Introduced in the 1950s, monoamine oxidase inhibitors (MAOIs) were often prescribed for depression. However, the use of MAOIs declined after the introduction of selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs). These newer antidepressants often offer relief with fewer side effects. Yet MAOIs are effective and might be a good choice for patients with atypical or treatment-resistant depression.

How MAOIs Work

Depression is thought to be related to the levels of certain chemicals in the brain. These chemicals, called neurotransmitters, influence communication between brain cells. Low levels of some of these chemicals—including serotonin, norepinephrine, and dopamine—are associated with depression. MAOIs work to increase the levels of these neurotransmitters in the brain.

Monoamine oxidase is an enzyme that is responsible for the breakdown of norepinephrine, serotonin, and dopamine in the brain. By blocking the action of monoamine oxidase, MAOIs effectively increase the levels of available norepinephrine, serotonin, and dopamine.

Who Should Take MAOIs?

Monoamine oxidase is present throughout the body. It’s particularly active in the digestive system, where it breaks down tyramine, a chemical that affects blood pressure and is found in many foods and drinks. Because MAOIs affect tyramine levels, users must follow special dietary restrictions to avoid experiencing high blood pressure.

MAOIs are a good choice for patients who have failed to respond to treatment with other antidepressants. The best candidates for MAOI therapy are those who are willing to follow the diet and drug guidelines that accompany treatment. Patients taking MAOIs should avoid:

  • alcohol, especially Chianti, vermouth, and draft beers. Some experts believe that small amounts of wine (about a ½ cup) may be okay.
  • aged cheeses, such as brie, cheddar, Swiss, blue, parmesan, and gouda
  • cured meats, including sausage, bologna, pepperoni, and salami
  • sauerkraut
  • tofu
  • fava beans
  • raisins and dried fruit
  • fermented soy products, including soy sauce, teriyaki, and tempeh
  • any fish or meat refrigerated more than 24 hours

MAOIs should not be taken with any other antidepressants or herbal preparations such as St. John’s wort. Taking MAOIs with these treatments increases the risk of serotonin syndrome, a serious condition marked by confusion, rapid or irregular heartbeat, dilated pupils, fever, and, occasionally, unconsciousness. To decrease the risk of serotonin syndrome, patients who stop taking an MAOI should observe a 14-day “washout” period before starting any other antidepressants. The washout period gives the body time to clear the medication before another drug is introduced.

At least one newer MAOI, selegiline, is considered a selective MAOI because it blocks MAO-B, the form of monoamine oxidase that’s primarily present in the brain and not MAO-A, the form of monoamine oxidase that predominates in the gut.

Women who are pregnant or nursing should avoid MAOIs. Although some experts think that selegiline might be safe during pregnancy, little research has been done to determine its safety.

Possible Side Effects

Side effects may vary from medication to medication. If you experience unpleasant side effects while taking an MAOI, talk to your healthcare provider. Switching to a different medication might help.

Potential side effects include:

  • nervousness
  • muscle ache
  • daytime sleepiness
  • insomnia
  • weight gain
  • sexual dysfunction (inability to maintain an erection or orgasm)
  • low blood pressure
  • diarrhea
  • dry mouth
  • altered sense of taste
  • difficulty urinating
  • prickling or tingling sensation in the skin

Because selegiline selectively blocks MAO-B, it may have fewer side effects than other MAOIs. Talk to your doctor if you experience any troubling side effects. Never abruptly discontinue your medication. Stopping suddenly may cause nausea, vomiting, malaise, and, rarely, nightmares, agitation, convulsions, and psychosis.

Types of MAOIs

There are a number of MAOIs on the market. The generic names are listed below with their brand-name counterparts in parentheses.

  • isocarboxazid (Marplan)
  • phenelzine (Nardil)
  • tranylcypromine (Parnate)
  • selegiline (Emsam, Eldepryl, Zelapar): Selegiline is available in an oral form and as a patch that is applied to the skin once per day. The patch might yield fewer side effects.

What the Expert Says

“The MAOIs are probably among the most effective of the antidepressants,” says Dr. Danny Carlat, M.D., associate clinical professor of psychiatry at Tufts University School of Medicine. “They’re also the ones that we try after we’ve already been through three or four other antidepressants. We sometimes find that the MAOIs work well in patients where other medications haven’t worked.”