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II. Formulation and Implementation
of a Treatment Plan
The treatment of Alzheimer's disease and related
dementias is inherently multidisciplinary and multimodal. It is guided
by the stage of illness and is focused on the specific symptoms
manifested by the patient. This discussion begins with general principles
of psychiatric management, essential to the treatment of the patient
with dementia, and then reviews specific treatments. These treatments
include the broad range of psychosocial interventions used in dementia as
well as the pharmacological options, which are organized in the
discussion by target symptom.
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A. Determining the Site of Treatment
and Frequency of Visits
Choice of specific treatments for a patient with dementia begins
with the establishment of a specific diagnosis and an assessment
of the symptoms being experienced by that patient. A multimodal
approach is often used, combining, for instance, behavioral and
psychopharmacological interventions as available and appropriate.
When multiple agents or approaches are being used and problems persist
(or new problems develop), it is advisable, if possible, to make
one change at a time so that the effect of each change can be assessed.
The continuing utility of all interventions must be regularly reevaluated.
The site of treatment for an individual with dementia is determined
by the need to provide safe and effective treatment in the least
restrictive setting. Approximately two-thirds of patients with dementia
live at home and receive care on an outpatient basis. The frequency
of office or facility visits is determined by a number of factors,
including the patient's clinical status, the likely rate
of change, and the need for specific monitoring of treatment effects.
Another factor is the reliability and skill of the patient's
caregivers, particularly regarding the likelihood of their notifying
the clinician if a clinically important change occurs. Most dementias
are progressive, and symptoms change over time. Therefore, in order
to offer prompt treatment, enhance safety, and provide timely advice
to the patient and family, it is generally necessary to see patients,
usually together with their caregivers, at regular follow-up visits.
Patients who are clinically stable or are taking stable doses of
medications should generally be seen at a minimum of every 3–6
months. Patients who require active treatment of psychiatric complications
should be seen regularly to adjust doses and monitor for changes
in target symptoms and side effects. Similarly, attempts to taper
or discontinue psychotropic medications require more frequent assessments
than are required for routine care. Weekly or monthly visits are
likely to be required for patients with complex, distressing, or
potentially dangerous symptoms or during the administration of specific
therapies. For example, outpatients with acute exacerbations of
depressive, psychotic, or behavioral symptoms may need to be seen
as frequently as once or twice a week, sometimes in collaboration with
other treating clinicians, or be referred to intensive outpatient
treatment or a partial hospitalization program.
Individuals with dementia may need to be admitted to an inpatient
facility for the treatment of psychotic, affective, or behavioral
symptoms. In addition, they may need to be admitted for treatment
of general medical conditions co-occurring with psychiatric conditions.
For patients who are very frail or who have significant general
medical illnesses, a geriatric psychiatry or medical psychiatric
unit may be helpful when available (1). Indications
for hospitalization include symptom severity (e.g., significant
threats of harm to self or others, violent or uncontrollable behavior,
inability to care for self or be cared for by others) and intensity
and availability of services needed (e.g., the need for continuous
skilled observation, electroconvulsive therapy, or a medication
or diagnostic test that cannot be performed on an outpatient basis)
(2, 3). The length of stay is similarly
determined by the ability of the patient to safely receive the appropriate
care in a less restrictive setting.
Decisions regarding the need for temporary or permanent placement
in a long-term-care facility often depend on the degree to which
the patient's needs can be met in the community, either
by relatives or other caregivers, either in an assisted living facility
or at home. The decision to remain at home should be reassessed
regularly, with consideration of the patient's clinical
status and the continued ability of the patient's caregivers
to care for the patient, manage the burden of care, and utilize
available support services. The appropriate level of care may change
over time, and patients often move from one level of care to another
during the course of dementia. If available, consultation with a
social worker or geriatric case manager may be beneficial to assess
the current support system and facilitate referrals to additional
services. At the end of life, many patients with dementia are cared
for in a hospice program.
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B. Psychiatric Management
Successful management of patients with dementia requires the
concurrent implementation of a broad range of tasks, which are grouped
under the term "psychiatric management." These
tasks help to maximize the patient's level of function
and enhance the safety and comfort of patients and their families
in the context of living with a difficult disease. In some settings,
psychiatrists perform all or most of these tasks themselves. In
others, they are part of multidisciplinary or interdisciplinary
teams. In either case, they must be aware of the full range of available
treatments and take steps to ensure that any necessary treatments
are administered. Good communication between the patient's
psychiatrist and primary care physician ensures maximum coordination
of care, may minimize polypharmacy, and may improve patient outcomes
(4).
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1. Establish and Maintain an Alliance
With the Patient and the Family
As with any psychiatric care, a solid therapeutic alliance is
critical to the treatment of a patient with dementia. The care of
a patient with dementia requires an alliance with the patient, as
well as with the family and other caregivers. Family members and
other caregivers are a critical source of information, as the patient
is frequently unable to give a reliable history, particularly as
the disease progresses. Because family members are often responsible
for implementing and monitoring treatment plans, their own attitudes
and behaviors can have a profound effect on the patient, and they
often need the treating physician's compassion and concern.
For these reasons, treatment is directed to the patient-caregiver system.
The needs of caregivers will vary based on factors such as their
relationship to the patient, their long-standing role in the family,
and their current customs. Clinical judgment is needed to determine
the circumstances in which it is appropriate or necessary to speak
with caregivers without the patient present, as well as how to proceed
with clinical care when there are disputes among family members.
A clear process for medical decision making should be delineated
for each patient, and a capacity assessment of the patient should be
performed when necessary.
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2. Perform a Diagnostic Evaluation
and Refer the Patient for Any Needed General Medical Care
Patients with dementia should undergo a thorough diagnostic
evaluation aimed at identifying the specific etiology of the dementia
syndrome, because knowledge of the etiology may guide specific treatment
decisions. In addition, the evaluation should determine if any treatable
psychiatric or general medical conditions (e.g., major depression,
thyroid disease, vitamin B12 deficiency,
hydrocephalus, structural brain lesion) might be causing or exacerbating
the dementia. The details of this evaluation are beyond the scope
of this guideline; the reader is referred to the American Academy
of Neurology practice parameter on the diagnosis of dementia (5),
the American Academy of Neurology practice parameter on early detection
of dementia and mild cognitive impairment (6), and
the Agency for Health Care Policy and Research clinical practice
guideline Recognition and Initial Assessment of
Alzheimer's Disease and Related Dementias (7)
for more complete descriptions of the evaluation of patients with
dementia. A brief summary follows.
The general principles of a complete psychiatric evaluation
are outlined in APA's Practice Guideline
for the Psychiatric Evaluation of Adults (8).
The evaluation of a patient with dementia frequently involves coordination
with a number of medical professionals, including the patient's
primary care physician (4). The physician with overall
responsibility for the care of the patient oversees the evaluation,
which should at a minimum include a clear history of the onset and
progression of symptoms; a review of the patient's medical
problems and medications (including over-the-counter and herbal
medications); assessment of functional abilities; a complete physical examination
and a focused neurological examination; and a psychiatric examination,
including a cognitive assessment that should include at least a
brief assessment of the cognitive domains of attention, memory,
language, and visuospatial skills, ideally used with age- and education-adjusted
norms (9, 10). An assessment for past
or current psychiatric illnesses that might mimic or exacerbate
dementia, such as schizophrenia or major depression, is also critical,
as are laboratory studies, including a complete blood count (CBC),
blood chemistry battery (including glucose, electrolytes, calcium, and
kidney and liver function tests), measurement of vitamin B12 level,
and thyroid function tests. For some patients, toxicology studies,
syphilis serology, erythrocyte sedimentation rate, HIV testing,
serum homocysteine, a lumbar puncture, or an electroencephalogram
may also be indicated. In general, many elements of the history
will need to be obtained from the caregiver or the documented medical
record as well as from the patient. Often, it may be necessary to
conduct a portion of the interview with the caregiver without the
patient present, in order to allow for full disclosure of sensitive
information.
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b. Neuropsychological Testing
Neuropsychological testing may be helpful in a number of ways.
It may help in deciding whether a patient with subtle or atypical
symptoms actually has dementia as well as in more thoroughly characterizing
an unusual symptom picture. It is particularly useful in the evaluation
of individuals who present with mild cognitive impairment (see Section
IV.F.2), which requires evidence of memory and/or
other cognitive difficulties in the presence of intact functioning,
and in the evaluation of individuals with the onset of dementia
early in life. Testing may help to characterize the extent of cognitive
impairment, to distinguish among the types of dementias, and to
establish baseline cognitive function. Neuropsychological testing
may also help identify strengths and weaknesses that could guide
expectations for the patient, direct interventions to improve overall
function, assist with communication, and inform capacity determinations.
The use of a structural neuroimaging study, such as computerized
tomography or magnetic resonance imaging (MRI) scan, is generally
recommended as part of an initial evaluation, although clinical
practice varies. Imaging is particularly important for those with
a subacute onset (less than 1 year), symptom onset before age 65,
vascular risk factors suggesting a higher likelihood of cerebrovascular
involvement in their dementia, or a history or neurological examination
findings suggesting a possible focal lesion. Nonetheless, clinically
important lesions may be found on neuroimaging in the absence of
these indications (11). The value of imaging in patients
with late-stage disease who have not been previously evaluated has
not been established. Functional neuroimaging using brain positron
emission tomography (PET) scans may contribute to diagnostic specificity
in certain instances and has been recently approved by Medicare
for the indication of differentiating between Alzheimer's
disease and frontotemporal dementia.
The development of additional imaging tools for improved diagnosis,
early recognition, and more precise assessment of disease progression
is a focus of current study. These additional tools include quantitative
MRI, functional MRI, use of investigational PET compounds, and other
methods aimed at imaging senile plaques in the brain (12, 13).
A wide variety of biomarkers are also under investigation with
the goal of enhancing diagnostic and prognostic knowledge (14).
Biomarkers of current interest include proteins such as tau and
amyloid beta protein in the cerebrospinal fluid (CSF) and plasma.
Except in rare circumstances (notably the use of CSF-14-3-3 protein
when Creutzfeldt-Jakob disease is suspected and recent stroke or
viral encephalitis can be excluded) (5, 15),
these techniques remain investigational, and there is insufficient
evidence for their utility in routine clinical practice. However,
this area is evolving rapidly, so recommendations may change with
new discoveries and the development of new markers and/or
therapies.
Although genes involved in a variety of dementia syndromes
have been identified (16), and family members of patients
with dementia are often concerned about their risk of developing
dementia, genetic testing is generally not part of the evaluation
of patients with dementia except in very specific instances (5).
In particular, testing for apolipoprotein E4 (APOE4)
is not recommended for use in diagnosis. Apolipoprotein E4 is one
form of a gene on chromosome 19 that is more common in individuals
with Alzheimer's disease than in elderly individuals without
dementia and is associated with late-onset Alzheimer's
disease occurring with or without a family history (17–19).
However, it is also found in many elderly patients who do not have
dementia and is not found in many patients who do have Alzheimer's
disease. Thus, the presence of an APOE4 allele
does not change the need for a thorough workup and does not add
substantially to diagnostic confidence (5, 20–22).
First-degree relatives of patients with Alzheimer's
disease have a risk of developing the disease that is two to four
times that of the general population. Three genes associated with the
disease have been identified in families with apparent autosomal
dominant inheritance of early-onset Alzheimer's disease.
These genes include the amyloid precursor protein (APP)
gene on chromosome 21 (23), presenilin 1 (PSEN1)
on chromosome 14 (24), and presenilin 2 (PSEN2)
on chromosome 1 (25). Genetic testing is commercially
available for PSEN1, which is likely
to be found in families with apparent autosomal dominant inheritance
and dementia developing before age 50 years. Testing for the other
two genes is not commercially available but can sometimes be performed
in the context of clinical genetics research. However, the role
of such testing in clinical practice has not yet been established. Because
no preventive treatments are currently available, testing should
only be offered in the setting of thorough pre- and posttest counseling
(26). In addition, genetic testing is best done in
conjunction with experts familiar with Alzheimer's disease
genetics, as test results require careful interpretation. A referral
to a local Alzheimer's Disease Research Center or the local
chapter of the Alzheimer's Association may be helpful in
locating someone who can provide the appropriate counseling and testing.
If specific Alzheimer's genetics resources are not available
locally, a referral to a professional genetic counselor or clinical
geneticist may help such families characterize their risk and find
appropriate resources (27, 28).
Genetic counseling and sometimes genetic testing may also
be appropriate for some patients with other dementias and a family
history of similar syndromes. In particular, individuals with a
clinical picture suggestive of frontotemporal dementia and a family
history suggesting autosomal dominant inheritance can be tested
for certain mutations (29, 30). Likewise,
individuals with a clinical picture suggestive of Huntington's
disease can be tested for the gene defect (31), and
those suspected of having CADASIL (cerebral autosomal dominant arteriopathy
with subcortical infarcts and leukoencephalopathy) can be tested
for associated Notch 3 gene polymorphisms
(32).
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3. Assess and Monitor Psychiatric
Status
Ninety percent of patients with dementia develop a neuropsychiatric
or behavioral symptom during the course of the disease (33).
It is therefore important for the psychiatrist to periodically assess
the patient for the presence of noncognitive psychiatric symptoms
as well as for the progression of cognitive symptoms.
Both cognitive and noncognitive neuropsychiatric and behavioral
symptoms of dementia tend to evolve over time, so regular monitoring
allows detection of new symptoms and adaptation of treatment strategies
to current needs. For example, among the neuropsychiatric disturbances
common in Alzheimer's disease, depression is reported more
commonly early in the illness, whereas delusions and hallucinations
are more common in the middle and later stages, although any of these
symptoms may occur at any stage of the disease (33, 34).
It is particularly important to look for the emergence of such symptoms
after a medication dose has been lowered or discontinued. Among
the cognitive deficits, memory loss is commonly the earliest symptom,
whereas language and spatial dysfunction become more overt somewhat
later.
Among the neuropsychiatric symptoms that require ongoing assessment
are depression (including major depression and other depressive
syndromes), suicidal ideation or behavior, hallucinations, delusions,
agitation, aggressive behavior, disinhibition, sexually inappropriate
behavior, anxiety, apathy, and disturbances of appetite and sleep.
Cognitive symptoms that almost always require assessment include
impairments in memory, executive function, language, judgment, and
spatial abilities. It is often helpful to track cognitive status
with a structured simple examination. If the same instrument is
used repeatedly, the clinician should watch for practice effects.
A detailed assessment of functional status may also aid the clinician
in documenting and tracking changes over time as well as providing
guidance to the patient and caregivers. Functional status is typically
described in terms of the patient's ability to perform
instrumental activities of daily living such as shopping, writing
checks, basic housework, and activities of daily living such as
dressing, bathing, feeding, transferring, and maintaining continence.
These regular assessments of recent cognitive and functional status provide
a baseline for assessing the effect of any intervention, and they
improve the recognition and treatment of acute problems, such as
delirium.
Whenever there is an acute worsening of cognition, functioning,
behavior, mood, or psychosis, the clinician should bear in mind
that elderly persons in general and patients with dementia in particular
are at high risk for delirium associated with medications, general
medical problems, and surgery. Newly developing or acutely worsening
agitation in particular can be a sign of an occult general medical
condition (e.g., urinary tract infection, dehydration), untreated
or undertreated pain, or physical or emotional discomfort. Elderly
patients may not manifest certain typical signs or symptoms such
as fever in the face of infection or pain during a myocardial infarction.
Thus, a thoughtful assessment of the patient's overall
status and a general medical evaluation must precede any intervention
with psychotropic medications or physical restraint, except in an
emergency. Assessments should also include examination of the patient's
sensory function, since sensory deficits can precipitate or worsen psychiatric
and cognitive symptoms and increase the risk that patients will
make medication errors.
Before undertaking an intervention, the psychiatrist should
enlist the help of caregivers in carefully characterizing the target
symptoms. Their nature, intensity, frequency, precipitants, and
consequences should be reviewed and documented. This process is
critical to revealing the cause of the symptoms, as well as monitoring
the impact of any intervention. This approach also assists caregivers
in beginning to achieve some mastery over the problematic symptom.
Before embarking on any intervention, it is also helpful if clinicians
explicitly review their own, the patient's, and the caregivers' expectations.
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4. Monitor and Enhance the Safety
of the Patient and Others
It is important for the psychiatrist treating a patient with dementia
to regularly assess cognitive deficits or behavioral difficulties
that potentially pose a danger to the patient or others. The psychiatrist
should 1) assess suicidality, 2) assess the potential for aggression
and agitation, 3) make recommendations regarding adequate supervision,
for example of medication administration, 4) make recommendations
regarding the prevention of falls and choking, 5) address nutritional
and hygiene issues, and 6) be vigilant regarding neglect or abuse. Patients
who live alone require careful attention. Events that indicate that
the patient can no longer live alone include several falls, repeated
hospitalization, dehydration, malnutrition, repeated errors in taking
prescribed medications, dilapidated living conditions, or other
signs of self-neglect. Other important safety issues in the management
of patients with dementia include interventions to decrease the
hazards of wandering and recommendations concerning activities such as
cooking, driving, hunting, and the operation of hazardous equipment
(see Section II.B.5). Caregivers
should be referred to available books that provide advice and guidance
about maximizing the safety of the environment for patients with
dementia (35).
All patients (and their caregivers) should be asked about the
presence of wishes for death, suicidal ideation, suicide plans,
as well as a history of previous self-injurious behavior. If suicidal
ideation occurs in patients with dementia, it tends to be earlier
in the disease, when insight is more likely to be preserved. It
is a particular concern in patients who are clinically depressed
but can also occur in the absence of major depression. Elderly persons
in general and elderly men in particular are at increased risk for
suicide, although the diagnosis of dementia is not known to confer
added risk. Interventions to address suicidal ideation are similar
to those for patients without dementia and include psychotherapy;
pharmacotherapy; removal of potentially dangerous items such as medications,
guns, or vehicles; increased supervision; and hospitalization. Factors
affecting the choice of intervention include the nature and intensity
of the suicidal ideation or behavior and the capacity and support
system of the patient (36).
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b. Agitation and Aggression
"Agitation" is an umbrella term that refers
to a range of behavioral disturbances, including physical aggression, combativeness,
threatening behavior, persistent or intermittent psychomotor hyperactivity,
and disinhibition. These behaviors pose a particular problem for
patients cared for at home, especially by frail spouses. Agitation
is more likely to occur later in the course of dementia and often
has multiple causes. New or worsened agitation can result from an
occult general medical problem, medication side effects, untreated or
undertreated pain, constipation, depression, psychotic symptoms,
or delirium. Thus, the first priority is a careful medical evaluation,
because the agitation will often resolve with treatment of an underlying
condition. The next step is an assessment of other features of the
patient's overall situation. Hunger or sleep deprivation
can provoke agitation, as can interpersonal or emotional stressors
such as undergoing a change in living situation, caregiver, or roommate
or experiencing frustration, boredom, loneliness, or overstimulation. Consequently,
attending to unmet needs, providing reassurance, redirecting activities,
or matching the level of stimulation to the patient's current
level of activation may resolve the problem (37).
In designing an intervention to treat a problematic behavior,
a structured approach should be taken to facilitate selecting the
optimal treatment and monitoring the effect of that treatment (38–40).
The first step is to carefully describe the target behavior, including
where, when, and how often it occurs. The next step is to assess
the specific antecedents and consequences of each problem behavior,
which will often suggest specific strategies for intervention. Activities
that consistently precede the problem behavior may be acting as
precipitants and should be avoided whenever possible. If the activity
is a necessary one, for example, bathing, it may be helpful to decrease
its frequency or to alter the environment so that the negative consequences
are minimized (e.g., switch bath time to allow a home health aid
to supervise, or change the location of baths to decrease the impact
of aggressive outbursts on family members or other patients). When
multistep activities such as dressing and eating precipitate problem
behaviors such as aggression, it often helps to simplify the activities
(e.g., using clothing with Velcro closures, serving several simple
nutritious snacks instead of a large meal). Whatever the intervention,
it is critical to match the level of demand on the patient with
his or her current capacity, avoiding both infantilization and frustration.
Likewise, behavior may also improve by modifying the environment
insofar as possible to compensate for the patient's deficits
and to capitalize on his or her strengths (41). In
assessing the effectiveness of interventions for problematic behaviors,
clinicians can recommend that caregivers maintain a log of specific
behaviors as well as their intensity, frequency, precipitants, and
consequences.
If the agitation is deemed dangerous to the patient or others,
it is important to undertake further measures to enhance safety.
Such additional measures may include providing one-on-one care,
instituting the behavioral measures discussed in Section
II.C.4, or initiating pharmacological treatment
as discussed in Section II.C.5.
If agitation and aggressive behavior cannot be brought under control,
hospitalization and/or nursing home placement must be considered.
Within hospital or nursing home settings, physical restraints
(e.g., Posey restraints, geri-chairs) are sometimes used to treat
agitation or combativeness that puts the patient or others at risk.
Nonetheless, principles of humane care as well as federal regulations
support minimizing restraint use as much as possible. In addition,
some evidence suggests that restraints may increase the risk of
falls and contribute to cognitive decline (42, 43)
and that reducing restraint use can decrease the rate of serious
injuries among nursing home residents (44).
Decisions regarding supervision of the patient should take into
consideration the patient's cognitive deficits, the home environment,
and the consequent risk of dangerous activities. For instance, a
patient with significant cognitive impairment may not be safe alone
at home because he or she might improperly administer medications,
be unable to cope with a household emergency, or use the stove,
power tools, or other equipment in a dangerous manner. Home occupational
therapy functional and safety assessments, as well as other community-based
services, may be helpful in determining whether increased supervision
is needed.
Psychiatrists caring for patients with dementia should be aware
that falls are a common and potentially serious problem for all
elderly individuals, especially those with dementia. Falls can lead
to hip fracture, head trauma, and a variety of other injuries, including
subdural hematomas, which may further worsen cognitive function.
A number of interventions to prevent falls in elderly people have
been shown to be effective (45). One of the most efficacious
is withdrawing medications that are associated with falls, central
nervous system sedation, or cardiovascular side effects (especially
orthostatic hypotension), when appropriate. If gait disturbances
are present, canes, walkers, or other supports may be helpful unless
they are otherwise contraindicated (e.g., if their use poses a hazard
to others). Patients at high risk for falling may need to be closely
supervised while walking.
Environmental modifications can also help reduce the risk of
falls. The removal of loose rugs, low tables, and other obstacles
can diminish risk. The use of lower beds, night-lights, bedside
commodes, and/or frequent toileting may help prevent falls
at night. Although bed rails are thought to prevent patients from
rolling out of bed, they may actually increase the risk of falls.
Therefore, other environmental modifications such as lowering the
bed or placing a mattress on the floor are typically recommended.
Bed and chair monitors have also been suggested as a way to alert
caregivers or nursing staff when patients may be getting out of
bed or leaving a chair. In addition, programs for muscle strengthening
and balance retraining have been shown to be helpful in reducing falls
in elderly people (45). A physical therapy evaluation
may be appropriate for certain patients. For patients in acute inpatient
or nursing home settings, restraints are occasionally used on a
temporary basis to reduce the likelihood of falling. Under such
circumstances, documentation should reflect the rationale for the
temporary use of restraints and should include a discussion of the
other measures that were tried and failed to bring the behavior
under control.
The psychiatrist should be alert to the possibility of elder abuse,
financial exploitation, and neglect. Individuals with dementia are
at particular risk for abuse because of their limited ability to
protest, their lack of comprehension, and the significant demands
and emotional strain on caregivers. Patients whose caregivers appear
angry or frustrated may be at even higher risk. Any concern, especially
one raised by the patient, must be thoroughly evaluated. Corroborating
evidence (e.g., from physical examination) should be sought in order
to distinguish delusions, hallucinations, and misinterpretations
from actual abuse. In many states, when neglect or abuse is suspected,
the psychiatrist is required to make a report to the appropriate
local or state agency responsible for investigating elder abuse.
Families should be advised that patients with dementia may
wander away from home and that wandering may be dangerous to patients.
Some patients are unable to find their way back, whereas others
lack the judgment to recognize and deal with dangerous situations.
Wandering has been associated with more severe dementia and dementia
of longer duration. It has also been associated with depression,
delusions, hallucinations, sleep disorders, neuroleptic medication
use, and male gender (46). Provision of adequate supervision
is important to prevent patients from wandering. However, since
walking may be beneficial, both as stimulation and exercise, it
should not be limited unnecessarily. Providing access to a large,
safe area for walking or opportunities for supervised walks is ideal.
Environmental changes may also be necessary to prevent unsupervised
departures. At home, the addition of a more complex or less accessible
door latch may be helpful. Electronic devices to reduce the risk
of in-home wandering are under development. If wandering occurs
at night when caregivers are asleep, pharmacological intervention
may be indicated. In institutional settings, electronic locks or
electronic devices that trigger an alarm when the patient tries
to leave may be used.
Although a number of interventions of visual and other selective
barriers such as mirrors, camouflage, and grids/stripes
of tape have been tried, there is no evidence that these subjective
barriers prevent wandering in cognitively impaired people (47).
If patients are prevented from leaving on their own, adequate supervision
must be provided to ensure emergency egress. Pharmacotherapy is
rarely effective in the treatment of wandering unless the wandering
is due to an associated condition such as mania.
In addition, provision should be made for locating patients
should wandering occur. Such measures include sewing or pinning
identifying information onto clothes, placing medical-alert bracelets
on patients, and filing photographs with local police departments.
Referrals to the Safe Return Program of the Alzheimer's
Association (1-888-572-8566; http://www.alz.org/safereturn)
or similar programs provided by local police departments or other
organizations should be considered for patients at risk of wandering.
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5. Advise the Patient and Family
Concerning Driving (and Other Activities That Put Other People at
Risk)
Most of the available evidence suggests that dementia, even
when mild, impairs driving performance to some extent and that the
risk of accidents increases with increasing severity of dementia
(48). For example, compared to age-matched controls,
individuals with probable Alzheimer's disease had more
difficulties comprehending and operating a driving simulator, drove off
the road more often, spent more time driving considerably slower
than the posted speed limit, applied less brake pressure in stop
zones, spent more time negotiating left turns, and drove more poorly
overall (49). Nonetheless, it is well documented that
many individuals with dementia, even some with fairly serious impairment, continue
to drive, raising significant public health concerns (50–54).
In an office or hospital setting, accurate assessment of functional
abilities such as driving is not possible (55). Furthermore,
the influence of neuropsychiatric impairments or behavioral symptoms
on driving performance is neither clear-cut nor predictive (56, 57).
However, risks of driving should be discussed with all patients
with dementia and their families, and these discussions should be
carefully documented. Discussions should include an exploration
of the patient's current driving patterns, transportation
needs, and potential alternatives. The psychiatrist should also
ask the family about any history of getting lost, traffic accidents,
or near accidents. For patients with dementia who continue to drive,
the issue should be raised repeatedly and reassessed over time.
This is especially true for patients with Alzheimer's disease
or other progressive dementias in which driving risk will predictably
worsen over time (58).
At this time, there is no clear consensus regarding the threshold
level of dementia at which driving should be curtailed or discontinued
(48, 58–61). In
mild dementia, the driving risk is greater than for age-matched
individuals without dementia, although it is less than that for
cognitively intact young drivers (e.g., younger than age 25 years)
(48). Thus, some clinicians argue that in mild dementia
the benefits to the patient of continued independence and access to
needed services outweigh the risk of an accident. Other clinicians
argue that no patient with a diagnosis of dementia should drive,
because the risk of an accident is elevated even in patients with
mild dementia, and it is impossible to say at what point this risk
becomes unacceptable. In an evidence-based review of driving and
Alzheimer's disease from the American Academy of Neurology,
it was found that driving was only mildly impaired in drivers with
a Clinical Dementia Rating (CDR) of 0.5 (mild cognitive impairment),
but those with a CDR of 1 (mild or early stage dementia) were found
to pose significant risks from increased vehicular accidents and poorer
driving performance (48) (see Section
I.V.E for information on the staging of dementia).
Additional increases in risk may also be associated with a diagnosis
of dementia with Lewy bodies. Concomitant neurological symptoms
such as motor deficits (e.g., due to stroke or a parkinsonian syndrome,
impairments in praxis), sensory deficits (e.g., spatial neglect,
visual loss, deafness), or deficits in judgment, coordination, processing
speed, and reaction time are also thought to increase risk, although
this view has not been confirmed by research (56, 62–64).
Finally, general medical problems (e.g., symptomatic cardiac arrhythmia,
syncope, seizures, poorly controlled diabetes) or the use of sedating
medications may also impair driving ability. A history of at-fault
traffic incidents may also signal increased risk (65).
Thus, in individuals with mild dementia and one or more of these
additional factors, driving cessation may be particularly indicated.
Patients with milder impairment may also need to consider
giving up driving. For those who are unwilling to do so, it may
be helpful to advise them to limit their driving to conditions likely
to be less risky (e.g., familiar locations, modest speeds, good
visibility, clear roads) (66). The patient's
spouse or other individual may act as a navigator or assessor of
driving skill, but the utility of this strategy is unproven, and
passengers may be injured in the event of an accident (60,
61). Mildly impaired patients who wish to have an independent
assessment of their driving skills may be referred to an occupational
therapist, rehabilitation center, driving school, or local department
of motor vehicles, but the predictive value of these assessments
for actual driving performance has not been established.
In individuals with moderate impairment (e.g., those who cannot
perform moderately complex tasks, such as preparing simple meals,
household chores, yard work, or simple home repairs), there is some
evidence and strong clinical consensus that driving poses an unacceptable
risk and patients should be instructed not to drive (48, 59–61).
risk and patients should be instructed not to drive (48, 59–61).
Those with severe impairment are generally unable to drive and certainly
should not do so.
Advice about driving cessation should be communicated to
family members, as well as to the patient, because the burden of
implementing the decision often falls on families. The psychiatrist
can also lend moral authority and support to family members who
wish to restrict driving but are reluctant to take responsibility
for the decision (e.g., writing on a prescription pad, "DO
NOT DRIVE"). Eventually, when the point is reached where
the danger of continued driving is undeniable, the psychiatrist
can provide concrete advice regarding how best to accomplish cessation
of driving (e.g., confrontation regarding risks to grandchildren,
discussion of the impact on insurance coverage and rates, removing
the car from view, hiding the keys, or removing ignition wires).
The American Medical Association publication, "Physician's Guide
to Counseling and Assessing Older Drivers" (http://www.ama-assn.org/ama/pub/category/10791.html) may
be helpful to some clinicians (67). When making recommendations
to limit or stop driving, clinicians should be sensitive to the
significant psychological meaning of giving up driving. In addition,
patients and their families will need to make plans for alternative
modes of transportation (60, 61, 68).
A social service referral may be helpful for some families to help
with transportation arrangements and costs.
Psychiatrists should familiarize themselves with state motor
vehicle regulations for reporting individuals with dementia. In
some states, disclosure is forbidden. In others, a diagnosis of
dementia or Alzheimer's disease must be reported to the
state department of motor vehicles, and the patient and family should
be so informed. In many states, the physician may breach confidentiality
to inform the state motor vehicle department of a patient who is
judged to be a dangerous driver. This option is appropriate for
patients with significant dementia who refuse to stop driving and
whose families are unwilling or unable to stop them.
Although the data and recommendations just described refer
to the operation of motor vehicles, similar principles apply to
the operation of other equipment that puts the patient and others
at risk. Thus, patients whose leisure or work activities involve
firearms, use of heavy machinery, aircraft, lawn mowers, or other
dangerous equipment or material will need to have these activities
limited and discontinued as the disease progresses.
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6. Provide Education and Support
to Patients and Families
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a. Educate the Patient and Family
About the Illness and Available Treatments
An important task of the psychiatrist who cares for an individual
with dementia is providing or coordinating the education of the
patient and family regarding the illness and its natural history.
Often the first step is to communicate and explain the diagnosis
of dementia, including the specific dementia etiology, if known.
Terms should be clarified at the outset to facilitate communication.
Patients vary in their ability and desire to understand and discuss
their diagnosis. Most mildly and some moderately impaired individuals
are able to discuss the matter at some level, but the discussion
must be adapted to the specific concerns and abilities of the patient;
it may be helpful to seek the family's input regarding
the nature and timing of any discussion with the patient (69).
The issue of disclosure of the diagnosis to the patient is complex
because many patients cannot recognize their deficits. Decisions
about how to disclose should take into account factors such as cultural
issues that might modify the patient's desire to receive
such information (70). In most cases, the psychiatrist
will have an explicit discussion with family members regarding the
diagnosis, prognosis, and treatment options, adapted to the unique
concerns of the patient and family. This discussion will likely
span a number of office visits. Certain specific symptoms (e.g.,
psychosis, extrapyramidal symptoms) are predictive of more rapid
decline and thus may be used in tandem with other features to assess
prognosis (71).
It is important to educate the patient and family about the range
of symptoms that could develop in the current stage of dementia
or that may develop in the future. This education allows them to
plan for the future and to recognize emergent symptoms that should
be brought to medical attention. Family members and other caregivers
may be particularly concerned about behavioral and neuropsychiatric
symptoms, which they often associate with a loss of dignity, social stigma,
and an increased caregiving burden. It may be helpful to reassure
patients and their families that these symptoms are part of the
illness and are direct consequences of the damage to the brain.
Moreover, they may be relieved to know that although cognitive losses
are generally not reversible, neuropsychiatric symptoms, especially
the more disruptive ones, can often be improved or even eliminated
with treatment, resulting in an overall increase in functional status
and comfort. By treating these symptoms, educating family caregivers,
and providing them with alternative strategies to deal with the
patient's disruptive behaviors, the psychiatrist can help
to minimize the caregivers' negative reactions to the patient's
behavior (72). Section II.B.6.b includes
suggestions for reading materials that may be helpful in providing
education to families and caregivers.
The family should be educated regarding basic principles of
care, including 1) recognizing declines in capacity and adjusting
expectations appropriately, 2) bringing sudden declines in function
and the emergence of new symptoms to professional attention, 3)
keeping requests and demands relatively simple, 4) deferring requests
if the patient becomes overly upset or angered, 5) avoiding overly
complex tasks that may lead to frustration, 6) not confronting patients
about their deficits, 7) remaining calm, firm, and supportive and providing
redirection if the patient becomes upset, 8) being consistent and
avoiding unnecessary change, and 9) providing frequent reminders,
explanations, and orientation cues. For example, when arriving with
visitors, families should say, "This is your nephew, your
sister's son" rather than repeatedly testing a
patient's memory by saying "Do you remember who
this is?" It is also important to individualize the approach
to the patient's needs, and, in this regard, psychiatrists
and other mental health care professionals can offer more specific
behavioral interventions that caregivers can use to avoid or deal
with difficult behaviors. For additional details on such interventions,
see Sections II.B.4.b and II.C.4.
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b. Refer the Family to Appropriate
Sources of Care and Support
Family members often feel overwhelmed by the combination of
hard work and personal loss associated with caring for an individual
with dementia. The caring and pragmatic attitude of the psychiatrist
may provide critical support. This attitude may be expressed through
thoughtful inquiries about current needs and how they are being
met, advice about available sources of emotional and practical support,
referrals to appropriate community resources, and supportive psychotherapy.
Programs have been developed that reduce the burden and lessen
the stress and depression associated with long-term caregiving.
These interventions include psychoeducational programs for coping
with frustration or depression; psychotherapy focused on alleviating
depression and anxiety, and improving coping; exercise interventions
for caregivers; and workshops in stress management techniques (73–77).
In addition, extensive clinical experience and substantial scientific
literature demonstrate that support groups, especially those combining
education with support, improve caregiver well-being (78–85).
Support groups conforming to this general pattern are available
in many localities through local chapters of the Alzheimer's
Association and/or hospitals, community organizations,
and religious groups. Support groups may vary widely in their approaches
as well as composition, and caregivers may elect to try several
before finding one that suits them. In addition to providing helpful
information about the disease, how to care for someone with the
disease, and ways to decrease caregiver burden, these groups may
enhance the quality of life of patients and spouses or other caregivers
and may delay nursing home placement (79, 86–88).
Internet message boards and chat rooms may also be helpful for some
caregivers.
In addition to providing families with information on support
groups, there are a number of benefits of referral to the local
chapter or national office of the Alzheimer's Association
(1-800-272-3900; http://www.alz.org), the Alzheimer's Disease
Education and Referral Center (ADEAR) (1-800-438-4380; http://www.nia.nih.gov/Alzheimers/),
and other support organizations. Services offered by these organizations
include providing information about local resources, operating hotlines
staffed by well-informed volunteers, offering caregiver support
services, and distributing a wide array of educational material
written for patients, caregivers, and health professionals.
Many other resources provide logistical support for caregivers
who are trying to care for individuals with dementia at home. Respite
care allows the caregiver periods of relief from the responsibilities
of dementia care. It provides essential physical and emotional support,
serving the dual purposes of decreasing the burden of care and allowing
caregivers to continue to work, participate in recreational activities, or
fulfill other responsibilities. Respite care may last for hours
to weeks and may be provided through companions, home health aides,
visiting nurses, day care programs, and brief nursing home stays
or other temporary overnight care. Depending on the available local
resources and individual circumstances, these types of care may
be available from local senior services agencies, from the local
chapter of the Alzheimer's Association, religious groups,
U.S. Department of Veterans Affairs facilities, or other community
organizations. Although respite care clearly provides benefit for
the caregiver, the evidence is mixed as to whether these programs
actually delay institutionalization (89–93).
Clinical experience suggests that by decreasing caregiver burden
these programs may also improve the quality of life for patients
and their families. Other resources that may be helpful include
social service agencies, community-based social workers, home health
agencies, cleaning services, Meals on Wheels, transportation programs,
geriatric law specialists, and financial planners. Useful information
for caregivers from the Family Caregiver Alliance is available at http://www.caregiver.org.
Many clinicians also recommend that families read articles
or books written specifically for lay readers interested in understanding
dementia and its care, such as The Thirty-Six
Hour Day: A Family Guide to Caring for Persons With Alzheimer's
Disease, Related Dementing Illness, and Memory Loss in Later Life (94);
Mayo Clinic: Guide to Alzheimer's Disease:
The Essential Resource for Treatment, Coping, and Caregiving (95); Practical
Dementia Care (41); or The
Complete Guide to Alzheimer's-Proofing Your Home (35)
or view informational video media that may be available from the
local Alzheimer's Association chapter or public library.
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c. Watch for Signs of Caregiver Distress
With or without support, caregivers frequently become frustrated,
overwhelmed, or clinically depressed (96). Among the
causes of demoralization are the progressive nature of dementia
and the patient's lack of awareness of the extent of support
being provided. Psychiatrists caring for patients with dementia
should be vigilant for these conditions in caregivers, because they
increase the risk of substandard care, neglect, or abuse of patients
and are a sign that the caregivers themselves are in need of care.
Signs of caregiver distress include increased anger, social withdrawal,
anxiety, depression, exhaustion, sleeplessness, irritability, poor concentration,
increased health problems, and denial. When a caregiver is in significant
distress, his or her need for greater psychosocial support should
be evaluated. If treatment is indicated, it can be provided (according
to the preference of psychiatrist, patient, and caregiver) by the
patient's psychiatrist or through a referral to another
mental health professional.
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d. Support Families During Decisions
About Institutionalization
When family members feel that they are no longer able to care
for the patient at home, they may need both logistical and emotional
support in placing the patient in a long-term-care facility (i.e.,
continuing care retirement community, group home, assisted living
facility, or nursing home). Often, such transitions occur at times
of crisis (e.g., medical hospitalizations or caregiver illness).
The psychiatrist can be a valuable resource in informing families
about the available options and helping them evaluate and anticipate
their needs in the context of their values, priorities, and other
responsibilities. The question of referral to a long-term-care facility should
be raised well before it becomes an immediate necessity so that
families who wish to pursue this option have time to select and
apply for a suitable facility, plan for financing long-term care,
and make needed emotional adjustments. A referral to a social service
agency, social worker, or the local chapter of the Alzheimer's
Association may assist with this transition. Some social service
agencies provide comprehensive home service assessments that may
help families recognize and address their needs.
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7. Advise the Family to Address Financial
and Legal Issues
Patients with dementia usually lose the ability to make medical,
legal, and financial decisions as the disorder progresses, and consequently
these functions must be taken over by others (97).
Clinical evaluation, including cognitive testing when needed, can
assist in determining whether a patient with Alzheimer's
disease has the capacity to make medical decisions (98–100).
If family members act while the patient is still able to participate,
they can seek his or her guidance regarding long-term plans. This
approach can help in incorporating the patient's own wishes
and values into the decision-making process, as well as in avoiding
future conflict. Although the specific laws vary from state to state,
advance planning regarding health care and finances can help families
avoid the difficulty and expense of petitioning the courts for guardianship
or conservatorship should such arrangements become necessary later
in the illness. Issues that might be raised related to health care
in the later stages of the illness include preferences about medical
treatment, the use of feeding tubes, the care desired for infections
and other potentially life-threatening medical conditions, and artificial
life support. Medical decision making can be transferred in advance to
a trusted family member (or friend) in the form of a durable power
of attorney for health care or designation of a health care agent.
For some patients, a living will or advance directive may also be
appropriate, but which document is used and its specific features
depend on the prevailing state law.
Patients and family members should be offered the opportunity
to discuss preferences about participation in research studies early
in the course of the illness, while the patient is still able to
make his or her wishes known (101). The Alzheimer's
Association has developed recommendations for Institutional Review
Boards and investigators for obtaining research consent for cognitively
impaired adults (102).
An individual's capacity to understand and give consent to
a particular intervention (including taking of medications, particularly
those with potentially significant side effects) will vary over
time and with the nature and complexity of the intervention (99, 100).
As individuals with dementia become more impaired, responsible family
members are usually brought into the consent discussion. When a
patient's capacity is diminished but still sufficient to
give consent, consent or at least agreement is usually obtained
from both patient and family member. Once a patient no longer has
adequate decisional capacity, consent is obtained from either a
health care proxy decision maker designated in an advance directive
or a guardian, if either has been named. When such a legally designated
decision maker does not exist, the closest relative is typically asked
to provide consent. Nevertheless, the psychiatrist is encouraged
to be familiar with local jurisdictional requirements, because procedures
vary by state and some states require judicial review.
Patients may also transfer authority for legal and financial decision
making in the form of a durable power of attorney for financial
matters. At a minimum, it is recommended to include a family member
as a cosigner on any bank accounts so that payment of expenses can
proceed smoothly even when the patient is no longer able to complete
the task him- or herself. In some instances, it may be a good idea
to warn families about the vulnerability of individuals with dementia
to unscrupulous individuals seeking "charitable" contributions, selling
inappropriate goods, or promoting sweepstakes. If needed, the family
can ask the patient to give up charge cards, ATM cards, and checkbooks
to prevent the loss of the patient's resources. Clinicians
should remain vigilant for evidence of exploitation of patients.
Patients should be advised to complete or update their wills
while they are able to make and express decisions (103).
Patients and families should also be advised of the importance of
financial planning early in the illness. This advice may include
a frank discussion regarding the financing of home health care and/or
institutional care. Unfortunately, once the diagnosis of dementia
is established, it is often too late to purchase long-term-care
insurance, but careful planning in the early stages may help to
lessen the burden of nursing home care or home health services later
in the disease course. A patient with more complex financial issues
should be referred to an attorney or financial planner to establish
appropriate trusts, plan for transfer of assets, and make other
financial arrangements.
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C. Development and Implementation
of a Stage-Specific Treatment Plan
The treatment of dementia varies through the
course of the illness, because symptoms evolve over time. Although
many symptoms can and do occur throughout the illness, certain symptoms
are typical of the broad stages, as outlined in Section
IV.E. This outline of stages conforms most to
the typical course of Alzheimer's disease, but it does
not apply as well to other types of dementias, particularly the
frontotemporal dementia spectrum disorders.
The following sections provide general recommendations for
treating patients in three stages of illness (mild, moderate, and
severe) and specific recommendations for the implementation of select
psychotherapeutic and pharmacological treatments. The evidence supporting
the efficacy of these treatments is reviewed in Section
V of this guideline. At each stage of the illness,
the psychiatrist should be vigilant for cognitive and noncognitive symptoms
likely to be present and should help the patient and family anticipate
future symptoms. The family may also benefit from reminders to plan
for the care likely to be necessary at later stages.
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1. Mildly Impaired Patients
At the early stages of a dementing illness, patients and their
families are often dealing with acceptance of the illness and recognition
of associated limitations. They may benefit from pragmatic suggestions
for how to cope with these limitations (e.g., making lists, using
a calendar, avoiding overwhelming situations such as certain child-care
responsibilities). Patients may benefit from referral to health
promotion activities and recreation clubs (104). It
may be helpful to identify specific impairments and highlight remaining
abilities. Patients often experience a sense of loss and perceived
stigma associated with the illness. Consequently, psychotherapeutic
interventions may be helpful for patients who are struggling with
the diagnosis and its implications. Features of treatment plan development
for mildly impaired patients that have already been outlined in detail
include addressing the issue of driving cessation (see Section
II.B.5), assigning a durable power of attorney
and addressing other legal and financial matters (see Section
II.B.7), and addressing caregiver well-being
(see Section II.B.6.b). Support
groups for patients and families with mild Alzheimer's
disease exist in many communities.
Patients with early Alzheimer's disease should be
offered a trial of one of the three available cholinesterase inhibitors approved
and commonly used for the treatment of cognitive impairment (i.e.,
donepezil, rivastigmine, galantamine), after a thorough discussion
of their potential risks and benefits. Given the possible risks
of long-term high-dose vitamin E and selegiline and the minimal
evidence for their benefit, they are no longer recommended. Specific
recommendations for implementing these treatments are provided in Section
II.C.5.a. Mildly impaired patients may also
be interested in referrals to local research centers for participation
in clinical trials of experimental agents for the treatment of early
Alzheimer's disease. Additional information regarding such
trials may be obtained from a local or the national chapter of the
Alzheimer's Association, from the National Institute on
Aging, or at http://www.clinicaltrials.gov.
Mildly impaired patients should be evaluated for neuropsychiatric
symptoms, especially depressed mood or major depression, which may
require pharmacological or psychotherapeutic intervention, as described
in Section II.C.5.c. Patients
with moderate to severe major depression who do not respond to or
cannot tolerate antidepressant medications should be considered
for ECT. Mildly impaired patients should also be carefully assessed
for suicidality, even if they are not obviously depressed.
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2. Moderately Impaired Patients
As patients become more impaired, they are likely to require
more supervision to remain safe, and safety issues should be addressed
as part of every evaluation (see Section II.B.4).
Families should be advised about the possibility of accidents due
to forgetfulness (e.g., fires while cooking), of difficulties coping
with household emergencies, and of the possibility of wandering.
Family members should also be advised to determine whether the patient
is handling finances appropriately and to consider taking over the
paying of bills and other responsibilities. At this stage of the
disease, nearly all patients should not drive. Families should be
counseled to undertake measures to prevent patients from driving,
as many patients lack insight into the risk that their continued driving
poses to themselves or others (as described in Section
II.B.5).
As a patient's dependency increases, caregivers may
begin to feel more burdened. A referral for some form of respite care
(e.g., home health aid, day care, brief assisted living, or nursing
home stay) may be helpful. At this stage, families should begin
to consider and plan for additional support at home as well as discuss
the patient's possible transfer to a long-term-care facility.
Family members may differ in their opinion of the patient's
level of functioning and may have different psychological responses
to the patient's impairments, generating family conflict.
It may be beneficial to meet with family members to openly discuss
these issues.
Treatment for cognitive symptoms should also be considered.
For patients with Alzheimer's disease, currently available
data suggest that the combination of a cholinesterase inhibitor
plus memantine is more likely to delay symptom progression than
a cholinesterase inhibitor alone during this stage of the illness.
Specific implementation of these treatments is described in Section
II.C.5.a.
Delusions and hallucinations are prevalent in moderately impaired
patients, as are agitation and combativeness. The patient and family
may be troubled and fearful about these symptoms, and it may be
helpful to reassure them that the symptoms are part of the illness
and are often treatable. Therapeutic approaches to these symptoms
are described in Section II.C.5.b.
For patients in whom wandering is the only symptom, pharmacotherapy
will rarely be indicated. Depression often remains part of the picture
at this stage and should be treated vigorously (105).
The pharmacotherapy of behavioral and neuropsychiatric symptoms
is described in Sections II.C.5.b, II.C.5.c,
and II.C.5.d.
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3. Severely and Profoundly Impaired
Patients
At this stage of the illness, patients are severely incapacitated
and are almost completely dependent on others for help with basic
functions, such as dressing, bathing, and feeding. Families are
often struggling with a combined sense of burden and loss and may
benefit from a frank exploration of these feelings and any associated
resentment or feelings of guilt. They may also need encouragement
to get additional help at home or to consider transient respite
or relocation of the patient to a nursing home.
Of the cholinesterase inhibitors, only donepezil has thus far
been approved for use in late-stage disease, and some studies show
that other members of this class may also be beneficial (106, 107).
Memantine, which has been approved for use in severe dementia, may
provide modest benefits and has few adverse effects (108).
If the benefit of a medication is unclear, a brief medication-free
trial may be used to assess whether continued treatment is worthwhile.
Depression may be less prevalent and more difficult to diagnose
at this stage but, if present, should be treated vigorously. Psychotic
symptoms and agitation are often present and should be treated pharmacologically
if they cause distress to the patient or significant danger or disruption
to caregivers or to other residents of long-term-care facilities.
At this stage, it is important to ensure adequate nursing care,
including measures to prevent bedsores and contractures. The treatment
team should help the family prepare for the patient's death.
Ideally, discussions about feeding tube placement, treatment of
infection, cardiopulmonary resuscitation, and intubation will have
taken place when the patient could participate, but if they have
not, it is important to raise these issues with the family before
a decision about one of these options is urgently required.
Hospice care is an underused resource for patients with end-stage
dementia (109, 110). Hospice provides
physical support for the patient (with an emphasis on attentive
nursing care and relief of discomfort rather than medical intervention)
and emotional support for the family during the last months of life.
A physician must certify that the patient meets hospice criteria
for admission for hospice benefits to be available (111).
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4. Implementation of Psychosocial
Treatments
The psychiatric care of patients with dementia involves a broad
range of general psychosocial interventions for the patient and
his or her family, as introduced in Section II.B.
In addition, some patients may benefit from more specific psychosocial
interventions. These more specific psychosocial treatments for dementia
can be divided into four broad groups: behavior oriented, emotion
oriented, cognition oriented, and stimulation oriented. Although
these treatment approaches differ in philosophy, focus, and methods,
they share the broadly overlapping goals of improving quality of life
and maximizing function in the context of existing deficits (see
references 112 and 113 for a comprehensive
review). Many of these therapies have the improvement of cognitive
skills, mood, or behavior as an additional goal. All of these approaches
reflect a person-centered philosophy of care in which an understanding of
the individual is emphasized (114). For many individuals,
several modalities will be selected at the same time. Because these
treatments generally do not provide lasting effects, those that
can be offered regularly may be the most practical and beneficial.
These treatments are generally delivered daily or weekly. Beyond
these considerations, the choice of therapy is generally based on the
patient's characteristics and preference, availability
of the therapy, and cost. For instance, some approaches are available
only in institutional settings, such as nursing homes or day care
centers, whereas others can be used at home.
Behavioral techniques and interventions are in wide clinical
use with patients who have difficult-to-manage behavioral problems.
There is some evidence for modest benefits of such therapies, particularly
while the intervention is ongoing (112, 115, 116),
but additional well-designed clinical trials are needed. There also
is some evidence that behavioral interventions can reduce patients' depressive
symptoms (117, 118).
Stimulation-oriented treatments (e.g., recreational activities
or therapies, art therapies, exercise) are often included in the
care of patients with dementia as well. They provide the kind of
environmental stimulation that is recognized as part of humane care,
and modest efficacy data exist that support their use for improving
mood and reducing behavioral disturbances (117, 119–121).
Emotion-oriented treatments (e.g., reminiscence therapy, validation
therapy, supportive psychotherapy, sensory integration, simulated
presence therapy) are often used in the treatment of patients with
dementia to address issues of loss and to improve mood and behavior.
Although there is modest research support for the effectiveness
of reminiscence therapy for improvement of mood and behavior (122–124),
none of these modalities has been subjected to rigorous scientific
testing. Cognition-oriented treatments (e.g., reality orientation,
cognitive retraining, skills training) may provide mild short-term
improvements in selected domains of cognition, but such improvements,
when achieved, are not lasting (125, 126).
Short-term adverse emotional consequences have sometimes been
reported with psychosocial treatments. This is especially true of
the cognitively oriented treatments, during which frustration, catastrophic
reactions, agitation, and depression have been reported (86, 127).
Thus, treatment regimens must be tailored to the cognitive abilities
and frustration tolerance of each patient.
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5. Implementation of Pharmacological
Treatments
The following summarizes principles that underlie the pharmacological
treatment of elderly patients and those with dementia (128).
First, elderly individuals have decreased renal clearance and slowed
hepatic metabolism, which alter the pharmacokinetics of many medications.
Moreover, because elderly individuals may have multiple coexisting
medical conditions and therefore may take multiple medications,
it is important to consider how these general medical conditions
and associated medications may interact to further alter the absorption,
serum protein binding, metabolism, and excretion of the medication
(129). Therefore, low starting doses, small dose increases,
and long intervals between dose increases are necessary. This is true
even in the inpatient setting, where utilization review pressures
may encourage physicians to employ rapid titration schedules. However,
some patients may ultimately need doses as high as would be appropriate
for younger patients.
Pharmacodynamics may also be altered in elderly patients and
those with dementia. As a result, certain medication side effects
pose particular problems for elderly patients and those with dementia;
medications with these side effects must therefore be used judiciously.
Anticholinergic side effects may be more burdensome for elderly
patients owing to coexisting cardiovascular disease, prostate or
bladder disease, or other general medical conditions. These medications may
also lead to worsening cognitive impairment, confusion, or even
delirium (130). Orthostasis is common in elderly patients
because of decreased vascular tone and medication side effects.
As a result, elderly patients, especially those with dementia, are more
prone to falls and associated injuries. Medications associated with
central nervous system sedation may worsen cognition, increase the
risk of falls, and put patients with sleep apnea at risk for additional
respiratory depression. Finally, elderly patients, especially those
with Alzheimer's disease, Parkinson's disease,
or dementia with Lewy bodies, are especially susceptible to extrapyramidal
side effects.
For all these reasons, medications should be used with considerable
care, and polypharmacy should be avoided whenever possible. In nonemergency
situations or when neuropsychiatric symptoms are not severe, nonpharmacological approaches
should be attempted first to avoid the very significant morbidities
associated with psychotropic medication use in elderly patients.
Nonetheless, many elderly individuals with dementia manifest neuropsychiatric
symptoms that do not respond to psychosocial or environmental interventions
but may respond to psychotropic medications individually or in combination.
The sections that follow describe somatic therapies used to
treat the cognitive symptoms and functional losses associated with
dementia, as well as the prevalent neuropsychiatric symptoms of
psychosis, anxiety, agitation, depression, apathy, and sleep disturbances.
Although the sections are organized by these specific target symptoms,
many medications have broader impact in actual practice.
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a. Treatments for Cognitive and Functional
Losses
Because there is no cure for most cases of dementia, the primary
goal of medication treatment for cognitive symptoms in dementia
is to delay the progression of symptoms, with the hope that this
delay will translate into a preservation of functional ability,
maintaining the patient for as long as possible at a particular
level of symptom severity. However, no medication treatment has
been shown to delay the progression of neurodegeneration.
A number of psychoactive medications are used to achieve these
goals. The only FDA-approved medications for dementia or cognitive
impairment are the cholinesterase inhibitors (tacrine, donepezil,
rivastigmine, and galantamine), memantine, and the combination of
ergoloid mesylates (approved for nonspecific cognitive decline).
In addition, other drugs, including vitamin E, ginkgo biloba, and selegiline
(approved by the FDA for treatment of Parkinson's disease
and in patch form for the treatment of depression), are occasionally
used for this purpose in selected patients, although they are not
generally recommended, because their efficacy and safety are uncertain.
Several other medications that had been proposed for the treatment
or prevention of cognitive decline, including NSAIDs, statin medications,
and estrogen supplementation (with conjugated equine estrogens),
have shown a lack of efficacy and safety in placebo-controlled trials
in patients with Alzheimer's disease and therefore are
not recommended. Many additional agents are currently being tested.
Participation in clinical trials is another option available to
patients with dementia.
Certain interventions for specific medical conditions such as
the use of antihypertensive medications to control blood pressure,
use of aspirin to prevent further strokes, and prescription of levodopa
as a general treatment of Parkinson's disease may also
lead to positive effects on cognition but are beyond the purview
of this practice guideline.
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1. Cholinesterase inhibitors
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a. Alzheimer's disease and
general considerations
In 1993 tacrine became the first agent approved specifically
for the treatment of cognitive symptoms in Alzheimer's disease.
Tacrine is a reversible cholinesterase inhibitor with evidence for
efficacy from multiple double-blind placebo-controlled trials (131–135)
that is thought to work by increasing the availability of intrasynaptic
acetylcholine in the brains of patients with Alzheimer's
disease. The FDA approved other cholinesterase inhibitorsdonepezil,
rivastigmine, and galantaminein 1997, 2000, and 2001,
respectively, for treatment of cognitive decline in mild to moderate
Alzheimer's disease. These agents are now preferred over
tacrine because of tacrine's reversible hepatic toxicity
and the requirement that it be given 4 times per day. Evidence for
the efficacy of these medications in mild to moderate Alzheimer's
disease also comes from a substantial number of randomized, double-blind,
placebo-controlled trials of donepezil (136–146),
rivastigmine (147–152), and galantamine
(153–159). Results of a smaller
number of clinical trials (106, 107) suggested
that cholinesterase inhibitors might have some limited benefits
in severe Alzheimer's disease. In 2006, donepezil was approved
by the FDA for this indication.
Given the evidence from randomized controlled trials for modest
improvement in some patients treated with cholinesterase inhibitors
and the lack of established alternatives, it is appropriate to offer
a trial of one of these agents for patients with mild or moderate
Alzheimer's disease for whom the medication is not contraindicated.
Many clinicians in fact prescribe cholinesterase inhibitors for
patients with the entire range of Mini-Mental State Examination
(MMSE) scores, with moderate medical or psychiatric comorbidity,
or with possible Alzheimer's disease, even though these
patients would not have been eligible for most clinical trials completed
to date. Whenever cholinesterase inhibitors are prescribed, patients
and their families should be apprised of the limited potential benefits
as well as the potential costs.
Results of the numerous large placebo-controlled trials of individual
cholinesterase inhibitors have suggested similar degrees of efficacy,
although tolerability may differ among the medications. Nonetheless,
currently available data do not allow a fair, unbiased direct comparison
among the cholinesterase inhibitors. Four clinical trials have compared
cholinesterase inhibitors (two compared donepezil and galantamine,
and two compared donepezil and rivastigmine) (160–163),
but a number of these studies have significant methodological problems
and none resolves the question of superiority (164).
There are also no data on whether or how to switch from one cholinesterase
inhibitor to another.
As would be expected with cholinesterase inhibitors, common
side effects in clinical trials are associated with cholinergic
excess, particularly nausea and vomiting, but these symptoms tend
to be mild to moderate in severity for all agents. In the randomized
clinical trials noted earlier, these side effects were observed
in approximately 10%–20% of patients
(136–159). Additional cholinergic side effects
include muscle cramps; bradycardia, which can be dangerous in individuals with
cardiac conduction problems; decreased appetite and weight; and
increased gastrointestinal acid, a particular concern in those with
a history of ulcers. These side effects occur infrequently with
these agents, but bradycardia should be considered a relative contraindication
to their use. In general, cholinergic side effects tend to wane
within 2–4 days, so if patients can tolerate unpleasant
effects in the early days of treatment, they may be more comfortable
later on. Finally, cholinesterase inhibitors may induce or exacerbate
urinary obstruction, worsen asthma and chronic obstructive pulmonary
disease, cause seizures, induce or worsen sleep disturbance, and
exaggerate the effects of some muscle relaxants during anesthesia.
Reversible, direct medication-induced hepatotoxicity with
hepatocellular injury is a unique property of tacrine, occurring
in approximately 30% of those taking it 6–8 weeks after
initiating the medication (165). Because of this hepatotoxicity,
tacrine is very uncommonly used. Hepatotoxicity has not been associated
with donepezil, rivastigmine, or galantamine.
The main contraindication to use of cholinesterase inhibitors
is hypersensitivity to the individual drugs. Some considerations
in limiting treatment include the existence of gastrointestinal
disorders such as gastritis, ulcerative disease, or undiagnosed
nausea and vomiting, because cholinesterase inhibitors will increase
gastric acid secretions. Cholinesterase inhibitors should also be
used with care in patients with sick sinus syndrome or conduction
defects, cerebrovascular disease, or seizures, as well as in patients
with asthma or chronic obstructive pulmonary disease.
With respect to dosing and dosage, donepezil is given once
per day, usually starting at 5 mg/day. This dosage can
be increased to 10 mg/day, if tolerated. Some clinicians
start treatment with 2.5 mg/day for patients who are frail
or very sensitive to medication side effects and increase the dose
by 2.5-mg increments. Galantamine is started at 8 mg/day
in divided doses and increased gradually to a target range of 16–24
mg/day in divided doses, although certain patients may benefit
from dosages up to 32 mg/day. A once-daily formulation
of galantamine has recently been released. Rivastigmine is started
at 3 mg/day in divided doses and increased gradually to
a target range of 6–12 mg/day in divided doses. Doses
may be titrated upward every 4 weeks. Slower titration can be helpful
in managing side effects, if these occur. Higher dosages may be
effective in some patients when lower dosages are not; therefore,
patients who have not shown clear benefit while taking a lower dosage
should receive an increased dose, if tolerated, before the conclusion
is made that the medication is ineffective. Minimal effective dosages
are 5 mg/day for donepezil, 16 mg/day for galantamine,
and 6 mg/day for rivastigmine.
It is uncertain how long patients should be treated with cholinesterase
inhibitors. Data from placebo-controlled clinical trials have demonstrated
benefits over placebo for 6 months to 2 years with donepezil (136, 137, 139),
for up to 1 year with rivastigmine (150), and for up
to 6 months with galantamine (156). A number of open-label
extension clinical trials have been conducted examining the efficacy
of these agents beyond the time in which placebo controls were actually
used. Subjects who continued to take the study drug were compared
to a "historical" control group, namely a projection
of the decline of a placebo control group. The authors of these studies
claimed to demonstrate ongoing efficacy beyond the conclusion of
the actual placebo-controlled trials, but comparisons using projected
outcomes of a placebo group are methodologically problematic and
do not establish efficacy.
In practice, the decision whether to continue treatment with
cholinesterase inhibitors is a highly individualized one. Reasons
that patients choose to stop taking these medications include side
effects, adverse events, lack of motivation, lack of perceived efficacy,
and cost. Individual patients may be observed to have some stabilization
of symptoms or slowing of their decline. Under these circumstances,
a physician might consider continuing the medication. Conversely,
a patient who is declining rapidly despite taking cholinesterase inhibitors
may be considered a medication nonresponder, and the medication
can be discontinued. Discontinuation of cholinesterase inhibitor
medication during placebo-controlled trials after 12–24
weeks has been associated with a regression of cognitive improvement
to the level of the associated placebo group. Whether resumption
of the cholinesterase inhibitor reverses this symptomatic worsening
is unclear. Some patients have shown pronounced deterioration within
several weeks of discontinuing cholinesterase inhibitors and improvement
when the medication has been restarted. In contrast, the results
of one study suggested that donepezil-treated patients who had treatment
interrupted for 6 weeks and then restarted treatment never regained
cognition back to the level achieved before medication discontinuation
(166).
+
b. Vascular dementia and mixed dementia
(Alzheimer's disease and vascular dementia)
Trials of cholinesterase inhibitors in patients with vascular
dementia and mixed dementia have produced inconclusive results.
In addition, serious concerns about safety and potential increases
in mortality have arisen with the use of these medications in this
patient population (167). As a result of these factors,
as well as the lack of FDA approval for this indication (see Sections
III.B.4 and V.B.1.a.2),
no specific recommendation can be made in favor of the routine use
of cholinesterase inhibitors in patients with vascular dementia
at this time, although individual patients may benefit from their
use.
+
c. Dementia with Lewy bodies
Cholinesterase inhibitors could be considered for patients with
dementia with Lewy bodies. Dosing and titration are similar to those
for patients with Alzheimer's disease (168, 169).
+
d. Dementia of Parkinson's
disease
Cholinesterase inhibitors should be considered for patients
with mild to moderate dementia associated with Parkinson's
disease. Only rivastigmine has been studied in a randomized, double-blind,
placebo-controlled trial (170) with an open-label extension
(171) and approved by the FDA for this indication.
Nevertheless, there is no reason to believe the benefit is specific
to this cholinesterase inhibitor. Dosing and titration are similar
to those for patients with Alzheimer's disease.
+
e. Mild cognitive impairment
The term "mild cognitive impairment" describes
a heterogeneous group of individuals, with some patients in the
earliest stages of Alzheimer's disease and others suffering
from other conditions. There are no FDA-approved medications for
the treatment of mild cognitive impairment at this time. Clinical
trials of cholinesterase inhibitors for mild cognitive impairment
have enrolled a narrower and better defined population of patients
with mild cognitive impairment than most clinicians actually treat
in practice, but even with these well-defined patients the evidence
from clinical trials supporting use of cholinesterase inhibitors
is weak (172, 173). Given the inconclusive
data, the potential safety concerns that exist with this class of
medications in this patient population, and the lack of FDA approval
for this indication (reviewed in Sections V.B.1.a.4 and II.C.5.a.1.a),
no specific recommendation can be made in favor of routine use of
cholinesterase inhibitors in patients with mild cognitive impairment
at this time. Nonetheless, individual patients may benefit from
their use.
Memantine is a noncompetitive NMDA receptor antagonist approved
by the FDA for the treatment of moderate to severe Alzheimer's
disease.
Given the evidence for its efficacy in randomized controlled
trials (174, 175), memantine should be
considered for treatment of patients with moderate to severe Alzheimer's
disease. Memantine can be prescribed for people either currently
taking or not taking a cholinesterase inhibitor. There is modest
evidence that the combination of memantine and donepezil is better
than donepezil alone (175), but there is no evidence
that this combination is better than memantine alone. There are
not yet data to argue for or against the use of memantine beyond
6 months (108, 176).
In patients with mild Alzheimer's disease, the evidence
is suggestive of a small clinical benefit of memantine over placebo
(108, 177), although this result is not
conclusive and additional trials should be performed. Given that
there are few safety concerns with the use of memantine in mild
Alzheimer's disease, clinicians may consider using it for
individual patients.
For vascular dementia, the evidence does not support the use
of memantine (178, 179), although further
trials are necessary.
Reported adverse events with memantine are infrequent, appear
to be mild, and include confusion, dizziness, headache, sedation,
agitation, falls, and constipation (174, 175, 177).
Dropout rates during clinical trials have generally been the same
for memantine as for placebo.
Memantine treatment begins at 5 mg once daily, and this dosage
is increased by 5 mg/day every week until a target dosage
of 10 mg b.i.d. is reached. A therapeutic dosage range for memantine
has not been conclusively established. One study demonstrated efficacy
at a dosage of 10 mg/day (180), and the effects
of dosages above 20 mg/day have not been studied. Because
memantine is cleared primarily by the kidneys, lower dosages (e.g.,
10 mg/day) should be considered in patients with compromised
renal function.
Vitamin E is no longer recommended for the treatment of cognitive
symptoms of dementia. Previous recommendations for its use had balanced
the weakness of the evidence for its efficacy with the perceived
lack of risk with use of vitamin E. However, new safety concerns,
namely the unexpected findings of increased dose-dependent mortality
in a meta-analysis of vitamin E clinical trials (181)
and an increased rate of heart failure with vitamin E treatment
in a large randomized trial of cancer and heart disease prevention
in individuals with diabetes mellitus and/or vascular disease
(182), make the case for its use much less compelling.
The evidence from the one placebo-controlled, double-blind, multicenter
trial of vitamin E for the treatment of moderate Alzheimer's
disease is limited (183). Furthermore, vitamin E failed
to show efficacy in one study of individuals with mild cognitive
impairment (173). In this trial nearly one-half of
the subjects later received a diagnosis of Alzheimer's
disease during the 3 years of observation and hence had early Alzheimer's
disease at the beginning of the trial. Nevertheless, after considering
the potential risks and benefits of vitamin E, some physicians and their
patients may elect to use it, particularly at doses at or below
400 IU daily. Because vitamin E has been associated with worsening
of coagulation defects in patients with vitamin K deficiency (184),
it should be avoided in this population.
A number of medications marketed for other indications have
been proposed for the treatment of dementia on the basis of epidemiological
data or pilot studies (185–189), but they
are not recommended for routine use at this time because of lack
of efficacy in subsequent studies (190–200)
and potential for adverse effects. These other agents include aspirin
and other NSAIDs, hormone replacement therapy, the hormone melatonin,
the botanical agent ginkgo biloba, the chelating agent desferrioxamine,
the irreversible monoamine oxidase B (MAO-B) selective inhibitor
selegiline, and a mixture of ergoloid mesylates currently marketed
under the trade name Hydergine. Because some of these agents are
popular, psychiatrists should routinely inquire about their use
and should advise patients and their families that some of these
agents are marketed with limited quality control and have not been
subjected to adequate efficacy evaluations.
+
b. Treatments for Psychosis and Agitation
As discussed in Section II.B.3,
psychosis and agitation occur commonly in patients with dementia
and are important targets of psychiatric intervention. In DSM-IV-TR
Alzheimer's disease and other dementias with delusions
and hallucinations and Alzheimer's disease with behavioral
disturbances are classified separately, and provisional criteria
for psychosis of Alzheimer's disease have been published
(201). In clinical practice, however, these symptoms
frequently co-occur.
Treatments that decrease psychotic symptoms (delusions and
hallucinations) and associated or independent behavioral disturbances
such as aggression, combativeness, and agitation are often essential
to increasing the comfort and safety of patients and easing the
burden of provision of care by families and other caregivers.
Clinicians facing the challenge of treating patients with significant
psychosis or behavioral disturbances must weigh the risk of not
treating these complications of dementia against the risks of active
treatment described below in Sections II.C.5.b.1, II.C.5.b.2, II.C.5.b.3,
and II.C.5.b.4. This weighing
of risks also includes consideration of the evidence supporting
the efficacy of the agent in question, the patient's overall
medical condition, and the evidence of risk and benefit of any potential
treatment alternatives, followed by documentation of the reasons
for using the medication and the fact that a discussion has taken
place with the patient or caregiver.
As outlined in Section II.C.4,
there are a number of nonpharmacological interventions that can
be used before a trial of an antipsychotic or other medication is
begun. Consideration and use of behavioral, psychosocial, and psychotherapeutic
treatments is particularly critical, given the large number and
potential severity of side effects associated with pharmacotherapy.
Interventions for psychosis should be guided by the patient's
level of distress and the risk to the patient, caregivers, or other
patients. If psychotic symptoms cause minimal distress to the patient and
are unaccompanied by agitation or combativeness, they are best treated
with environmental measures, including reassurance and redirection.
If the symptoms do cause significant distress or are associated
with behavior that may place the patient or others at risk, treatment
with low doses of antipsychotic medication is indicated in addition
to nonpharmacological interventions. Treatment with an antipsychotic medication
is also indicated if a patient is agitated or combative in the absence
of psychosis, as this indication for antipsychotic use has significant
support in the literature. The use of these agents should be reevaluated
and their benefit documented on an ongoing basis. When antipsychotics
are ineffective, carbamazepine, valproate, or an SSRI may be used
in a careful therapeutic trial. If behavioral symptoms are limited to
specific times or settings (e.g., a diagnostic study), or if other
approaches fail, a low-dose benzodiazepine may prove useful, although
side effects in elderly patients can be problematic (see Section
II.C.5.b.2). Although mood stabilizers and SSRIs
are commonly used in clinical practice to treat agitation, delusions,
and aggression, they have not been consistently shown to be effective
in treating these symptoms, nor is there substantial evidence for
their safety. Thus, in making decisions about treatment, these agents
should not be seen as having improved safety or comparable efficacy,
compared to antipsychotic medications.
As a dementing illness evolves, psychosis and agitation may
wax and wane or may change in character. As a result, the continued
use of any intervention for behavioral disturbances or psychosis
must be evaluated and justified on an ongoing basis. In the nursing
home setting, this clinical recommendation is also a requirement
under regulations of the Federal Nursing Home Reform Act of the
Omnibus Budget Reconciliation Act of 1987 (see Section
III.C.3). In addition, periodic reevaluation
and revision of the treatment plan, including a change in dose,
a change in medication, or medication discontinuation, may be indicated.
Patients whose symptom severity was relatively low at the time of
medication initiation may be more easily withdrawn from psychotropic
medications than those with more severe symptoms at the time of
treatment initiation (202).
Antipsychotics are the primary pharmacological treatment available
for psychotic symptoms in dementia. They are also the most commonly
used and best-studied pharmacological treatment for agitation. There
is considerable evidence from randomized, double-blind, placebo-controlled trials
and meta-analyses for the efficacy of both first-generation (203–217)
and second-generation agents (201, 212, 218–227),
although this benefit is often modest. Findings from the Clinical
Antipsychotic Trials of Intervention Effectiveness (CATIE-AD) study,
funded by the National Institute of Mental Health (NIMH), failed
to demonstrate conclusive benefits of second-generation antipsychotics
over placebo in patients with Alzheimer's disease and psychosis
or aggression, although there were advantages to the medications
on certain outcome variables and the discontinuation rate due to
lack of efficacy was lower with olanzapine and risperidone than
it was for placebo or quetiapine (228).
Given the side effects and potential toxicity of antipsychotic
agents (225, 228), the risks and benefits
of these medications must be reassessed on an ongoing basis. The
lowest effective dose should be sought, and emergent side effects
should first be treated by dose reduction. Because of the risks
involved with the use of antipsychotics, indications for their use
should be generally limited to psychosis or behavioral disturbances, and
they should not be used primarily for sleep disorders or anxiety.
In addition, periodic attempts (e.g., every several months) to reduce
or withdraw antipsychotic medications should be considered for all
patients, while weighing the probability of a relapse and the dangerousness
of the target behavior(s) (229). In general, agents
with significant anticholinergic properties should be avoided in
patients with dementia, although they may be considered under specific
circumstances.
Mild to moderate adverse effects of antipsychotics include
akathisia, parkinsonism, sedation, peripheral and central anticholinergic
effects, delirium, postural hypotension, cardiac conduction defects,
urinary tract infections, urinary incontinence, and falls. Antipsychotic
agents are also associated with a risk of more serious complications
that must be considered in weighing the risks and benefits of antipsychotic
treatment (see Section V.B.2.a.2 for
additional details). Serious complications include tardive dyskinesia
(the incidence of which increases with dose and duration of treatment
and which occurs more commonly in women, in individuals with dementia
or brain injury, and in elderly patients in general), neuroleptic
malignant syndrome (a rare but potentially lethal adverse effect
of antipsychotic medications that occurs less frequently with second-generation
antipsychotic agents), agranulocytosis (with clozapine), hyperlipidemia,
weight gain, diabetes mellitus, cerebrovascular accidents, and death.
An increased risk of cerebrovascular accidents has recently been
found with the second-generation antipsychotics aripiprazole, olanzapine, and
risperidone, although not with quetiapine. Meta-analyses of clinical
trials of the second-generation antipsychotics aripiprazole, olanzapine,
quetiapine, and risperidone (225), as well as of first-generation
antipsychotics (230), have found an increased mortality
when used in elderly patients with dementia. These concerns have
led to "black box" warnings on the second-generation
antipsychotics (231).
Accepted clinical practice is to prescribe antipsychotic agents
at standing doses rather than as needed, although as-needed doses
may be appropriate for symptoms that occur infrequently. Oral administration
is generally preferred, although an intramuscular injection may
sometimes be used in an emergency or when a patient is unable to
take medications by mouth (e.g., for a surgical procedure). Low
starting dosages are recommended, e.g., 0.25–0.5 mg/day
of haloperidol, 0.25–1.0 mg/day of risperidone,
12.5 mg/day of clozapine, 1.25–5.0 mg/day
of olanzapine, 12.5–50 mg/day of quetiapine. The
best starting dosages for aripiprazole and ziprasidone are not known,
although the available evidence suggests that 5 mg/day
of aripiprazole may be safe for most patients. The dose can be increased
on the basis of the response of the target symptom(s). The usual
maximum dosages of these agents for patients with dementia are 2
mg/day of haloperidol, 1.5–2 mg/day of
risperidone, 75–100 mg/day of clozapine, 200–300
mg/day of quetiapine, 10 mg/day of olanzapine,
and 15 mg/day of aripiprazole. In addition, risperidone
causes fewer extrapyramidal symptoms when used at dosages of 1 mg/day
than when used at higher doses (218). Clinicians should
keep in mind that these medications take time to work and that increasing
doses too rapidly may lead to the development of side effects rather
than more rapid efficacy. Although most patients with dementia do
best with dosages below these maxima, younger and less frail individuals
may tolerate and respond to somewhat higher doses, and very severely
agitated patients may also need higher dosages. In contrast, antipsychotic
agents must be used with extreme caution in patients with dementia
with Lewy bodies or Parkinson's disease, who can be exquisitely
sensitive to the extrapyramidal effects of these agents (232).
There are few relative efficacy data to guide the choice among
second-generation antipsychotic agents. The CATIE-AD trial did not
find significant differences in efficacy or tolerability among olanzapine,
quetiapine, and risperidone, although the time to discontinuation
due to lack of efficacy was longer for olanzapine and risperidone
than for quetiapine (228). Instead, the choice is based
most often on the side effect profile. As the overall side-effect
burden appears to be lower with second-generation agents, drugs
in this class are usually selected first. Widespread clinical practice
is to select the agent whose most common side effects are least
likely to cause problems for a given patient. For instance, clozapine might
be avoided if the patient is likely to be sensitive to anticholinergic
effects, or an agent lacking significant motor side effects such
as aripiprazole, clozapine, or quetiapine might be chosen if the
patient has Parkinson's disease, dementia with Lewy bodies,
or other sensitivity to extrapyramidal side effects. Aripiprazole
and quetiapine may be better first choices because their overall
side effect profile is more benign than that of clozapine (233–237).
The side effects of some medications might actually be beneficial
for certain patients. For example, a more sedating medication could
be given at bedtime for a patient who has difficulty falling asleep
in addition to agitation or psychosis. Antipsychotics are most commonly
administered in the evening, so that maximum blood levels occur
when they will help foster sleep and treat behavioral problems that
peak in the evening hours (sometimes called "sundowning").
Most of these medications have long half-lives, and once-a-day dosing
is generally sufficient. The one exception may be quetiapine, which
is usually administered twice daily. However, morning doses or twice-a-day
doses of the other agents may be helpful for patients with different
symptom patterns.
The availability of a specific formulation of an antipsychotic
may also contribute to the choice of a particular agent. Some antipsychotics
are available in liquid form (e.g., aripiprazole, risperidone, ziprasidone,
fluphenazine, haloperidol), and some (e.g., clozapine, olanzapine,
risperidone, aripiprazole) are available as rapidly dissolving wafers. Olanzapine,
ziprasidone, aripiprazole, fluphenazine, and haloperidol are available
in a rapid-onset injectable form, whereas risperidone, haloperidol,
and fluphenazine are available in long-acting injectable forms.
With the exception of olanzapine (223), these formulations
have not been studied in patients with dementia.
Benzodiazepines may have a higher likelihood of side effects
and a lower likelihood of benefit than antipsychotics (223, 238–243);
nonetheless, they are occasionally useful in treating agitation
in certain patients with dementia, particularly those in whom anxiety
is prominent. Their long-term use is generally to be avoided, but
they may be particularly useful on an occasional as-needed basis
for patients who have only rare episodes of agitation or those who
need to be sedated for a particular procedure, such as a tooth extraction
or a diagnostic study. Given the risk of disinhibition and consequent
worsening of target behaviors, oversedation, falls, and delirium, their
use should be kept to a minimum, with a maximum of 1–3
mg of lorazepam (or equivalent doses of other benzodiazepines) in
24 hours.
Among the benzodiazepines, many clinicians favor agents such
as oxazepam and lorazepam that do not require oxidative metabolism
in the liver and have no active metabolites. Temazepam shares these
characteristics but is more problematic because of its long half-life.
Oral lorazepam (or intramuscular in the event of an emergency) may
be given on an as-needed basis in doses from 0.5 to 1.0 mg every
4–6 hours. Standing oral doses of 0.5–1.0 mg may
be given from 1 to 4 times per day. Oxazepam is absorbed more slowly,
so it is less useful on an as-needed basis. Standing doses of 7.5–15.0
mg may be given 1 to 4 times per day. Some clinicians prefer long-acting
agents, such as clonazepam (starting at 0.5 mg/day with
increases up to 2 mg/day) (244). However,
such agents must be used with caution as described in the next paragraph.
The most commonly reported side effects with benzodiazepines
are sedation, ataxia, amnesia, confusion (even delirium), and possibly
paradoxical anxiety. These can lead to worsening cognition and behavior
and increase the risk of falls (245). Benzodiazepines
also carry a risk of respiratory suppression in patients with sleep-related
breathing disorders. Because all of these effects are dose related,
the minimum effective dose should be used. Agents with long half-lives (e.g.,
clonazepam) and long-lived metabolites (e.g., diazepam, chlordiazepoxide,
clorazepate, flurazepam) can take weeks to reach steady-state levels,
especially in elderly patients, so they generally are not used in
this patient population. Under unusual circumstances when they have
to be used, it must be with particular caution, with very low starting
doses and very gradual dosage increases. Elderly patients taking
long-acting benzodiazepines are more likely to fall, and to suffer
hip fractures, than those taking short-acting agents (246),
although it is possible that the total dose, not the duration of
action, is responsible for the increased fall risk (247).
Clinical experience suggests that like alcohol, benzodiazepines
may lead to disinhibition, although there are few data to support
this association. The risk of benzodiazepine dependence is also
a concern. If benzodiazepines are prescribed for an extended period
(e.g., 1 month), they should be tapered rather than stopped abruptly
because of the risk of withdrawal.
There is some evidence to suggest that carbamazepine may have
modest benefit for agitation when used in low doses in patients
with dementia (248–252). However, given the
relatively small body of clinical trials evidence, the high risk
of drug-drug interactions, and the known tolerability problems expected
with long-term use, carbamazepine is not recommended for the routine
treatment of agitation in patients with dementia.
Routine use of valproate to treat behavioral symptoms in dementia
is not recommended based on the current evidence. Most (253–255),
but not all (256), randomized placebo-controlled trials
showed no benefit of valproate, compared with placebo. In addition,
a 2004 Cochrane review (257) concluded that the various
formulations of valproate had not yet been shown to be effective.
Nonetheless, a therapeutic trial of carbamazepine or valproate
may be considered in individual cases (258), for example,
in patients who are sensitive or unresponsive to antipsychotics,
who have significant vascular risk factors, or who do not have psychosis
but are mildly agitated. Given the potential toxicity of both of
these anticonvulsant agents, it is important to identify and monitor
target symptoms and to discontinue the medication if no improvement
is observed.
If used, carbamazepine may be given in two to four doses per
day, started at a total dosage of 50–100 mg/day,
and increased gradually as warranted by behavioral response and side
effects or until blood levels reach 8–12 ng/ml.
Divalproex sodium may be given in two or three doses per day and should
be started at 125–250 mg/day, with gradual increases based
on behavioral response and side effects or until blood levels reach
50–60 ng/ml (or, rarely, 100 ng/ml).
The principal side effects of carbamazepine include ataxia,
falls, sedation, and confusion, all of which are of particular concern
for elderly patients and those with dementia. Carbamazepine can
cause drug interactions through its effect on the cytochrome P450
system. In rare instances, carbamazepine can lead to bone marrow
suppression or hyponatremia through the syndrome of inappropriate
antidiuretic hormone secretion. Valproate's principal side
effects are sedation, gastrointestinal disturbances, confusion,
ataxia, and falls. Bone marrow suppression, hepatic toxicity, thrombocytopenia,
and hyperammonemia can occur. Many clinicians monitor the CBC and
electrolyte levels in patients taking carbamazepine and monitor
the CBC and liver function values in patients taking valproate,
owing to the possibility of bone marrow suppression, hyponatremia,
and liver toxicity. However, these practices are not followed by
all clinicians. A particularly cautious approach is warranted when
treating elderly patients and those with dementia, who may be more vulnerable
to adverse effects, particularly central nervous system effects,
and yet less likely to be able to report warning symptoms.
For additional details concerning the assessment and monitoring
necessary during use of these agents, along with their side effects
and potential toxicities, the reader is referred to APA's Practice
Guideline for the Treatment of Patients With Bipolar Disorder,
2nd edition (259).
Support for the use of trazodone or buspirone is limited to data
from case series and small clinical trials (214, 260–269).
Therefore, neither agent can be recommended for the routine treatment
of agitation and psychosis in patients with dementia. Although the
evidence suggesting efficacy of SSRIs for agitation is somewhat
stronger (262, 270, 271),
further study is needed before they can be recommended for routine
use. Nonetheless, a therapeutic trial of trazodone, buspirone, or
an SSRI may be appropriate for some nonpsychotic but agitated patients,
especially those with relatively mild symptoms or those who are
intolerant of or unresponsive to antipsychotics.
When patients are taking SSRIs, clinicians need to keep in mind
the serotonin syndrome, caused by excessive serotonergic activity,
usually as a result of serotonergic medications being combined (including
buspirone and SSRIs). Symptoms include delirium, autonomic instability,
and increased neuromuscular activity, such as myoclonus.
When trazodone is used, the principal side effects are postural
hypotension, sedation, and dry mouth. Priapism can occur but is
uncommon. Trazodone is generally given before bedtime but can be
given in two or three divided doses per day. It can be started at
25–50 mg/day and gradually increased to a maximum
dosage of 150–250 mg/day.
When male patients display inappropriate sexual behavior,
a particular problem in patients with frontal lobe dementias, medroxyprogesterone
and related hormonal agents are sometimes recommended (272–274),
a recommendation supported only by case series at present. Because
SSRIs may reduce libido and are probably safer, they may be tried
before hormonal agents (275).
Lithium carbonate has also been suggested as a treatment for
agitation because of its occasional utility for agitated patients
with mental retardation, but support for it is quite limited, and
side effects and toxicity are common, including delirium (210).
Therefore, routine use of lithium to treat agitation in patients
with dementia is not recommended.
Beta-blockers, notably propranolol, metoprolol, and pindolol,
have also been reported to be helpful for some agitated patients
with dementia (276). However, most of the patients
included in the case reports had somewhat atypical clinical features,
raising questions about the generalizability of these reports. In
addition, large dosages (e.g., 200–300 mg/day
of propranolol) were used, and such dosages create a considerable
risk of bradycardia, hypotension, and delirium for elderly patients.
One small randomized, double-blind, placebo-controlled trial of propranolol
in patients with Alzheimer's disease and behavioral disturbance
did show benefit over placebo for certain symptoms although it was
noted that beta-blocker use was contraindicated for many subjects
who would otherwise have been eligible for the study (277).
Therefore, routine use of beta-blockers to treat agitation in patients
with dementia is not recommended.
+
c. Treatments for Depression and
Related Symptoms
Recognition and treatment of depression is crucial in individuals
with dementia, because the presence of depression has been associated
with higher rates of disability, impaired quality of life, and greater
mortality (278). The best approach to diagnosing depression
in the context of dementia is not yet clear. Provisional criteria
for depression of Alzheimer's disease have been proposed
but not yet validated (279). The Depression and Bipolar
Support Alliance Consensus Statement Panel reported that the diagnostic
criteria for depression in individuals with dementing disorders
must be revised (105). They recommended that the criteria
take into account the instability and fluctuation of symptoms over
time, the reduction in positive affect or pleasure, and the inclusion
of irritability, social withdrawal, and isolation as indicators
of depression. Until criteria for depression in dementia are established,
patients should be carefully evaluated for any of the symptoms of
depression outlined in DSM-IV-TR. Even those patients with depressive
symptoms who do not meet the diagnostic criteria for major depression
should be considered as candidates for depression treatment. The
presence of neurovegetative symptoms, suicidal ideation, and mood-congruent
delusions or hallucinations may indicate a need for more vigorous
and aggressive therapies (such as higher medication dosages, multiple
medication trials, or ECT).
Depression may worsen cognitive impairment associated with
dementia. Therefore, one goal of treating depression in dementia
is to maximize cognitive functioning. Sometimes cognitive deficits
partially or even fully resolve with successful treatment of the
depression. Nonetheless, because as many as one-half of such persons
do develop dementia within 5 years (280, 281),
caution is urged in ruling out an underlying early dementia in patients
with both affective and cognitive symptoms, particularly when the
first episode of depression is in old age. Treatment of depression
may also reduce other neuropsychiatric symptoms associated with
depression such as aggression, anxiety, apathy, and psychosis (282, 283).
When treatment for depression is being considered, patients
should be evaluated for conditions that may be causing or contributing
to the depression. Among these conditions are other psychiatric
disorders (e.g., alcohol or sedative-hypnotic dependence), other
neurological problems (e.g., stroke, Parkinson's disease),
general medical problems (e.g., thyroid disease, cardiac disease,
or cancer), and the use of certain medications (e.g., corticosteroids,
benzodiazepines).
As described in APA's Practice Guideline
for the Treatment of Patients With Major Depressive Disorder
,
2nd edition (284), many well-designed clinical trials
support the efficacy of antidepressants in depressed elderly patients
without dementia (285–288). However, these
data may not extrapolate to patients with co-occurring dementia.
Placebo-controlled trials of antidepressants in patients with dementia
have shown mixed results (289–296). Despite
this mixed evidence, clinical consensus supports a trial of an antidepressant
to treat clinically significant, persistent depressed mood in patients
with dementia. SSRIs may be preferred because they appear to be
better tolerated than other antidepressants (297–299).
Some patients with dementia and depression do not tolerate the dosages
needed to achieve full remission. When a rapid response is not critical,
a very gradual dosage increase may increase the likelihood that
a therapeutic dosage will be reached and tolerated. After prolonged
use, medications should be withdrawn gradually whenever possible,
in order to avoid withdrawal symptoms.
The reader is referred to APA's Practice
Guideline for the Treatment of Patients With Major Depressive Disorder
,
2nd edition (284) for a detailed discussion of the
side effects of antidepressant agents. Side effects, divided by
medication class, are briefly summarized here.
Compared to cyclic antidepressants and monoamine oxidase inhibitors
(MAOIs), SSRIs tend to have a more favorable side-effect profile
and generally have fewer anticholinergic and cardiovascular side
effects. However, SSRIs can produce nausea and vomiting, agitation
and akathisia, parkinsonian side effects, sexual dysfunction, weight
loss, and hyponatremia. Some of these effects are more common with specific
SSRIs than with the entire class. As with most psychotropic medications,
SSRI use is associated with an increased risk of falls in elderly
patients (300). Physicians prescribing SSRIs should
also be aware of the many possible medication interactions associated
with the metabolism of these agents through the cytochrome P450 system.
Alternative agents to SSRIs include but are not limited to venlafaxine,
mirtazapine, and bupropion. The serotonin-norepinephrine reuptake
inhibitor venlafaxine is metabolized through the cytochrome P450
system, but because it does not induce or inhibit these enzymes,
it is less likely to interact with other drugs metabolized through
the same system. One side effect more commonly seen with venlafaxine than
other antidepressants is an elevation in blood pressure, which may
be less likely with the sustained release formulation. Duloxetine,
another inhibitor of serotonin and norepinephrine reuptake, is commonly
used to treat major depression, but clinical experience with its
use in geriatric patients with dementia is limited, and there are
no published clinical trials to support its use. Mirtazapine, a
noradrenergic/specific serotonergic antidepressant, can
produce sedation and weight gain, especially at low doses. Rare
but potentially serious side effects of mirtazapine are liver toxicity
and neutropenia. Bupropion, a norepinephrine-dopamine reuptake inhibitor,
has been associated with a risk of seizures, especially at high
doses, in patients with anorexia or with structural neurological
problems. Trazodone, a serotonin-2 antagonist/reuptake
inhibitor, has sedative side effects and can be used when insomnia
or severe agitation are prominent. At higher doses, significant
side effects include postural hypotension and priapism.
Cyclic antidepressants or MAOIs can be used to treat depression
in patients with dementia if other classes of agents have failed
or are contraindicated. However, the prominent cardiovascular and
anticholinergic side effects associated with these agents make them
undesirable first- or second-line agents. The most problematic side
effects are cardiovascular effects, including orthostatic hypotension
and cardiac conduction delay, and anticholinergic effects, including
blurred vision, tachycardia, dry mouth, urinary retention, constipation,
sedation, impaired cognition, and delirium. If a cyclic antidepressant
is used, agents with significant anticholinergic properties such
as imipramine and amitriptyline should be avoided. In terms of MAOI
treatment, only the reversible MAOI moclobemide has been studied
for treating depression in patients with dementia. Although moclobemide
is less toxic than the irreversible MAOIs, it is not currently available
in the United States. If nonselective irreversible MAOIs are prescribed,
the required dietary restrictions necessitate close monitoring of
food intake, because a patient with dementia cannot be relied on
to adhere to these restrictions.
As with most other medications, low starting doses, small dose
increases, and long intervals between dose increases are generally
necessary when implementing antidepressants for elderly patients.
Citalopram is started at 5–10 mg/day and increased
at several-week intervals to a maximum of 40 mg/day. Sertraline
may be started at 12.5–25.0 mg/day and increased
at 1–2-week intervals up to a maximum dosage of 150–200
mg/day.
If these agents are ineffective and other agents are chosen, the
starting doses are as follows. Venlafaxine can be started at a dosage
as low as 25 mg/day (extended release, 37.5 mg/day)
and increased at approximately weekly intervals up to a maximum
dosage of 375 mg/day in divided doses (extended release,
225 mg/day). If venlafaxine is prescribed, careful monitoring
of blood pressure is indicated. Mirtazapine can be started at a
dosage as low as 7.5 mg at bedtime and increased by 7.5-mg or 15-mg
increments to 45–60 mg at bedtime. Lower dosages have been
associated with sedation and appetite increase, both of which may
be beneficial for depressed patients with insomnia or anorexia.
Less sedation is found in dosages over 15 mg/day. Caution
should be used in prescribing this agent for patients with liver
dysfunction or renal impairment and for patients who develop signs
of infection. Bupropion can be started at 37.5 mg once or twice per
day (sustained release, 100 mg/day) and increased slowly to
a maximum dosage of 300 mg/day in divided doses (sustained
release, 300 mg/day). No more than 150 mg of immediate
release bupropion should be given within any 4-hour period because
of the risk of seizures. Duloxetine can be started at 20–40
mg/day and increased slowly to a maximum of 60–80
mg/day, typically in divided doses.
+
2. Psychostimulants and dopamine
agonists
There is a small amount of evidence (301, 302)
that dopaminergic agents such as psychostimulants (d-amphetamine,
methylphenidate), amantadine, bromocriptine, and bupropion may be
helpful in the treatment of severe apathy in patients with dementia.
Psychostimulants have also received some support for the treatment
of depression in elderly individuals with severe general medical
disorders (303–305). In general, these agents
may be associated with tachyarrhythmias, hypertension, restlessness,
agitation, sleep disturbances, psychosis, confusion, dyskinesias,
and appetite suppression, particularly at high doses, and amantadine
may also be associated with significant anticholinergic effects. Starting
dosages of dextroamphetamine and methylphenidate are 2.5–5.0
mg in the morning. The starting dose can be increased by 2.5 mg
every 2 or 3 days to a maximum of 30–40 mg/day.
+
3. Electroconvulsive therapy
Although the data supporting the efficacy and safety of ECT
in the treatment of depression in dementia are limited to one small
retrospective chart review study, there are significant data supporting
its use in geriatric depression in patients without dementia (306–308).
Therefore, in the presence of dementia, ECT should only be considered
for treating depression that is severe, life-threatening, or does
not respond to other treatments. The most common significant side
effect is transient confusion, which in turn increases the risk
of falls, dehydration, and other complications. Twice weekly rather
than thrice weekly and high-dose unilateral (309) or
bifrontal rather than bitemporal ECT may decrease the risk of cognitive
side effects after ECT. Clinicians should refer to The
Practice of Electroconvulsive Therapy. Recommendations for Treatment,
Training, and Privileging: A Task Force Report of the American Psychiatric
Association (310) for a full discussion
of the use of ECT and other potential side effects of ECT treatment.
+
d. Treatments for Sleep Disturbance
Sleep problems have been reported in 25%–50% of
patients with dementia (311, 312), and
provisional criteria for sleep disturbances associated with Alzheimer's
disease have been proposed (313). Major causes of sleep
disturbances in this population include physiological changes associated
with aging (fragmented nocturnal sleep, multiple and prolonged awakenings, relative
decrease in slow-wave sleep percentage, and increased daytime napping),
pathological involvement of the suprachiasmatic nucleus, the effects
of co-occurring medical or psychiatric disorders or medications,
untreated pain, and poor sleep hygiene (314, 315).
Cholinesterase inhibitors can also cause insomnia (141).
Some over-the-counter sleep medications (e.g., diphenhydramine)
can contribute to delirium and paradoxically worsen sleep. Thus,
it is important to ask if the patient is using over-the-counter
diphenhydramine or other over-the-counter or herbal preparations
to treat sleep disturbance.
Treatment of sleep disturbance in dementia is aimed at decreasing
the frequency and severity of insomnia, interrupted sleep, and nocturnal
confusion in patients with dementia. In addition to addressing the
sleep complaints of people with dementia, treatment goals are to
increase patient comfort, decrease disruption to families and caregivers,
and decrease nocturnal wandering and nighttime accidents.
Available data do not support the recommendation of a specific
course of action for treating sleep disturbances in patients with
dementia. Although the data are sparse, clinical practice favors
beginning with nonpharmacological approaches when the sleep disorder
is an isolated problem. There are few studies of behavioral, environmental,
or pharmacological interventions to improve sleep in this population,
although there is some evidence that training caregivers in how
to implement proper sleep hygiene can result in improved sleep for
patients with dementia (316, 317). A number
of trials of bright light therapy have been conducted but have failed
to demonstrate significant clinical benefit (315, 318–322).
Nevertheless, the psychiatrist treating a patient for a sleep disorder
can follow a number of general clinical guidelines in developing
a treatment plan. In meeting the needs of both the patient and his
or her caregivers, clinicians should consider behavioral and environmental
interventions, combine nonpharmacological and pharmacological therapies, and
seek to avoid use of multiple psychotropic medications (314).
Other initial steps may include establishing regular sleep and waking
times, limiting daytime sleeping, avoiding fluid intake in the evening,
establishing calming bedtime rituals, and providing adequate daytime
physical and mental activities (323–325).
Underlying medical and psychiatric conditions that could disturb
sleep should be evaluated and treated. Medications that could interfere
with sleep should be adjusted if possible. If the patient lives
in a setting that can provide adequate supervision without causing
undue disruption to others, allowing the patient to sleep in the
daytime and be awake at night is an alternative to pharmacological
intervention. Pharmacological treatment should be instituted only
after other measures have been unsuccessful and the potential benefits outweigh
the risk of side effects. It is particularly important to identify
sleep apnea (326), which may affect 33%–70% of
patients with dementia (324). This condition is a relative
contraindication to the use of benzodiazepines or other agents that
suppress respiratory drive.
If another behavioral or neuropsychiatric condition is present,
and medications used to treat that condition have sedative properties,
clinical practice favors prescribing that agent at bedtime, if appropriate,
to assist with treatment of insomnia. For example, an antidepressant
with sedative properties (e.g., mirtazapine or trazodone) can be
given at bedtime if both sleep disorder and depression are present.
If the patient has psychotic symptoms and sleep disturbance, second-generation
antipsychotics may be the initial treatment of choice. If there
are clear deficits in the patient's sleep hygiene, then
education and behavioral management might be the preferred treatment
course.
Pharmacological interventions include a number of agents.
Some clinicians prefer 25–100 mg of trazodone at bedtime
for sleep disturbances, whereas others prefer the nonbenzodiazepine
hypnotics such as zolpidem (5–10 mg at bedtime) or zaleplon
(5–10 mg at bedtime). Benzodiazepines (e.g., 0.5–1.0
mg of lorazepam, 7.5–15.0 mg of oxazepam) may be used but
are generally recommended only for short-term sleep problems because
of the possibility of tolerance, daytime sleepiness, rebound insomnia,
worsening cognition, falls, disinhibition, and delirium. Rebound
insomnia and daytime sleepiness can occur with any of these agents
(327). Triazolam is not recommended for individuals
with dementia because of its association with amnesia. Diphenhydramine,
which is found in most over-the-counter sleep preparations, is used
by some clinicians, but it is not recommended for the treatment
of patients with dementia because of its anticholinergic properties.