Monoamine oxidase inhibitors (MAOIs) were among the first antidepressants to be developed for treating depression and other mental disorders like Parkinsonism. They were hugely popular in the late fifties, sixties and the seventies.

Their popularity began to wane when it was found that they caused serious life-threatening interactions with sympathomimetic drugs and tyramine-containing foods.

According to the National Institutes of Health, Monoamine oxidase inhibitors (MAOIs) antidepressants are used today only when the patient has not responded to other antidepressants.

This is because though they can be effective against stubborn depression, they can also be dangerous due to these interactive properties with certain drugs and foods.

The interaction mechanism of MAOIs

The interaction between MAOIs and certain drugs and foods can result in two potentially fatal conditions:

  1. A hypertensive crisis, which can lead to a vascular accident such as a stroke. Hypertensive crisis is defined when the systolic blood pressure is 180 mm Hg or more and the diastolic pressure is 120 or higher.
  2. Serotonin syndrome, which can be fatal

MAOIs act by inhibiting the action of Monoamine oxidase (MAO). Monoamine oxidase is involved in breaking down and removing the neurotransmitters norepinephrine, serotonin and dopamine along with tyramine from the brain.

By inhibiting the action of MAO, MAOIs allow the levels of these neurotransmitters to stay high. The level of tyramine also increases, which is the main danger of using this drug.

A high level of these neurotransmitters makes the person feel elated and improves his mood. This is the mechanism of action due to which MAOIs are used to treat depression. But, the simultaneous rise in tyramine can be disastrous.

Tyramine is a vasoactive amine (an organic compound) naturally produced in the body and which promotes the rise of blood pressure.

MAOIs, therefore, can cause high levels of tyramine in the body. This interaction between MAOIs and tyramine can cause a severe rise in blood pressure.

Then there are certain drugs, like sympathomimetic drugs, which also promote the rise in blood pressure. When such drugs are taken with MAOIs it can promote a severe rise in blood pressure and cause a hypertensive crisis, which can lead to a vascular accident like a stroke.

Certain drugs that increase the levels of neurotransmitters such as serotonin, when taken with MAOIs can cause high levels of serotonin in the body. This can lead to serotonin syndrome, a potentially fatal condition that is triggered by too much nerve cell activity promoted by too much serotonin.

Below is the list of drugs and foods that can interact with MAOIs, which you should avoid when taking this drug.

Interacting drugs to avoid with MAOIs

Avoid these drugs that can interact with MAOIs and cause serious side effects are:

  • Other antidepressants such as SSRIs like paroxetine fluoxetine, amitriptyline, nortriptyline, bupropion, mirtazapine
  • Herbal preparations such as St. John’s Wort
  • Pain medications like methadone, tramadol, and meperidine
  • Cough suppressant such as  dextromethorphan
  • Muscle relaxants like cyclobenzaprine (Amrix, Fexmid)

MAOIs can interact with the above-mentioned drugs and cause serotonin syndrome (high serotonin levels), which can lead to confusion, increased blood pressure, tremors, coma, and death.

Other drugs to be avoided are:

  • Seizure medicines like carbamazepine (Tegretol Tegretol XR, Equetro, Carbatrol) and oxcarbazepine (Trileptal)
  • Sympathomimetic drugs such as pseudoephedrine, phenylephrine, ephedrine, and phenylpropanolamine.

The combination of MAO inhibitors and these drugs can cause an acute hypertensive crisis, which can lead to a cerebrovascular accident.

To sum up:

Combining MAOIs with other antidepressants can cause high levels of serotonin due to the synergistic action of both.

Combining MAOIs with sympathomimetic drugs lead to a hypertensive crisis because MAOIs act by increasing the concentration of noradrenaline in the sympathetic nerve endings, which increases the blood pressure while the sympathomimetic drugs cause increased blood pressure by directly narrowing the blood vessels. The synergistic effect of both these drugs can cause the blood pressure to rise very high.

Interacting dietary foods to avoid when on MAOIs

Eating foods rich in tyramine, typically high-protein foods and drinks can cause tyramine levels to rise dangerously high if you are on MAOIs. This can lead to a very high rise in blood pressure.

The reason for this is that the enzyme monoamine oxidase (MAO) present in the digestive tract keeps tyramine levels within a safe range. MAOIs, as the name suggests inhibits the action of the MAO causing the tyramine levels to rise.

This gives rise to serious symptoms such as headaches, nausea, vomiting, visual disturbances, confusion, severe high blood pressure, and heart problems.

Excessive concentrations of tyramine in the blood can cause a hypertensive crisis due to the release of norepinephrine (NE), which causes blood vessels to constrict.

Ordinarily, MAO would destroy the excess of norepinephrine; however, when MAO is inhibited by MAOI, norepinephrine levels rise very high, leading to a dangerous increase in blood pressure.

Tyramine is typically found in foods that are fermented, old, or spoiled.

Cheese

Avoid aged and matured cheese because they contain a high amount of tyrosine. You can, however, eat cottage cheese, cream cheese, ricotta, and American processed cheese provided they have not been refrigerated for more than two weeks.

Meat

Mayo clinic also contraindicates eating of smoked or pickled meats and cured meats such as sausages, salami, pastrami, and pepperoni when on MAOIs.

You can, however, eat fresh packaged meat, fish, poultry and dairy products that have been stored in the refrigerator for not more than three days.

Vegetables

Avoid fermented vegetable products like tofu, sauerkraut, soy sauce, yeast extracts, fava beans, Italian green beans, or snow peas, teriyaki, soybean paste, miso soup, tamari, natto, and tempeh.

Fruits

Overripe fruits containing tyramine that should be avoided with MAOIs are spinach, overripe bananas and banana peels, raisins and prunes, avocados, raspberries, fava beans, Italian green beans, or snow peas.

Beverages

Avoid chocolate and caffeinated beverages.

Alcohol

Avoid beer, especially tap or homebrewed beer, red wine, sherry, and liqueurs because of their high tyrosine content. Avoid alcohol in any form when taking MAOIs because it can worsen your depression when you cross the safe limit of two standard drinks.

MAOIs and alcohol combination makes you feel very drowsy, which can be dangerous if you drive or operate heavy machinery.