C H A P T E R 2 2
Psychotherapeutic agents
341
Adverse effects
The adverse effects associated with the antipsychotic
drugs are related to their dopamine-blocking, anticho-
linergic, antihistamine and alpha-adrenergic activities.
The most common CNS effects are sedation, weakness,
tremor, drowsiness, extrapyramidal side effects (EPS),
pseudoparkinsonism, dystonia, akathisia, tardive
dyskinesia and potentially irreversible neuroleptic
malignant syndrome. Anticholinergic effects include
dry mouth, nasal congestion, flushing, constipation,
urinary retention, impotence, glaucoma, blurred vision
and photophobia. Cardiovascular (CV) effects, which
are probably related to the dopamine-blocking effects,
include hypotension, orthostatic hypotension, cardiac
arrhythmias, congestive heart failure and pulmonary
oedema. Ziprasidone is associated with prolongation of
the QT
c
interval, which could lead to serious or even
fatal cardiac arrhythmias. People receiving this drug
should have a baseline and periodic electrocardiogram
(ECG) during therapy. In late 2003, the FDA issued
a requirement that all of the atypical antipsychotics
include warnings that there is a risk for the develop-
ment of diabetes mellitus when these drugs are used.
Consequently, when people are maintained on any
of the atypical antipsychotics, they should be moni-
tored regularly for the signs and symptoms of diabetes
mellitus.
Respiratory effects such as laryngospasm, dyspnoea
and bronchospasm may also occur. The phenothiazines
(chlorpromazine, fluphenazine, prochlorperazine and
promethazine) often turn the urine pink to reddish-brown
as a result of their excretion. Although this effect may
cause great concern to the person, it has no clinical sig-
nificance. In addition, bone marrow suppression is a
possibility with some antipsychotic agents.
Clinically important drug–drug interactions
Because the combination of antipsychotics with
beta-blockers may lead to an increase in the effect
of both drugs, this combination should be avoided
if possible. Antipsychotic–alcohol combinations
result in an increased risk of CNS depression and
antipsychotic–anticholinergic combinations lead to
increased anticholinergic effects, so dose adjustments
are necessary. People who take either of these combina-
tions should be monitored closely for adverse effects and
supportive measures should be provided. People should
not take ziprasidone with any other drug that is associ-
ated with prolongation of the QT
c
interval.
Evening primrose
People with schizophrenia should be advised to avoid the
use of evening primrose.This herb has been associated
with increased symptoms and CNS hyperexcitability.
Herbal and alternative therapies
BOX 22.5
Prototype summary: Chlorpromazine
Indications:
Management of manifestations
of psychotic disorders; relief of preoperative
restlessness; adjunctive treatment of tetanus; acute
intermittent porphyria; severe behavioural problems
in children; control of hiccups, nausea and vomiting.
Actions:
Blocks postsynaptic dopamine receptors
in the brain; depresses those parts of the brain
involved in wakefulness and emesis; anticholinergic;
antihistaminic; alpha-adrenergic blocking.
Pharmacokinetics:
Route
Onset
Peak
Duration
Oral
30–60 mins 2–4 hours 4–6 hours
Intra-
muscular 10–15 mins 15–20 mins 4–6 hours
T
1/2
:
2 hours, then 30 hours; metabolised in the liver,
excreted in the urine.
Adverse effects:
Drowsiness, insomnia, vertigo,
extrapyramidal symptoms, orthostatic hypotension,
photophobia, blurred vision, dry mouth,
nausea, vomiting, anorexia, urinary retention,
photosensitivity.
Prototype summary: Clozapine
Indications:
Management of severely ill people
with schizophrenia who are unresponsive to
standard drugs; reduction of risk of recurrent
suicidal behaviour in people with schizophrenia or
schizoaffective disorder.
Actions:
Blocks dopamine and serotonin receptors;
depresses the RAS; anticholinergic; antihistaminic;
alpha-adrenergic blocking.
Pharmacokinetics:
Route Onset
Peak
Duration
Oral
Varies
1–6 hours
Weeks
T
1/2
:
4–12 hours; metabolised in the liver, excreted
in the urine and faeces.
Adverse effects:
Drowsiness, sedation, seizures,
dizziness, syncope, headache, tachycardia, nausea,
vomiting, fever, neuroleptic malignant syndrome.
