C H A P T E R 2 1
Antidepressant agents
323
MONOAMINE OXIDASE INHIBITORS
Monoamine oxidase (MAO) inhibitors
(Table 21.2) irre
versibly inhibit MAO, an enzyme found in nerves and
other tissues (including the liver), to break down the
biogenic amines noradrenaline, dopamine and 5HT,
and relieve depression. At one time, MAO inhibitors
were used more often, but now they are used rarely
because they require a specific dietary regimen to
prevent toxicity. There are some people, however, who
only seem to respond to these particular drugs, so they
remain available. Agents still in use include phenelzine
(
Nardil
), and tranylcypromine (
Parnate
). The choice of
an MAO inhibitor depends on the prescriber’s experi
ence and individual response. A person who does not
respond to one MAO inhibitor may respond to another.
Therapeutic actions and indications
Blocking the breakdown of the biogenic amines
noradrenaline, dopamine and 5HT allows these amines
to accumulate in the synaptic cleft and in neuronal
storage vesicles, causing increased stimulation of the
postsynaptic receptors. It is thought that this increased
stimulation of the receptors causes relief of depression.
The MAO inhibitors are generally indicated for treat
ment of the signs and symptoms of depression in people
who cannot tolerate or do not respond to other, safer,
antidepressants (see Table 21.2).
Pharmacokinetics
The MAO inhibitors are well absorbed from the GI
tract, reaching peak levels in 2 to 3 hours. They are
metabolised in the liver primarily by acetylation and
are excreted in the urine. People with liver or renal
impairment and those known as “slow acetylators” may
require lowered doses to avoid exaggerated effects of the
drugs. The MAO inhibitors cross the placenta and enter
breast milk (see Contraindications and cautions).
Contraindications and cautions
Contraindications to the use of MAO inhibitors include
allergy to any of these antidepressants
because of the
risk of hypersensitivity reactions
; phaeochromocytoma
because the sudden increases in noradrenaline levels
could result in severe hypertension and CV emergencies
;
CV disease, including hypertension, coronary artery
disease, angina and congestive heart failure,
which
could be exacerbated by increased NE levels
; and
known abnormal CNS vessels or defects
because the
potential increase in blood pressure and vasoconstric-
tion associated with higher noradrenaline levels could
precipitate a stroke.
A history of headaches may also be
a contraindication.
Other contraindications include renal or hepatic
impairment,
which could alter the metabolism and
excretion of these drugs and lead to toxic levels,
and
myelography within the past 24 hours or in the next
48 hours
because of the risk of severe reaction to the dye
used in myelography. MAO inhibitors may cause idio-
syncratic hepatotoxicity if used in people with hepatic
impairment
In addition, caution should be used with people with
mental health problems,
who could be overstimulated or
shift to a manic phase as a result of the stimulation asso-
ciated with MAO inhibitors
, and in people with seizure
disorders or hyperthyroidism,
both of which could be
exacerbated by the stimulation of these drugs.
There is
a black box warning on all drugs of this class to bring
awareness to a possible risk of suicidality, especially with
children and adolescents, in people using these drugs.
Care should also be taken with individuals who are soon
to undergo elective surgery
because of the potential for
unexpected effects with noradrenaline accumulation
during the stress reaction
, and with women who are
pregnant or breastfeeding
because of potential adverse
effects on the fetus and neonate;
these drugs should be
used during pregnancy and breastfeeding only if the
benefit to the mother clearly outweighs the potential risk
to the neonate.
Adverse effects
The MAO inhibitors are associated with more adverse
effects, more of which are fatal, than most other anti
depressants. The effects relate to the accumulation of
noradrenaline
in the synaptic cleft. Dizziness, excite
ment, nervousness, mania, hyper-reflexia, tremors,
confusion, insomnia, agitation and blurred vision may
occur.
MAO inhibitors can cause liver toxicity. MAO
inhibitors may cause idiosyncratic hepatotoxicity if used
in people with hepatic impairment. Other GI effects can
TABLE 21.2
DRUGS IN FOCUS Monoamine oxidase (MAO) inhibitors
Drug name
Dosage/route
Usual indications
phenelzine (Nardil)
15 mg PO t.d.s.; maintenance 15 mg/day PO
Treatment of depression not responsive to
other agents
tranylcypromine (Parnate)
30 mg/day PO in divided doses; maximum
60 mg/day
Treatment of adult reactive depression
