Second edition

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lorazepam without any loss of control. The anti-epileptic
drug is then continued for a week or more until the withdrawal
has run its course, at which time it may be tapered
and discontinued over a few days.
Mania
In cases of mania wherein significant agitation has
appeared, emergent care is almost always required, and
treatment may be undertaken with either divalproex
(McElroy et al. 1996) or an antipsychotic (e.g., haloperidol
[McElroy et al. 1996], aripiprazole [Zimbroff et al. 2007],
or olanzapine [Tohen et al. 2002]), or, often, with a combination
of divalproex and an antipsychotic. Divalproex may
be given in a loading dose of 20 mg/kg/day in two or three
divided doses, with subsequent adjustments based on clinical
response, side-effects, and blood levels. Haloperidol,
aripiprazole, or olanzapine may be given as described
above, under psychosis. Once the mania is controlled, it is
often possible to taper and discontinue the antipsychotic.
Depression
In most cases of agitated depression, reassurance coupled
with ongoing treatment with an antidepressant, will suffice.
Emergent treatment, occasionally, may be required
when agitation is extreme. In such cases, case reports suggest
an effectiveness for benzodiazepines such as alprazolam
(Gilbert and Hendrie 1987), and case series, for
low-dose divalproex (Debattista et al. 2005).
Concluding remarks
Good clinical judgment often dictates a course of treatment
that differs from those recommended above. Doses
must often be reduced in elderly or frail patients, and in
those with significant hepatic dysfunction. Antipsychotics
other than risperidone, haloperidol, and olanzapine are
often used successfully, and haloperidol, given its tendency
to cause extrapyramidal side-effects, is falling into disfavor.
Lorazepam is used quite routinely, and its sedative effect is
often quite welcome. In some cases, certain medications
are relatively contraindicated: for example, in cases of
dementia secondary to diffuse Lewy body disease haloperidol
should probably not be used, given the risk of severe,
even fatal, parkinsonism (McKeith et al. 1992).
6.5 ANXIETY
Pathologic anxiety occurs in two forms. In one, anxiety is
more or less persistent, whereas in the other it occurs in
discrete attacks.
Clinical features
Persistent anxiety tends to come on gradually, and waxes
and wanes over time. The anxiety itself is typically accompanied
by autonomic signs such as tremor, tachycardia, and
diaphoresis. Patients complain of a sense of tremulousness,
6.5 Anxiety 225
and the tremor itself is fine and postural. Tachycardic patients
may complain that the heart is ‘racing’ and there may be palpitations.
Diaphoresis may be evident when one shakes the
patient’s hand. The duration of this persistent form of anxiety
depends on the underlying cause and may, for example, range
from years or decades in the case of generalized anxiety disorder
to weeks or less in alcohol withdrawal.
Anxiety attacks typically arise acutely, over minutes,
and symptoms crescendo rapidly. In addition to the anxiety,
which may be quite extreme, patients also typically
experience a variety of other symptoms, including tremor,
tachycardia, palpitations, diaphoresis, dyspnea, lightheadedness,
nausea, and parasthesiae. The duration of the
attack, although determined by the underlying cause, is
generally brief, lasting from minutes to an hour or more.
Etiology
The various causes of anxiety are listed in Table 6.5, where
they are divided into those causing persistent anxiety and
those causing anxiety attacks.
PERSISTENT ANXIETY
The most common cause of persistent anxiety is an idiopathic
disorder, namely generalized anxiety disorder
(Anderson et al. 1984; Nisita et al. 1990). This disorder
generally has an onset in adolescence or early adult years,
and the characteristic anxiety tends to persist, in a waxing
and waning fashion, for from years to decades.
Toxic causes include caffeine (Greden 1974; Hughes
et al. 1991a) and sympathomimetics such as ephedrine
and phenylpropanolamine (Sawyer et al. 1982) and ephedra
alkaloids, found in many ‘herbal supplements’ (Haller and
Benowitz 2000). Others include theophylline (Trembath
and Boobis 1979) and levodopa (Celesia and Barr 1970).
Although, in general, anxiety only occurs with high doses,
some patients may be quite sensitive to these medications
and experience considerable anxiety at ‘therapeutic’ doses.
Metabolic causes include hypocalcemia, as may be seen
in hypoparathyroidism (Carlson 1986; Denko and
Kaelbling 1962; Lawlor 1988), and the hypoxia and hypercarbia
associated with respiratory failure, as in advanced
chronic obstructive pulmonary disease (Brenes 2003) and
severe congestive heart failure.
Substance or medication withdrawals are considered
next. Of the substance withdrawals, alcohol withdrawal
(Isbell et al. 1955) probably constitutes one of the most
common causes of persistent anxiety seen in general hospital
practice, and the diagnosis is often missed, given that
patients in withdrawal typically either minimize their alcohol
use or deny it altogether. A similar scenario may occur
in patients withdrawing from sedative/hypnotics, such as
benzodiazepines (Rickels et al. 1990). Nicotine withdrawal
is typified by anxiety, irritability, and a craving for a ‘smoke’
(Hughes and Hatsukami 1986; Hughes et al. 1991b), and