McKenna's Pharmacology for Nursing, 2e

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C H A P T E R 2 1 Antidepressant agents

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

15 mg PO t.d.s.; maintenance 15 mg/day PO

Treatment of depression not responsive to other agents Treatment of adult reactive depression

phenelzine (Nardil)

tranylcypromine (Parnate)

30 mg/day PO in divided doses; maximum 60 mg/day