Agitate Elderly

7/28/2019 Agitate Elderly

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The Case of Mr. S 69 y/o man presented to medical service w/

confusion, tremor, lower extremity pain &weakness, lability, intermittent aggression,

insomnia Recent poor po intake except for 4 beers

per night Hx bipolar d/o, tardive dyskinesia, chronic

pain, CVA, chronic renal insufficiency Baseline: cognitively impaired for months,

mood unstable, tinkers with meds, refusesto see psych, long hx anger dyscontrol


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The Case of Mr. S Outpatient meds: lithium, alprazolam,

clonazepam, bupropion XL, metoprolol,lisinopril

Labs: Li 1.96, TSH 8.3, BUN 41, creat 2.32,Na 132, UA neg, Utox-benzos, BAL-not done

Uncooperative with MRI of brain despite5mg lorazepam, haloperidol, & quetiapine

MSE: lethargic, disoriented, garbled speech,bursts of belligerence, flushed & diaphoretic,intermittent restlessness, no tremor or rigidityexcept jaw thrust laterally (chronic)


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The Case of Mr. S Differential Diagnosis:

Delirium: Li toxicity, ?CVA, ?infection, low

Na, ?high NH3, ?dehydration, etc

EtOH withdrawal/intox, benzo withdrawal

Dementia: EtOH, cerebrovascular, Alz

Adverse rxn to benzos or other meds Mania +/- psychosis


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The Case of Mr. S Management:

One to one sitter and prn soft wrist restraints/4point restraints

No more lithium, clonazepam, alprazolam

No more tinkering with meds

Judicious use of lorazepam for EtOH withdrawal &benzo withdrawal

Olanzapine IM, Zydis, tabs

Valproic acid to therapeutic levels

Gabapentin for insomnia


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What does agitated really

mean? Restless? Paranoid? Aggressive? Impulsive? Hallucinating? Disinhibited?

These adjectives aremuch more useful andspecific. Use them andteach staff to use them!

Intrusive?

Pacing?

Yelling?

Resistant to care?

Wandering?

Hypersexual?


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Determine the Context of the

Disturbed Behavior Is this a sudden change in behavior or

mental status?

Is this an acute exacerbation of achronic problem?

What is the patients baseline level of

cognition & behavior?Are there patterns of or triggers for the

problematic behaviors?


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Obtain the History ?Accompanying changes in sleep, interest

level, appetite/fluid intake, mood, affect, levelof alertness & orientation, bowel/bladderfunction, pain, etc

Is the patient psychotic?

Has the patients environment changed?

Are there new medications or symptoms ofmedical illness?

Is there a history of psychiatric illness?


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Differential Diagnosis of

Agitation Delirium

Dementia-related behavior disturbance

Exacerbation of psychiatric illness Medical or somatic problem

Pain, constipation, urinary retention, etc

Adverse reaction to meds or withdrawal from

meds **Often a combination of the above and

more likely to be seen in vulnerable brains


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Exacerbation of Pre-existing

Psychiatric Illness Bipolar disorder

Manic or mixed state can include psychosis &

irritability/anger and mimic delirium Schizophrenia / Schizoaffective Disorder

Minority of cases are late-onset

Psychotic depression

Can present with thought disorganization,catatonia, paranoia that triggers anger

Anxiety disorders


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Definition of Delirium A transient organic mental syndrome

featuring an acute change in mental status

Global cognitive impairment: thinking, perception,& memory are affected

Attentional abnormalities

Reduced level of consciousness

Increased or decreased psychomotor activity Disturbed sleep-wake cycle

Rapid onset over hours to days


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Characteristics of Delirium Symptoms fluctuate in severity, worse at night

Relatively brief duration (auditory, also can

have tactile; benign or frightening

Thinking is often disorganized, judgement is poor, e.g. pullingout Foley, leaving AMA Delusions: fixed false beliefs, usually persecutory; changeable

in response to events, unlike schizophrenia


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Characteristics of Delirium Disorientation of time>place>person common

Patient can be hyperactive & restless or

hypoactive with little spontaneity (lowermaintenance pts are just as ill)

Emotional lability and assaultiveness arecommon

Sxs may be quite subtle & only noticed byfamily or pre-hospital caregivers


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Predisposing factors Brain disease / injury of any origin (dont

assume brain is normal because CT is)

Advanced age Impaired vision & hearing

Reduced neurotransmitter synthesis(Acetylcholine)

Changes in drug metabolism

Sleep deprivation Sensory deprivation

Immobilization & restraints


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Predisposing factors

Male gender

Premorbid cognitive impairment

Illness severity

Low albumin

Change in environment

Psychosocial stress


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The Bottom Line

Delirium results if the sum of thepatients chronic predisposingfactors PLUS acute stressorsexceeds the patients deliriumthreshold!

ANYONE can become delirious ifthe conditions are right!


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Acute causes of delirium

Often more than one of these is involved

Primary cerebral disease

Neoplasmprimary or metastatic Stroke

CNS infection

Epilepsy

Traumatic brain injury

Presume the intubated or unconscious/semi-consciousICU MVA pt has a TBI until proven otherwise


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Systemic diseases affecting the brain Infection-- UTI, URI, dental, decubiti, lines, etc

Organ failure cirrhosis, ESRD, etc Metabolic or electrolyte disturbances low K, low

Na, high or low glu, dehydration, etc

Cardiovascular or pulmonary disease high CO2,low O2 (those pts who wont wear O2)

Malnutrition

Urinary retention or severe constipation (especiallyin dementia pts)


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Intoxication or withdrawal from alcohol, illicit drugs,OTC meds (cold meds, Benadryl), SNRIs/SSRIs, etc

Adverse rxn to prescribed meds Narcotics none are benign Anticholinergics Benadryl, Amitriptyline, Cogentin, etc.

Benzodiazepines Lorazepam, Alprazolam, etc

Anti-Parkinsons meds Sinemet, etc

Prednisone

General anesthesia

Psychotropics (but these often get blamed unnecessarily)

Sleep meds


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Diagnosis of delirium

Frequently missed therefore treatment is delayed,never given, or incorrect

Two steps: Recognize the signs & sleuth out the

acute cause Take a history from family or caregiver (that means

call them if theyre not present) & ask about recentabrupt changes in cognition or behavior; has pt beendelirious before when ill? Any psych hx?

When youre interviewing the patient does he/shestay awake? Know location, name, & date? Seemrestless? Grab at invisible things in the air? Payattention? Appear frightened or suspicious?


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Test attention via serial 7s or spelling a wordbackwards

Obtain a THOROUGH medication hx & dont forgetherbal supplements, OTC meds, old meds no longerprescribed, etc Having family clean out the medicine cabinet & bring in all

meds is never a bad idea

Approximately 1/3 of delirium cases are due to med toxicity

Is this pt cognitively capable at baseline of self-administeringmeds? Is their spouse cognitively capable of helping them?


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Laboratory work-up

Electrolytes, glu, NH3, drug levels, BUN/creat,

TSH, UA/culture, CBC, EKG, ESR, etc. Radiology: Head CT, CXR, etc.

EEG

Alcohol withdrawal: low voltage fast activity

General delirium: background slowing


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Treatment of delirium

Consider a psychiatric consult if feasible

Eliminate/stabilize offending medical problem Discontinue potentially deliriogenic meds

Document sxs SPECIFICALLY: not agitation

Start EtOH withdrawal protocol if indicated

Do not yell at the patient; this will notimprove their comprehension & may maketheir behavior worse


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Medications for delirium

NEVER, EVER use a benzodiazepine 1st

line unless the pt has an alcohol/benzo

withdrawal-induced delirium Benzos can cause paradoxical

disinhibition, increase fall risk, and

worsen deliriumAntipsychotics are 1st-line but off-label


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Antipsychotics in Delirium

Treatment of choice but literature is limited

Haloperidol/Haldol remains 1st-line

IV form least likely to cause EPS but now carriesFDA warning re need for cardiac monitoring due tosmall risk of QT prolongation, Torsades, etc.

IV form often necessary in ICU setting & for otherNPO or uncooperative pts

Also can be given IM, PO tablets & concentrate Dosing 0.5mg-2mg q 2 hrs starting

Watch for EPS, akathisia, NMS (fever, rigidity, etc)


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Antipsychotics in Delirium

Atypical (2nd generation) antipsychotics havelower risk of EPS, NMS, akathisia, etc. butliterature re efficacy & dosing in delirium issparse; widely used despite this Risperidone/Risperdal: liquid, tabs, & M-tabs

Olanzapine/Zyprexa: IM, tabs, & Zydis

Quetiapine/Seroquel: tabs

Ziprasidone/Geodon: IM, tabs

Aripiprazole/Abilify: IM, dissolving tabs, tabs

Paliperidone/Invega: tabs


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Dementia-related BehaviorDisturbances

Approximately 75% of dementiapatients have aggression, wandering, or

agitation Up to 60% are psychotic, with

hallucinations or paranoia

10-25% of dementia patients aredepressed

There are no FDA-approved meds


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Agitated Dementia Patients:Research Findings

There seems to be a disconnect betweenresearch results and real-world experience,i.e. individual patients often benefit but that

finding is difficult to reproduce in studies Studies often include both behaviorally

disturbed patients with psychosis andwithout; ironically, antipsychotics often

perform better vs. non-psychotic behaviorsthan vs. psychosis There is no agreed-upon 1st-line drug and no

benign drug


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Treatment Rules to Live By

Start low & go slow..but go!

Monitor closely for adverse effects or

paradoxical reactions Avoid polypharmacy if possible

Make only one change at a time

Patience is a virtue

Reduce or stop (taper) meds when they arenot helping

Treat the patient, not the caregiver


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Dementia-related BehaviorDisturbances

In an emergency or urgent setting, treat theagitation as you would psychosis, especially ifpatient needs to be medicated to proceedwith medical evaluation or to prevent harm

For chronic, intermittent agitation, try to fitthe patients behavior into a symptom clusterthat resembles a psychiatric disorder, thenchoose a medication thats appropriate forthat disorder

Everything is off-label


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Symptom Clusters andAppropriate Medications

Agitation resembling major depression

Changes in sleep, appetite, energy, affect, mood,

interest level/enjoyment Trial of antidepressant or ECT

SSRIs, SNRIs, Mirtazapine, etc

Agitation resembling anxiety

Worry, pacing/hand-wringing, somatic sxs Antidepressants, Buspirone, Gabapentin

Beware of paradoxical disinhibition,etc w/ benzos


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Symptom Clusters andAppropriate Medications

Agitation resembling bipolar disorder

Cyclical pattern with poor sleep, irritable or

elevated mood, hyperactivity, disinhibition Mood stabilizer: valproic acid,

carbamazepine, atypical antipsychotics

Pure aggression or anger dyscontrol Mood stabilizers, propranolol, buspirone,

etc


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Treatment of Psychosis in theGeriatric Patient

70% of prescriptions for atypicals are off-label i.e. not for psychosis

No antipsychotic is FDA-approved in the

elderly but the use of atypicals in nursinghomes is on the rise Up to 25% of Medicare NH pts Allegations of chemical restraint

Atypicals are 1st-line tx but not w/o risktherefore must discuss risks & benefits withpatient and/or family


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FDA Boxed Warning forAtypical Antipsychotic Class

Elderly patients with dementia-related psychosistreated with atypical antipsychotics are at increasedrisk of death compared to placebo. Analyses of 17

placebo-controlled trials (modal duration 10 weeks)in these subjects revealed a risk of death in the drug-treated subjects of between 1.6 & 1.7 times thatseen in placebo-treated subjects (4.5 vs 2.6%).Although the causes of death were varied, most

appeared to be either CV (e.g. heart failure, suddendeath) or infectious (e.g. pneumonia) in nature.


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Controversies RegardingBoxed FDA Warning

NEJM December 2005 Older antipsychotics associated with 37% higher

risk of death than atypicals in elderly patients with

or without dementia, in or out of nursing homes Greatest risk occurred during 1st 40 days tx & with

higher doses of older meds

No warning exists for older meds If we arent supposed to prescribe atypicals

then what should we prescribe? Some studies show no increased risk. More

studies are needed!


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FDA Warning for AtypicalAntipsychotics & CVAEs

Issued in 2005 following manufacturerswarnings (03 Risperdal, 04 Zyprexa)

Affects only Risperdal, Zyprexa, Abilify, &Invega- ? because they have the data

Cerebrovascular events (e.g. stroke,transient ischemic attack), including fatalities,

were reported in patients with dementia-related psychosis in trials of _____.


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Controversies SurroundingCVaE Warning

Two out of four Risperdal studies showed NOincreased risk of CVaEs & two showed

increased risk Multiple Risperdal & Zyprexa studies showed

no increased incidence of CVaEs requiringhospital admission

5 out of 6 patients in the Australian studywho had strokes had vascular dementia andall 6 had risk factors for stroke


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CATIE-AD Study:NEJM October 2006

36 week study of Alzheimers patients in homeor ALF settings, not NH, 421 subjects

Olanzapine (mean dose 5.5mg), Quetiapine(56.5mg), Risperidone (1mg), vs placeboMeasured time to discontinuation for any reason

D/C due to side effects favored placebo (fewer SEs) D/C due to lack of efficacy favored Zyprexa & Risperdal,

i.e. pts stayed on these longer (22.1 wks & 26.7 wks vs 9wks for placebo & Quetiapine)

D/C due to any reason (overall), placebo = meds statist-ically, stopped at 8 weeks, 77 to 85% by studys end 26 to 32% of those on meds improved, 21% on placebo

but these were not significantly different statistically Authors concluded that the adverse effects of atypicals

offset advantages in efficacy


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Treatment Options

Haloperidol (Haldol) Still frequently preferred due to IV option but for

short-term use at low dose

Clozapine (Clozaril): must fail other meds 1st Most benign motorically (Parkinsons)

HS dosing preferred due to sedation

6.25 to 12.5mg initially, titrate SLOWLY, checkblood levels

Constipation, agranulocytosis, seizures

Monitor glucose & lipids


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Treatment Options

Risperidone (Risperdal) Randomized controlled studies show it is effective

in elders with schizophrenia & dementia-related

psychosis Also studied in delirium Most likely atypical to cause rigidity, tremor,

akathisia Can cause hypotension, sedation, appetite

increase; monitor glucose & lipids 0.125mg to 1mg preferred dose range, HS

preferred, liquid & dissolving tabs available


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Treatment Options

Olanzapine (Zyprexa) Randomized controlled studies show it is effective

in elders with schizophrenia & dementia-related

psychosis As effective as haloperidol in delirium Can cause sedation, abnormal gait, increased

appetite; monitor glucose & lipids 1.25mg to 15mg max, usually hs dosing;

dissolving tablets available IM form should not be combined with other

agents due to risk of death (e.g. due torespiratory arrest)


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Treatment Options

Quetiapine (Seroquel) Limited randomized controlled data but

widely used May be tx of choice in Parkinsons due to

benign motor profile & no weekly lab tests

Can cause hypotension, sedation,

increased appetite, syncope (especiallywith rapid titration)

12.5mg to 300 +/-mg , HS dose>a.m.


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Treatment Options

Ziprasidone (Geodon)

No double-blind placebo-controlled studies in

elderly Warning regarding QT prolongation makes it not a

1st-line choice

Avoid use if cardiac conduction defects, post-MI, CHF, orif on loop- or thiazide diuretics

20mg to


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Treatment Options

Aripiprazole (Abilify)

Randomized controlled study showed effectiveness

in elders with dementia-related psychosis (mostelderly in clinical trials had this type of psychosis,not schizophrenia)

Can be sedating at higher doses, activating atlower in younger pts, the opposite in elderly ispossible; beware of akathisia & dystonia

New IM form; dissolving tablets available


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Treatment Options

Paliperidone (Invega)

Newest atypical so little known about its

use in elderly Can cause modest QT prolongation

One 6 week study of 147 elderly schizo-

phrenic pts; no overall differences in safetyor effectiveness except possible increasedcreatinine so may need to decrease dose


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Agitated Elderly:The Bottom Line

Psychosis and aggression in peoplewith dementia is a serious problem and

is difficult to treat. Antipsychotics aremodestly effective when used

judiciously and there are no

demonstrated, effective pharmacologicalternatives. Lon Schneider, MD (Mar 2006 Am J Geri Psych)


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One Last Quote

The serious consequences of psychosisand agitation in dementia, the

problematic risk-benefit profile ofantipsychotic medications for suchsymptoms, and the paucity of data onother treatment alternatives combine to

create a clinical conundrum for whichthere are no immediate or simplesolutions. Dilip Jeste, MD

Agitate Elderly

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