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12 - Central Nervous System Disorders |

347

using nonopioid analgesics if possible or the

lowest opioid dose possible, has been shown

to reduce the incidence of delirium.

Melatonin

has been used successfully at low doses to help

maintain the sleep-wake cycle.

Treatment or Removal of Underlying

Cause

Early identiﬁcation and treatment of delirium

is expected to improve outcomes, but data to

support this are lacking. However, not every case

of delirium can be prevented. After delirium is

identiﬁed, the ﬁrst step is to conduct an assess-

ment for the underlying cause(s). The history,

physical examination, and basic laboratory

testing to identify infection, myocardial infarction

(MI), electrolyte abnormalities, pain, or a change

Serum drug levels

and/or a urine drug screen may provide valu-

able information. Medical or surgical treatment

to correct the underlying cause is imperative for

the patient to regain previous cognitive function.

Supportive Measures

Supportive measures should be instituted simul-

taneously with treatment of the underlying cause.

Having a friend or family member present to reas-

sure and redirect the patient can help avoid the

need to apply restraints, which usually worsen

delirium. In addition, patients may injure them-

selves as they attempt to get out of bed while in

restraints. But if the patient is at risk for injuring him-

or herself or others, restraints may be required.

The redirection by a caregiver at the bedside

distracts the patient from pulling out a parenteral

line or catheter. It is useful to remind the patient of

the time, and placement of a clock, calendar, and

family pictures may help with this task. In commu-

nicating with the patient in delirium, it is best to use

clear language, little medical terminology, a tran-

quil voice, and few abstractions.

The environment should be kept at a comfort-

able temperature, with controlled excesses of

noise. A radio or television can be soothing if

tuned into appropriate programming. Lighting

should be adequate during the daytime, and a

nightlight may be helpful. If the patient wears

glasses, hearing aids, or dentures, have them

in place as much as possible to reduce sensory

deﬁcits and possible misperceptions. Both over-

and understimulation should be avoided.

A nonpharmacologic approach to improving

sleep in patients with insomnia may improve

delirium. Use of warm drinks (noncaffeinated

tea or milk), soothing music, and back massage

have been used. Hospital or nursing home

noises and interruptions should be minimized

during the night to prevent waking patients.

Inadequate hydration was identiﬁed as a

risk factor for delirium in nursing home residents.

Frail elderly patients frequently reduce intake of

nutrition and ﬂuids in response to infection, pain,

or other insult, quickly resulting in dehydration,

given that elderly persons already have lower

total body water compared to younger patients.

Quick attention to providing maintenance ﬂuids

either orally, intravenously, or through hypoder-

moclysis may prevent severe dehydration and

its related morbidity or risk for delirium.

Pharmacologic Management

When nonpharmacologic measures are in place

and steps to address the underlying cause of

delirium are implemented, the patient should be

re-evaluated. If the behaviors associated with

delirium are not problematic, no further therapy

is necessary. However, in some cases agitation

and combative behavior must be managed phar-

macologically to prevent danger to the patient

or others and to allow evaluation and treatment

by the medical team. This should be a small

minority of patients. Pharmacologic measures for

delirium management can be considered chem-

ical restraints when used to control behavior

that is undesirable but innocuous, especially if

administered for extended periods of time.

Review of Evidence Base

Supporting Treatment

Recommendations for Elderly

Patients

Little published data are available to guide the

use of medications in this situation, and no medi-

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348

| Fundamentals of Geriatric Pharmacotherapy

cations have FDA approval for use in delirium.

A systematic review of antipsychotic medica-

tion in older surgical patients concluded that

low-dose haloperidol, risperidone, or olanzapine

administered prophylactically reduced the risk of

delirium, but many of the included studies were

of low quality and high bias.

Small uncontrolled

studies provide limited evidence that low-dose,

short-term use of antipsychotics reduce severity

of an established delirium by 43% to 70%.

Given the lack of strong evidence and risk of

adverse drug effects, antipsychotic agents are

presently recommended only for patients with

hyperactive delirium that poses a risk of harm to

the patient or others. Doses recommended for

elderly patients with delirium are signiﬁcantly

lower than for younger adults, as shown in Table

12-5. In an elderly patient, haloperidol 0.5–

1 mg is the preferred drug and dose, to be used

as needed. Patients should be re-evaluated no

sooner than 30–60 minutes after the dose. The

dose may be repeated after this time until the

patient is manageable or until a maximum of

haloperidol 5 mg is reached. The goal of treat-

ment is not to convert a hyperactive delirium

into the hypoactive form. If longer therapy is

needed, atypical antipsychotic agents should

be considered.

Benzodiazepines have been used as

second-line treatment when antipsychotic agents

were not effective. Again, their use in delirium is

not well studied, and, as CNS depressants, they

may worsen confusion and sedation. Further-

more, benzodiazepines are associated with

increasing incidence of delirium. Lorazepam is

most frequently used, as it is more water-soluble

than other benzodiazepines, has an interme-

diate elimination half-life, and is available in oral,

intramuscular, and intravenous formulations.

P D

Etiology, Epidemiology, and

Clinical Presentation

PD affects approximately 1% of the population

over the age of 60 and 4% to 5% over the age of

85.

45,46

Next to AD, it is the second most common

neurodegenerative disease.

The primary cause of PD is believed to

be the depletion of the dopamine-producing

neurons in the substantia nigra pars compacta.

Symptoms of the disease are believed to become

present when ~80% of these neurons have

Table 12-5. Antipsychotic Agents Used in Delirium with Older Adults

Medication

Initial Recommended

Dose

Maximum

Daily Dose Comments

Aripiprazole 5 mg po 15 mg Case series and reports in young and older

adults

Haloperidol 0.25–0.5 mg po or IV 2–5 mg IV route is off-label and associated with QTc

prolongation

Olanzapine 2.5–5 mg po 10 mg Anticholinergic side effects

Quetiapine 12.5–25 mg po 150 mg Postural hypotension

Risperidone 0.25–0.5 mg po 4 mg EPS with higher doses

Ziprasidone 20 mg IM 100 mg Case reports in young, critically ill patients;

signiﬁcant risk for dose-related QTc

prolongation

EPS, extrapyramidal symptoms; IM, intramuscular; IV, intravenous; po, by mouth.

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12 - Central Nervous System Disorders |

349

been destroyed. The decrease in dopamine is

the primary target of symptomatic treatment, as

currently there is no cure or disease-modifying

therapy available. The disease is slowly progres-

sive, which makes follow-up absolutely neces-

sary.

Clinically, patients with PD present with

one or more of the following motor symptoms:

resting tremor, bradykinesia, stiffness, and

postural instability. Typically, a person presents

asymmetrically, with symptoms being worse or

only present on one side of the body. As the

disease progresses, there is bilateral involve-

ment. There are also many nonmotor compli-

cations of the disease, which may be present

at initial presentation or may occur as the

disease progresses. The nonmotor symptoms

include micrographia, a masked appearance

of the face, anosmia, urinary incontinence,

depression, dementia, orthostatic hypotension,

constipation, sialorrhea, increased sweating

and oily skin, as well as sexual dysfunction.

These nonmotor symptoms will not occur in

all patients, and complaints of these problems

may occur at any point in the disease process.

However, it is important to realize the signiﬁ-

cant impact these nonmotor symptoms have on

quality of life. Patients with PD may even rate

nonmotor symptoms as more bothersome than

the motor symptoms of the disease.

The initial

presentation is no different in an elderly patient

compared to a younger cohort; however, the

reasons attributed to symptom presentation

may be different. The stiffness and slowness

experienced with PD may be attributed to other

disease states in older adults, such as osteoar-

thritis. Elderly patients may present later in the

disease course, as their ability to manipulate

their daily routine may be easier, compared to a

younger individual who may still be employed.

Attributing symptoms of PD to “getting old”

may be another reason elderly patients do

not present as early in the disease course as

younger patients.

KEY POINT:

Elderly patients may

attribute symptoms of PD, such as

slowing of movement and rigidity, to

other disease states or “getting old.”

As the disease progresses,

motor compli-

cations

may arise. These can include wearing off

between doses and dyskinesias, which are invol-

untary, repetitive movements typically seen when

a person with PD is in the “on,” or treated, state.

Dyskinesias occur in approximately 40% of patients

with PD at some point in their disease process.

PD has a signiﬁcant impact on both the lives

of patients affected with PD as well as their care-

givers. People with PD lose their ability to func-

tion independently as the disease progresses,

and early in the disease process they commonly

lose their ﬁne-motor skills. Also, approximately

50% of PD patients will experience depression.

As the disease progresses and functional

deﬁcits increase, so does caregiver strain. The

caregiver’s quality of life is typically impacted

negatively as care demands increase.

Some of

the factors that can increase the risk of nursing

home placement include impairment of func-

tion of the person with PD, decreased ability

to complete activities of daily living (ADL),

dementia, and hallucinations.

Summary of Standard Treatment

The American Academy of Neurology (AAN)

produces guidelines for the initially presenting

patient, as well as the patient experiencing

motor complications, which may occur as the

disease progresses and dopaminergic therapy

is continued.

51,52

The gold standard of symptom-

atic treatment, levodopa/carbidopa, is an avail-

able option for treating the initially presenting

patient (see Table 12-6). However, due to the

risk of dyskinesias seen with long-term use of

levodopa, clinicians will typically elect to delay

starting levodopa in younger patients and utilize

alternative agents as ﬁrst-line therapy unless

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350

| Fundamentals of Geriatric Pharmacotherapy

Table 12-6. Drugs, Common Dosages, and Required Dose Adjustments

Adjustment Required

Drug

Daily Dose

(mg)

Mild-Moderate

Renal

Impairment

Moderate-Severe

Renal

Impairment

Hepatic

Impairment

Levodopa 200–1,000+ No No No

Carbidopa 25–75 No No No

Amantadine 200–400 Ye

s Yes No

Dopamine Agonists

Bromocriptine 15–90 No No Use with caution

Pramipexole IR 1.5–4.5 Yes Yes No

Pramipexole CR 1.5–4.5 Yes Yes No

Ropinirole IR 1.5–24 No Use with caution

Use with caution

Ropinirole CR 2–24 No Use with caution

Use with caution

Rotigotine 2–8 No No No

Apomorphine 3–6 Yes Use with caution

Use with caution

COMT Inhibitors

Entacapone 400–1600 No No Use with caution

Tolcapone 300–600 No Use with caution Do not use

MAO-B Inhibitors

Selegiline 5–10 No No No

Selegiline ODT 1.25–2.5 No No No

Rasagiline 0.5–1 No Use with caution Yes

Anticholinergics

Benztropine 0.5–4 No No No

Trihexyphenidyl 1–6 No No No

COMT, catechol-O-methyltransferase; MAO, monoamine oxidase.

Not studied in this speciﬁc subset of patients.

See reference 128 for additional information.

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12 - Central Nervous System Disorders |

351

symptoms of PD are overly bothersome and

impact quality of life. Other initial options avail-

able for the patient with mildly bothersome

symptoms include the monoamine oxidase type

B inhibitors, selegiline and rasagiline, as well the

dopamine agonists bromocriptine, pramipexole,

ropinirole,

and rotigotine.

Selegiline has been

shown to decrease the rate of decline in motor

scores of the United Parkinson’s Disease Rating

Scale,

51,53,54

and rasagiline has shown improve-

ment of the ADL and motor subscales.

Dopa-

mine agonists are typically not the ﬁrst choice in

those experiencing PD symptoms that are having

a signiﬁcant impact on function and quality of

life. Practitioners typically employ levodopa/

carbidopa in these patients.

51,56,57

Over time, wearing off and dyskinesias

are seen with long-term use of levodopa/carbi-

dopa. The AAN offers guidance on managing

these complications.

The addition of entaca-

pone or rasagiline are both level A evidence

interventions in those individuals experiencing

wearing off between doses of levodopa/carbi-

dopa. The addition of ropinirole, pramipexole,

or rotigotine is also an option in the patient

experiencing wearing off. It is important to

remember that the dose of levodopa should

be empirically decreased, as add-on therapies

can worsen dyskinesias by increasing the peak

level of levodopa. Apomorphine has level C

evidence for use in wearing off, and is used clini-

cally for episodes of sudden “off” or freezing.

Apomorphine, however, is only appropriate for

as-needed use and should not be used as a

scheduled medication unless freezing is occur-

ring at consistent times. It also requires the

scheduled dosing of an anti-emetic because of

its tendency to cause extreme nausea. Although

not supported by evidence, the practice of

decreasing the dosing interval (increasing the

number of daily doses) is also a viable option for

wearing off. Changing from immediate-release to

sustained-release levodopa/carbidopa for relief

of wearing off is not supported by evidence and

is not clinically effective for this problem.

KEY POINT:

Doses of levodopa/

carbidopa should be empirically

decreased when a dopamine agonist,

catechol-O-methyltransferase inhibitor,

or monoamine oxidase type B inhibitor

is added to a regimen to decrease the

incidence of peak-dose dyskinesias.

Dyskinesias, resulting from levodopa/carbi-

dopa doses, can be extremely bothersome, and

the addition of amantadine has level C evidence

to support its use.

Although evidence is not

available to support the practice, decreasing the

dose of levodopa/carbidopa and decreasing the

dosing interval at the same time is used clinically

to assuage dyskinesias.

Although there is currently no cure for PD,

the search for disease-modifying or “neuro-

protective” interventions draws much research

interest. The DATATOP trial with selegiline

and

the ADAGIO trial with rasagiline failed to show

a disease-modifying beneﬁt of those drugs.

58,59

The use of coenzyme Q10 has shown mixed

results in several small trials, and a meta-analysis

suggested amitriptyline may have the poten-

tial for disease modiﬁcation

; however, nothing

deﬁnitive has emerged. Obviously, the use of a

tricyclic antidepressant is not a good choice in

any elderly patient regardless of indication.

Review of Evidence Supporting

Treatment Recommendations in the

Elderly

On initial presentation, the clinician treating the

elderly patient is faced with the challenge of

balancing good symptom control and improved

quality of life with the side effect burden of

currently available treatment options. The clini-

cian must also ensure drug interactions are

avoided and make certain to not exacerbate

other disease states with the therapy. These

tenets continue to be important as the disease

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352

| Fundamentals of Geriatric Pharmacotherapy

progresses and motor complications develop

as well as when electing to treat the nonmotor

symptoms responsive to drug therapy.

The AAN does not currently have a guide-

line for speciﬁcally treating the elderly patient

with PD. However, keeping the patient’s concom-

itant diseases and agent characteristics in mind

will help circumvent major problems in treatment.

Because of the increased incidence of the

disease with age, virtually all clinical trials of

agents for the treatment of PD have no maximum

age at which individuals are excluded. However,

most trials of agents include the common, broad-

and loosely-deﬁned exclusion criteria of individ-

uals with severe systemic disease, dementia,

depression, or other psychiatric illnesses. This

prevents the inclusion of a more aged cohort into

these trials, and the typical average age seen is

between 60 and 65.

Currently, there are no clinical trials that

speciﬁcally target the safety and efﬁcacy of

agents for elderly PD patients in a randomized

fashion. A retrospective analysis of the dopa-

mine agonists in a small cohort of patients 80

and older showed >50% of patients were unable

to tolerate dopamine agonists or did not demon-

strate efﬁcacy with the use of the agents.

Hallu-

cinations were seen in 21% and 25% of patients

receiving pramipexole and ropinirole, respec-

tively. Orthostasis was also seen in 5% to 6% of

patients receiving a nonergot alkaloid dopamine

agonist. A retrospective analysis of rotigotine

trials showed those 75 and older with early PD

were more likely to experience nausea and dizzi-

ness compared to those under age 75.

And,

in the same analysis, those with advanced PD

aged 75 and older were more likely to experi-

ence nausea and falls compared to the under-75

cohort. A few post hoc analyses of rasagiline

showed those older than 70 were no more likely

to experience adverse effects with the drug

compared to younger patients and experienced

similar efﬁcacy.

63,64

Common Problems Encountered

in the Senior Population with

Parkinson Disease

Agent-Related

Levodopa/carbidopa will likely become part of

any PD regimen at some point during the disease

course, and in geriatric individuals many times

will be the starting point of therapy. Individuals

taking levodopa/carbidopa typically commence

with three times daily dosing. However, as the

disease progresses this dosing interval typically

decreases, with some patients taking greater

than eight doses of levodopa/carbidopa per

day. This can be difﬁcult for patients to manage,

especially in those with other concomitant

disease states for which medications are taken.

The ability to adhere to such a regimen should

always be considered. Levodopa/carbidopa

is also a medication for which timely medica-

tion administration is important, and for those

patients residing in long-term care facilities,

where dosing schedules are fairly rigid, this can

prove difﬁcult. A small study of patients with

PD in a nursing home noted patients were very

likely to spend a high proportion of their day in

the “off” state and have signiﬁcant motor impair-

ment.

Dietary considerations with levodopa/

carbidopa also make it a difﬁcult medication to

administer. Preferably, it should be taken on an

empty stomach, and dietary protein should be

avoided close to medication administration. This

is because of the body’s preferred uptake of

dietary protein when exposed to levodopa/carbi-

dopa, which can result in a decreased blood

level as well as a delay in “on.” However, as the

disease progresses and levodopa is taken more

often, this is made much more difﬁcult; there-

fore, an appropriate patient counseling point for

people with PD would be to keep protein intake

as consistent as possible and to adjust levodopa

doses as needed to account for the patient’s

protein intake.

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12 - Central Nervous System Disorders |

353

The dopamine agonists are still considered

by many to be ﬁrst-line therapy to delay use

of levodopa/carbidopa. However, the elderly

patient is more likely to experience the halluci

nations and confusion that can be seen with the

dopamine

agonists.

In 2009, the Positive Beers

criteria, which suggest potentially beneﬁcial

medications in certain contexts, noted a prefer

ence for the use of ropinirole in the elderly (in

addition to stating a preference for levodopa and

entacapone), although this recommendation was

not supported by evidence.

Sleep attacks, the

experience of suddenly and unexpectedly falling

asleep, are a problem with increasing dopamine

by any means but are seen with increased inci

dence in those receiving dopamine agonists.

Case r

eports of repetitive, compulsive behaviors,

such as gambling, eating, drinking, and sexual

behaviors, are becoming more common. And

although the elderly are not speciﬁcally more

prone to these behaviors when compared to a

younger cohort, this has become an important

counseling point for patients and caregivers.

Ropinirole immediate release and controlled

release and pramipexole immediate release are

currently available as nonbranded products. Roti

gotine patch offers a novel drug-delivery mecha-

nism for patients with PD in a patch applied once

daily to the skin. This can beneﬁt patients with

the swallowing difﬁculties seen in PD. However,

those 75 and older account for <10% of enrolled

individuals, and it is unknown how the skin

changes that occur with aging affect the efﬁcacy

of this product. A dopamine agonist withdrawal

syndrome has been described in the literature,

and while elderly patients are not necessarily at

increased risk, it is important to note this potential

adverse effect in those whose dopamine agonist

is being decreased or discontinued.

The monoamine oxidase type B inhibitor,

selegiline, has an amphetamine-like metabo-

lite, which can be a problem in a person with

concomitant hypertension or cardiovascular

disease. This metabolite may decrease appetite

and, therefore, has the potential to cause weight

loss. Insomnia is also believed to be a side effect

of selegiline, and typically the last dose of the

day is given no later than noon. Rasagiline is

without an amphetamine-like metabolite and

could potentially be a less bothersome agent. A

small subgroup analysis showed no age-related

effect on experiencing an adverse event with the

use of rasagiline.

The drug interaction proﬁle

of the monoamine oxidase inhibitors is quite

extensive, making their use in the elderly difﬁ-

cult, given the extensive polypharmacy seen

within the population. Rasagiline trials, however,

included participants on a number of drugs and

drug classes stated to be contraindicated within

the package insert. Fluoxetine and ﬂuvoxamine,

however, were not used likely because of their

long half-lives. Clinically, PD patients can use

concomitant SSRIs typically without incident.

However, close monitoring of blood pressure,

speciﬁcally, and other symptoms of serotonin

syndrome is warranted if monoamine oxidase

type B inhibitors are used concomitantly.

KEY POINT: Concomitant use of

rasagiline with SSRIs is common, and

selected SSRIs have been used in

combination with rasagiline in clinical

trials. However, close monitoring of blood

pressure and other symptoms of serotonin

syndrome is extremely important in the

rst few weeks of concomitant therapy.

The catechol-O-methyltransferase (COMT)

inhibitor, tolcapone, has signiﬁcant monitoring

associated with its use because of reports of

hepatotoxicity and is, therefore, rarely used

clinically. Entacapone is typically well tolerated

overall and is available in a combination tablet

with levodopa/carbidopa for ease of dosing.

The cost of the combination product is typi-

cally similar to buying each agent separately;

however, this ﬁxed dose combination does not

allow for easy tailoring of levodopa doses. There

has been concern raised regarding an increased

risk of MI with entacapone

; however, there is

also evidence of no increased risk.

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354

| Fundamentals of Geriatric Pharmacotherapy

The anticholinergics, benztropine and

trihexyphenidyl, are typically used for treating

bothersome tremor. However, these agents are

a poor choice in an elderly patient because of

their cadre of side effects, including constipa-

tion, urinary retention, dry mucous membranes,

tachycardia, and, most disturbing in an elderly

patient, confusion. Because of their risk-beneﬁt

ratio, these agents are included on the Beers

criteria.

Another agent with anticholinergic

activity, in addition to its other effects, is aman-

tadine. It is used most often to treat dyskinesias

and has an increased risk of CNS side effects

in the elderly patient, such as confusion and

psychosis.

72,73

Of particular note for the elderly

patient, amantadine requires dose adjustment

for renal impairment.

Apomorphine, an agent available for relief of

freezing episodes, is a subcutaneously delivered

dopamine agonist. The most distressing side

effect of this medication is the extreme hypo-

tension that can be seen shortly after a dose is

given. The manufacturer requires the ﬁrst dose

to be given in the care provider’s ofﬁce or under

their care. This hypotension can increase the risk

of falls and subsequent fracture. The agent can

also cause nausea and vomiting, which typically

requires scheduled dosing with an antiemetic

such as trimethobenzamide. However, the 5HT3

receptor antagonists (e.g., ondansetron) are

absolutely contraindicated due to the risk of

additive hypotension.

Disease-Related

Autonomic dysfunction is a common occur-

rence in PD, manifesting as one or more of the

following: constipation, urge urinary inconti-

nence, orthostatic hypotension, sexual dysfunc-

tion, seborrheic dermatitis, profuse sweating,

sialorrhea, and thermal dysregulation. Although

no clinical trials exist to address these autonomic

abnormalities in the elderly with PD speciﬁcally,

general treatment principles outlined elsewhere

in this text are prudent management. Avoidance

of medications that may exacerbate these condi-

tions is especially important, when practical. An

interesting clinical dilemma is the patient with

orthostatic hypotension and concomitant hyper-

tension. Usually, these individuals are on anti-

hypertensive medications, as their blood pres-

sures can be signiﬁcantly elevated when in the

supine position. If the patient can safely be taken

off the antihypertensive, every effort should be

made to do so. However, if this is not possible,

the addition of ﬂudrocortisone or midodrine may

help. The patient should be educated to avoid

lying in the supine position when one of these

medications is given in order to avoid extremely

high blood pressure.

PD may cause drowsiness or lethargy,

and many of the medications used to treat the

symptoms of PD may cause drowsiness. While

the AAN practice parameter supports the use of

modaﬁnil in this instance, its use in the elderly,

especially those with concomitant cardiovas-

cular disease, is questionable.

Sleep patterns

are often disrupted in PD. Insomnia may also

occur as a result of uncontrolled PD symp-

toms or restless legs syndrome, a concomi-

tant syndrome with PD. Often, maximizing PD

therapy around bedtime can ameliorate this,

as well as education on proper sleep hygiene.

Chapter 13 provides information on treatment of

insomnia that can be applied to patients with PD.

Anosmia or hyposmia can be a presenting

symptom of the disease. This inability to smell,

and thereby taste, is especially concerning in

elders who have stopped eating or decreased

eating because they are no longer able to taste,

and thereby enjoy, their food. This can lead to

weight loss, which in a nursing home resident is

monitored closely but is a concern in any senior

individual.

Depression, dementia, and psychosis occur

in the PD population with increased frequency

over age-matched counterparts. Although the

disease process can be implicated in these

psychiatric nonmotor complications, medica-

tions must always be reviewed to ascertain

whether these psychiatric manifestations may

be an untoward side effect. Depression can

be seen in approximately 50% of patients with

PD at some point in their disease course, and

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12 - Central Nervous System Disorders |

355

although there is no speciﬁc literature existing

for the elderly with PD, SSRIs are typically

employed in clinical practice with good results.

The Movement Disorder Society makes mention

that there is evidence to support the antidepres-

sant effect of pramipexole, and that the tricy-

clic antidepressants (TCAs) nortriptyline and

desipramine are “likely efﬁcacious.”

However,

multiple trials assessing the efﬁcacy of SSRIs

in patients with PD and depression have noted

efﬁcacy and present a safer alternative to the

TCAs. Dementia in PD is also experienced with

increased frequency as the disease progresses.

The CIs rivastigmine and donepezil both have

level B evidence to support their use in dementia

associated with PD; however, rivastigmine is the

only FDA-approved product for this indication.

Psychosis, typically resulting from medica-

tions, is especially burdensome and is a common

reason for nursing home placement.

Hence,

dopamine agonists are used cautiously in the

elderly with PD. When symptoms are controlled

on a PD medication regimen and psychosis is

experienced, the clinician may elect to treat

the psychosis, rather than change the regimen.

The atypical antipsychotics quetiapine and

clozapine are the ﬁrst- and second-line agents,

respectively, for treating this side effect.

77,78

And

whereas the dopamine antagonism of the anti-

psychotic medications as a class would seem

to contribute to disease exacerbation, these two

agents do not. When quetiapine is not effec-

tive, or side effects to this agent prevent its use,

clozapine is employed. However, the agranu-

locytosis seen with this agent requires signiﬁ-

cant monitoring, which can be burdensome to

patients, caregivers, and providers.

KEY POINT:

Quetiapine and

clozapine are appropriate choices for

the treatment of psychosis that may be

experienced secondary to PD therapies,

as they decrease psychotic symptoms

yet do not exacerbate PD symptoms.

Slowness of movement is not limited to the

extremities, and many patients with PD experi-

ence slowing of the GI tract, which may mani-

fest as swallowing difﬁculties, delayed gastric

emptying, and constipation. Swallowing difﬁcul-

ties in PD must always be at the forefront of any

care plan for the elderly. This includes both the

therapies used to treat PD as well as other disease

states. Crushing medications to help with admin-

istration is common when swallowing problems

occur. However, it is prudent to consider a medi-

cation regimen review when crushing medica-

tions is employed, as long-acting or enteric-

coated formulations may need to be changed.

Non-oral routes may also be considered when

swallowing becomes difﬁcult. With regard to

constipation, the product containing polyeth-

ylene glycol 3350 has evidence of beneﬁt in PD

but must be used on a scheduled basis to have

an effect.

S

Etiology, Epidemiology, and

Clinical Presentation of Seizures

A seizure is an abnormal electrical activity in the

brain manifesting with or without convulsions.

Elderly patients may experience a single seizure

as a result of electrolyte abnormalities or other

acute illness. Epilepsy is a disease manifested

by multiple seizures. Status epilepticus is typi-

cally deﬁned as continuous seizure activity of 30

minutes or more, or multiple seizures without full

recovery of consciousness between seizures.

Cerebrovascular disease is the most

common cause of new-onset seizures in seniors,

with poststroke seizures accounting for ~55% of

new-onset seizures in this population.

Those

who experience a stroke in the cortical region

of the brain are more likely to have seizures

than those with a stroke in subcortical regions.

Brain tumors, trauma, and dementias are other

causes of new-onset seizures in this popula-

tion.

81,82

Iatrogenic causes must always be ruled

https://t.me/medicina_free

356

| Fundamentals of Geriatric Pharmacotherapy

out, with offending agents removed as quickly as

possible. Status epilepticus occurs at a higher

incidence in the elderly, with almost twice the

incidence of the general population, and a much

higher mortality rate.

79,83,84

Status epilepticus that

occurs along with an ischemic stroke has been

shown to increase the risk of mortality by three

times compared to ischemic stroke alone.

Seizures typically fall into one of two catego-

ries, partial or generalized.

86,87

Partial seizures

start in one hemisphere of the brain and mani-

fest as unilateral motor symptoms. If conscious-

ness is not lost, these are deemed simple partial

seizures; however, with loss of conscious-

ness, these are categorized as complex partial

seizures. Generalized seizures involve both

hemispheres of the brain and manifest as bilateral

motor involvement. The tonic-clonic seizure is an

example of a generalized seizure. If a seizure

starts as a partial seizure, but becomes gener-

alized, these seizures are deemed secondary

generalized and are typically treated as partial

seizures. Generalized absence seizures are typi-

cally manifested without motor symptoms but

with a sudden “interruption of ongoing activities,

a blank stare and possibly a brief upward rota-

tion of the eyes.”

In general, absence seizures

occur in a much younger population and will not

be addressed in this chapter.

The clinical presentation of seizures in

the elderly may differ from the presentation

in younger people. For instance, seniors are

less likely to have auras associated with their

seizures.

Seizures in a senior population may

also be confused with an acute confused state,

or syncope, which makes the diagnosis of a

seizure in an elderly person quite difﬁcult.

Generalized seizures are also less common in

the elderly than in a younger group, and partial

seizures are much more common.

89,90

Although

clinical presentation may be different, seizures

can have a signiﬁcant impact on quality of life

in the elderly, just as they do in younger people

with seizures.

KEY POINT:

e acetylcholinesterase

inhibitors and memantine have the

potential to decrease seizure threshold

and should be used with caution in those

with a prior history of seizure disorder.

Summary of Standard Treatment

The goal of any treatment for epilepsy is to acutely

stop the clinical and electrical seizure activity

and to prevent future seizures. A single seizure

may not require chronic therapy, especially if

an underlying illness is corrected. Although a

common primary endpoint of seizure medication

trials is a decrease in seizure frequency by 50%,

the goal number of seizures in an individual is

always zero. Minimizing side effects, maximizing

quality of life, and retaining independence and

conﬁdence are goals of treatment in all patients.

Standard treatment of seizures depends on

the type of seizure being treated. Status epilep-

ticus typically is treated with an intravenous

benzodiazepine ﬁrst-line, followed by either intra-

venous phenytoin or intravenous fosphenytoin.

Table 12-7 identiﬁes the agents recom-

mended for monotherapy of newly diagnosed

epilepsy, for refractory epilepsy, and as add-on

therapy by AAN and the American Epilepsy

Society.

92,93

Initial choice of an agent should be

individualized, and all agents listed have efﬁcacy

data to support their use. However, the Interna-

tional League Against Epilepsy (ILAE) evidence

review notes level A evidence for carbamaze-

pine, levetiracetam, phenytoin, and zonisamide

as initial monotherapy in partial-onset seizures in

adults.

Forty to ﬁfty percent of adults who are

refractory to the ﬁrst antiepileptic drug (AED) they

are given will have adequate seizure control on

another AED as monotherapy.

However, if two

agents as monotherapy at maximum dosages

are ineffective, adjunctive therapy should be

considered.

Valproate is the supported treat-

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