MAOIs — Learn about the benefits, side effects and risks of these older antidepressants. By Mayo Clinic Staff

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 They're effective, but they've generally been replaced by antidepressants that are safer and cause fewer side effects.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 because they 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.

Antidepressants such as MAOIs ease depression by affecting chemical messengers (neurotransmitters) used to communicate between brain cells. Like most antidepressants, MAOIs work by changing the levels of one or more of these naturally occurring brain chemicals.

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. This is thought to boost mood by improving brain cell communication.

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.

The Food and Drug Administration (FDA) has approved these MOAIs 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.

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
  • Skin reaction at the patch site
  • Dizziness or lightheadedness

Other possible side effects include:

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

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 you're 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, such as soy sauce, miso or tofu. You may be able to have limited amounts of wine and bottled or canned beer, but check with your doctor to be sure. The interaction of tyramine with MAOIs can cause dangerously high blood pressure. Ask your doctor for a complete list of dietary restrictions.
  • Drug interactions. MAOIs can also cause serious reactions when you take them with certain other medications. Examples of medications to avoid include other antidepressants, certain pain medications, certain cold and allergy medications, and some herbal supplements. Always check with your doctor or pharmacist before taking any new prescription medication, 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. This is known as serotonin syndrome. It most often occurs when two medications that raise serotonin are combined. These include other antidepressants, certain pain or headache medications, and the herbal supplement St. John's wort. Signs and symptoms of serotonin syndrome include anxiety, agitation, sweating, confusion, tremors, restlessness, lack of coordination and rapid heart rate. Seek immediate medical attention if you have any of these signs or symptoms.

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 your doctor or get emergency help.

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

Talk to your doctor before you stop taking an MAOI. Stopping treatment with MAOIs has been associated with flu-like symptoms, including nausea, vomiting and feeling generally unwell (malaise).

If you stop an MAOI suddenly, you're more likely to experience a withdrawal-type reaction. Rarely, discontinuation syndrome can occur, which causes uncommon withdrawal symptoms such as insomnia, confusion, detachment from reality (psychosis), agitation and convulsions. You may need to wait two or more weeks between the use of MAOIs and other antidepressants to avoid serotonin syndrome.

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

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 will take into account your symptoms, what health problems you have, what 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. The study of how genes affect a person's response to drugs is called pharmacogenomics. However, other variables besides genetics can affect your response to medication.

Typically, it takes several weeks or longer before an antidepressant is fully effective and for initial side effects to ease up. You may need to try several antidepressants before you find the right one, but hang in there. With patience, you and your doctor can find a medication that works well for you.

Jun. 21, 2013