psychiatry and the older adult - amazon web...
TRANSCRIPT
Psychiatry and The Older Adult
Ericka L. Crouse, PharmD, BCPP, BCGP, FASCP, FASHPVirginia Commonwealth University Health System
Disclosures
• Ericka Crouse discloses that she has received honorarium for speaking or developing educational materials for the American Pharmacists Association (APhA), the College of Psychiatric and Neurologic Pharmacists (CPNP) and the Virginia Geriatrics Society (VGS)
Learning Objectives
At the conclusion of this application-based activity, participants should be able to:
1. Identify signs and symptoms of major depression in high risk elderly patients.
2. Differentiate the pharmacologic treatments for geriatric depression.
3. Describe the treatment approach for cognitive symptoms in dementia.
4. Develop a plan for the management of behavioral disturbances in patients with dementia.
Differentiating the 3 D’sSymptoms Delirium Dementia (AT) Depression
Symptom onset Acute, rapid, sudden
Hours to days
Progressive, Insidious, slow indeterminate, chronicMonths to years
Can be variableRecent, rapidConcurrent changes in mood
Alertness Fluctuates, waxes and wanes
Early: normalLate: not alert
Normal
Duration Hours to weeks Progressive Variable Orientation Confused, disoriented, with
lucid periodsAltered Normal
Hallucinations Present; often visual May present in later stages Occurs in cases of depression with psychotic features
Disabilities Inattention, incoherent speech
Short-term memory deficitsAttempt to conceal by patient
Answering questions
Distracted, incorrect answers
Near answers, guesses or confabulates
Often “I don’t know” lack of motivation; delay in response
Sleep cycle Changes, “sundowning” “sundowning” InsomniaEarly morning awakening
Course Usually reversible Irreversible ReversibleLong-term consequences
Prolonged hospitalizationIncreased Mortality
Impaired languageDecreased ADLs and IADLsSexually inappropriate behaviorsAgitation/aggression
Reduced socialization and physical activity Deconditioning, painExtended hospital stays NoncomplianceIncreased mortality/ suicide
Treatment Antipsychotics Acetylcholinesterase inhibitors NMDA antagonists
AntidepressantsIf psychotic features present an antipsychoticElectroconvulsive therapy
Which of the following patients would you be concerned about depression in?
• A 67 yo who recently retired• A 78 yo who just moved into a nursing home • A 77 yo male whose wife of 50 years passed away 1 week ago• A 68 yo female with a h/o DM, HTN and ESRD who is on
dialysis• A healthy 89 yo female who has outlived 3 of her 4 children
and most of her friends• A 79 yo who attempted suicide by carbon monoxide poisoning• An otherwise healthy 68 yo recently diagnosed with a new
chronic condition requiring medications
Which of the following patients would you be concerned about depression in?
A 67 yo who recently retired A 78 yo who just moved into a nursing home A 77 yo male whose wife of 50 years passed away 1 week
ago A 68 yo female with a h/o DM, HTN and ESRD who is on
dialysis A healthy 89 yo female who has outlived 3 of her 4
children and most of her friends A 79 yo who attempted suicide by carbon monoxide
poisoning An otherwise healthy 68 yo recently diagnosed with a new
chronic condition requiring medications
Risk Factors for Geriatric Depression
• Family History
• Chronic medical illness
• Female gender
• Single, widowed or divorced
• Social isolation
• Lower socioeconomic status
• Stressful life events• Death of a loved one or
spouse• Disease• Injury• Disability/functional
impairment
• A meta-analysis of 20 studies identified 5 major risk factors for depression in elderly: • Grief• Sleep problems• Disability• History of previous episodes
of depression• Female gender
Cole MG, et al. Am J Psychiatry 2003;160:1147-56. Castillo S, et al. 2013 Formulary J. http://formularyjournal.modernmedicine.com/formulary-journal/content/tags/alzheimers-disease/depression-elderly-pharmacist-s-perspective
The Geriatric Depression Scale
1. Are you basically satisfied with your life? Yes/NO
2. Have you dropped many of your activities and interests? YES/No
3. Do you feel your life is empty? YES/No
4. Do you often get bored? YES/No
5. Are you in good spirits most of the time? Yes/NO
6. Are you afraid that something bad is going to happen to you?
YES/No
7. Do you feel happy most of the time? Yes/NO
8. Do you often feel helpless? YES/No
9. Do you prefer to stay at home, rather than going out and doing new things?
YES/No
10. Do you feel you have more problems with memory than most people?
YES/No
11. Do you think its wonderful to be alive? Yes/NO
12. Do you feel pretty worthless the way you are now? YES/No
13. Do you feel full of energy? Yes/NO
14. Do you feel that your situation is hopeless? YES/No
15. Do you think that most people are better off than you are? YES/No
Scoring: 0-4: no depression5-10: mild depression> 10: severe depression
GDS has been shown to have 92% sensitivity and 89% specificity
http://clas.uiowa.edu/socialwork/files/socialwork/NursingHomeResource/documents/GDS.pdf; Yesavage, et al. J Psychiatr Res 1983;17:37-49.
Mini Mental State Exam (MMSE) in Depression
• Orientation: often miss points because they do not put forth effort or do not care enough to answer; stating “I don’t know”. If you give them ample time often will (delayed) correctly answer
• Concentration: often cannot focus enough to make the 3 objects a memory; cannot focus or require extra time to complete the DLROW or serial 7s
• Write a sentence: often will have a very negative sentence
DSM-5 Criteria≥ 5 of the following most days for at least 2 weeks• Depressed mood* • Loss of interest or pleasure*• Weight changes• Sleep changes• Psychomotor agitation or retardation• Fatigue or reduction in energy• Worthlessness or guilt• Decreased concentration• Suicidal ideation or attempt
• * At least one of the bolded criteria must be met
SuicidalInterestGuiltEnergyConcentrationAppetitePsychomotor agitation/retardation Sleep
DSM-5 Am Psych Assoc 2013
Geriatric Specific Symptoms of Depression
• May not report depression or sadness• Memory problems or confusion• Insomnia• Reduction in appetite• Increase in irritability• Often have somatic complaints
***Remember that elderly patients make up a large portion of completed suicides
Case Vignette
A 83 yo WF with a PMH of osteoporosis, osteoarthritis, COPD and recent hospitalization for pneumonia presents for follow up in primary care. She has had a 4 kg weight loss, is complaining of early morning awakening, no longer goes and plays cards with her friends, reports her pain is “worse than ever.” GDS = 9; MMSE = 25
She denies depression and suicidal thoughts. However states she is not sure why she “is still here” and sometimes thinks she should stop taking her medications and “let nature take its course”
Audience Discussion
What symptoms of depression is she experiencing?
Change in Suicidality with Antidepressant Therapy
Age (years) Difference in number of cases of suicidality per 1,000 treated patients [drug vs placebo]
Increases compared to placebo
< 18 14 more cases
18-24 5 more cases
Decreases compared to placebo
25-64 1 less case
≥ 65 6 less cases
Antidepressant prescribing information
Which Medication?Which medication are you most likely to start?
Case Vignette
Would your initial recommendation have changed IF: A 72 yo WF with a PMH of osteoporosis, COPD and recent hospitalization for pneumonia presents for follow up in primary care. She has had a 15 kg weight loss, is complaining of difficulty falling asleep, no longer goes and plays cards with her friends, reports her pain is “worse than ever”; GDS = 14; MMSE = unwilling to cooperate She denies depression and suicidal thoughts. However states she is not sure why she “is still here” and sometimes thinks she should stop taking her medications and “let nature take its course”
Pharmacologic Treatment Strategies
Initial
• SSRIs
• SNRIs, mirtazapine, bupropion
Alternatives
• TCAs - in limited cases in elderly
• Combination therapy
Resistant
• Augmentation Strategies
• ECT
Dosing in the Elderly SSRIs/SNRIs Initial Frequency Usual Range Maximum
Selective Serotonin Reuptake Inhibitors
Citalopram 10 mg Daily 20-40 (60) mg 20 mg
Escitalopram 5 mg Daily 5-20 mg 20 mg (?10 mg)
Fluoxetine 10 mg Daily 10-60 mg 80 mg
Fluvoxamine 25-50 mg Bedtime or BID 100-300 mg 300 mg
Paroxetine 10 mg Daily 10-40 mg 40 mg
Sertraline 25 mg Daily 50-150 mg 200 mg
Serotonin Norepinephrine Reuptake Inhibitors
Desvenlafaxine 50 mg Dailya 50 - 100 mg 100 mgb
Venlafaxine 25 mg BID or 37.5 mg XR/d
IR: BID-TIDXR: Daily
75 – 225 mg 225 mg (300 mg)
Duloxetine 20-30 mg Daily or BID 30 – 120 mg 120 mgb
Levomilnacipran 20 mg Daily 40 – 120 mg 120 mgb
a. every other day in renal impairment b. renal dosage adjustments required, see separate slideLapid MI, et al Mayo Clin Proc 2003;78:1423-9.; prescribing information
Dosing in the ElderlyInitial Frequency Range Maximum
Tricyclic Antidepressants
Nortriptyline 10-25 mg At bedtime 25-100 mg*50-150 mg
150 mg
Desipramine 10-25 mg At bedtime 25-100 mg75-150 mg
150 mg
Other Second Generation Antidepressants
Bupropion 100 mg SR daily IR: TIDSR: BIDXL: Daily
SR: 100-400 mgXL 150 – 450 mg
IR: 450 mgSR: 400 mgXL: 450 mg
Mirtazapine 7.5-15 mg At bedtime>30 mg in AM
7.5-45 mg 45 mg
Vilazodone 10 mg Daily 10-40 mg 40 mg
Vortioxetine 5 mg Daily 10-20 mg 20 mg
* Monitoring of levels is recommended if dosage exceeds 100 mg/day Lapid MI, et al Mayo Clin Proc 2003;78:1423-9.; prescribing information
Choosing an AntidepressantTake into Account:
Target Symptoms
Concurrent Disease States
Renal & Hepatic Function
Concurrent Medications/Drug Interactions
Cost & Formulary Considerations
Target Symptoms
Preferred Not Ideal
Anxiety SSRI, SNRI, or secondary TCA Bupropion
Lack of energy BupropionSSRI (fluoxetine) Stimulants
Insomnia Mirtazapine, secondary TCA SSRI, SNRI
Weight loss/ no appetite
MirtazapineParoxetine, secondary TCAs
Fluoxetine and bupropion
Incontinence or diarrhea
Consider secondary TCA Paroxetine
Pain Duloxetine, secondary TCAs
Potentially inappropriate medications in older adults based on disease state
Disorder Beers List 2003 Beers List 2012 Update
Beers List 2015
Seizure disorder Bupropion Bupropion
Delirium All TCAs All TCAs, Paroxetine
Syncope/falls (2003)H/O Falls/fractures (2012)
TCAs (only givesexamples of tertiary TCAs*)
All TCAs and SSRIs All TCAs, SSRIs
SIADH SSRIs SSRIs, SNRIs, mirtazapine, TCAs
SSRIs, SNRIs, mirtazapine, TCAs
Constipation TCAs* Tertiary TCAs* Removed as a category
Anorexia/malnutrition Fluoxetine Removed removed
*In 2003 examples of TCAs only included amitriptyline, imipramine and doxepin
Beers Criteria JAGS 2003, 2012, 2015
SIADH = Syndrome of Inappropriate Antidiuretic Hormone
SSRI Adverse Events
• Gastrointestinal (GI) – nausea, vomiting, diarrhea
• Falls
• Hyponatremia
• Platelet dysfunction and GI bleeding
• Appetite changes
• QTc prolongation (citalopram)
• Tremor
• Teeth grinding
Syndrome of Inappropriate Antidiuretic Hormone (SIADH)
69 yo 59 kg white female taking: • Escitalopram 10 mg
• Levothyroxine 75 mcg daily
• Fenofibrate 145 mg daily
• ASA 81 mg
mEq
/L
• Risk Factors• Advanced age
• Female
• Concomitant use of diuretics (most common -thiazide)
• Recent history of pneumonia
• Dose mg/kg body weight
• Low body weight
• Low baseline sodium level (< 138 mEq/L [mmol/L])
• Time Course• Average onset 13 days
(range 3 – 120)
• Resolves 2 days – 6 weeks (2 weeks average) after discontinuation
• Rechallenge• Risk of recurrence if
rechallenged with same or another SSRI
• Mirtazapine?
• Bupropion?
Hyponatremia and Syndrome of Inappropriate Antidiuretic Hormone (SIADH)
Jacob S, et al. Ann Pharmacother 2006;40:1618-22
Dosage Adjustment in Renal and Hepatic Impairment
Renal Impairment Hepatic Impairment
Requires Dosage Adjustment
If CrCl 30-59 mL/min• Levomilnacipran – max 80 mg/dayIf CrCl 11-29 mL/min • Reduce mirtazapine by ~30%• Desvenlafaxine – max 50 mg/day• Paroxetine - levels 4x normal• Venlafaxine – t ½ prolonged • Levomilnacipran – max 40 mg/day
• Paroxetine – 2 fold increase in levels• Citalopram – max dose 20 mg/day• Escitalopram – max dose 10 mg/day• Venlafaxine reduce dose by 50%• Fluoxetine – lower dose or less
frequent administration
If CrCl < 10mL/min or ESRD • Mirtazapine reduce by 50%• Bupropion reduce by 50%• Desvenlafaxine – max 50 mg every
OTHER day
Severe• Desvenlafaxine – maximum dose is
100 mg/day• Venlafaxine reduce dose by > 50%
Use caution • Mirtazapine, Sertraline
Not recommended
• If CrCl < 30 mL/min• Duloxetine
• Duloxetine – warning for hepatotoxicity
Avoid • Nefazodone
Prescribing information; www.dailymed.nlm.nih.gov
Dosage Adjustment in Renal and Hepatic Impairment
Renal Impairment Hepatic Impairment
Requires Dosage Adjustment
If CrCl 11-39 mL/min • Reduce mirtazapine by ~30%• Desvenlafaxine – maximum dose
50 mg/day• Paroxetine - levels 4x normal• Venlafaxine – t ½ prolonged
• Paroxetine – 2 fold increase in levels• Citalopram – max dose 20 mg/day• Escitalopram – max dose 10 mg/day• Venlafaxine reduce dose by 50%• Fluoxetine – lower dose or less
frequent administration
If CrCl < 10mL/min or ESRD • Mirtazapine reduce by 50%• Bupropion reduce by 50%• Desvenlafaxine – maximum dose
50 mg every OTHER day
Severe• Desvenlafaxine – maximum dose is
100 mg/day• Venlafaxine reduce dose by > 50%
Use with caution • Mirtazapine• Sertraline
Not recommended • If Cr Cl < 30 mL/min• Duloxetine
• Duloxetine – warning for hepatotoxicity
Should be avoided • Nefazodone (removed from Canadian market)
Prescribing information; www.dailymed.nlm.nih.gov
Dosage adjustments not noted: with vilazodone (renal or hepatic)
with sertraline, citalopram, escitalopram, fluoxetine, vortioxetine (renal)
Drug Interactions
WEAK Inhibitors
Citalopram
Escitalopram
Sertraline
Venlafaxine
MODERATE Inhibitors
Sertraline, Duloxetine CYP2D6
Fluoxetine, Fluvoxamine CYP3A4
POTENT Inhibitors
Paroxetine, Bupropion CYP2D6
Fluvoxamine CYP1A2, CYP2C9/19
Fluoxetine CYP2C9/19, CYP2D6
Which Medication?
• A 62 yo with a history of A.Fib and a PE 3 months ago is currently treated with metoprolol 12.5 mg BID and warfarin 2.5 mg 3 times per week (MWF) and 5 mg 4 times per week (TTSS). They have been struggling since their hospitalization, and their spouse is concerned about depression. Which antidepressants are MOST likely to interact with current regimen?
A. Fluvoxamine
B. Sertraline
C. Paroxetine
D. Fluoxetine
Warfarin Interactions
CYP1A2
Major R-warfarin
CYP2C9
Major S-warfarin
CYP2C19
Minor R-warf
CYP3A4 Minor R-warf
CYP Inhibitors
Fluvox
Parox
Fluox
Fluvox
Fluox
Fluvox
Norfluox-etine
S-warfarin – active form
The release of serotonin by platelets is important for maintaining hemostasis. Case-control and cohort studies have shown that the combined use of SSRIs and anticoagulants has been associated with an increased risk of bleeding.
Which Medication?
• A 72 year old male with a history depression treated with fluoxetine 20 mg presents with symptoms of not eating, delusions that he has no money, voices telling him he is worthless… Diagnosis: Depression with psychotic features. Which antipsychotic will interact with his current regimen and put him at increased risk of antipsychotic side effects if dose not adjusted?
A. LurasidoneB. QuetiapineC. OlanzapineD. Risperidone
Electroconvulsive Therapy (ECT)
• Role in treatment of Depression• Treatment-resistant depression
• Failure of multiple antidepressants
• Depression with psychotic features
• Depression with catatonic features
• Rapid response needed
• Severe suicide risk
Audience Assessment
Which of the following is the maximum dose of citalopram in the elderly?
A. 10 mgB. 20 mgC. 40 mgD. 60 mg
When is 20 mg the max dose of citalopram?
• Hepatic impairment• Persons > 60 years of age (in US); > 65 years (in Canada)• CYP 2C19 poor metabolizers• Persons taking potent 2C19 inhibitors:
• Cimetidine• Omeprazole? ( noted in prescribing information as a
potent CYP2C19 inhibitor)
http://www.fda.gov/Drugs/DrugSafety/ucm297391.htmCitalopram prescribing information www.dailymed.nlm.nih.govSmall GW. JAMA 2014:311(7):677-8.https://www.lundbeck.com/upload/ca/en/files/pdf/productcommunication/Celexa%20HPC_ENG_%20e-signature_20Jan2012.pdf
Dose dependent change in QTcinterval
Dose Change in QTc (95% CI), ms
Citalopram(n=119)
20 mg40 mg*60 mg
8.5 (6.2-10.8)12.6 (10.9-14.3)18.5 (16.0-21.0)
Escitalopram(n=113)
10 mg20 mg*30 mg
4.5 (2.5-6.4)6.6 (5.3-7.9)10.7 (8.7-12.7)
* Estimate based on relationship between concentration and QT inteval
https://www.fda.gov/drugs/drugsafety/ucm297391.htmhttp://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2012/14672a-eng.php?_ga=1.118672201.1545592573.1487284591
Veterans Affairs dataCitalopram > 40 mg (n=618,898) had LOWER risk of ventricular arrhythmia, all-cause mortality and non-cardiac mortality versus citalopram 1-20 mg.
Which Medication?
• A 79 year old presents with symptoms anxiety regarding her memory [MMSE 28/30]. Her GDS was 12. She was last treated for depression in her 30s after the loss of her father. She also reports she no longer enjoys golfing and prefers to stay home.
Which of the following antidepressants would you recommend for initial therapy?A. Sertraline 25 mg dailyB. Paroxetine 10 mg daily C. Bupropion SR 100 mg daily D. Venlafaxine XR 150 mg daily
Which Medication?
• A 66 year old presents with symptoms of depression including a significant delay in response, lack of motivation, no longer engaging in activities, weight loss secondary to no energy to cook or eat. They prefer to lay around in bed all day.
Which of the following would you recommend?A. Sertraline 25 mg dailyB. Fluoxetine 10 mg daily C. Bupropion SR 100 mg daily D. Methylphenidate 2.5 mg BID
Which Medication?• A 74 year old with a newly diagnosed seizure disorder reports
symptoms of depression. They are treated with levetiracetam 500 mg every 12 hrs. Which of the following antidepressants is contraindicated?
A. Bupropion SR 100 mg daily B. Fluoxetine 10 mg daily C. Mirtazapine 15 mg at bedtimeD. Citalopram 10 mg daily E. Vortioxetine 10 mg daily
Which Medication?• A 69 year old presents with symptoms of depression including
a 13 kg weight loss over the last 2 months, due to lack of appetite and is experiencing insomnia and feels guilty that they are a burden on their family.
Which of the following would you recommend?A. Bupropion SR 100 mg daily B. Olanzapine 5 mg at bedtimeC. Mirtazapine 15 mg at bedtimeD. Nortriptyline 10 mg at bedtimeE. Sertraline 25 mg daily + quetiapine 25 mg at bedtime
If at first you don’t succeed
NO response
•Try another SSRI
•Switch to a different class of antidepressant (SNRIs, mirtazapine, bupropion, TCA with less anticholinergic risk (e.g. nortriptyline))
Partial Response
•Monotherapy preferred in elderly if possible
•Combination therapy: Add bupropion or buspirone
•Adult Augmentation Strategies: Lithium, liothyronine, antipsychotics – however lithium and antipsychotics have a high risk of adverse effects in elderly;
•May be a role for stimulants in elderly
Resistant
•Refer to a geriatric psychiatrist
•Electroconvulsive Therapy (ECT)
Switching Antidepressants
• A 65 year old has been treated an SSRI for the last 7 years. Recently their symptoms of depression have worsened. Which of the following most likely would require a cross-taper strategy?
A. Paroxetine 20 mg to fluoxetine 20 mg
B. Sertraline 100 mg to venlafaxine 75 mg
C. Escitalopram 10 mg to sertraline 25 mg
D. Fluoxetine 20 mg to fluvoxamine 50 mg
Switching Antidepressants
• A 65 year old has been treated an SSRI for the last 7 years. Recently their symptoms of depression have worsened. Which of the following most likely would require a cross-taper strategy?
A. Paroxetine 20 mg to fluoxetine 20 mg
B. Sertraline 100 mg to venlafaxine 75 mg
C. Escitalopram 10 mg to sertraline 25 mg
D. Fluoxetine 20 mg to fluvoxamine 50 mg
Psychiatry and the Older AdultDementia
Change in Terminology
DSM-IV
• Dementia
DSM-5
• Neurocognitive Disorder
DSM-5 Am Psych Assoc 2013
Types of Neurocognitive Disorder• Alzheimer’s Disease (AD) • Vascular Disease• Lewy Body• Parkinson’s• Frontotemporal (a.k.a. Pick’s disease)
Other: alcohol-related, HIV infection, traumatic brain injury, Huntington’s, substance use, prion disease
DSM-5 Am Psych Assoc 2013
The Numbers…
• United States• > 5 million Americans suffer from Alzheimer’s disease
• Every 66 seconds someone develops Alzheimer’s in the United States
• By 2050 Estimated > 13 million will have Alzheimer’s
• Canada• As of 2016 an estimated 564,000 Canadians are living
with dementia
• By 2031 estimated 937,000 will have dementia
http://www.alzheimer.ca/~/media/Files/national/Core-lit-brochures/factsheet_alzheimers_2015_e.pdfhttp://www.alz.org/facts/overview.asp
Symptoms and Clinical Manifestations of Alzheimer’s Disease
1. Memory loss a. Difficulty remembering new formation
2. Reduced executive functioninga. Difficulty handling complex tasks (e.g. finances)
3. Not oriented to time or place 4. Difficulty with visual-spatial relationships5. Language changes
• Repeat themselves• Stop midsentence (lose the word)• Name objects incorrectly
6. Impaired judgement7. Changes in behavior or personality http://www.alz.org/10-signs-symptoms-alzheimers-dementia.asp
McKhann GM et al. Alzheimers Dement 2011;7(3):263-9.
Screening Tools
• Folstein or Mini Mental State Exam (MMSE)• Montreal Concentration Assessment (MOCA)• Blessed Orientation Memory Concentration (BOMC)• Saint Louis University Mental Status (SLUMS)• Clinician’s Interview-Based Impression of Change
(CIBIC)• Clinical Dementia Rating Scale (CDR)• Cognitive Performance Scale (CPS) – (RAI-MDS 2.0)
https://www.cihi.ca/sites/default/files/outcome_rai-mds_2.0_en_0.pdfhttps://www.cihi.ca/sites/default/files/outcome_rai-mds_2.0_en_0.pdf
Goals of Pharmacotherapy
• Maintain current level of function• Minimize adverse effects• Prevent or slow decline • Target behaviors
Audience Assessment
• A 73 yo WF is brought in by her husband because of concerns of worsening memory. She constantly repeats the same question despite him answering it. She has become suspicious that someone is breaking into their house and stealing her purse. You complete an MMSE and she scores a 12. Does she meet the criteria for:
A. Mild Cognitive Impairment
B. Mild Dementia
C. Moderate Cognitive Impairment
D. Severe Cognitive Impairment
Audience Assessment
• Interpreting an MMSE• No cognitive impairment 24-30
• Mild Cognitive Impairment 18-23
• Severe Cognitive Impairment ≤ 17
Note some scoring references suggest:
Mild 19-23Moderate 10-18Severe < 10
http://www.dementiatoday.com/wp-content/uploads/2012/06/MiniMentalStateExamination.pdf
Based on her MMSE score today of 12 what would you recommend?
A. Watch and waitB. Donepezil 5 mg PO dailyC. Rivastigmine 4.6 mg transdermal D. Galantamine 4 mg PO BIDE. Donepezil 5 mg PO + Memantine 5 mg PO daily
Audience Assessment
Selecting Therapy - US
Mild
• Begin acetylcholinesterase inhibitor
• Reevaluate in 2-4 weeks for adverse effects
Moderate/Severe
• Begin acetylcholinesterase inhibitor ±memantine
• If initially mild and deteriorates consider addition of memantine
Winslow BT, et al. Am Fam Physic 2011;83(12):1403-12.
2014 American Psychiatric Association Guideline
• Evidence remains modest regarding efficacy of Acetylcholinesterase inhibitors (AChI) in mild to moderate Alzheimer’s Disease (AD) and memantine for moderate to severe AD
• Higher doses of donepezil did not show clinically meaningful benefit
• Higher doses of transdermal rivastigmine may show greater benefit
• 3 new trials of memantine in mild-moderate AD did not confer benefit
• Newer trials show slight or unclear significance in adding memantine to AChI
• Newer long-term evidence regarding safety of AChI including anorexia, weight loss, falls, hip fractures, syncope, bradycardia, and increase pacemakers
Rabins PV, et al. American Psychiatric Association 2014http://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/alzheimerwatch.pdf
Medication Indications
Medication Alzheimer’s Type Vascular Parkinson’s
Donepezil Mild-moderateModerate-severe
Galantamine Mild-moderate
Rivastigmine Mild-moderate(PO)Mild - severe: (transdermal only)
Mild-moderate
Memantine Moderate-severe
Combo: Donepezil + Memantine
Moderate-severe
Prescribing information. www.dailymed.nlm.nih.gov
When have you recommended discontinuation of an acetylcholinesterase inhibitor?
Audience Discussion
When to Discontinue?
• Non-adherence
• Continued deterioration
• Becomes terminally ill or serious comorbidity
• Patient or caregiver choice
Winslow BT, et al. Am Fam Physic 2011;83(12):1403-12.Herrmann N, Gauthier S. CMAJ 2008;179:1279-87
When have you recommended discontinuation of an acetylcholinesterase inhibitor?
Audience Discussion
When to Discontinue?
• Non-adherence
• Continued deterioration
• Becomes terminally ill or serious comorbidity
• Patient or caregiver choice
Winslow BT, et al. Am Fam Physic 2011;83(12):1403-12.Herrmann N, Gauthier S. CMAJ 2008;179:1279-87
CMAJ – Canadian Guidelines also state Should NOT be stopped simply because a patient has been admitted to a long-
term care facility
“Domino Trial” in 2012 of patients [n = 295] with moderate to severe AD treated with donepezil for at least 3 months.Randomized to:• Continue donepezil• Switch to placebo (essentially d/c donepezil)• Switch to placebo + memantine • Continue donepezil and add memantine
Results: • Continuation of donepezil saw ~ 32% less decline• Discontinuation of donepezil saw a worsening of MMSE and
Bristol Activities of Daily Living• Those who discontinued donepezil but received memantine
had less pronounced worsening (~20% decline)• Those continued on donepezil and memantine was added
conferred no additional benefit.
Treatment Discontinuation
Howard R et al, NEJM 2012; 366(10):893-903
APA Guidelines 2014
• Newer long-term evidence regarding safety of acetylcholinesterase inhibitors including:• Anorexia
• Weight loss
• Falls and hip fractures
• Syncope
• Bradycardia and increase pacemakers
Rabins PV, et al. American Psychiatric Association 2014http://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/alzheimerwatch.pdf
Gastrointestinal (GI)
• Nausea• Underweight patients (especially with donepezil 23 mg) were more
likely to experience• Rates: Rivastigmine: 24-47%; Galantamine: 20%; Donepezil 23 mg:
11.8% vs 10 mg: 3.4%
• Vomiting
• Diarrhea
• Management Strategies:• Prolonged titration is targeted at minimizing these adverse effects• Take with food• Discontinue treatment for several days; restart either the same
dose or previous lower dose Prescribing information; Psychiatric Pharmacotherapy Review 2016 CPNP
Anorexia or Weight Loss
Rates:
• Donepezil 7-9% vs placebo 6-8%
• Donepezil 10 mg 1.7% vs donepezil 23 mg 5.3%
• Rivastigmine• Weight loss: 26% of women on high dose > 9 mg• Anorexia: 17%
• May be more common with rivastigmine/galantamine vs other studies suggest galantamine is least likely to cause weight loss
• Management Strategies:• Take with food• Discontinue treatment for several days
• Restart either the same dose or previous lower dose
Prescribing information; Psychiatric Pharmacotherapy Review 2016 CPNP
Cardiovascular Adverse EffectsSyncope and Bradycardia • Population-based study of hospital visits for (cholinesterase
inhibitor vs control):• Syncope 31.5 vs 18.6 per 1000 person years (HR=1.76; 95% CI, 1.57-1.98)• Bradycardia 6.9 vs 4.4 per 1000 person years (HR=1.69; 95% CI, 1.32-2.15)• Pacemaker Insertion 4.7 vs 3.3 per 1000 person years (HR=1.49; 95% CI,
1.12-2.00)• Hip fracture 22.4 vs 19.8 per 1000 person years (HR=1.18; 95% CI, 1.04-
1.34)
• Another health care record review identified 1,009 elders hospitalized for bradycardia within 9 months of initiation of a cholinesterase inhibitor• 17/161 cases (11%) required a pacemaker
• Flipside – Canadian health-care database review of all pacemaker insertions found ~ 4% were on cholinesterase inhibitors and considered this “rare”
Gill SS, et al. Arch Intern Med 2009;169(9):867-73.Parke-Wyllie LY, et al. PLoS Med. 2009;6(9):e1000157Huang AR, et al. BMC Neurol. 2015 Apr 28;15:66.
Urinary Incontinence
Medications to treat urinary incontinence
Acetylcholinesterase Inhibitors
Rates: Donepezil ~ 3 %
All cholinesterase inhibitors could cause bladder outflow obstruction
• Rivastigmine – reports of urinary obstruction
Management Strategies:
• Pros/cons of agents that treat incontinence
Acetylcholine
Behavioral Disturbances
Nursing Home Initiative
• National Partnership to Improve Dementia Care in Nursing Homes• Center for Medicare and Medicaid Services is partnering
with federal agencies, state agencies, nursing homes, and caregivers to improve dementia care
• National goal was to reduce antipsychotic medications in nursing home residents by 25% by the end of 2015; 30% end of 2016
• In 2015, an antipsychotic measure was added to CMS calculations for each nursing home ratings on the Five Star Quality Rating System
Behavioral Disturbances
• Alzheimer’s Disease (or related dementia) affects around 44 million people worldwide
• In the US its estimated 5.3 million have Alzheimer’s Disease
• Behavioral disturbances are seen • ≥ 80% of Alzheimer’s dementia patients will experience
agitation
• ~ 40% of patients with Alzheimer’s dementia experience aggression
http://www.alzheimers.net/resources/alzheimers-statistics/
http://www.alz.org/facts/overview.asp
American Psychiatric Association Guideline• 2016 New Guideline:
• Available at: http://psychiatryonline.org/doi/pdf/10.1176/appi.books.9780890426807
Reus VI, et al. Am J Psychiatry 2016;173:543-6.
APA 2016
• Statement 1: Assess symptoms for the type, frequency, severity, pattern, and timing
Reus VI, et al. Am J Psychiatry 2016;173:543-6.
ABC’s of BPSD
• Antecedents – What triggered the behavior?
• Behavior – What type of behavior? Is it a target for intervention?
• Consequences – To whom? the patient or others?
www.istockphoto.com
BPSD Symptom Clusters and Consequences
Cluster Symptoms Consequences
Depression Sadness, crying, hopelessness, guilt, anxiety
Poor self careWeight loss
Apathy Withdrawal, lack of pleasure Isolation
Aggression Resistance to care; physical or verbal
Altercations or injuries
Psychomotoragitation
Wandering, pacing, sleep disturbances, repetitive actions, intrusiveness
EscapingAltercations
Psychosis Delusions, hallucinations IsolationRefusal of care
APA 2016
• Statement 2: Assess for pain or other potentially modifiable contributors to symptoms. Consider other factors such as subtype of dementia.
Reus VI, et al. Am J Psychiatry 2016;173:543-6.
Case Vignette
• A 78 yo female admitted for concerns of depression (no longer leaving her room) and being combative with care if someone tried to help turn her in bed. Two weeks prior to admission patient was ambulatory and not agitated.
APA 2016
• Statement 4: Recommend a documented treatment plan that includes person-centered non-pharmacologic and pharmacologic interventions
Reus VI, et al. Am J Psychiatry 2016;173:543-6.
Non-Pharmacologic Approaches
http://www.hsrd.research.va.gov/publications/esp/Dementia-Nonpharm.pdf; Holmes C, et al. Int J Geriatr Psychiatry 2002; Burns A et al. Dement Geriatr Cog Disord 2011;31(2):158-64.; Filan SL et al. International Psychogeriatrics 2006; 18(4):597-611; Chung JC et al. Cochrane database review 2002;(4):CD003152; http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3711645/table/T1/Evaluate hearing/adjust hearing aidshttp://www.isna-mse.org/pdf/English/Dementia_and_Snoezelen.pdfhttp://www.best-alzheimers-products.com/doll-therapy-for-alzheimers-disease-baby-doll-therapy.html#prettyPhoto/0/https://www.gardenvillahealth.com/alzheimers/doll-therapy-something-love/ Accessed March 2017
Targets
Reminiscence Therapy Depression, Apathy
Stimulated Presence Therapy Depression, Apathy, Agitation
Aromatherapy Apathy, Agitation
Hearing evaluation Hallucinations
Eye exams Hallucinations
Snoezelen Environment Agitation
Doll Therapy/Stuffed Animals Agitation, Mood, Hypersexual behaviors
Music Therapy Depression, Apathy
Animal Assisted Therapy Aggression, Agitation
APA 2016
• Statement 5: Recommends nonemergent antipsychotic medication should only be used for the treatment of agitation or psychosis in dementia IF symptoms are: • Severe
• Dangerous
• Cause significant distress to the patient
Reus VI, et al. Am J Psychiatry 2016;173:543-6.
APA 2016
• Statement 6: Review response to nonpharmacologic strategies prior to use of an antipsychotic for dementia-related psychosis and agitation
Reus VI, et al. Am J Psychiatry 2016;173:543-6.
Prior to Antipsychotics –Pharmacologic StrategiesMedication Targets Evidence
Cholinesterase Inhibitors
Agitation, aggression, anxiety, delusions
Mixed/ modest
CMAJ - No
Anticonvulsants Agitation, aggression, mood lability
Lacking2014 guidelines modest benefit with carbamazepine Recommended against VPA
Antidepressants Depression, apathy, agitation, aggression, anxiety
Cit-AD citalopram 30 mg
Buspirone Anxiety, behaviors Small positive study; Dose 25.7 mg ± 12.5
***Not part of guideline; it did not address non-antipsychotic pharmacologic treatments
http://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/alzheimerwatch.pdfMadhusoodanan S, et al. World J Psychiatr 2014; 4(4):72-9; Freund-Levi Am J Geriatr Psychiatr 2014;22(4):341-8.; Rodda J, et al. Int psychogeriatr 2009; 21(5):813-824.; Tariot et al. JAGS 2001;49:1590-9. Feldman H, et al. Neurol2001;57:613-20; Rabins PV. APA Guideline 2014 ; Freund-Levi Am J Geriatr Psychiatry 2014;22(4):341-8; Porsteinsson AP. JAMA 2014;Santa Cruz, MR. Int Psychogeriatr 2017; 26:1-4
APA 2016• Statement 7: Prior to nonemergency treatment
with an antipsychotic, assess risks and benefits and discuss with patient (if feasible) and patients surrogate decision maker with input from family
Reus VI, et al. Am J Psychiatry 2016;173:543-6.Schneider LS, et al. NEJM 2006;355(15):1525-38
Benefit Risk
Potential Benefits of Antipsychotics for BPSD
• Dangerous agitation
• Minimize risk of violence
• Reduce distress
• Improve patient’s quality of life
• Reduce caregiver burden
http://psychiatryonline.org/doi/pdf/10.1176/appi.books.9780890426807
BPSD = Behavioral and Psychological Symptoms of Dementia
Evidence
• Best Evidence • Agitation – risperidone
• Psychosis – risperidone
• Overall BPSD – aripiprazole
• Caregiver burden – modest reduction with SGA > placebo
http://psychiatryonline.org/doi/pdf/10.1176/appi.books.9780890426807
CATIE-AD – Improvement Observed (%)
%
Schneider LS, et al. NEJM 2006;355(15):1525-38
CATIE-AD = Clinical Antipsychotic Trials of Intervention Effectiveness for Alzheimer’s Disease
CATIE-AD Conclusions
• No significant differences among treatment in time to discontinuation for any reason (range 5.3-8.1 weeks)• Time to discontinuation for lack of efficacy favored olanzapine
and risperidone over quetiapine and placebo
• Symptoms of anger, aggression, and paranoia did improve with active treatment with antipsychotics
• Exercise caution when prescribing these agents because of the risk of significant adverse effects, including orthostatic hypotension, sedation, falls, and an increase in cerebrovascular events and death often outweigh benefit.
Schneider LS, et al. NEJM 2006;355(15):1525-38Schneider LS, et al. NEJM 2006;355(15):1525-38
A bit of history….
Prescribing information of Antipsychotics (both first generation
and second generation)
2003 Risperidone
Stroke
April 2005 SGAs Death
June 2008 FGAs Death
2013 APA Choosing
Wisely
Feb 2017
Falls, Fractures
A Bit of History….Federal Drug Administration (FDA)
Prescribing information of Antipsychotics (both first generation
and second generation)
2003 Risperidone
Stroke
April 2005 SGAs Death
June 2008 FGAs Death
2013 APA Choosing
Wisely
Feb 2017
Falls, Fractures
Later olanzapine
and aripiprazole
1-2% higher than
placebo; 2x higher,
respectively
Mortality relative risk
1.6-1.7 vs. placebo; rate
4.5% vs. 2.6%
Based on a meta-
analysis of 15 trials
Schneider LS et al.
JAMA 2005
Observational
Analysis
Based on trials
with risperidone,
olanzapine,
quetiapine and
aripiprazole
Schneider LS. Arch Neurol 2011;68(8):991-8.
FDA labeling
change
Risk of
somnolence,
OH, motor
instabilityOH = orthostatic hypotension
FDA Warning on ALL Antipsychotics
“Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Analyses of seventeen placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients of between 1.6 to 1.7 times the risk of death in placebo-treated patients. Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo group. Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. Observational studies suggest that, similar to atypical antipsychotic drugs, treatment with conventional antipsychotic drugs may increase mortality. The extent to which the findings of increased mortality in observational studies may be attributed to the antipsychotic drug as opposed to some characteristic(s) of the patients is not clear. [INSERT ANTIPSYCHOTIC] is not approved for the treatment of patients with Dementia-Related Psychosis”
Prescribing information of Antipsychotics (both first generation
and second) www.dailymed.nlm.nih.gov generation)
Choosing Wisely…
American Psychiatric Association Don’t
• #3 use antipsychotics as first choice to manage behavioral and psychological symptoms of dementia
Don’t
• #12 use antipsychotics as first choice to manage behavioral and psychological symptoms of dementia
American Geriatrics Society
Don’t
• #2 use antipsychotics as first choice to manage behavioral and psychological symptoms of dementia
• #6 prescribe cholinesterase inhibitors for dementia without periodic assessment for perceived cognitive benefits and adverse GI effects
• #10 use physical restraints to manage behavioral symptoms of delirium in hospitalized elderly
http://www.choosingwisely.org/doctor-patient-lists/american-geriatrics-society/
http://www.choosingwisely.org/wp-content/uploads/2013/09/102913_F64_46-APA-5things-List_Draft-5.pdfhttp://www.choosingwiselycanada.org/recommendations/psychiatry/ (number 12)
Choosing Wisely Canada
APA 2016
• APA Statement 8: If decision that risk/benefit discussion favors use of an antipsychotic, initiate treatment at a low dose and titrate to minimumeffective dose
http://www.acrbc.ca/pdf/Fact%20Sheet2%20Antipsychotic%20Medications%20in%20Long%20Term%20Care%20Nov%202012.pdfReus VI, et al. Am J Psychiatry 2016;173:543-6.
Choosing an Antipsychotic with Consideration of Concurrent Disease States
Concurent disease Consider Avoid/Caution
Diabetes ZiprasidoneAripiprazoleRisperidone
ClozapineOlanzapine
BPH Risperidone Olanzapine
Parkinson’s disease QuetiapineClozapine AripiprazolePimavanserin
Haloperidol, FGAs, risperidone
Lewy Body Dementia [visual hallucinations]
QuetiapineAripiprazole
Haloperidol, FGAs, risperidone
Delusions/ hallucinations Risperidone Quetiapine
Recent Myocardial Infarction
Ziprasidone
Seizures Clozapine
FGA = first generation antipsychotic
Antipsychotic DosingMedication Initial Dosage
adjustmentsMaximumMax OBRA dose
Frequency Versus Adult dosing in Schizophrenia
Olanzapine 2.5 mg 2.5 mg increments
5 mg10 mg
Once per day at bedtime
20 mg (FDA max) 40 mg clinically
Risperidone 0.25-0.5 mg
0.25-0.5 mgincrements
2 mg2 mg
1-2 times per day 4-6 mg
Quetiapine 12.5-25 mg
12.5-25 mgincrements
200 mg200 mg
BedtimeTID
400-600 mg
Aripiprazole 2-5 mg 2-5 mg increments
NA Once daily Up to 30 mg
Ziprasidone 20 mg 80 mgNA
BID with meals (at least 500 calories)
80 mg BID with meals
Haloperidol 0.5-2 mg 2 mg4 mg
Bedtime up to TID 10-20 mg
http://www.alzbrain.org/pdf/handouts/5021.pdf
OBRA = omnibus budget reconciliation act 1990 (also known as the nursing home reform act of 1987)
Audience Assessment
Which antipsychotic is approved Behavioral and Psychological Disturbances in Dementia in Canada?
A. Quetiapine
B. Risperidone
C. Olanzapine
D. Clozapine
APA 2016
• APA 2016 Statement 9: If a patient with dementia experiences a clinically significant side effect, rereview the risks and benefits of antipsychotic and determine if the medication should be tapered or discontinued
http://www.acrbc.ca/pdf/Fact%20Sheet2%20Antipsychotic%20Medications%20in%20Long%20Term%20Care%20Nov%202012.pdfReus VI, et al. Am J Psychiatry 2016;173:543-6.
Antipsychotic Monitoring in the Elderly• Extrapyramidal Symptoms (EPS)
• Sedation
• Metabolic Effects
• Pneumonia
• Cerebrovascular events
• Hip fractures
• Death
McKean A. CNS Drugs 2012;26(5):383-90.
Extrapyramidal Symptoms
• EPS includes• Acutely: parkinsonism,
dystonia, akathisia
• Long-term: Tardive Dyskinesia (TD)
• Elderly patients are more susceptible to drug-induced Parkinsonism
Antipsychotics
Cholinesterase Inhibitors
Dopamine
Acetylcholine
Kaplan and Saddocks 2003Lexi-comp 2015
Unique Adverse Effects of Antipsychotics in the Elderly• Parkinsonism presentations:
• Pisa syndrome –• Case reports with quetiapine, olanzapine
• Case reports with cholinesterase inhibitors also
• Camptocormia – Greek words: kamptos (to bend) and kormos (trunk)] (case reports with olanzapine)
Robert F, et al. J Med Case Rep 2010;4:192. Vela L. Mov Disord 2006; 21(11):1977-80. Walder A, et al. Prog Neuropsychopharmacol Biol Psychiatry 2009;33(7):1286-7. Perrone V, et al. J Neuropsychiatry Clin Neurosci 2012;24(3):E31-2. Knol W. J Am Geriatr Soc. 2008;56(4):661-6.
Sedation
• Increases risk of aspiration pneumonia
• Increases risk of falls, fractures
• Increases risk of DVT/PE
• Sleep through meals
• Monitor for HYPOactive delirium
McKean A. CNS Drugs 2012;26(5):383-90.
Unique Adverse Effects of Antipsychotics in the Elderly• Listed in the prescribing information of all
antipsychotics
• Difficulty swallowing/dysphagia • Risk factor for choking or aspiration pneumonia
• May result in eating less
Robert F, et al. J Med Case Rep 2010;4:192. Vela L. Mov Disord 2006; 21(11):1977-80. Walder A, et al. Prog Neuropsychopharmacol Biol Psychiatry 2009;33(7):1286-7. Perrone V, et al. J Neuropsychiatry Clin Neurosci 2012;24(3):E31-2. Knol W. J Am Geriatr Soc. 2008;56(4):661-6. Prescribing information www.dailymed.nlm.nih.gov
Consequences of Dysphagia
Fall Risk
• February 2017 – Warnings section updated
• Somnolence, postural hypotension, motor or sensory instability, may lead to falls or injury (including fracture)
• Risk of OrthostasisMediated by α1 antagonism
Lower
Aripiprazole
Ziprasidone
Haloperidol
Moderate
Risperidone
Quetiapine
High
Clozapine
Iloperidone
Chlorpromazine
Figure: Risk of orthostasis
ADA/APA MetabolicMonitoring Guidelines 2014
Base 4 week 8 week 12 week
Quarterly Annually every 5 years
Family History
X X
Wgt/BMI X X X X X
Waist Circum
X X
Blood Pressure
X X X
Fasting glucose
X X X
Lipid Panel X X X
J Clin Psych 2004
Olanzapine Metabolic Effects
Day2 Day 4 Day 6 Day 8 Day 10
started olanzapine 2.5 mg
olanzapine 7.5 mg Receives 4
units of insulin when BG > 300 mg/dLBG > 16.6 mmol/L
Home Med: Glargine 14 units HS
Mmol/L
27.7
22.2
16.6
11.1
5.5
mm
ol/
L
Metabolic Effects of Olanzapinenote one value was > 600 mg/dL [> 33.3 mmol/L]
started olanzapine 5 mg2 days later increased to 10 mg
75 yo M with PMH of DM with Major Neurocognitive DO with Behavioral Disturb
Maximum dose in 24 hours was 17.5 mg
Mmol/L
33.3
27.7
22.2
16.6
11.1
5.5
mm
ol/
L
Adverse Effect MonitoringFGAs greatest risk SGAs greatest risk
Sedation Low potency –chlorpromazine
Quetiapine
Parkinsonism High-potency (e.g. Haloperidol, fluphenazine)
Risperidone
Akathisia High potency AripiprazoleLurasidone
Metabolic Low potency Olanzapine Clozapine
Orthostasis Low potency QuetiapineClozapineIloperidone
QTc ThioridazinePimozideHaloperidol Intravenously
Ziprasidone, quetiapine, iloperidone,clozapine
Agranulocytosis Clozapine
APA 2016 Recommendations on Dosing, Duration, Monitoring of Antipsychotics• If benefit outweighs risk
• Start at low dose and titrate to MINIMUM effective dose
• If no response after a 4-week trial taper and withdraw
• If experiences adequate response, an attempt to taper or withdraw the antispychotic should be made within 4 months of initiation; unless has a history of symptom recurrence with tapering
• If taper is attempted, assess symptoms monthly during the taper and for at least 4 months after discontinuation
Reus VI, et al. Am J Psychiatry 2016;173:543-6.
US Nursing Home (NH) Regulations for Residents on Antipsychotics
• Safety Monitoring: • Abnormal Involuntary Movement Scale (AIMS) required at
least twice per year to screen for Tardive Dyskinesia (TD)
• Reassess/Revaluate • Residents who use antipsychotic drugs receive gradual
dose reductions, and behavioral interventions, unless clinically contraindicated, in an effort to discontinue these drugs
• Discontinue if the targeted behavior is not improving
https://oig.hhs.gov/oei/reports/oei-02-00-00491.pdfhttp://www.alosafoundation.org/wp-
content/uploads/2014/07/APMs_EvidenceDocument.pdf
Gradual Dose Reductions (GDR)
• Within the first year of admission to a NH the facility must attempt a GDR in 2 separate quarters (with at least one month between the attempts), unless contraindicated
• After the first year, a GDR must be attempted annually (unless contraindicated)
https://www.cms.gov/Medicare/Provider-Enrollment-and-Certification/SurveyCertificationGenInfo/Downloads/Survey-and-Cert-
Letter-16-15.pdf
NH Contraindications to GDRs
• Reasons for contraindication: • Target symptoms returned/worsened after GDR attempt• Physician documented the clinical rationale as to why
additional GDR attempts would impair the residents functioning or increase distressed behaviors
• For patients receiving antipsychotics for a psychiatric disorder (other than dementia); for example schizophrenia, bipolar disorder, depression with psychotic features a GDR may be contraindicated if: • Continued use is in line with current guidelines/standard of
care and the physician has documented need a GDR would exacerbate underlying psychiatric condition.
• Target symptoms returned/worsened after GDR attempt and MD documented rationale
https://www.cms.gov/Medicare/Provider-Enrollment-and-Certification/SurveyCertificationGenInfo/Downloads/Survey-and-Cert-
Letter-16-15.pdf
Behavioral DisturbancesCase Vignettes
Case VignetteA 72 yo widow with a history of Alzheimer’s Dementia. She gets worked up every evening around dinner time because her “husband has not come home from work.” She refuses to eat most nights because she does not want to eat without him.What interventions do you recommend?A. Gently remind her that her husband has passed awayB. Reminiscence therapy C. Stimulated presence therapyD. Cholinesterase inhibitor E. Antidepressant F. Appetite stimulantG. Antipsychotic
Case Vignette
• A 73 year old retired furniture mover recently admitted to a NH facility. He perseverates on needing to leave to get to work, constantly checks door locks, seems very anxious about being there and being late to work. What do you consider?
A. Redirection
B. Antidepressant
C. Benzodiazepine
D. Antipsychotic
Which Medication?• A 82 year old with a history of Parkinson’s disease has
developed agitated behaviors. Attempt was made to reduce their carbidopa/levodopa without success. Which of the following should be AVOIDED in this patient?A. Haloperidol 1 mg B. Aripiprazole 5 mgC. Olanzapine 2.5 mg D. Risperidone 0.5 mgE. Quetiapine 12.5 mg
Which Medication?• A 82 year old with a history of Parkinson’s disease and dementia
has developed disturbing hallucinations resulting in agitation. Attempt was made to reduce their carbidopa/levodopa without success. Which of the following would you consider recommending in this patient?A. Haloperidol 2 mgB. Aripiprazole 5 mgC. Olanzapine 2.5 mg D. Risperidone 0.5 mgE. Quetiapine 12.5 mg
Case Vignette
• A 72 WM with a history of dementia. He can no longer verbalize his needs. He was admitted for agitated behaviors surrounding meal times. He has edentia and is served pureed foods. He was started on olanzapine 5 mg at bedtime 3 months ago…• Separate him from others during meals?
• Change his antipsychotic?
Case Vignette
A 73 yo WF visiting her daughter in Las Vegas from the Lake Mead area. Brought to hospital because “the drug dealers followed her.” Their “dealings” are broadcast over her radio and also her daughter’s
• Medication List• HCTZ 25 mg for blood pressure
• Donepezil 10 mg for Alzheimer’s
• Divalproex sodium 125 mg TID for delusions
Summary
Assess for pain, infection. Rule out delirium
Remove deliriogenic medications
Behavioral interventions
Education of caregivers and staff
Add cholinesterase inhibitor
Consider antidepressant
If no other options remain…consider an antipsychotic
Educate benefit vs. risk and reevaluate continued indication (every 6 months) OR APA every 4 months
DeMers S, et al. Med Clin NA. 2014; 98:1145–1168. Reus VI, et al. Am J Psychiatry 2016;173:543-6.
Sink K. et al. JAMA 2005;293(5):596–608.
Questions?