Monoamine oxidase inhibitors (MAOIs)

November, 15th, 2023

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Monoamine oxidase inhibitors (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 They’re effective, but they’ve generally been replaced by antidepressants that are safer and cause fewer side effects.

Use of MAOIs typically requires diet restrictions and avoiding certain other medications because MAOIs can cause dangerously high blood pressure when taken with certain foods or medications. In spite of side effects, these medications are still a good option for some people. In certain cases, they relieve depression when other treatments have failed.

How MAOIs work

Antidepressants such as MAOIs ease depression by affecting chemical messengers (neurotransmitters) used to communicate between brain cells. Like most antidepressants, MAOIs work by ultimately effecting changes in the brain chemistry that are operational in depression.

An enzyme called monoamine oxidase is involved in removing the neurotransmitters norepinephrine, serotonin and dopamine from the brain. MAOIs prevent this from happening, which makes more of these brain chemicals available to effect changes in both cells and circuits that have been impacted by depression.

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

MAOIs approved to treat depression

The Food and Drug Administration (FDA) has approved these MAOIs to treat depression:

• Isocarboxazid (Marplan)
• Phenelzine (Nardil)
• Selegiline (Emsam)
• Tranylcypromine (Parnate)

Selegiline is available as a skin (transdermal) patch. Using a patch may cause fewer side effects than MAOIs taken by mouth. If you’re using the lowest dose patch, you may not need diet restrictions, but ask your doctor.

Side effects of MAOIs

Because of side effects and safety concerns, MAOIs are most often tried when other antidepressants don’t work.

The most common side effects of MAOIs include:

• Dry mouth
• Nausea, diarrhea or constipation
• Headache
• Drowsiness
• Insomnia
• Dizziness or lightheadedness
• Skin reaction at the patch site

Other possible side effects include:

• Involuntary muscle jerks
• Low blood pressure
• Reduced sexual desire or difficulty reaching orgasm
• Weight gain
• Difficulty starting a urine flow
• Muscle cramps
• Prickling or tingling sensation in the skin (paresthesia)

Safety concerns with MAOIs

Consider these issues and discuss them with your doctor before taking an MAOI:

• Antidepressants and pregnancy. Some antidepressants may harm your child if you take them during pregnancy or while breast-feeding. If you’re considering getting pregnant, talk to your doctor or mental health provider about the possible dangers of certain antidepressants. Don’t stop taking your medication without contacting your doctor first.
• Food and beverage interactions. MAOIs can cause dangerous interactions with certain foods and beverages. You’ll need to avoid foods containing high levels of tyramine — an amino acid that regulates blood pressure — such as aged cheeses, sauerkraut, cured meats, draft beer and fermented soy products (for example, soy sauce, miso and tofu). The interaction of tyramine with MAOIs can cause dangerously high blood pressure. Ask your doctor for a complete list of dietary restrictions, including alcohol restrictions.
• Drug interactions. MAOIs can cause serious reactions when you take them with certain medications, such as other antidepressants, certain pain drugs, certain cold and allergy medications, and some herbal supplements. Always check with your doctor or pharmacist before taking any other prescription or over-the-counter medication, herbs or other supplements while you’re taking an MAOI.
• Serotonin syndrome. Rarely, an MAOI can cause dangerously high levels of serotonin, known as serotonin syndrome. It most often occurs when two medications that raise serotonin are combined. These include, for example, other antidepressants, certain pain or headache medications, and the herbal supplement St. John’s wort.
  • Signs and 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. Seek immediate medical attention if you have any of these signs or symptoms.

Suicide risk and antidepressants

Most antidepressants are generally safe, but the FDA requires that all antidepressants carry black box warnings, the strictest warnings for prescriptions. In some cases, children, teenagers and young adults under 25 may have an increase in suicidal thoughts or behavior when taking antidepressants, especially in the first few weeks after starting or when the dose is changed.

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, immediately contact a doctor or get emergency help.

Keep in mind that antidepressants are more likely to reduce suicide risk in the long run by improving mood.

Stopping treatment with MAOIs

Talk to your doctor before you stop taking an MAOI. Stopping treatment with MAOIs has been associated with anxiety, agitation and insomnia, as well as flu-like symptoms such as sweating, chills, nausea, headache and feeling generally unwell (malaise).

If you stop an MAOI suddenly, you’re more likely to experience a withdrawal-type reaction, sometimes called discontinuation syndrome. Rarely, uncommon withdrawal symptoms such as confusion, detachment from reality (psychosis) and convulsions can occur.

You may need to wait two or more weeks between the use of MAOIs and other antidepressants to avoid serotonin syndrome. During those two weeks, you should continue food and beverage restrictions and avoid taking drugs that can cause serious interactions with MAOIs.

Work with your doctor to gradually and safely decrease your dose.

Finding the right antidepressant

Each person reacts differently to a particular antidepressant and 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 doctor takes into account your symptoms, any health problems you have, other medications you take and what has worked for you in the past.

Inherited traits play a role in how antidepressants affect you. In some cases, where available, results of special blood tests may offer clues about how your body may respond to a particular antidepressant. However, other variables can affect your response to medication.

It may take several weeks or longer before an antidepressant is fully effective and for initial side effects to ease up. Your doctor may recommend some dose adjustments or different antidepressants, but with patience, you and your doctor can find a medication that works well for you.