higher probability of QT-interval prolongation in patients
using any intravenous antipsychotic drug, or any
antipsychotic drug or combination of antipsychotic drugs
with doses exceeding the recommended maximum. Cases of
sudden death have occurred.
Hyperglycaemia and weight gain
Hyperglycaemia, and sometimes diabetes, can occur with
antipsychotic drugs, particularly clozapine, olanzapine,
quetiapine, and risperidone. All antipsychotic drugs may
cause weight gain, but the risk and extent varies. Clozapine
and olanzapine commonly cause weight gain. Olanzapine is
associated with more weight gain than other second
generation antipsychotic drugs. Weight gain happens soon
after treatment with olanzapine has started.
Hypotension and interference with temperature regulation
Hypotension and interference with temperature regulation
are dose-related side-effects. Clozapine, chlorpromazine,
and quetiapine can cause postural hypotension (especially
during initial dose titration) which may be associated with
syncope or reflex tachycardia in some children.
Neuroleptic malignant syndrome
Neuroleptic malignant syndrome (hyperthermia,fluctuating
level of consciousness, muscle rigidity, and autonomic
dysfunction with pallor, tachycardia, labile blood pressure,
sweating, and urinary incontinence) is a rare but potentially
fatal side-effect of all antipsychotic drugs. Discontinuation
of the antipsychotic drug is essential because there is no
proven effective treatment, but bromocriptine and
dantrolene have been used. The syndrome, which usually
lasts for 5 – 7 days after drug discontinuation, may be unduly
prolonged if depot preparations have been used.
Blood dyscrasias
Perform blood counts if unexplained infection or fever
develops.
Choice
The antipsychotic drugs most commonly used in children are
haloperidol p. 245 , risperidone p. 253 , and olanzapine p. 251.
There is little meaningful difference in efficacy between each
of the antipsychotic drugs (other than clozapine p. 250 ), and
response and tolerability to each antipsychotic drug varies.
There is nofirst-line antipsychotic drug which is suitable for
all children. Choice of antipsychotic medication is influenced
by the child’s medication history, the degree of sedation
required (although tolerance to this usually develops), and
consideration of individual patient factors such as risk of
extrapyramidal side-effects, weight gain, impaired glucose
tolerance, QT-interval prolongation, or the presence of
negative symptoms.
Negative symptoms
Second generation antipsychotic drugs may be better at
treating the negative symptoms of schizophrenia.
Extrapyramidal side-effects
Second-generation antipsychotic drugs may be prescribed if
extrapyramidal side-effects are a particular concern. Of
these, aripiprazole p. 249 , clozapine, olanzapine, and
quetiapine p. 252 are least likely to cause extrapyramidal
side-effects. Although amisulpride p. 248 is a dopamine-
receptor antagonist, extrapyramidal side-effects are less
common than with thefirst-generation antipsychotic drugs
because amisulpride selectively blocks mesolimbic dopamine
receptors, and extrapyramidal symptoms are caused by
blockade of the striatal dopamine pathway.
QT interval
Aripiprazole has negligible effect on the QT interval. Other
antipsychotic drugs with a reduced tendency to prolong QT
interval include amisulpride, clozapine, olanzapine,
perphenazine p. 246 , risperidone, and sulpiride p. 247.
Diabetes
Schizophrenia is associated with insulin resistance and
diabetes; the risk of diabetes is increased in children with
schizophrenia who take antipsychotic drugs. First-
generation antipsychotic drugs are less likely to cause
diabetes than second-generation antipsychotic drugs, and of
thefirst-generation antipsychotic drugs, haloperidol has the
lowest risk. Amisulpride and aripiprazole have the lowest
risk of diabetes of the second-generation antipsychotic
drugs. Amisulpride, aripiprazole, haloperidol, sulpiride, and
trifluoperazine p. 248 are least likely to cause weight gain.
Sexual dysfunction and prolactin
The antipsychotic drugs with the lowest risk of sexual
dysfunction are aripiprazole and quetiapine. Olanzapine
may be considered if sexual dysfunction is judged to be
secondary to hyperprolactinaemia. Hyperprolactinaemia is
usually not clinically significant with aripiprazole, clozapine,
olanzapine, and quetiapine treatment. When changing from
other antipsychotic drugs, a reduction in prolactin
concentration may increase fertility.
Children should receive an antipsychotic drug for
4 – 6 weeks before it is deemed ineffective. Prescribing more
than one antipsychotic drug at a time should be avoided
except in exceptional circumstances (e.g. clozapine
augmentation or when changing medication during
titration) because of the increased risk of adverse effects
such as extrapyramidal symptoms, QT-interval
prolongation, and sudden cardiac death.
Clozapine is used for the treatment of schizophrenia in
children unresponsive to, or intolerant of, other
antipsychotic drugs. Clozapine should be introduced if
schizophrenia is not controlled despite the sequential use of
two or more antipsychotic drugs (one of which should be a
second-generation antipsychotic drug), each for at least
6 – 8 weeks. If symptoms do not respond adequately to an
optimised dose of clozapine, plasma-clozapine
concentration should be checked before adding a second
antipsychotic drug to augment clozapine; allow 8 – 10 weeks’
treatment to assess response. Children must be registered
with a clozapine patient monitoring service.
Monitoring
Full blood count, urea and electrolytes, and liver function
test monitoring is required at the start of therapy with
antipsychotic drugs, and then annually thereafter.
Blood lipids and weight should be measured at baseline, at
3 months (weight should be measured at frequent intervals
during thefirst 3 months), and then yearly.
Fasting blood glucose should be measured at baseline, at
4 – 6 months, and then yearly.
Before initiating antipsychotic drugs, an ECG may be
required, particularly if physical examination identifies
cardiovascular risk factors, if there is a personal history of
cardiovascular disease, or if the child is being admitted as an
inpatient.
Blood pressure monitoring is advised before starting
therapy and frequently during dose titration of antipsychotic
drugs.
Other uses
Nausea and vomiting, choreas, motor tics, and intractable
hiccup.
Equivalent doses of oral antipsychotics
These equivalences are intendedonlyas an approximate
guide; individual dosage instructions shouldalsobe
checked; children should be carefully monitored afterany
change in medication. Equivalent daily dose of antipsychotic
drug:
.Chlorpromazine 100 mg
.Clozapine 50 mg
.Haloperidol 2 – 3 mg
.Pimozide 2 mg
.Risperidone 0. 5 – 1 mg
.Sulpiride 200 mg
.Trifluoperazine 5 mg
Important: These equivalences mustnotbe extrapolatedBNFC 2018 – 2019 Psychoses and schizophrenia 243
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