What Are MAOIs?
Monoamine Oxidase Inhibitors
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Medically reviewed by Steven Gans, MD
Monoamine oxidase inhibitors (MAOIs) are the oldest class of antidepressants. They were created in the 1950s and are still used to treat some forms of depression and other nervous system conditions, like Parkinson's disease.
However, due to the associated side effects, dietary restrictions, and other potential complications that go along with their use, MAOIs usually are not prescribed unless other treatments are unsuccessful.
In this article, learn more about MAOIs.
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Understanding MAOIs
MAOIs are the first type of antidepressant created. Initially, they were used to treat the lung disease tuberculosis. However, scientists found that they were effective at improving depressive symptoms as well.
MAOIs can have severe interactions with certain foods and drugs, resulting in significant side effects and even fatalities. Over the years, MAOIs have been replaced with newer antidepressants that are safer and have fewer adverse interactions.
Healthcare providers still prescribe MAOIs but generally only after other antidepressants or treatments have failed.
Related:What Are Antidepressants?
What Are MAOIs Used For?
Although they are not a first-line treatment, healthcare providers use MAOIs to treat various forms of depression and other conditions.
A healthcare provider may prescribe MAOIs to treat depression that has not responded to other antidepressants.
Other conditions that MAOIs can treat include:
Related:What Is Atypical Depression?
How Do MAOIs Work?
MAOIs work similarly to other antidepressants by affecting neurotransmitters (the chemical messengers in the brain that allow nerve cells to communicate with one another). Specifically, MAOI is an inhibitor of an enzyme called monoamine oxidase. "Inhibitor" means the drug blocks monoamine oxidase from performing its usual function.
The enzyme monoamine oxidase removes neurotransmitters like dopamine, serotonin, and norepinephrine from the brain. Low levels of those neurotransmitters are associated with depression.
Monoamine oxidase treats depression by preventing monoamine oxidase from removing those neurotransmitters. MAOIs keep dopamine, serotonin, and norepinephrine higher in the brain, which thereby helps reduce depression.
Side Effects and Restrictions
Below is information on the various side effects, risks, and dietary restrictions associated with MAOI use.
MAOIs and Blood Pressure
The way that MAOIs work to treat depression is also its downfall when it comes to associated side effects.
In addition to lowering levels of neurotransmitters, the enzyme monoamine oxidase has a vital role in removing tyramine. Tyramine is a chemical that is found in certain foods. High tyramine levels can cause sudden increases in blood pressure.
When you take MAOIs, monoamine oxidase can't perform its usual function, which may result in abnormal levels of tyramine and, therefore, unmanaged blood pressure.
In some cases, if a person eats high-tyramine foods (like certain cheeses), they may get a "cheese reaction" or, in scientific terms, a "tyramine pressor response." This can lead to a hypertensive crisis (dangerously high blood pressure), potentially leading to a cerebral hemorrhage and death in rare cases.
MAOIs can also cause orthostatic hypotension, a sudden drop in blood pressure when standing or sitting from lying down.
MAOI Dietary Restrictions
To avoid a blood pressure emergency, people taking MAOIs must follow dietary restrictions, which typically require removing high-tyramine foods.
Foods to be avoided or eaten with caution when taking MAOIs include:
Specific aged cheese (e.g., long-aged artisanal cheese)
Cured or aged meat (e.g., liver, salami, turkey, sausage)
Broad bean pods (avoid)
Dried, aged, or smoked fish
Soy products and tofu
Sauerkraut and kimchi
Overripe or dried fruits
Note that tyramine increases as food ages. Most of the above foods involve some process of aging or fermenting. If you are taking an MAOI, eating fresh foods like fresh fruits, vegetables, and newly cooked meat is better.
MAOIs can also dangerously interact with other medications and supplements. These include medications that increase serotonin such as certain other antidepressants, Sainti-John's-wort, dextromethorphan (found in cough medicines), and medicines that can increase sympathetic nervous system activity, such as phenylephrine (decongestant) and certain anesthetics.
Related:Lowering Tyramine-Foods to Eat and Avoid
Other Side Effects
Beyond the potential for hypertensive crisis and serious medication interactions, MAOIs can also cause other side effects, including:
Dizziness
Sexual dysfunction
Headaches, including migraine
Weight gain
Insomnia
Antidepressant discontinuation syndrome (if abruptly stopped)
Related:Study: There’s No Perfect Way to Wean Yourself off of Antidepressants
Types
Four MAOIs are currently approved by the Food and Drug Administration (FDA) to treat depression. MAOI antidepressants include:
Nardil (phenelzine)
Parnate (tranylcypromine)
Marplan (isocarboxazid)
Emsam (selegiline transdermal patch)
Additionally, Azilect (rasagiline) is another type of MAOI approved to treat Parkinson's disease in the United States.
Related:How Depression Is Treated
Benefits
A healthcare provider may recommend MAOIs to some people because the benefits of treating depression, Parkinson's, or other conditions outweigh the risks of possible side effects.
A 2021 systematic review found that Nardil, a type of MAOI, was one of the most effective of the antidepressants compared in the clinical trials examined.
The study also found that all four FDA-approved MAOI types were comparable with other antidepressants, including selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs), regarding their effectiveness and acceptability among people with depression.
As a result, the reviewers concluded that MAOIs are currently underutilized, despite their side effects and risks.
Summary
MAOIs are the original antidepressant. This class of antidepressants was developed in the 1950s and is still used. However, due to potential side effects, interactions, and dietary restrictions, MAOIs are not generally used unless other treatments have failed. There is some evidence suggesting that these potentially effective agents may be currently underutilized.
