318
P A R T 4
Drugs acting on the central and peripheral nervous systems
MAO inhibitors
work here to
prevent the
breakdown of
dopamine,
noradrenaline
and serotonin
TCAs
work here to
block the reuptake
of serotonin and
noradrenaline
Neurotransmitter release:
may be noradrenaline,
dopamine or serotonin
Presynaptic cell
Postsynaptic cell
SSRIs
work here to
specifically block the
reuptake of serotonin
Postsynaptic receptor
Inactive product
to blood vessel
Varying block of
reuptake of
noradrenaline
and/or serotonin
COMT
Into blood vessel
Return to
presynaptic cell
cAMP
Neurotransmitter
Building blocks (from diet)
become neurotransmitters
Ca+
Ca+
bupropion
desvenlafaxine
mirtazapine
reboxetine
venlafaxine
FIGURE 21.1
Sites of action for the
antidepressants: monoamine oxidase
(MAO) inhibitors, tricyclic antidepressants
(TCAs), selective serotonin reuptake
inhibitors (SSRIs), and other agents, cAMP,
cyclic adenosine monophosphate; COMT,
catecholamine-
O
-methyltransferase.
BOX 21.1
Drug therapy across the lifespan
Antidepressant agents
CHILDREN
Use of antidepressant drugs with children poses a
challenge.The response of the child to the drug may be
unpredictable, and the long-term effects of many of these
agents are not clearly understood. Studies have not shown
efficacy in using these drugs to treat depression in children
and also indicate that there may be an increase in suicidal
ideation and suicidal behaviour when antidepressants are
used to treat depression in children.
Of the tricyclic drugs (TCAs), clomipramine,
imipramine, nortriptyline and trimipramine have
established paediatric doses in children older than 6 years.
Children should be monitored closely for adverse effects,
and dose changes should be made as needed.
Monoamine oxidase (MAO) inhibitors should be
avoided in children if at all possible because of the
potential for drug–food interactions and the serious
adverse effects.
The selective serotonin reuptake inhibitors (SSRIs) can
cause serious adverse effects in children. Fluvoxamine
and sertraline have established paediatric dose
guidelines for the treatment of obsessive–compulsive
disorders. Fluoxetine is widely used to treat depression
in adolescents, and a 2000 survey of off-label uses of
drugs showed that it was being used in children as young
as 6 months. Dosage regimens must be established
according to the child’s age and weight, and a child
receiving an antidepressant should be monitored very
carefully. Underlying medical reasons for the depression
should be ruled out before antidepressant therapy is
begun. Again, these children should be monitored for any
suicidal ideation.
ADULTS
Adults using these drugs should have medical causes
for their depression ruled out before therapy is begun.
Thyroid disease, hormonal imbalance and cardiovascular
disorders can all lead to the signs and symptoms of
depression.
The person needs to understand that the effects of
drug therapy may not be seen for 4 weeks and that it is
important to continue the therapy for at least that long.
PREGNANCY AND BREASTFEEDING
These drugs should be used very cautiously during
pregnancy and breastfeeding because of the potential
