C H A P T E R 2 1
Antidepressant agents
317
W
hen you ask people how they feel, they may say
“pretty good” or “not so great”. People’s responses are
usually appropriate to what is happening in their lives,
and they describe themselves as being in a good mood or
a bad mood. Some days are better than others.
Affect
is a term that is used to refer to people’s feelings
in response to their environment, whether positive and
pleasant or negative and unpleasant. All people experi
ence different affective states at various times in their
lives. These states of mind, which change in particular
situations, usually do not last very long and do not often
involve extremes of happiness or depression. If a person’s
mood goes far beyond the usual normal “ups and downs”,
they are said to have an affective disorder. Mental health
is a National Priority Area for the Australian Government
so is an important area for nurses and midwives to under
stand and be able to respond to (AIHW, 2013).
DEPRESSION AND ANTIDEPRESSANTS
Depression
is a very common affective disorder involving
feelings of sadness that are much more severe and longer
lasting than the suspected precipitating event, and the
mood of affected individuals is much more intense. The
depression may not even be traceable to a specific event
or stressor (i.e. there are no external causes). People
who are depressed may have little energy, sleep disturb
ances, lack of appetite, limited libido and inability to
perform activities of daily living. They may describe
overwhelming feelings of sadness, despair, hopelessness
and disorganisation.
In many cases, the depression is never diagnosed,
and the person is treated for physical manifestations of
the underlying disease, such as fatigue, malaise, obesity,
anorexia, or alcoholism and drug dependence. Clinical
depression is a disorder that can interfere with a person’s
family life, job and social interactions. Left untreated, it
can produce multiple physical problems that can lead to
further depression or, in extreme cases, even suicide.
Biogenic amine theory of depression
Research on the development of the drugs known to be
effective in relieving depression led to formulation of
the current hypothesis regarding the cause of depres
sion. Scientists have theorised that depression results
from a deficiency of
biogenic amines
in key areas of
the brain; these biogenic amines include noradrenaline,
dopamine and serotonin (5HT). Both noradrenaline and
5HT are released throughout the brain by neurons that
react with multiple receptors to regulate arousal, alert
ness, attention, moods, appetite and sensory processing.
Deficiencies of these neurotransmitters may develop
for three known reasons. First, monoamine oxidase
(MAO) may break them down to be recycled or restored
in the neurons. Second, rapid fire of the neurons may
lead to their depletion. Third, the number or sensitivity
of postsynaptic receptors may increase, thus depleting
neurotransmitter levels.
Depression may also occur as a result of other, as
yet unknown, causes. This condition may be a syndrome
that reflects either activity or lack of activity in a number
of sites in the brain, including the arousal centre (reticu
lar activating system [RAS]), the limbic system and basal
ganglia.
Drug therapy
The use of agents that alter the concentration of neuro
transmitters in the brain is the most effective means
of treating depression with drugs. The antidepressant
drugs used today counteract the effects of neurotrans
mitter deficiencies in three ways. First, they may inhibit
the effects of MAO, leading to increased noradrenaline
or 5HT in the synaptic cleft. Second, they may block
reuptake by the releasing nerve, leading to increased
neurotransmitter levels in the synaptic cleft. Third,
they may regulate receptor sites and the breakdown of
neurotransmitters, leading to an accumulation of neuro
transmitter in the synaptic cleft.
Antidepressants may be classified into three groups:
the tricyclic antidepressants (TCAs), the MAO inhibitors
and the selective serotonin reuptake inhibitors (SSRIs).
Other drugs that are used as antidepressants similarly
increase the synaptic cleft concentrations of these neuro
transmitters (see Figure 21.1). For information on how
antidepressants affect people from young to old, see
Box 21.1.
TRICYCLIC ANTIDEPRESSANTS
The
tricyclic antidepressants (TCAs)
, including the
amines, secondary amines and tetracyclics, all reduce
the reuptake of 5HT and noradrenaline into nerves.
Because all TCAs are similarly effective, the choice of
TCA depends on individual response to the drug and tol
erance of adverse effects. A person who does not respond
to one TCA may respond to another drug from this class.
TCAs that are available include the amines amitripty
line (
Endep, Amitrip
), clomipramine (
Anafranil, Placil
),
dosulepin hydrochloride, dothiepin (
Dothep
), doxepin
(
Deptran
,
Sinequan
), imipramine (
Tofranil
) and trimi
pramine (
Surmontil
) and the secondary amines such as
nortriptyline (
Allegron
). Table 21.1 shows the relative
frequency of the occurrence of adverse effects by specific
type of TCA.
Therapeutic actions and indications
The TCAs inhibit presynaptic reuptake of the neuro
transmitters 5HT and noradrenaline, which leads to an
