Treatment options for agitation in dementia.
Current Treatment Options in Neurology, 21(7), 30.

16. Guiding
Principles
• Identify dementia etiology as symptoms
and treatments vary
• Differentiate delirium, terminal
restlessness, and dementia-related
behaviors
• Evaluate and manage all contributors
• Identify the target symptoms to be
treated, and characterize impact on
patient/caregiver
• Non-pharmacologic interventions
– Person-centered
– Caregiver
– Environment
• Pharmacologic treatment

17. Definition of Delirium
Ayalon, L., et al. (2006). Effectiveness of nonpharmacological interventions for the management of neuropsychiatric symptoms in patients with dementia:
A systematic review. Archives of Internal Medicine, 166(20), 2182-2188.
Inouye, S., et al. (1990). Clarifying confusion: The confusion assessment , C., method: A new method for detection of delirium. Annals of Internal Medicine, 113(12), 941-948.
Acute Onset and Fluctuating
Course + Inattention,
plus either
Altered Level of
Consciousness
Disorganized
Thinking
Delirium

18. Terminal
Restlessness
Freemon, F. (1981). Delirium and Organic Psychosis. Organic Mental Disease, 81-94. Springer, Dordrecht.
THE USUAL
ROAD
THE DIFFICULT
ROAD

19. Dementia
Behaviors
Thought and
Perceptual
Disturbances
• Delusions
• Paranoia
• Hallucination
Mood
Disturbances
• Anxiety
• Depression
• Irritability
Ringman, J., & Schneider, L. (2019). Treatment options for agitation in dementia.
Current Treatment Options in Neurology, 21(7), 30.
Activity Disturbance
• Agitation
• Aggression
• Wandering
• Purposeless
hyperactivity
• Apathy
• Impulsivity
• Socially inappropriate
behavior
• Sleep problems
• Repetitive behavior

20. Guiding
Principles
• Identify dementia etiology, as symptoms
and treatments vary
• Differentiate delirium, terminal restlessness,
and dementia-related behaviors
• Evaluate and manage all contributors
• Identify the target symptoms to be
treated, and characterize impact on
patient/caregiver
• Non-pharmacologic interventions
– Person-centered
– Caregiver
– Environment
• Pharmacologic treatment

21. Ringman, J., & Schneider, L. (2019). Treatment options for agitation in dementia. Current Treatment Options in Neurology, 21(7), 30.
Contributors to Behaviors
Contributor Causes Approach
Physical symptom Pain, SOB Opioid
Psychological symptom Depression, anxiety SSRI, SNRI CBT
Medical illness Delirium, infection, constipation Treat condition
Unmet need Hunger, thirst, cold Attend to need
Sensory impairment Poor vision/hearing Adaptive
Environment Under-/over-stimulation Modify
Pharmacologic Dig, caffeine, benzo Discontinue
Dementia AD, mixed, LBD AChEI

22. Guiding
Principles
• Identify dementia etiology as symptoms
and treatments vary
• Differentiate delirium, terminal restlessness,
and dementia-related behaviors
• Evaluate and manage all contributors
• Identify the target symptoms to be
treated and characterize impact on
patient/caregiver
• Non-pharmacologic interventions
– Person-centered
– Caregiver
– Environment
• Pharmacologic treatment

23. Ringman, J., & Schneider, L. (2019). Treatment options for agitation in dementia. Current Treatment Options in Neurology, 21(7), 30.
Behaviors in
Dementia
and Health-
Related
Outcomes
• Patient
– Increased morbidity and mortality
– Increased likelihood of hospitalization
and longer length of stay
– Early placement in a nursing home
• Caregiver
– Stress and strain
– Depression and anxiety
– Reduced income from employment
– Lower quality of life
• Behaviors and their management contribute
to one-third of total dementia-related costs

24. Guiding
Principles
• Identify dementia etiology as symptoms
and treatments vary
• Differentiate delirium, terminal restlessness,
and dementia-related behaviors
• Evaluate and manage all contributors
• Identify the target symptoms to be treated
and characterize impact on
patient/caregiver
• Non-pharmacologic interventions
– Person-centered
– Caregiver
– Environment
• Pharmacologic treatment

25. Dementia
Behavior
Models
• Person with dementia
– Unmet need; behavior as an
underlying need
– Agitation etiology, remaining abilities,
level of cognitive functioning, and
past/present interests
• Caregiver
– Learning and behavioral (ABC)
– Behavior Consequence Reinforces
behavior
• Environment
– Environmental vulnerability and
reduced stress thresholds: a mismatch
between the setting and the patient’s
ability to deal with it
Ayalon, L., et al. (2006). Effectiveness of nonpharmacological interventions for the management of neuropsychiatric symptoms in
patients with dementia: A systematic review. Archives of Internal Medicine, 166(20), 2182-8. doi: 10.1001/archinte.166.20.2182.

26. Non-
Pharmacologic
Approaches
for Persons
With Dementia:
Inconclusive
Evidence
• Reminiscence therapy (discussion of
past experiences)
• Validation therapy (working through
unresolved conflicts)
• Simulated presence therapy (use of audiotaped
recordings of family members’ voices)
• Aromatherapy (use of fragrant plant oils)
• Snoezelen®
(placing the person with
dementia in a soothing and stimulating
multi-sensory environment known as a
“Snoezelen room”)
• Cognitive training and rehabilitation
• Acupuncture
• Light therapy
Ayalon, L., et al. (2006). Effectiveness of nonpharmacological interventions for the management of neuropsychiatric symptoms in
patients with dementia: A systematic review. Archives of Internal Medicine, 166(20), 2182-8. doi: 10.1001/archinte.166.20.2182.

27. Non-
Pharmacologic
Approaches for
Persons With
Dementia
Evidence Exists in 2 or More Randomized
Clinical Trials (RCTs)
• Physical activity positively impacts
depression and sleep
• Hand massage
• Personalizing the bathing experience
Ayalon, L., et al. (2006). Effectiveness of nonpharmacological interventions for the management of neuropsychiatric
symptoms in patients with dementia: A systematic review. Archives of Internal Medicine, 166(20), 2182-8. doi:
10.1001/archinte.166.20.2182.
Gitlin, L., et al. (2006). A randomized trial of a multicomponent home intervention to reduce functional difficulties in
older adults. Journal of the American Geriatric Society, 54(5), 809-16. doi: 10.1111/j.1532-5415.2006.00703.

28. Non-
Pharmacologic
Approaches
for Caregivers:
Most Robust
Evidence
• Engage in problem-solving with a family caregiver:
– Identify precipitating and modifiable causes
of symptoms
– Deploy efforts to modify these causes with
selected non-pharmacologic strategies
• Explore caregiver programs:
– REACH II and REACH VA: Coping approaches and
tailored behavioral management
– The Tailored Activity Program (TAP):
Occupational Therapy
– The Caregiver Training (ACT):
Health Professionals
A meta-analysis of 23 randomized clinical trials,
involving almost 3,300 community dwelling
patients and their caregivers:
• Significantly reduced behavioral symptoms
(effect size 0.34, 0.20 to 0.48)
• Similar to antipsychotics for behavior; similar to
cholinesterase inhibitors for memory
Ayalon, L., et al. (2006). Effectiveness of nonpharmacological interventions for the management of neuropsychiatric symptoms in
patients with dementia: A systematic review. Archives of Internal Medicine, 166(20), 2182-8. doi: 10.1001/archinte.166.20.2182.

29. Non-
Pharmacologic
Environmental
Factors:
Paucity of
RCTs, Positive
Impact
• Overstimulation (e.g., excess noise,
people, or clutter in the home)
• Understimulation (e.g., lack of anything
of interest to look at)
• Safety problems (e.g., access to
household chemicals or sharp objects;
easy ability to exit the home)
• Lack of activity and structure (e.g., no
regular exercise or activities that match
interests and capabilities)
• Lack of established routines (e.g., frequent
changes in the time, location, or sequence
of daily activities)
Ayalon, L., et al. (2006). Effectiveness of nonpharmacological interventions for the management of neuropsychiatric symptoms in
patients with dementia: A systematic review. Archives of Internal Medicine, 166(20), 2182-8. doi: 10.1001/archinte.166.20.2182.

30. Responses
to Non-
Pharmacologic
Interventions
Greater Response
• Higher levels of
cognitive function
• Fewer difficulties
with ADLs
• Speech
• Communication
• Responsiveness
Cohen-Mansfield, Jet al. (2014). Predictors of the impact of non-pharmacologic interventions for agitation in nursing home
residents with advanced dementia. Journal of Clinical Psychiatry, 75(7), 666-671. doi: 10.4088/jcp.13M08649.
Less Response
• Staff barriers
(refuse to participate)
• Patient in pain

31. Guiding
Principles
• Identify dementia etiology as symptoms and
treatments vary
• Differentiate delirium, terminal restlessness,
and dementia-related agitation
• Evaluate and manage all contributors
to agitation
• Identify the target symptoms to be treated and
characterize impact on patient/caregiver
• Non-pharmacologic interventions
– Person-centered
– Caregiver
– Environment
• Pharmacologic treatment

32. Dementia
Behaviors and
Pharmacologic
Treatment
Helpful
• Agitation and
aggression
• Psychosis
– Delusions
– Hallucinations
– Paranoia
• Depression
• Irritability
Ballard, C., et al. (2009). Management of agitation and aggression associated with Alzheimer’s disease.
Nature Reviews Neurology, 5(5), 245-55. doi: 1038/nrneurol.2009.39.
Not Helpful
• Day/night reversal
• Calling out
• Repetitive behaviors
• Wandering
• Apathy
• Resistance to care

33. Pharmacologic Treatment of Agitation
Antonsdottir, I., et al. (2015). Advancements in the treatment of agitation in Alzheimer’s disease. Expert Opinion on Pharmacotherapy, 16(11), 1649-1656. https://doi.org/10.1517/14656566.2015.1059422.
Ballard, C., et al. (2009). Management of agitation and aggression associated with Alzheimer’s disease. Nature Reviews Neurology, 5(5), 245-55. doi: 1038/nrneurol.2009.39.
Therapeutic Class Trial Side Effects
Trazodone + RCT Sedation, hypotension
SSRI (citalopram) + RCT Nausea, diarrhea, QTc inc > 20mg daily
Dextromethorphan/quinidine + RCT Falls, dizziness, diarrhea, UTIs
Lorazepam + RCT Sedation, falls, ataxia, agitation
Antipsychotics + RCT Stroke, infection, sz, QTc inc, DM, death
Carbamazepine-Valproic acid
- RCT
- RCT
Sedation, anemia, liver toxicity, sedation
NMDA antagonist - RCT/+obs Constipation, dizziness
AChEI - /+RCT/+obs Nausea, dizziness, weight loss
Cannabinoids - RCT Low dose used, oral form

34. Trazodone
• Several small randomized controlled
trials indicate benefit
– Cochrane review inconclusive evidence
• Dosing: 25-20mg BID-TID and q 2hrs
PRN, maximum dose 400mg daily
• Adverse effects:
– Orthostasis, syncope,
hypotension, dizziness
– Priapism
– SIADH
– Somnolence
– QTc prolongation
Antonsdottir, I., et al. (2015). Advancements in the treatment of agitation in Alzheimer’s disease. Expert Opinion on
Pharmacotherapy, 16(11), 1649-1656. https://doi.org/10.1517/14656566.2015.1059422.

35. Citalopram for Agitation in
Alzheimer’s Disease
Antonsdottir, I., et al. (2015). Advancements in the treatment of agitation in Alzheimer’s disease. Expert Opinion on Pharmacotherapy, 16(11), 1649-1656. https://doi.org/10.1517/14656566.2015.1059422.
Neurobehavioral Rating Scale (NBRS)-Agitation Subscale
No. of participants
Citalopram 94 87 85 86
Placebo 92 84 84 81

36. Citalopram
Considerations
• QTc prolongation, which is dose-dependent
above 20mg
• Starting dose 10mg up to 40mg daily
• Consider twice-daily dosing
– 10mg daily for 2 weeks
– 10mg twice daily thereafter
• Other SSRI side effects
• Onset of action within a week in one study

37. Antipsychotics
• Best-studied pharmacologic intervention
for dementia-related agitation
• Moderate efficacy across trials and agents
– Typical antipsychotics
– Atypical antipsychotics
• Substantial side effects
• Black box warning: cerebrovascular events
and death
Meeks, T., & Jeste, D. (2008). Beyond the black box: What is the role for antipsychotics in dementia? Current Psychiatry, 7(6), 50–65.

38. Antipsychotics (cont.)
Antipsychotic
Recommended
Dose
Formulations Frequency Characteristics
Risperidone 0.5-2.0mg Tab, liquid, IM 2 times a day
Extrapyramidal
symptoms
Olanzapine 2.5-15mg Tab Daily
Weight gain,
increased sugar
Quetiapine 25-400mg Tab
3 times a day
(unless ER)
Sedating, least
extrapyramidal
Aripiprazole 5-30mg Tab, liquid, IM Daily Less QT
Haloperidol 0.5-5mg
Tab, liquid, IM, IV,
sub q
2-4 times a day
Chlorpromazine 10-200mg Tab, liquid, IV, rectal 2-3 times a day Very sedating
Meeks, T., & Jeste, D. (2008). Beyond the black box: What is the role for antipsychotics in dementia? Current Psychiatry, 7(6), 50–65.

39. Schneider, L., et al. (2006). Effectiveness of atypical antipsychotic drugs in patients with Alzheimer's disease.
The New England Journal of Medicine, 355(15), 1525-1538.
CATIE-AD

40. CATIE-AD (cont.)
Schneider, L., et al. (2006). Effectiveness of atypical antipsychotic drugs in patients with Alzheimer's disease.
The New England Journal of Medicine, 355(15), 1525-1538..

41. Schneider, L., et al. (2006). Effectiveness of atypical antipsychotic drugs in patients with Alzheimer's disease.
The New England Journal of Medicine, 355(15), 1525-1538.
CATIE-AD (cont.)

42. Antipsychotics
Summary
• Modest efficacy for treatment of behaviors
in dementia
– NNT 5 to 14
• Studies usually short duration: 6-12 weeks
• Large placebo effect: 30% on average
• No difference in efficacy between typical
and atypical antipsychotics
• Typical antipsychotics: greater side effects
Meeks, T., & Jeste, D. (2008). Beyond the black box: What is the role for antipsychotics in dementia? Current Psychiatry, 7(6), 50–65.

43. Anxiolytics
• Binds to GABA receptor in CNS
• Anxiolytic, sedative, and hypnotic
effects (anterograde memory)
• Increased risk of adverse events
– Falls
– Cognitive impairment/confusion
– Hip fracture
– Sedation
– Paradoxical agitation

44. Agitation and Dementia: Lorazepam
Meehan, K., et al. (2002). Comparison of rapidly acting intramuscular olanzapine, lorazepam, and placebo:
A double-blind, randomized study in acutely agitated patients with dementia. Neuropsychopharmacology, 26(4): 494-504
-10
-9
-8
-7
-6
-5
-4
-3
-2
-1
0
30 60 90 120
Mean
Change
from
Baseline,
PANSS
Excited
Component
Time (mins)
Olanzapine 5.0 mg IM Olanzapine 2.6 mg IM Lorazepam 1.0 mg IM Placebo IM

45. Common Pharmacologic Agents
Benzodiazepine Half-life Dosage range
Diazepam
20-50 hours
Over 100 OA
2-10mg
2-4 times a day
Lorazepam 12 hours
0.5-2mg
2-3 times a day
Alprazolam
16 hours
(9-27 range)
0.25-3mg
2-4 times a day
Clonazepam 30-40 hours
0.25-5mg
2-3 times a day

46. Dextromethorphan-Quinidine for Dementia
Agitation in Alzheimer’s Disease
93 93 90 83 82 83
66 65 65 60 60 60
Cummings, J., et al. (2015). Effect of dextromethorphan-quinidine on agitation in persons with Alzheimer’s disease dementia.
A randomized clinical trial. JAMA, 314(12), 1242-54.

47. Dextromethorphan-
Quinidine
Considerations
• FDA-approved for the treatment of
pseudobulbar affect
• Modulates glutamate, serotonin,
and norepinephrine
• Only 1 randomized controlled trial
to date for agitation
• Side effects include
– Falls
– UTIs
– Diarrhea
– Dizziness
• QTc prolongation
Cummings, J., et al. (2015). Effect of dextromethorphan-quinidine on agitation in persons with Alzheimer’s disease dementia.
A randomized clinical trial. JAMA, 314(12), 1242-54..

48. Phenobarbital
• 30mg to 120mg ATC and q2 PRN
• NO DATA AVAILABLE
• Many clinicians, health systems, and
long-term care facilities embrace
the treatment
• Adverse reactions include:
– Respiratory depression
– Stevens-Johnson syndrome
– Anemia, TTP, and blood dyscrasias
– Withdrawal symptoms with abrupt
withdrawal
– Lethargy and drowsiness
– Nausea, vomiting, and hepatitis

49. Summary:
DICE
• Describe the behavior
• Investigate the underlying
contributors/causes
• Create intervention (non-pharmacologic
and pharmacologic)
• Evaluate the intervention’s effectiveness
Kales, H. et al. (2014). Management of neuropsychiatric symptoms of dementia in clinical settings: Recommendations from a
multidisciplinary expert panel. Journal of the American Geriatrics Society, 62(4), 762–769.

50. Case 1
• 61-year-old with Huntington’s disease who
presents to the hospice inpatient unit (IPU)
with impulsivity and agitation
– Has not slept in 2 days; is more confused,
pacing, eating food out of garbage
• Patient recently admitted to hospice with
functional decline, falls, weight loss,
dysphagia, and worsening behaviors
• Interventions to date: Haldol 5mg every
6 hours and every 2 hours as needed,
mirtazapine 30mg at night, sertraline 50mg
daily, lorazepam 1mg every 6 hours and
1 hour as needed, amantadine 200mg daily
• Urinalysis and bloodwork were unremarkable;
patient was transferred to the IPU for further
management of impulsivity and agitation

51. Case 1
(cont.)
Describe: Huntington's with impulsivity and
agitation/restlessness
Investigate: Medication regimen
Create:
• Discontinue amantadine, mirtazapine, and sertraline
• Decrease Haldol 1mg every 6 hours, and
Lorazepam 0.5mg every 8 hours and PRN
• Start Trazodone 50mg morning and 100mg
QHS and PRN, start Citalopram 10mg twice daily
Evaluate 1:
• Increase Trazodone 100mg morning and
200mg QHS
• Start dextromethorphan and quinidine
Evaluate 2:
• Continue current treatment and discharge
home to wife

52. Case 2
• 86-year-old with cerebral atherosclerosis with
recent functional decline
– In the past 2 weeks: bedbound, fall, stage II
sacrum, poor appetite, weight loss, and
increased agitation/aggression
• Daughter took patient out of ALF after patient
hit and tried to bite several staff
– Patient spends most of the day yelling,
swearing, kicking; is very restless in bed
• Comorbidities: hard of hearing, poor vision,
arthritis, peripheral vascular disease, history of
stroke, hypertension, depression, and heart failure
• Bloodwork and urinalysis were unremarkable;
patient admitted to hospice and transferred
to the IPU for management of vocalizations and
agitation/aggression
• Medications: sertraline 100mg daily

53. Case 2
(cont.)
Describe: Agitation and aggression, including
hitting and biting, worse when patient is
approached, touched, or moved
Investigate: Pain, hearing loss, and vision loss
Create:
• APAP 1,000mg every 6 hours, corrective
glasses and hearing aids, speak to patient
before approaching, Trazodone 25mg morning
and 50mg night and PRN, morphine 5mg PRN
Evaluate 1
• Citalopram 10mg twice daily
• Increase Trazodone 50mg morning and
100mg evening
Evaluate 2
• Risperidone 0.5mg twice daily

54. Questions?

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