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Monoamine Oxidase Inhibitors (MAOIs)

Reviewed by: HU Medical Review Board | Last reviewed: September 2023

Monoamine oxidase inhibitors (MAOIs) were the first drugs used to treat depression. But they have many risks and side effects. They also can have severe interactions with other drugs and foods. Because of this, MAOIs are used less often than newer antidepressants to treat major depressive disorder (MDD).1-4

MAOIs are most often prescribed for depression when other drugs have not worked. They also may be prescribed when a person has another health condition that MAOIs can treat (like Parkinson’s disease).1-4

In addition to MDD, MAOIs are prescribed to treat:1-3

  • Panic disorder
  • Social phobia or social anxiety disorder
  • Parkinson’s disease
  • Eating disorders, like bulimia nervosa
  • Persistent depressive disorder
  • Depression with atypical features (like severe overeating or oversleeping)

How do MAOIs work?

MAOIs prevent the breakdown of certain neurotransmitters in the body. Neurotransmitters are chemicals the brain and nerve cells use to send signals. These signals help our body carry out many functions, including digestion, movement, and blood pressure control. Symptoms of depression may be related to changes in the balance of mood-affecting neurotransmitters.4,5

After neurotransmitters are released in the body and carry their messages, they are broken down. This prevents messages from being sent for too long or at the wrong times. A protein called monoamine oxidase helps with this breakdown process. MAOIs block the action of this protein. In this way, they prevent neurotransmitters from being broken down.1-3

Because the neurotransmitters are not broken down, they stay active for longer periods. This can impact the way they send signals. Experts think that increasing the activity of certain neurotransmitters can treat the symptoms of depression.4,5

Some of the neurotransmitters that MAOIs affect are serotonin, dopamine, norepinephrine, and tyramine. But many of these chemicals affect processes other than mood and behavior. When their activity is increased, side effects and risks can occur.1,2

Examples of MAOIs

The most common MAOIs used in the United States include:1,3,6

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

Choosing the right MAOI for you will depend on your past treatment history, other drugs you take, and what other health issues you have.1,7

What are the possible side effects?

Side effects can vary based on the specific drug you are taking. Common side effects of MAOI drugs include:1-3,6

  • Dizziness, especially when standing up
  • Nausea
  • Restlessness
  • Trouble sleeping
  • Constipation
  • Dry mouth
  • Headache
  • Blurry vision
  • Drowsiness
  • Trouble urinating
  • Issues with sexual function, like decreased sexual desire or trouble reaching orgasm
  • Weight gain

If your MAOI comes as a skin patch, you may also have skin irritation at the patch site.1

MAOIs have a boxed warning, the strictest warning from the US Food and Drug Administration (FDA). They have this warning because they may increase the risk of suicidal thoughts or behaviors when starting a new drug or changing doses.3,6

These are not all the possible side effects of MAOIs. Talk to your doctor about what to expect when taking an MAOI. You also should call your doctor if you have any changes that concern you when taking MAOIs.

Other things to know

As with other antidepressants, there are some serious risks of MAOIs, including hypertensive crisis. This is an episode of very high blood pressure that can be dangerous. One of the neurotransmitters that MAOIs affect, tyramine, helps regulate blood pressure. You will need to avoid foods containing high levels of tyramine while taking an MAOI. These foods include aged cheeses, cured meats, beer, and fermented soy products.1-3,7,8

If you notice any of these issues or new symptoms you are not used to, seek medical attention right away.

Before you start taking an MAOI, tell your doctor if you are pregnant or planning to become pregnant. Some MAOIs may cause harm to an unborn baby, so your treatment plan may need to be adjusted.1,7

It may take many tries to find the right antidepressant for you. Each person reacts differently. Most people will start with 1 of the newer antidepressant drugs, like a selective serotonin reuptake inhibitor (SSRI) or serotonin and norepinephrine reuptake inhibitor (SNRI). If you do not have success with those, your doctor may prescribe an MAOI.7

Almost all MAOI drugs come in oral form. But some, like selegiline, can come as a skin patch. This may have some benefits over the oral form, like fewer side effects. You and your doctor will decide together which drug, dose, and form is best for you.1,7

MAOIs can interact with many other drugs and supplements. Some of these interactions can be life-threatening. Before beginning treatment for MDD, tell your doctor about all your health conditions and any drugs, supplements, and vitamins you are taking. This includes over-the-counter drugs.

Your doctor will monitor you closely for any mental health side effects when you start or change doses of an antidepressant. If you have thoughts of harming yourself or others, seek immediate support. You can call or text the Suicide & Crisis Lifeline at 988, or chat with them online, anytime.9

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