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Ambulatory Geriatrics Curriculum for Internal Medicine Residents
Module on BPSD: Agitation and Behavioral Problems in Dementia
A. Introduction to Module:
In 2012, 5.4 million Americans are diagnosed with Alzheimer’s Disease. Lifetime risk of experiencing BPSD
is nearly 100%. BPSD is associated with increased morbidity and nursing home placement and is potentially
treatable. The information in this curriculum has been created to help the general internist have a structured
approach to the evaluation and management of BPSD.
B. Learning Objectives:
At the conclusion of this module, learners will be able to:
1. Define BPSD
2. Evaluate BPSD
3. Discuss the Guidelines for Management of BPSD
• Nonpharmacologic Interventions
• Pharmacologic Interventions
Curriculum, Resources and Handout for Residents:
Behavioral and Psychological Symptoms of Dementia
I. What Is BPSD?
B(ehavioral)_________
P(sychological)______
Mood Symptoms
Psychotic Symptoms
Sleep Disturbances
S(ymptoms)_________
D (ementia)_________
Non-cognitive manifestations of dementia
Behavioral Symptoms
“Agitation”
Related to resistiveness to care
Physical vs Verbal
Aggressive vs Nonaggressive
Hitting, biting, yelling vs pacing, wandering, hoarding
Psychological Symptoms
Mood Symptoms
Psychotic Symptoms
Sleep Disturbances
II. Why Is BPSD Important?
1 in 8 Americans > 65 yrs of age has AD (ie 5.4 million)
1. Lifetime risk is nearly 100%
2. Associated with increased morbidity and nursing home
placement
3. Potentially treatable
III. REVIEW UNFOLDING CLINICAL CASE WITH ANSWERS AND APPENDIX
Developed by Christine Chang, MD
December 2014
10-18-15
PART A: You are seeing Mrs. Robbin Green, a 78-year-old with mild Alzheimer’s disease (MMSE 23 of 30),
hypertension, osteoarthritis, and urinary incontinence who comes to the office with her daughter for “acting up”
for past 2 weeks. Daughter reports that she repeats stories and packs her bags several times a day, stating that
she is “going home.” She is up frequently at night, pacing and wandering. The other day, she struck her home
attendant.
Medications: donepezil 5 mg daily, hydrochlorothiazide 25 mg daily, lisinopril 10 mg daily, baby aspirin,
tolterodine LA 2 mg, and acetaminophen 500 mg once daily.
1. How would you approach this case?
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
2.
Careful Physical & Neurologic Exam
Assess Mental Status
Pay attention to:
• Appearance and Behavior
• Speech
• Mood
• Thoughts and Perceptions
• Cognitive Function
• Attention
3.
Lab Studies
• CBC, metabolic panel and drug levels in all cases of new onset BPSD
• Brain imaging, EKG, CXR, and urinalysis based on the history and exam
R/O Delirium
• Acute Conditions such as acute infection like pneumonia and UTI, angina,
endocrine abnormality, electrolyte imbalance, pain and constipation
• Medication Toxicity or adverse effects of medications due to new or
existing medications
R/O Environmental Causes
1) Make sure basic physical needs are met
2) Environmental Precipitant
• Disruptions in routine-new or sick caregiver
• Over Stimulation
• Under Stimulation
After medical, environmental, and care giving causes are excluded, it can be
concluded that the primary cause is progression of the dementia
Developed by Christine Chang, MD
December 2014
10-18-15
PART A continued: Daughter reports that patient has been more incontinent these days but has had no fevers,
chills, flank pain or hematuria. Pt has been eating a little less as well but reports no nausea, vomiting, diarrhea
or constipation. ROS is otherwise negative. There are no new medications and no changes in the care giving
environment.
Physical exam is unremarkable except for Temp 100.1, mild suprapubic tenderness without guarding or rebound
or CVA tenderness. Neurological exam is non-focal though technically difficult. She is oriented only to person
and easily distracted.
Labs are unremarkable except for urine with positive nitrites and leukocyte esterase, and CBC with mild
leukocytosis with left shift.
2. What is the most appropriate treatment?
Treat UTI and employ NonPharmacologic Interventions
PART B: Mrs. Green is seen as an urgent visit 2 months later for being more agitated. Daughter reports that
the patient has been screaming and scratching the new home attendant mainly during bathing. Daughter
normally tries to help the home attendant with her mother’s care but has been busier these days as her
grandchildren have been visiting. Daughter/pt denies fever, chills, cough, shortness of breath, pain, urinary or
bowel symptoms. She has been eating and sleeping as usual. No other symptoms reported nor are there any
new medications. Physical exam is unremarkable. Repeat MMSE remains 23/30
3. What is the most appropriate approach?
a.
b.
c.
d.
e.
Start haloperidol 0.5 mg at night
Start risperidone 1 mg at night
Increase donepezil to 10 mg
Start citalopram 10 mg daily
Review NonPharmacologic, patient-centered Interventions
Guideline for Management of BPSD
2012 Non-pharmacologic mgt of BPSD by Gitlin LN, Kales HC, Lyketsos CG1
2013 Management of the Behavioral and Psychological Symptoms of Dementia. NaRCAD (the National Resource
Center for Academic Detailing) with support from a grant from the Agency for Healthcare Research and Quality 2
Nonpharmacologic Interventions First
Why?
•
•
•
40% of BPSD symptoms spontaneously resolve; “they come and go”
Placebo response can be quite substantial
No FDA approved medications for psychosis in AD
4 Effective Nonpharmacologic Interventions (Review Appendix A) 1-18
1. CG Interventions
2. Unmet Needs Interventions
3. Behavioral Interventions
4. Psychosocial Interventions
Developed by Christine Chang, MD
December 2014
10-18-15
PART C: In a visit one year later, Mrs. Green is brought in for an urgent visit by her daughter with complaints
of trouble sleeping for the past month. Mrs. Green confirms trouble falling sleep but is unable to provide a more
comprehensive history. Daughter reports that her mother is usually active in the daytime, but for the last month
has caught her napping in the daytime. Patient denies being sad or depressed and appetite and weight are stable.
Physical exam and lab studies were within normal limits. PHQ9 was negative.
4.
a.
b.
c.
d.
e.
f.
For Sleep-wake Cycle Disturbance >1 Month
What is your first intervention?
Evaluation for Potential underlying causes of Insomnia
Prescribe zolpidem 5 mg
1. Obtain a complete Medication list with timing
Recommend melatonin 1.5 mg
• Diuretic (nocturia)
Prescribe triazolam 0.125 mg
• Stimulants/sympathomimetic
Prescribe trazodone 25 mg
(nicotine, caffeine, bronchodilators)
• Anticholinergics, sedating (sinemet, analgesics)
Prescribe mirtazapine 7.5 mg
• SSRI can decrease REM
Counsel about non-pharmacologic interventions
2. Complete a Sleep Diary to assess for patterns or triggers
to promote sleep
for insomnia
3.
Review Appendix B21-23
R/O depression + other psychiatric conditions
REVIEW: McCurry SM et al. “Nighttime insomnia treatment and education
for Alzheimer's disease: a RCT.” JAGS. 2005 (Appendix B)21-23
5. What is your next approach if your first intervention fails?
a.
b.
c.
d.
e.
f.
Prescribe diphenhydramine 25 mg
Prescribe zolpidem 5 mg
Prescribe melatonin 1.5 mg
Increase donepezil to 10 mg
Prescribe trazodone 25 mg
Prescribe mirtazapine 7.5 mg
REVIEW Appendix C-Hypnotics
Recommend: E-trazodone
2007 APA 31 + GRS 8 32 recommends22,23:
• Trazodone 303
• Zolpidem and zaleplon
• Mirtazapine
REM-dys-control  clonazepam and cholinesterase inhibitors
(eg, rivastigmine, pramipexole, melatonin 29,30)
Avoid:
• Benzodiazepines
• Antihistamines especially diphenhydramine
Key Points 21-33
• Pharmacologic treatment of the demented elder with insomnia should be reserved for those deemed to have
primary insomnia and who have not responded to more conservative, nonpharmacologic interventions.
• If the decision is made to treat with medication, the lowest possible effective dose should be used for a
time-limited trial, and ‘‘as needed’’ dosing should be the rule. Use of these medications should be tapered
or discontinued gradually, mindful of potential for rebound insomnia after discontinuation. Of the choices
listed, trazodone is considered the safest and least addictive.
• Prescribed treatments should continue to be used in concert with non-pharmacologic and sleep hygiene
measures.
Developed by Christine Chang, MD
December 2014
10-18-15
Part D: For the next 6 months, Mrs. Green’s course is unremarkable as the donepezil 10 mg with the
intermittent trazodone 25mg has helped.
During today’s visit, Mrs. Green reports feeling depressed about her loss of function and memory. She is no
longer interested in going outdoors or watching some of her favorite TV shows. Patient reports anorexia and has
lost 4.5 kg (10 lb) in past four months. Pt reports no suicidal ideation. On exam, patient affect appears flatten.
PHQ9= 15 (c/w moderate-severe depression) but MMSE remains 23 which is unchanged. Physical exam is
otherwise unremarkable. Lab work up including chemistries, CBC and TSH are negative.
6. What are the differential diagnoses?
DDX:
• Depression
• Dementia progression
• Hypothyroid
• Medication SE: donepezil
• Cancer
7. How would you treat 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 citalopram 10 mg
e. ECT (Electroconvulsive Therapy)
2013 Management of the Behavioral and Psychological
Symptoms of Dementia. National Resource Center for Academic
Detailing with support from a grant from the Agency for Healthcare
Research and Quality 2
NON-EMERGENT vs EMERGENT BPSD 34-39
Consider Antidepressants –1st line: SSRIs 33, 40-48
 Citalopram
 Sertraline
(improved depressive symptoms & ADLS w/o improving cognition)
Avoid fluoxetine and paroxetine (cyt 2D6 INH)
PART E: Mrs. Green’s returns 2 weeks later and reports that the initial treatment was unhelpful.
8. What would you do next?
a. Switch to another agent in same class
b. Switch to another agent in another class
c. Titrate dose of initial medication
d. Add methylphenidate 5 mg daily
If a first agent has failed an adequate therapeutic dose for 3-6 weeks,
consider alternatives 33-47:
 Bupropion (Dop/NE reuptake INH)
 Mirtazapine 47 (SNA)
 Venlafaxine 43 (SNRI)
 Cymbalta (SNRI)
 Tricyclic agents (desipramine + nortriptyline)
*Switch vs add- on but WATCH for Serotonin Syndrome:
 MAOI + tramadol, DM, codeine, methadone + sumatryptan
 Cyt3A4 deceases with AGE (grapefruit juice or azithromycin)
 Cyt2D6 decreased in 5-10% Caucasian SLOW metabolizers
 Bacterial endotoxin lipopolysaccharide
For partial responders to an antidepressant, consider augmentation
strategies—watch for psychostimulant effect
 Methylphenidate 49 ????
 Modafinil??
If depression remains and patient is in danger of serious weight loss or
suicidal ideas despite several antidepressant trials, consider
Developed by Christine Chang, MD
December 2014
10-18-15
ElectroConvulsive Therapy 50
*No RCT in geriatric patients with dementia
PART F: Mrs. Green responds well to citalopram 20 mg which you continue for the next 12 months. Over the
next 2 years, daughter reports that Mrs. Green gradually requires more assistance with all of her ADLs despite
addition of memantine 10 mg twice a day. She has developed urinary incontinence over past six months. The
daughter has hired Carol to help with Mrs. Green’s care six months ago. Today daughter reports that Mrs.
Green has been more and more resistant to personal care including bathing, shower and toileting over past two
months. In few instances she became physically aggressive toward her daughter and her aide Carol. The
daughter and Carol have employed appropriate non-pharmacologic interventions without much success. Again
there are no new medications, no change in the care giving environment. Her physical exam and laboratory
workup are negative. Delirium has been ruled out. Pain is optimized.
9. When would you consider any medications?
2013 Management of the behavioral and psychological symptoms of
dementia. National Resource Center for Academic Detailing with
support from a grant from the AHRQ 2
When pt is a danger to self and others after NPI has failed
FOR EMERGENT BPSD 34-39, 60
Antipsychotics:
 Use faster acting, higher risk medications
 Limited evidence for longer term efficacy (≥6
months)
 Genetic variability: T allele vs C allele of
5HT2A T102C polymorphism
NONemergent BPSD 2, 34-39, 51-54, 61, 67
•
•
•
•
•
Aggression: consider risperidone 51, 54-56, abilify, ?olanzepine vs
SSRI 40-48, prazosin 61, propranolol 65
Psychosis: Consider risperidone 51,54-56
PD/LBD: Consider Cholinesterase inhibitors, Namenda66,
Quetiapine and Clozapine
FTD: Consider SSRIs
Bipolar-mood lability-hypersexual: consider carbamazepine 68.
Oral/depot progesterone, or anti-estrogen leuprolide, SSRI
Avoid valproic acid 67
10. What medication would you consider in treating her symptoms?
a.
b.
c.
d.
e.
Time-limited trial of haloperidol 0.5 mg
Time-limited trial of risperidone 0.5 mg
Time-limited trial of olanzapine 5 mg
Time-limited trial of valproate 250 mg
Start a trial of prazosin 1mg daily
Review Appendix D (BPSD TX guidelines) 2, 34-39, 51-54, 60, 61, 67
Appendix E (Pharmacologics)
Appendix F (Black Box warning) 71-73
Risperidone has modest but significant improvement in aggression 51, 5456
(dose 2 mg, over 6-12 weeks of treatment)
Haldol might be effective in treating aggression in patients with dementia but
side effects limits its use (extrapyramidal symptoms) 56-58
Part G: Mrs. Green does not respond to the risperidone 0.5 mg so you titrate it to 1mg and the symptoms
subside. You continue this for 4 weeks and eventually you are able to wean it off74.
Always remember to wean antipsychotics if possible when BPSD improves given Black Box warning 71-73
Developed by Christine Chang, MD
December 2014
10-18-15
TAKE HOME POINTS:
• Always obtain a thorough history 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
Appendix A: 4 Effective Nonpharmacologic Interventions 1-20
1. CG education Interventions about
1. Disease, prognosis, realistic expectations
2. 5 Techniques to minimize development of BPSD
1) Maintain a structured daily routine of meaningful activities
2) Environmental modifications-safe, comfortable, orienting
3) Communication Techniques-speak slowly, clearly, in nonconfrontational manner
4) Encourage independence in ADLs
• Correct sensory impairments
• Simplify routines, set up, limit choices
• Finger foods, Velcro, snaps
5) Patient –Centered Care ie Person-Centered Showers and Towel Baths12
(www.bathingwithoutabattle.unc.edu) 13
http://www.alz.org/care/alzheimers-dementia-bathing.asp14
Suggests the following:
• 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
2. Unmet Needs Interventions- make sure hunger, thirst, pain, boredom are addressed as pt may “act out”
when they are unable to communicate their needs
3. Behavioral Interventions
a. 3 R’s (Repeat, Reassure, Redirect)
 Positive reinforcement (by praising, encouraging or reassuring) to encourage desirable
behaviors
 Distraction technique-redirection
b. Be a Sleuth: Do the “ABC’s” and Avoid triggers –look at the Antecedant Behaviors that lead to a
particular Consequence and AVOID itIdentify the precipitating factor and avoid the triggers
4. Psychosocial Interventions
a. 5 Techniques to minimize development of BPSD (above)
b. Preferred Calming Music
c. Aromatherapy-lavender
d. Thermal bath
e. Bright Light and Pet Therapy
f. Snoezelen-Multisensory: light, sound, aroma, massage
g. Exercise and Structured activity therapies
***Physical restraints should be avoided
Developed by Christine Chang, MD
December 2014
10-18-15
*alz.org-caregiver centerget supportTraining and Resources
* http://www.agingbraincare.org/. Look under Tools, then ABC Care Protocols. The nonpharmacologic protocols are
available in the Care Protocols upon registration20.
Appendix B: Non-pharmacologic Interventions for Insomnia: McCurry SM et al.
Nighttime insomnia treatment and education for Alzheimer's disease: a RCT. JAGS. 200521—
employs 4 of the 6 traditional techniques for insomnia mgt: sleep hygiene, stimulus control, sleep restriction
and circadian rhythm manipulators (No Cognitive Behavioral Therapy (CBT) or “relaxation”)
1. Follow Structured sleep and rising times that were not to deviate no more than 30 minutes from the
selected times (circadian)
2. Encouraged patients not to nap after 1 PM and limit naps to 30 minutes or less (sleep hygiene,
circadian, sleep restriction)
3. Walk for 30 minutes, exercise daily (circadian)
4. Bright light tx at dawn/dusk (circadian)
5. Eliminate triggers for nighttime awakenings ie control night time pain, give nightly snack, take
activating meds in the AM (stimulus control)
6. Reduce light/noise levels in their sleeping areas (stimulus control)
7. Switch to decaffeinated drinks and reduce evening fluid consumption (stimulus control)
8. If nocturia affected sleep, encourage toileting schedules at night, use of incontinence pads, exclude
urinary tract infections (stimulus control)
Appendix C:
APPROVED Hypnotics for INSOMNIA
1. BZO R Agonists
BZO
Temezepam, Triazolam
Non-BZO
Zolpidem*
Zaleplon*
Eszopiclone
2.
Melatonin R Agonist
Ramelteon
3.
Orexin R blocker
Suvorexant-Belsomra
NON-APPROVED for INSOMNIA
1. Sedating Antidepressant
Trazodone *
Mirtazapine
Doxepin 10
2. Antipsychotics
3. Anticonvulsants
NONPRESCRIPTION AGENTS
1. Sedating Antihistamines
2. Melatonin
3. Tryptophan-milk/honey
4. Valeria, Kava, St. John’s Wort
Appendix D: 2013 Management of the Behavioral and Psychological Symptoms of Dementia. NaRCAD (the National Resource
Center for Academic Detailing) with support from a grant from the Agency for Healthcare Research and Quality 2,34-39, 51-54, 61-64, 67
• Nonpharmacologics
• Pharmacologics:
– FOR EMERGENT BPSD 34-39 60
• Antipsychotics:
• Use faster acting, higher risk medications
• Limited evidence for longer term efficacy (≥6 months)
– NONemergent BPSD 2, 31-36, 48-51, 58,-61, 64
• Memantine
• Carbamazepine
• Citalopram
• Prazosin
Developed by Christine Chang, MD
December 2014
10-18-15
Appendix E: Possible medication for Agitation, Aggression, and Psychotic symptoms in BPSD.
(Medications listed are not FDA approved to treat BPSD and are off-label recommendations)
Class
Starting Theraputic Comments
Dose
Dose
Black Box warning
Antipsychotics
Watch for: Extrapyramidal effects, tardive diskinesia, neuroleptic malignant
syndrome, hypotension, QTc prolongation and torsades de pointes, anticholinergic
side effects (ie Constipation, xerostomia, and somnolence), agranulocytosis,
blurred vision, May Lowers seizure threshold
0.5-2mg
*Class effect as above. Watch esp for Extrapyramidal effects can occur with doses
Haloperidol
56-58
q2-12 hrs
>4.5 mg/d
*More effective for treating aggressive agitation
* Available as Oral, IV , IM, subcutaneous
0.25-0.5
1-2mg
*Class effect as above and EPS with doses > 1 mg/day
Risperidone
51, 54-56
mg
* Clinical experience suggest better results in patients with hypoactive delirium
*Risperidone and olanzepine effective for aggressive agitation but risperidone
may be more helpful for psychotic symptoms.
* Available as tablet, rapidly dissolving tablet, liquid concentrate, IM
2.5-5 mg
5-15 mg
*Class effect as above. Watch especially for hyperglycemia and cerebrovascular
Olanzapine
events in patients with dementia.
*Risperidone and olanzepine effective for aggressive agitation.
*Literature suggests that older age, preexisting dementia, and hypoactive delirium
are associated with poor response
*Available as tablet, rapidly dissolving tablet, IM injection
12.5100–200 mg *Class effect as above. Watch especially for orthostatic, and hyperglycemia.
Quetiapine
25mg
* Preferred in patients with Parkinson disease or Lewy body dementia due to
its lower risk of extrapyramidal adverse effects
*Ophthalmologic exam recommended every 6 months
*Available as tablet
2.5-5 mg
5-15mg
*Class effect as above. Watch especially for increased cerebrovascular events in
Aripiprazole
dementia, hyperglycemia and weight gain
*Clinical experience suggests better results in hypoactive delirium
*No adjustment needed with age, renal or hepatic impairment
*Available as Tablet, disintegrating tablet, liquid concentrate, IM (convert to oral
ASAP)
* Ziprasidone and clozapine are both poorly tolerated in older adult.
Might consider in rare refractory cases.
Note. CBCs = complete blood cell counts
EPS = extrapyramidal symptoms
IM = intramuscular
Anticonvulsants Starting
Therapeutic Comments
dose
dose
*Main side effects are sedation, ataxia, nausea
Carbamazepine 50-100mg 200-1000mg
68
*Monitor for hyponatremia and pancytopenia
125250-1000mg *Main side effects nausea and sedation.
Divalproex
sodium 70
250mg
*Monitor for Liver function abnormality, thrombocytopenia,
pancreatitis.
* NOT recommended in most recent guidelines and
Cochrane review 2004, 2009
Appendix F: Black Box Warning for Typical and Atypical Antipsychotics 71-73
http://www.fda.gov/cder/drug/infopage/antipsychotics/default.htm April 2005
• Increased risk of mortality. Rate of death was 1.6 to 1.7 times that of placebo in 6-12 wks of use
• Death appeared to be heart related or from infections (eg, pneumonia)
• Diabetes mellitus, hyperglycemia, ketoacidosis, and hyperosmolar states
Developed by Christine Chang, MD
December 2014
10-18-15
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