2.3 Depression
Antidepressant drugs
Overview
Depression in children should be managed by an appropriate
specialist and treatment should involve psychological
therapy.
Choice
The major classes of antidepressant drugs include the
tricyclics and related antidepressant drugs, the selective
serotonin re-uptake inhibitors (SSRIs), and the monoamine
oxidase inhibitors (MAOIs).
Antidepressant drugs should not be used routinely in mild
depression, and psychological therapy should be considered
initially; however, a trial of antidepressant therapy may be
considered in cases refractory to psychological treatments or
in those associated with psychosocial or medical problems.
Drug treatment of mild depression may also be considered in
children with a history of moderate or severe depression.
Choice of antidepressant drug should be based on the
individual child’s requirements, including the presence of
concomitant disease, existing therapy, suicide risk, and
previous response to antidepressant therapy.
When drug treatment of depression is considered
necessary in children, the SSRIs should be consideredfirst-
line treatment; following a safety and efficacy review,
fluoxetine p. 237 is licensed to treat depression in children.
Tricyclic antidepressant drugs should be avoided for the
treatment of depression in children.
St John’s wort(Hypericum perforatum) is a popular herbal
remedy on sale to the public for treating mild depression in
adults. It should not be used for the treatment of depression
in children because St John’s wort can induce drug
metabolising enzymes and a number of important
interactions with conventional drugs, including
conventional antidepressants, have been identified.
Furthermore, the amount of active ingredient varies between
different preparations of St John’s wort and switching from
one to another can change the degree of enzyme induction.
If a child stops taking St John’s wort, the concentration of
interacting drugs may increase, leading to toxicity.
Management
Children should be reviewed every 1 – 2 weeks at the start of
antidepressant treatment. Treatment should be continued
for at least 4 weeks before considering whether to switch
antidepressant due to lack of efficacy. In cases of partial
response, continue for a further 2 – 4 weeks. Following
remission, antidepressant treatment should be continued at
the same dose for at least 6 months. Children with a history
of recurrent depression should continue treatment for at
least 2 years.
Hyponatraemia and antidepressant therapy
Hyponatraemia (possibly due to inappropriate secretion of
antidiuretic hormone) has been associated with all types of
antidepressants; however, it has been reported more
frequently with SSRIs than with other antidepressant drugs.
Hyponatraemia should be considered in all children who
develop drowsiness, confusion, or convulsions while taking
an antidepressant.
Suicidal behaviour and antidepressant therapy
The use of antidepressant drugs has been linked with
suicidal thoughts and behaviour. Where necessary, children
should be monitored for suicidal behaviour, self-harm, and
hostility, particularly at the beginning of treatment or if the
dose is changed.
Serotonin syndrome
Serotonin syndrome or serotonin toxicity is a relatively
uncommon adverse drug reaction caused by excessive
central and peripheral serotonergic activity. Onset of
symptoms, which range from mild to life-threatening, can
occur within hours or days following the initiation, dose
escalation, or overdose of a serotonergic drug, the addition
of a new serotonergic drug, or the replacement of one
serotonergic drug by another without allowing a long
enough washout period in-between, particularly when the
first drug is an irreversible MAOI or a drug with a long half-
life. Severe toxicity, which is a medical emergency, usually
occurs with a combination of serotonergic drugs, one of
which is generally an MAOI.
The characteristic symptoms of serotonin syndrome fall
into 3 main areas, although features from each group may
not be seen in all patients—neuromuscular hyperactivity
(such as tremor, hyperreflexia, clonus, myoclonus, rigidity),
autonomic dysfunction (tachycardia, blood pressure
changes, hyperthermia, diaphoresis, shivering, diarrhoea),
and altered mental state (agitation, confusion, mania).
Treatment consists of withdrawal of the serotonergic
medication and supportive care; specialist advice should be
sought.
Important safety information: Depressive illness in children
and adolescents
The balance of risks and benefits for the treatment of
depressive illness in individuals under 18 years is considered
unfavourable for the SSRIs citalopram, escitalopram,
paroxetine, and sertraline, and for mirtazapine and
venlafaxine. Clinical trials have failed to show efficacy and
have shown an increase in harmful outcomes. However, it is
recognised that specialists may sometimes decide to use
these drugs in response to individual clinical need; children
and adolescents should be monitored carefully for suicidal
behaviour, self-harm or hostility, particularly at the
beginning of treatment. Onlyfluoxetine has been shown in
clinical trials to be effective for treating depressive illness in
children and adolescents. However, it is possible that, in
common with the other SSRIs, it is associated with a small
risk of self-harm and suicidal thoughts. Overall, the balance
of risks and benefits forfluoxetine in the treatment of
depressive illness in individuals under 18 years is considered
favourable, but children and adolescents must be carefully
monitored as above.
Anxiety
Management ofacute anxietyin children with drug treatment
is contentious. Forchronic anxiety(of longer than 4 weeks’
duration), it may be appropriate to use an antidepressant
drug before a benzodiazepine.
Tricyclic antidepressants are not effective for treating
depression in children.
Some tricyclic antidepressant drugs may have a role in
some forms ofneuralgia, and innocturnal enuresisin
children.
Dosage
It is important to use doses that are sufficiently high for
effective treatment but not so high as to cause toxic effects.
Low doses should be used for initial treatment.
In most children the long half-life of tricyclic
antidepressant drugs allowsonce-dailyadministration,
usually at night; the use of modified-release preparations is
therefore unnecessary.Other drugs used for DepressionLithium carbonate, p. 233
.Lithium citrate, p. 234BNFC 2018 – 2019 Depression 235
Nervous system4