Drug interactions · everyday safety

Medicines and MAOIs: a precise rule, not a vague fear.

As with food, the drug-related danger of classic MAOIs (Parnate, Nardil and Marplan) rests on identifiable mechanisms, not a fog of prohibitions. There are two adverse events to avoid, contraindicated combinations and others that require specialist supervision — with one golden rule: tell every healthcare professional that you take an MAOI.

The rule fits into one sentence: never add a medicine, supplement or recreational drug without professional verification, and observe a safety interval when changing treatment. Many medicines remain usable, but compatibility depends on the specific substance and sometimes the dose.
Adverse event no. 1 · serotonin

Serotonin syndrome: too much serotonin at once. Triggered by substances that strongly block reuptake or release serotonin.

Adverse event no. 2 · blood pressure

A hypertensive crisis: a sudden surge in blood pressure. Triggered by stimulants (sympathomimetics) — and, in food, by tyramine.

Why these two mechanisms? See Misconceptions. For food, see the tyramine diet.

Avoid — contraindicated Caution — under medical supervision Generally compatible — usual precautions
Avoid — the short but firm list
SSRIs, SNRIsserotonergic antidepressants — the classic cause of serotonin syndrome
Clomipraminethe most serotonergic tricyclic (other tricyclics: caution and medical advice)
Tramadol, pethidine, tapentadolserotonergic painkillers — to be distinguished from other opioids (see “caution”)
Dextromethorphanthe cough suppressant in many over-the-counter cough syrups
Certain decongestantspseudoephedrine and ephedrine — products for colds or hay fever (risk of a rise in blood pressure)
Stimulant drugs and high doses of amphetaminescocaine, MDMA/ecstasy and medium or high doses of amphetamines
St John's wort, tryptophana “natural” herb and supplement — but nevertheless serotonergic
Linezolid, methylene bluean antibiotic (itself an MAOI) and a dye used in surgery
Caution — possible, but supervised by a physician
Other opioidsmorphine, oxycodone, fentanyl and hydromorphone: different profiles from the contraindicated painkillers, but the combination must be supervised
Triptanssome may be used at a reduced dose; sumatriptan and zolmitriptan, which are metabolised by MAO, require particular caution
Prescribed stimulantsmethylphenidate, modafinil or a low dose of amphetamine: sometimes combined by a specialist, with a low initial dose and monitoring
Direct sympathomimeticsphenylephrine, adrenaline and related medicines: sometimes usable at a reduced dose and under medical supervision
Anaesthesia & surgerynever stop the MAOI on your own: tell the anaesthetist, who can provide “MAOI-compatible anaesthesia” (avoiding pethidine and indirect sympathomimetics)
Dental anaesthesiacartridges containing adrenaline at usual dental doses are now considered safe; an adrenaline-free option exists. Simply tell the dentist
Changing antidepressantnever overlap them: a safety interval must be observed (below)
Generally compatible — with the precautions specific to each medicine
Paracetamolthe first-choice painkiller and fever reducer while taking an MAOI
Ibuprofen, aspirinno interaction specific to MAOIs; their usual contraindications still apply
Most antibioticslinezolid is the major exception to know (see “avoid”)
Benzodiazepinesusual anxiolytics and sleeping medicines
Most antihistaminescaution: combination cold medicines often conceal a decongestant — read the ingredients

This list is not exhaustive. The safest reflex is also the simplest: before taking any new medicine — including an over-the-counter product — ask a physician or pharmacist, stating “I take an MAOI.”

Safety intervals (washout)

An MAOI continues to act until the disabled enzyme has been replaced — about two weeks. This is why intervals must be observed when starting, stopping or changing treatment.

SituationMinimum interval
Starting an MAOI after a serotonin inhibitor or releaser5 half-lives (often ≈ 8 days)
Starting an MAOI after vortioxetine≥ 14 days
Starting an MAOI after fluoxetine (Prozac)generally ≥ 6 weeks
Starting a serotonergic medicine after stopping an MAOI≥ 2 weeks
Switching from one MAOI to another≥ 2 weeks

Fluoxetine requires longer because its active metabolite is eliminated very slowly; an interval longer than six weeks may be chosen after a high dose or prolonged treatment. Never use a gradual overlap (“cross-taper”) between an MAOI and a serotonin inhibitor or releaser: the physician determines the exact interval for the medicines concerned. For details, see the summary of the prescribing guide.

One sentence to repeat: “I take an MAOI.”

Tell your physician, pharmacist, dentist, anaesthetist and emergency department. Most adverse events come from a medicine added without realising it — a prescription from another practitioner, an over-the-counter product or anaesthesia. Saying it in time helps prevent the problem.

⚠ Warning signs — act quickly

Blood-pressure surge (hypertensive crisis): a severe, pounding headache, stiff neck, palpitations, chest pain or blurred vision.

Excess serotonin (serotonin syndrome): agitation or confusion, fever, sweating, tremor, muscle rigidity or a rapid heartbeat.

In either case, do not wait for it to pass: call emergency services immediately.

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This website provides general information and cannot replace advice from a physician or pharmacist. Do not make any treatment decision without a healthcare professional. MAOIs involve real precautions — dietary and, above all, drug-interaction precautions — which are detailed on the relevant pages.