Tranylcypromine
MAOIs
Monoamine oxidase inhibitors (MAOIs)
An irreversible MAO inhibitor for depression that has not responded to other drugs. Needs a low-tyramine diet and many drug precautions.
Quick facts
- Group
- Monoamine oxidase inhibitors (MAOIs)
- Target
- Monoamine oxidase A and B
- Used for
- Depression that has not improved
- Key effects
- Dizziness on standing · Drowsiness or insomnia
- Monitor
- Blood pressure · Mood and suicidal thoughts
- ATC
- N06AF04
No doses: the clinician sets them by the current guideline.
Mechanism of action
The figure shows human MAO-B after tranylcypromine has reacted with it: the drug is bound to the FAD cofactor in the active site (as a phenylpropanal adduct).
Tranylcypromine, a non-hydrazine MAO inhibitor structurally related to amphetamine, binds monoamine oxidase A and B irreversibly. Serotonin, noradrenaline and dopamine are no longer broken down inside neurons, so more is stored and released. Gut and liver MAO-A also stop destroying dietary tyramine, which can then release noradrenaline and cause a hypertensive crisis. Enzyme activity returns only as new MAO is made, so the effect lasts for some time after stopping.
- Binds MAO-A and MAO-B irreversibly
- Serotonin, noradrenaline and dopamine accumulate
- Gut MAO no longer clears dietary tyramine
- Recovery needs new enzyme, after stopping
Indications
- Depression that has not improved with other medicines Major depressive disorder →
Adverse effects
Common
- Dizziness on standing
- Drowsiness or insomnia, restlessness
- Dry mouth, constipation or diarrhoea
- Tremor, muscle jerks, tingling
- Sexual dysfunction
Contraindications
- Phaeochromocytoma or other catecholamine-releasing paraganglioma
- Other antidepressants (other MAOIs, SSRIs, SNRIs, tricyclics, bupropion, vortioxetine and others), triptans, amphetamines and methylphenidate
- Sympathomimetic decongestants and weight-loss products (pseudoephedrine, phenylephrine, ephedrine)
- Pethidine (meperidine), dextromethorphan, tapentadol, buspirone, carbamazepine, levodopa, methyldopa, reserpine, tryptophan
Key interactions
- Tyramine-rich foods (aged cheese, cured or spoiled meat and fish, fermented products, some alcoholic drinks)
- Hypertensive crisis; the diet continues for two weeks after the last dose.
- SSRIs, SNRIs, tricyclics, pethidine, dextromethorphan, tryptophan
- Serotonin syndrome; a washout is needed in both directions when switching.
- Decongestants, amphetamines and other sympathomimetics
- Dangerous rise in blood pressure.
- Alcohol and other CNS depressants
- Used with caution: more drowsiness.
What is monitored
- Blood pressure, often
- Mood and suicidal thoughts
- Diet and every new medicine, including over-the-counter cough and cold products
- Signs of liver injury
Administration and safety
- Oral tablet; the dose is raised slowly, no more often than every one to three weeks.
- Not stopped suddenly; it is tapered.
- At least one week passes after stopping before another MAOI or a contraindicated antidepressant is started.
- Stopped at least ten days before elective surgery; anaesthetic and pain drugs are checked for interactions.
Pregnancy and breastfeeding
Limited reports describe placental problems and congenital anomalies; pregnant women are told of the possible risk to the fetus.
Nursing care
- Before: give a written list of foods and medicines to avoid.
- During: measure blood pressure regularly; teach the warning signs of a hypertensive crisis.
- Teach to rise slowly and to avoid alcohol and caffeine excess.
- Ask about mood, sleep and suicidal thoughts.
Pharmacokinetics
- Absorption
- Oral tablet.
- Onset and duration
- Full antidepressant effect may take three weeks or longer; the enzyme effect persists after the drug is stopped.
Test yourself
Think of the answer, then tap the question to see it.
Why can cheese cause a hypertensive crisis in a patient on tranylcypromine?
Gut and liver MAO-A no longer break down dietary tyramine, which then releases noradrenaline from nerve endings.
Why do the precautions continue for weeks after the drug is stopped?
Inhibition is irreversible; MAO activity returns only as new enzyme is made.
Which cough suppressant must be avoided with MAO inhibitors?
Dextromethorphan (serotonin syndrome).
Connections
← Back to the class: Monoamine oxidase inhibitors (MAOIs)
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: Tranylcypromine: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2017); TRANYLCYPROMINE tablet (DailyMed (U.S. National Library of Medicine), 2024); Human monoamine oxidase B with tranylcypromine (RCSB Protein Data Bank, 2010); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).
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Representative model, for educational purposes only.