C H A P T E R 2 2
Psychotherapeutic agents
339
Therapeutic actions and indications
The typical antipsychotic drugs block dopamine recep-
tors, preventing the stimulation of the postsynaptic
neurons by dopamine. They also depress the RAS,
limiting the stimuli coming into the brain. They also have
anticholinergic, antihistamine and alpha-adrenergic
blocking effects, all related to the blocking of the
dopamine-receptor sites. Newer atypical antipsychotics
block both dopamine and serotonin receptors. This
dual action may help to alleviate some of the unpleasant
neurological effects and depression associated with the
typical antipsychotics (see Table 22.1).
The antipsychotics are indicated for schizophrenia
and for manifestations of other psychotic disorders,
including hyperactivity, combative behaviour and severe
behavioural problems in children (short-term control);
some of them are also approved for the treatment of
bipolar disorder. Chlorpromazine, one of the older
antipsychotics, is also used to decrease preoperative
restlessness and apprehension, to treat intermittent por-
phyria, as an adjunct in the treatment of tetanus and
to control nausea, vomiting and intractable hiccups.
Haloperidol is frequently used to treat acute psychiat-
ric situations and is available for intravenous (IV) use
when prolonged parenteral therapy is required because
of swallowing difficulties or the acuity of the behav-
ioural problems. Prochlorperazine is also frequently used
to control severe nausea and vomiting associated with
surgery and chemotherapy. It has the advantage of being
available in oral, rectal and parenteral forms. Aripipra-
zole, one of the newer atypical antipsychotics, has been
found to be effective in treating schizophrenia, major
depressive disorder and bipolar disorders and has been
used parenterally for the treatment of acute agitation
associated with these disorders. Olanzapine and ziprasi-
done are also used for bipolar disorders and parenterally
to treat acute agitation. Quetiapine is also approved for
short-term treatment of acute manic episodes associated
with bipolar disease. Risperidone is used frequently to
treat irritability and aggression associated with autistic
disorders in children and adolescents, as well as for
acute manic episodes of bipolar disease. Any of these
drugs may be effective in a particular person; the selec-
tion of a specific drug depends on the desired potency
and tolerance of the associated adverse effects. A person
who does not respond to one drug may react success-
fully to another agent. (Responses may also vary because
of cultural issues [Box 22.3].) To determine the best
therapeutic regimen for a particular person, it may be
necessary to try more than one drug.
Pharmacokinetics
The antipsychotics are erratically absorbed from the
gastrointestinal (GI) tract, depending on the drug
and the preparation of the drug. Intramuscular doses
provide four to five times the active dose as oral doses
and caution is required if one is switching between
routes. The antipsychotics are widely distributed in the
tissues and are often stored there, being released for up
to 6 months after the drug is stopped. They are metabo-
lised in the liver and excreted through the bile and urine.
Children tend to metabolise these drugs faster than do
adults and elderly people tend to metabolise them more
slowly, making it necessary to carefully monitor these
people and adjust doses as needed. Clinical effects may
not be seen for several weeks and people should be
encouraged to continue taking the drugs even if they see
no immediate effectiveness. The antipsychotics cross the
placenta and enter breast milk (see Contraindications
and cautions).
Neuroleptic malignant syndrome is a rare but potentially
fatal adverse effect of all antipsychotic drugs. This
includes symptoms such as hyperthermia, fluctuating
level of consciousness, muscle rigidity, autonomic
dysfunction with pallor, tachycardia, labile blood
pressure, sweating and urinary incontinence. People
who presents with neuroleptic malignant syndrome
should seek specialist medical assessment immediately
as admission to a medical intensive care facility may be
necessary. Symptoms usually last for 5–7 days after the
drug is discontinued.
■■
BOX 22.2
Neuroleptic malignant syndrome
TABLE 22.1
DRUGS IN FOCUS Antipsychotic/neuroleptic drugs (continued)
Drug name
Potency
Common side effects
Usual dosage
Sedation Anticholinergic Hypotension Extrapyramidal
ziprasidone
(Zeldox)
Medium +++
++
+
+
Adult: 20–80 mg PO b.d.;
rapid control of as-stated
behaviour: 10–20 mg
IM, maximum dose
40 mg/day IM; monitor
QTc intervals
Each plus sign indicates increased incidence of the given adverse effect.
b.d., twice daily; IM, intramuscularly; PO, orally; PR, rectally; q.i.d., four times daily; q 4–6 hours, every 4–6 hours; q 4–8 hours, every 4–8 hours; q 6 hours,
every 6 hours; t.d.s., three times daily; XR, extended release.
