Monoamine Oxidase Inhibitors

Monoamine oxidase inhibitors (phenelzine, tranylcypromine, isocarboxazid, moclobemide, transdermal selegiline) are antidepressants reserved for depression that has not responded to other classes, atypical depression, and panic and social anxiety. They are effective but limited by dietary and drug interactions.

Mechanism. They inhibit monoamine oxidase, which breaks down serotonin, noradrenaline, dopamine and tyramine. Phenelzine, tranylcypromine and isocarboxazid are irreversible and non-selective. Moclobemide is reversible and selective for MAO-A. Selegiline is selective for MAO-B at low oral doses.

Pharmacokinetics. Irreversible agents act until new enzyme is made, about 2 weeks. Moclobemide effect lasts 24 hours.

Differences. Irreversible agents carry the full risk of hypertensive crisis with tyramine and sympathomimetics. Moclobemide has little tyramine effect and a modest efficacy. Tranylcypromine has amphetamine-like stimulant effects.

• Treatment-resistant depression, atypical depression: irreversible agents under specialist care.
• Moclobemide: depression and social anxiety, easier to use in primary care.
• Washout before starting: 14 days after other antidepressants (5 weeks after fluoxetine); 14 days after stopping an irreversible agent before another antidepressant.
• Diet: avoid tyramine-rich foods (aged cheese, cured and fermented meats, yeast extracts, soy sauce and fermented bean products, draught beer, broad beans) and give a written list.
• Drugs to avoid: sympathomimetics (pseudoephedrine, phenylephrine, amphetamines, methylphenidate), pethidine, tramadol, dextromethorphan, and other antidepressants.
• Surgery: stop irreversible agents 14 days before elective anaesthesia.

Special groups. Pregnancy: avoid. Breastfeeding: avoid. Children: not used. Older adults: postural hypotension and falls. Kidney impairment: caution. Liver impairment: avoid. Regional: khat contains cathinone, an amphetamine-like stimulant, and must be avoided with irreversible agents, and fermented foods and drinks add tyramine risk; advise carefully.

Adverse effects. Postural hypotension, insomnia, weight gain, oedema, sexual dysfunction, dizziness, and hepatotoxicity with hydrazine agents (phenelzine).

Hypertensive crisis. Severe headache, palpitations and a blood pressure over 180/120 mmHg after tyramine or a sympathomimetic. Stop the drug and give phentolamine 5 mg intravenously or another short-acting intravenous antihypertensive; avoid beta blockers alone.

Serotonin syndrome. With serotonergic drugs, including linezolid, which is a weak monoamine oxidase inhibitor.

Contraindications. Phaeochromocytoma, severe liver or cardiovascular disease, and concurrent serotonergic or sympathomimetic drugs.

Monitoring. Blood pressure lying and standing, liver enzymes, mood and suicidality, and dietary adherence.

Referral and escalation. Hypertensive crisis, serotonin syndrome, or any need to combine with other psychotropic drugs.