agitated depression. Antipsychotic drugs are used to
alleviate severe anxiety but this too should be a short-term
measure.Schizophrenia
The aim of treatment is to alleviate the suffering of the child
(and carer) and to improve social and cognitive functioning.
Many children require life-long treatment with antipsychotic
medication. Antipsychotic drugs relieve positive psychotic
symptoms such as thought disorder, hallucinations, and
delusions, and prevent relapse; they are usually less effective
on negative symptoms such as apathy and social withdrawal.
In many patients, negative symptoms persist between
episodes of treated positive symptoms, but earlier treatment
of psychotic illness may protect against the development of
negative symptoms over time. Children with acute
schizophrenia generally respond better than those with
chronic symptoms.
Long-term treatment of a child with a definitive diagnosis
of schizophrenia is usually required after thefirst episode of
illness in order to prevent relapses. Doses that are effective
in acute episodes should generally be continued as
prophylaxis.
First-generation antipsychotic drugs
Thefirst-generation antipsychotic drugs act predominantly
by blocking dopamine D 2 receptors in the brain. First-
generation antipsychotic drugs are not selective for any of
the four dopamine pathways in the brain and so can cause a
range of side-effects, particularly extrapyramidal symptoms
and elevated prolactin. Thephenothiazinederivatives can
be divided into 3 main groups:
.Group 1 : chlorpromazine hydrochloride p. 244 ,
levomepromazine p. 268 , and promazine hydrochloride,
generally characterised by pronounced sedative effects
and moderate antimuscarinic and extrapyramidal side-
effects.
.Group 2 : pericyazine p. 246 , generally characterised by
moderate sedative effects, but fewer extrapyramidal side-
effects than groups 1 or 3.
.Group 3 : perphenazine p. 246 , prochlorperazine p. 268 ,
and trifluoperazine p. 248 , generally characterised by
fewer sedative and antimuscarinic effects, but more
pronounced extrapyramidal side-effects than groups 1 and
2.
Butyrophenones(e.g. haloperidol p. 245 ) resemble the
group 3 phenothiazines in their clinical properties.
Diphenylbutylpiperidines(pimozide p. 247 ) and the
substituted benzamides(sulpiride p. 247 ) have reduced
sedative, antimuscarinic, and extrapyramidal effects.Second-generation antipsychotic drugs
The second-generation antipsychotic drugs (also referred to
as atypical antipsychotic drugs) act on a range of receptors in
comparison tofirst-generation antipsychotic drugs and have
more distinct clinical profiles, particularly with regard to
side-effects.
Prescribing of antipsychotic drugs in children with learning
disabilities
gWhen prescribing for children with learning disabilities
who are prescribed antipsychotic drugs and who are not
experiencing psychotic symptoms, the following
considerations should be taken into account:
.a reduction in dose or the discontinuation of long-term
antipsychotic treatment ;
.review of the child’s condition after dose reduction or
discontinuation of an antipsychotic agent;
.referral to a psychiatrist experienced in working with
children who have learning disabilities and mental health
problems ;
.annual documentation of the reasons for continuing a
prescription if the antipsychotic is not reduced in dose or
discontinuedh.Side effects of antipsychotic drugs
Side-effects caused by antipsychotic drugs are common and
contribute significantly to non-adherence to therapy.
Extrapyramidal symptoms
Extrapyramidal symptoms occur most frequently with the
piperazine phenothiazines (fluphenazine, perphenazine,
prochlorperazine, and trifluoperazine), the butyrophenones
(benperidol and haloperidol), and thefirst-generation depot
preparations. They are easy to recognise but cannot be
predicted accurately because they depend on the dose, the
type of drug, and on individual susceptibility.
Extrapyramidal symptoms consist of:
.parkinsonian symptoms(including tremor), which may
occur more commonly in adults or the elderly and may
appear gradually;
.dystonia(abnormal face and body movements) and
dyskinesia, which occur more commonly in children or
young adults and appear after only a few doses;
.akathisia(restlessness), which characteristically occurs
after large initial doses and may resemble an exacerbation
of the condition being treated;
.tardive dyskinesia(rhythmic, involuntary movements of
tongue, face, and jaw), which usually develops on long-
term therapy or with high dosage, but it may develop on
short-term treatment with low doses—short-lived tardive
dyskinesia may occur after withdrawal of the drug.
Parkinsonian symptomsremit if the drug is withdrawn and
may be suppressed by the administration of antimuscarinic
drugs. However, routine administration of such drugs is not
justified because not all patients are affected and they may
unmask or worsen tardive dyskinesia.
Tardive dyskinesiais the most serious manifestation of
extrapyramidal symptoms; it is of particular concern because
it may be irreversible on withdrawing therapy and treatment
is usually ineffective. In children, tardive dyskinesia is more
likely to occur when the antipsychotic drug is withdrawn.
However, some manufacturers suggest that drug withdrawal
at the earliest signs of tardive dyskinesia (fine vermicular
movements of the tongue) may halt its full development.
Tardive dyskinesia occurs fairly frequently, especially in the
elderly, and treatment must be carefully and regularly
reviewed.
Hyperprolactinaemia
Most antipsychotic drugs, bothfirst- and second-generation,
increase prolactin concentration to some extent because
dopamine inhibits prolactin release. Aripiprazole reduces
prolactin because it is a dopamine-receptor partial agonist.
Risperidone, amisulpride, andfirst-generation antipsychotic
drugs are most likely to cause symptomatic
hyperprolactinaemia. The clinical symptoms of
hyperprolactinaemia include sexual dysfunction, reduced
bone mineral density, menstrual disturbances, breast
enlargement, and galactorrhoea.
Sexual dysfunction
Sexual dysfunction is one of the main causes of non-
adherence to antipsychotic medication; physical illness,
psychiatric illness, and substance misuse are contributing
factors. Antipsychotic-induced sexual dysfunction is caused
by more than one mechanism. Reduced dopamine
transmission and hyperprolactinaemia decrease libido;
antimuscarinic effects can cause disorders of arousal; and
alpha 1 -adrenoceptor antagonists are associated with
erection and ejaculation problems in men. Risperidone and
haloperidol commonly cause sexual dysfunction. If sexual
dysfunction is thought to be antipsychotic-induced, dose
reduction or switching medication should be considered.
Cardiovascular side-effects
Antipsychotic drugs have been associated with
cardiovascular side-effects such as tachycardia, arrhythmias,
and hypotension. QT-interval prolongation is a particular
concern with pimozide and haloperidol. There is also a242 Mental health disorders BNFC 2018 – 2019
Nervous system4