MAOIs were the first medications used as antidepressants. However, modern alternatives exist with fewer side effects.

To help those with depression better manage their symptoms, doctors and psychiatrists have long been searching for effective treatment options, including developing antidepressant medications.

Depression is a leading cause of disability worldwide, and in the United States alone, 19.4 million adults have experienced at least one major depressive episode.

Monoamine oxidase inhibitors — known as MAO inhibitors or MAOIs — were the first class of antidepressants to be developed.

Since then, other classes of drugs, like selective serotonin reuptake inhibitors (SSRIs), have become more popular treatment choices, because MAOIs tend to have more side effects and require dietary restrictions.

Nowadays, doctors typically prescribe MAOIs only when other medications have been unsuccessful. Still, it can be an effective medication option for some.

The first MAOI, iproniazid, was introduced in 1958 as an antidepressant.

MAOIs work by inhibiting (or blocking) the function of an enzyme called monoamine oxidase, which is involved in mood.

This medication appeared to help people with depression by improving their mood, making them feel happier and helping them be more alert. However, over time it was shown to cause severe liver damage, and its use was discontinued.

Though no longer in use, this discovery of a new way to treat depression led researchers to develop other medications, including modern MAOI antidepressants like isocarboxazid and phenelzine, which have less severe side effects.

MAOIs were developed to treat depression, but can also help treat panic disorder, social anxiety disorder, and other anxiety disorders.

Doctors may also prescribe them for treating the symptoms of:

MAOIs are also approved for managing depressive episodes in bipolar disorder.

One kind of MAOI — selegiline — is used to treat Parkinson’s disease.

MAOIs aren’t considered the first choice for treating depression anymore. Instead, MAOIs are typically only prescribed for treatment-resistant depression or when all other medication classes are unsuccessful.

The types of MAOIs approved by the Food and Drug Administration (FDA) today include:

An enzyme called monoamine oxidase naturally exists in the liver, nerve tissues, lungs, and gastrointestinal tract.

This enzyme plays several roles in your body, including helping your neurons work properly and breaking down brain chemicals (neurotransmitters) that are involved in mood, including:

MAOIs, as their name suggests, inhibit monoamine oxidase. This limits monoamine oxidase’s ability to remove neurotransmitters, which ultimately leaves more of them present in your brain.

While there’s no conclusive cause of depression, many believe it’s associated with low levels of certain neurotransmitters, and by increasing neurotransmitter levels in the brain, you may help alleviate some symptoms of depression.

MAOIs have a range of possible side effects.

Monoamine oxidase doesn’t just affect neurotransmitters — it also elevates levels of tyramine in the body, a chemical that helps regulate blood pressure. So when MAOIs affect this enzyme, it can increase your blood pressure.

If you take an MAOI, your doctor will carefully monitor your blood pressure throughout your treatment.

Additionally, because the MAOI will allow tyramine to build up in your body, you’ll need to follow some dietary restrictions to minimize your risks of serious health issues from the higher levels of tyramine.

When taking MAOIs, your doctor will advise you to avoid any food that’s aged, including:

  • cured or aged meats, like salami
  • aged cheeses, like brie, cheddar, or blue cheese
  • leftover foods from your fridge
  • sauerkraut
  • all nuts
  • soy sauce
  • fermented products
  • alcohol
  • dried fruits
  • tofu

Other possible side effects of MAOIs include:

  • nausea
  • restlessness
  • drowsiness
  • trouble sleeping
  • dizziness
  • digestive issues, such as diarrhea or constipation
  • dry mouth
  • weight gain
  • swelling (edema)
  • skin reactions if using the patch
  • muscle spasms
  • sexual dysfunction

People on MAOIs, along with other antidepressants, may have a higher chance of developing serotonin syndrome. The risk increases if you’re taking other antidepressants or St. John’s wort at the same time.

Serotonin syndrome is a medical emergency and may cause:

  • fever
  • irregular or rapid heartbeat
  • confusion
  • dilated pupils
  • unconsciousness

MAOIs also interact with a number of other medications, so it’s important to let all healthcare professionals know (including your dentist) if you’re taking an MAOI, especially if you have one of the following medical conditions:

  • high blood pressure
  • heart disease
  • diabetes
  • seizure disorders
  • kidney disease

MAOIs are only one type (or class) of antidepressant. Since the 1950s, doctors have started using a growing number of medications for treating depression.

Other antidepressant classes include:

Recently, two types of ketamine — racemic ketamine and esketamine — have gained FDA approval for people with treatment-resistant depression and major depression.

MAOIs hold a place in the history of mental health treatments as the first effective drug treatment for depression. But like most things in science and mental health, further research discovered newer and safer treatment options from the foundations that MAOIs built.

If your doctor or mental health professional believes you can benefit from an MAOI, regular check-ups will make sure you’re maintaining your blood pressure and tyramine levels.

Though MAOIs aren’t as common today, they can still be a very effective and beneficial alternative for people living with depression.