Second edition

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also occur as a side-effect to various medications, for example
bupropion. Pain may also cause patients to become agitated
and this is particularly the case in elderly patients with
dementia.
Differential diagnosis
Anxious patients may appear quite tense but generally are
not given to restless pacing, and certainly not to violent or
destructive behavior.
Akathisia, seen primarily as a side-effect to antipsychotics,
may appear very similar to agitation. Clues to the
correct diagnosis include a worsening of symptoms when
sitting or lying down and a tendency to ‘march in place’.
Treatment
Environmental measures can sometimes be remarkably
effective in calming an agitated patient (Alessi et al. 1999).
Overall stimulation should be kept to a minimum, and
patients should be provided with constructive and quietly
engaging activities. Interactions with the patient should
preferably be on a one-to-one basis and, if it is necessary to
have two people with the patient, it is important to ensure
that only one person does all the talking. When patients
tend to roam, they should generally be allowed to do so,
provided that their behavior endangers neither themselves
nor others. A private room should be provided, and if that
is not possible then a calm patient should be selected as a
roommate; in all cases, the room should have a large clock
and calendar, and a window. Visitors should be screened, as
in some cases certain visitors will agitate patients further; in
general, there should be only one visitor at a time. Sitters are
often utilized, and may obviate the need for restraints but,
like visitors, sitters should be carefully screened: although
some have a good ‘way’ with agitated patients, others may
simply worsen the situation. Seclusion or restraints may at
times be required and one must not be shy about ordering
them, as they may at times be life-saving.
In all instances of agitation, it is also necessary to dovetail
the symptomatic treatment of agitation with other
aspects of treatment of the parent syndrome, and the
reader is directed to the appropriate chapter on dementia,
delirium, etc.
Pharmacologic treatment is typically required: agents
utilized include antipsychotics (e.g., risperidone, haloperidol,
quetiapine, or olanzapine), anti-epileptic drugs (e.g.,
divalproex and carbamazepine), and benzodiazepines (e.g.,
lorazepam). As noted above, agitation usually occurs as
part of a larger syndrome and the choice of pharmacologic
agent is often dictated by the syndrome within which the
agitation is occurring. In the following, each of the more
common syndromes is considered in turn, with recommendations
for both non-emergent and emergent treatment;
all of the recommendations, except where otherwise
6.4 Agitation 223
noted, are based on double-blind studies. Importantly, as
noted under the concluding remarks, these recommendations
are offered as guidelines only: clinical reality often dictates
alternative approaches and good clinical judgment is
absolutely required.
Dementia
For non-emergent care, effectiveness has been demonstrated
for risperidone (Brodaty et al. 2003; De Deyn et al.
2005), quetiapine (Zhong et al. 2007), haloperidol (Allain
et al. 2000), and olanzapine, with haloperidol being of equal
effectiveness to olanzapine (Verhey et al. 2006) and risperidone
of equal effectiveness to olanzapine (Fontaine et al.
2003). In a partially blinded study (Porsteinsson et al. 2001)
divalproex was effective, but a double-blinded study found
it to be no more effective than placebo (Sival et al. 2002). In
addition, one study found trazodone to be of similar efficacy
to haloperidol (Sultzer et al. 1997).
In looking at more specific kinds of dementia, the effectiveness
of haloperidol in Alzheimer’s disease is uncertain:
one study (Devanand et al. 1998) supported its use, whereas
another (Teri et al. 2001) did not. Olanzapine (Street et al.
2000) appeared effective in a comparison with placebo, and
in a large study olanzapine and risperidone were more effective
than either quetiapine or placebo (Schneider et al.
2006). Carbamazepine (Olin et al. 2001; Tariot et al. 1998)
appears effective but valproic acid is not (Hermann et al.
2007; Tariot et al. 2005). Trazodone does not appear to be
effective (Teri et al. 2001). There is an intriguing study suggesting
that citalopram may be effective (Pollock et al. 2002).
In Parkinson’s disease and diffuse Lewy body disease, quetiapine
was not effective (Kurlan et al. 2007).
Overall, for the non-emergent treatment of agitation in
dementia, it may be best to begin with a low dose of risperidone,
perhaps 0.25 or 0.5 mg/day, with a gradual titration up
to a maximum of perhaps 2 mg. Should this be ineffective or
not tolerated then consideration may be given to quetiapine,
beginning at 25 mg and increasing the dose gradually, if necessary,
to 200 mg, or to olanzapine, beginning with a low
dose of perhaps 2.5 mg and titrating gradually, if necessary,
to a maximum of 10 mg. Consideration may also be given to
carbamazepine and, perhaps, divalproex: in either case, the
initial dose should be low, with very gradual titration to
effectiveness, limiting side-effects, or a blood level within the
therapeutic range, whichever comes first.
In emergent cases, consideration may be given to
intramuscular olanzapine in a dose of 5 mg (Meehan et al.
2002), with repeat doses if needed.
Before leaving this section, some words are in order
regarding the risk of death or stroke in elderly demented
patients treated with antipsychotics. Although these
risks are indeed increased for second-generation agents
(Kryzhanovskaya et al. 2006), and even more so for firstgeneration
agents (Wang et al. 2005), this increased risk, as
with any medical treatment, must be weighed against the
benefits obtained with treatment.