Successful treatment of depression should be continued for at least
6 months, then the dosage should be slowly tapered. When response to treatment is inadequate, the most common reason
is inadequate dosage. The dose should be increased every 1 to 2 weeks until depressive symptoms resolve, side effects occur,
or the maximum allowable dose is reached. If depressive symptoms persist after a reasonable therapeutic trial, an antidepressant
from a different class should be prescribed. When no response is achieved despite adequate trials of multiple agents, the
diagnosis of depression should be reconsidered and the patient referred to a psychiatrist. More aggressive
treatment in patients with refractory depression may include use of a monoamine oxidase inhibitor, stimulants, or electroconvulsive
therapy. The need for continued therapy should be reassessed often, because worsening dementia may resolve depressive
symptoms and signs.
Families of patients with dementia can often tolerate agitation, delusions,
and wandering as long as nighttime sleep remains uninterrupted. However, when behavioral disturbances occur day and night,
families often feel compelled to resort to institutionalization. Educating families about strategies for
preventing or correcting sleep problems may help delay nursing home placement.
Many factors can contribute to poor sleep habits in persons with dementia, including
disrupted sleep patterns, alterations in circadian rhythm, concurrent medical problems that cause frequent urination, daytime
use of sedating medication, and frequent napping. In our experience, the chief causes of sleep disruption are frequent napping
and excessive expectation of sleep needs.
Families often report that the patient wakes and dresses for morning activities
at 3 AM. On further questioning, they may reveal that the patient naps while watching television during the day and goes to
bed at 8 PM. In this common scenario, the patient's early morning awakening is not abnormal. Daily sleep requirements do not
increase as a person ages, and the patient is often sleeping more than the 7 to 8 hours required for most persons to feel
rested. In addition, caregivers often see the patient's nap time as an opportunity
to accomplish tasks around the house. This is a shortsighted view that many come to regret.
The first step in reestablishing a normal sleep pattern is to limit daytime napping.
Leaving a patient with dementia in front of a television set almost always leads to napping. To prevent
this, caregivers should engage patients in activities that are tailored to the degree of dementia, such as simple handicrafts,
household tasks and, most important, regular physical exercise. Such activities can be carried out at home, but many
patients and families benefit from the added structure of adult day care.
Once poor sleep hygiene has become established, it is much
more difficult to eradicate. The first steps in correcting sleep problems are to set a more reasonable bedtime and
prevent napping. The patient's activity level should be increased, and fluid intake should be decreased in the hours before
bedtime. After a few difficult nights, the patient will begin to sleep for longer periods. For families who cannot accept
the possibility that the problem will worsen before improving, limited use of a hypnotic or sedating drug (eg,
trazodone, zolpidem tartrate [Ambien], a short-acting benzodiazepine) may be considered. However, long-term reliance
on sleeping medication, especially benzodiazepines, is rarely successful.
Environmental lighting may also have a role in sleep disturbance.
Light is an important modulator of circadian rhythms, which may be disrupted in dementia.
Increased lighting during afternoon and early evening hours may improve sleeping patterns. Van Someren and associates (2)
studied the effect of increased daytime illumination in 22 patients with dementia. Improvement in the rest-activity rhythm
occurred in patients with intact vision but not in visually impaired patients. A clinical trial assessing the efficacy of
melatonin in the treatment of sleep disturbance in Alzheimer's disease is under way, but results are not yet available.
The most difficult part of managing sleep problems is the need for continued adherence
to a rigid schedule. Families should be taught that periodic disruption of the schedule will likely result in a return to
irregular sleep patterns. Authorizing use of a hypnotic agent for periodic administration is helpful and provides families
with a sense of control.
Agitation and aggression
Agitation occurs at some time in about half of all patients with dementia (3).
Associated behaviors include aggression, combativeness, disinhibition, and hyperactivity. As with
all behavioral problems, the first step in treatment is to identify the precipitants. Evaluation
should include assessment for common systemic causes (eg, infection, dehydration, constipation, other illnesses) as well as
changes in medication.
Families should be informed about potential causes of agitation, such as excessive
stimulation, and about the need to make educated guesses about circumstances that trigger inappropriate behavior. Patients
with dementia often become agitated when rushed; therefore, avoiding time-critical events, if possible,
is useful. The patient's day should be structured to provide a predictable routine. Orientation materials (eg, calendar, clock,
family pictures) should be prominently displayed, and the living environment should be well lit, even in the daytime, to avoid
misperception of stimuli. Behaviors that are disruptive but not harmful (eg, pacing) should be tolerated. Physical restraint
is rarely necessary and usually serves to escalate the degree of agitation.
Agitation and aggression continued
If environmental measures are insufficient
to control agitated or aggressive behavior, medication is needed. High-potency
neuroleptics (eg, haloperidol [Haldol], thioridazine hydrochloride [Mellaril]) are effective for controlling agitation,
especially when psychotic features are present (3). Although there is no evidence to suggest that one neuroleptic agent is
more effective than another, the atypical antipsychotics (ie, clozapine [Clozaril], risperidone [Risperdal],
olanzapine [Zyprexa], and quetiapine fumarate [Seroquel]) have a lower frequency of extrapyramidal side effects (eg, parkinsonism,
tardive dyskinesia). They are very useful in patients with Parkinson's disease because their selective dopaminergic
blockade does not interfere with dopamine's therapeutic effect in the basal ganglia. However, atypical antipsychotics are
expensive. Benzodiazepines can also be used to treat anxiety or infrequent agitation, but they are less effective than other
agents for long-term treatment.
In general, when agitation is a consistent problem and neuroleptic treatment
is required, start with a low dose (eg, 0.5 mg of haloperidol or 1 mg
of risperidone) and administer it on a regular basis rather than attempting to treat specific episodes
of agitation. Trying to treat a patient who is already agitated makes administering
medication difficult, requires larger doses, and is likely to cause sedation and further clouding of thought.
The anticonvulsants carbamazepine and divalproex sodium (Depakote)
are effective in treating behavioral disturbances in dementia and have a different side-effect profile than that of neuroleptics.
In a double-blind study, Tariot and colleagues (4) examined the effect of carbamazepine on agitation in 51 nursing home patients.
Global improvement was noted in 77% of patients receiving carbamazepine and 21% of those receiving placebo. Analysis
of the data confirmed that the positive changes were due to decreased agitation and aggression. The drug was well tolerated,
and no change in cognition or functional status occurred. The modal carbamazepine dose was 300 mg a day, and the mean
serum level was 5.3 micrograms/mL. Carbamazepine also appears to be effective when added to neuroleptic therapy in patients
with refractory agitation (5). Divalproex is an effective treatment for mania in bipolar affective
disorder (6) as well as agitation in dementia (7).
Other classes of drugs are useful for treating agitation.
Antidepressants, especially SSRIs and trazodone, are effective even in the absence of clear depressive
symptoms. The acetylcholinesterase inhibitors, donepezil hydrochloride (Aricept) and tacrine hydrochloride
(Cognex), decrease agitation, possibly by stimulating attention and concentration (8). The beta blocker propranolol
hydrochloride (Inderal) inhibits impulsive behavior after frontal lobe injury and can be used to
decrease agitation and aggressive behavior in dementia, but it may cause bradycardia and hypotension
The need for continued pharmacologic treatment of agitation should be regularly
reassessed. Medication for agitation should not be viewed as long-term
therapy (10). In one study, neuroleptic treatment was discontinued after agitation
was successfully treated in nine patients with dementia (10). A placebo was then administered, and behavior was monitored
for the next 6 weeks. Eight of the nine patients did not need additional pharmacologic treatment. Interestingly, five of the patients were less agitated after drug treatment was stopped.
Delusions and hallucinations
Delusions (ie, false fixed beliefs) are common in dementia. Patients with Alzheimer's
disease often become suspicious of family members and may accuse them of stealing. Some patients believe that intruders are
trying to break into their house or that long-dead family members are alive. Visual and auditory hallucinations may also occur.
Some hallucinations, such as seeing an imaginary child playing on the floor, are nonthreatening, whereas
other hallucinations are threatening and may precipitate agitation or violence.
Before pharmacotherapy is initiated, the cause of the psychosis (eg, onset of another
illness, a medication effect) should be determined, if possible. If no cause is found, environmental changes, such as increased
lighting and decreased social isolation, can help. An increase in environmental noise (eg, from a radio or television) is
beneficial in some patients but may increase delusions in other patients.
Psychotic features are disturbing to caregivers, even when the patient does not appear
to be bothered by them. Nonthreatening delusions and hallucinations need not be treated. Families should
be reassured about the benign nature of these features and informed of the potential side effects of drug therapy.
When short-term pharmacologic treatment is needed, it should be initiated with low doses of a high-potency or atypical antipsychotic.
Haloperidol is effective in patients with dementia, but dosages higher than
3 mg a day often lead to excessive sedation and parkinsonian side effects. Low-potency antipsychotics should be avoided
because of their anticholinergic effects. For long-term treatment, we use one of the drugs suggested for agitation (eg, an
SSRI, acetylcholinesterase inhibitor, or anticonvulsant) and begin tapering the antipsychotic medication as soon as possible.
Behavioral problems in patients with dementia are common. Fortunately, nonpharmacologic
and pharmacologic therapies are often effective and can dramatically improve the quality of life for patients as well as their
families. However, treatment is rarely successful immediately. The old treatment adage "start low and go slow" is a key to