Monoamine oxidase inhibitors (MAOIs)

Monoamine oxidase inhibitors, also called MAOIs, were the first type of antidepressant developed. Learn about the benefits, side effects and risks of these antidepressants.

By Mayo Clinic Staff

Monoamine oxidase inhibitors, also called MAOIs, were the first type of antidepressant developed. They’re effective, but they’ve generally been replaced by antidepressants that are safer and cause fewer side effects.

If you take an MAOI, you may need to stay away from certain foods and medicines. Eating foods that are high in the amino acid tyramine or taking certain other medicines while taking an MAOI can cause dangerously high blood pressure. MAOIs are still a good choice for some people. Sometimes they lessen depression when other treatments have failed.

How MAOIs work

Antidepressants such as MAOIs ease depression by controlling chemical messengers called neurotransmitters that carry messages between brain cells and affect mood. MAOI antidepressants block an enzyme called monoamine oxidase from doing its work. This enzyme breaks down neurotransmitters known as norepinephrine, serotonin and dopamine, sometimes lowering their levels too much. By blocking this process, MAOIs can raise the levels of these neurotransmitters in the brain and ease depression.

MAOIs also affect other neurotransmitters in the brain and digestive system, which can cause side effects. MAOIs sometimes are used to treat conditions other than depression, such as Parkinson’s disease.

MAOIs approved to treat depression

The U.S. Food and Drug Administration, also called the FDA, has approved these monoamine oxidase inhibitors to be taken by mouth to treat depression:

Isocarboxazid (Marplan).
Phenelzine (Nardil).
Tranylcypromine (Parnate).

Another MAOI, selegiline (Emsam), is available as a skin patch. Using a skin patch may cause fewer side effects than MAOIs taken by mouth. If you’re using the lowest dose patch, you may not need to limit foods that have the amino acid tyramine. But ask your healthcare professional to be sure.

Side effects of MAOIs

MAOIs most often are tried when other antidepressants don’t help.

The most common side effects of MAOIs include:

Dry mouth.
Upset stomach.
Diarrhea or constipation.
Headache.
Sleepiness during the day.
Trouble sleeping at night.
Dizziness or lightheadedness.
Skin irritation at the patch site.

Less common side effects include:

Muscle cramps or jerks.
Low blood pressure.
Less sexual desire or trouble reaching orgasm.
Weight gain.
Trouble starting a urine flow.
Prickling or tingling feeling in the skin.

Safety issues with MAOIs

Talk with your healthcare professional about these safety issues before you take an MAOI.

Antidepressants and pregnancy. Some antidepressants may harm your child if you take them during pregnancy or while breastfeeding. If you are pregnant, are thinking about getting pregnant or are breastfeeding, talk with your healthcare professional about the possible dangers of certain antidepressants. Don’t stop taking your medicine without talking with your healthcare professional first.
Food and beverage interactions. MAOI antidepressants block an enzyme called monoamine oxidase. This enzyme breaks down tyramine, an amino acid in the body. Blocking the enzyme means that the body can’t get rid of extra tyramine. For some people, eating or drinking foods or beverages high in tyramine while taking an MAOI causes dangerously high blood pressure.

While you take an MAOI and for a few weeks after stopping, stay away from foods high in tyramine. These include aged cheeses, cured meats, draft beer, and other fermented, aged, overripe or spoiled foods. Ask your healthcare professional for a complete list of foods and beverages to stay away from. Also ask if you need to limit caffeine or alcohol.
Medicine interactions. MAOIs can cause serious reactions when you take them with certain medicines. These medicines may include other antidepressants, certain pain medicines, and certain cold and allergy medicines. Some herbal supplements also can cause reactions when taken with MAOIs. Always check with your healthcare professional or pharmacist before you take any other prescription or nonprescription medicine, herbs or other supplements while taking an MAOI.
Serotonin syndrome. Rarely, an MAOI can cause dangerously high levels of serotonin in the body. This is known as serotonin syndrome. It most often happens when you take two medicines that both raise serotonin levels. This includes taking an MAOI with other antidepressants, certain pain or headache medicines, or the herbal supplement St. John’s wort.

Symptoms of serotonin syndrome include anxiety, agitation, high fever, sweating, confusion, tremors, restlessness, lack of coordination, major changes in blood pressure, and rapid heart rate. Get medical help right away if you have any of these symptoms.

Suicide risk and antidepressants

Most antidepressants are generally safe. But the FDA says that all antidepressants must carry boxed warnings, the strictest warnings for prescriptions. In some cases, children, teenagers and young adults under age 25 may have an increase in suicidal thoughts or behavior when taking antidepressants. This is more likely in the first few weeks after starting the medicine or when the dose is changed. There has been no evidence that this increase in suicidal thoughts or behaviors has resulted in completed suicides.

MAOIs are generally not prescribed for children, but anyone taking an antidepressant should be watched closely for worsening depression or unusual behavior. If you or someone you know has suicidal thoughts when taking an antidepressant, call your healthcare professional right away or get emergency help.

Keep in mind that depression that’s not treated is a more concerning risk factor for suicide. And antidepressants may lessen suicide risk in the long run by improving mood for many people.

Stopping treatment with MAOIs

Talk with your healthcare professional before you stop taking an MAOI.

Typically, MAOIs are not habit-forming. But if you stop an MAOI suddenly, you’re more likely to have discontinuation symptoms. This is sometimes called discontinuation syndrome. These symptoms can include:

Restlessness, irritability or anxiety.
Upset stomach.
Feelings of tingling or burning.
Flu-like symptoms, such as chills, sweating, feeling generally unwell and muscle aches.
Trouble sleeping.
Sluggishness, tiredness or sleepiness.
Headache.
Confusion.
Dizziness.

You’ll likely need to wait two or more weeks after the use of MAOIs before starting other antidepressants. This will help you avoid serotonin syndrome, where you have dangerously high levels of serotonin. During those two weeks, continue food and beverage restrictions and don’t take medicine that can cause serious interactions with MAOIs.

Work with your healthcare professional to slowly and safely lower your dose over time.

Finding the right antidepressant

Each person reacts differently to a particular antidepressant. Some people may be more likely to have certain side effects. Because of this, one antidepressant may work better for you than another. When choosing an antidepressant, your healthcare professional considers your symptoms, any health issues you have, other medicines you take and what has worked for you in the past.

Genes passed down in your family may play a role in how antidepressants affect you. For some people, where available, results of blood tests may offer clues about how their bodies may respond to a particular antidepressant. But other things besides your genes can affect your response to medicine.

It may take several weeks or more for an antidepressant to have a full effect. It also can take several weeks or longer for initial side effects to ease up. Your healthcare professional may recommend dose changes or a different antidepressant. With patience, you and your healthcare professional can find a medicine that works well for you.

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Monoamine oxidase inhibitors (MAOIs) – Mayo Clinic