MAOIs (Monoamine Oxidase Inhibitors)

What are MAOIs?

MAOIs (monoamine oxidase inhibitors) are a class of antidepressants that help treat depression symptoms. Healthcare providers prescribe them for other conditions as well.

MAOIs were the first type of antidepressant invented. However, providers don’t often prescribe them for depression today due to several dietary restrictions, side effects and safety concerns. Providers typically only prescribe them if all other classes of antidepressants haven’t improved depression symptoms.

What are the types of MAOIs?

MAOIs (and their brand names) that healthcare providers can currently prescribe in the United States include:

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

What conditions do MAOIs help treat?

Each type of MAOI has different U.S. Food and Drug Administration (FDA) approval. In other words, you can take each medication for certain conditions.

Isocarboxazid and tranylcypromine are only FDA-approved to treat major depressive disorder.

The FDA-approved uses for phenelzine include treatment-resistant:

• Depression.
• Panic disorder.
• Social anxiety disorder.

The FDA-approved uses for selegiline include:

• Major depressive disorder.
• Additional treatment in the management of Parkinson’s disease.

Off-label uses

Healthcare providers sometimes prescribe MAOIs for other conditions. This is considered an off-label, or non-FDA-approved, use of the medication.

For example, providers sometimes prescribe Selegiline as an off-label treatment for attention-deficit/hyperactivity disorder (ADHD).

They may prescribe tranylcypromine off-label for:

• Treatment-resistant social anxiety disorder.
• Treatment-resistant panic disorder.
• Atypical depression.

How do MAOIs work?

MAOIs work by increasing the levels of certain neurotransmitters (chemical messengers) in your brain to boost your mood and improve other depression symptoms.

More specifically, MAOIs (monoamine oxidase inhibitors) work by blocking the monoamine oxidase enzyme. This enzyme breaks down different types of neurotransmitters in your brain, including:

• Serotonin.
• Norepinephrine.
• Dopamine.
• Tyramine.

By blocking the enzyme and the breakdown of these neurotransmitters, the MAOI increases the levels of these neurotransmitters in your brain.

Serotonin, norepinephrine and dopamine all play important roles in regulating your mood, sleep-wake cycle and memory. Serotonin also affects your appetite, social behavior and sexual desire. Norepinephrine and dopamine also increase alertness, arousal and attention.

Tyramine is considered a “false neurotransmitter.” It’s an amino acid that helps regulate your blood pressure. It occurs naturally in your body and certain foods.

What’s the difference between MAOIs and SSRIs?

MAOIs and SSRIs (selective serotonin reuptake inhibitors) are both classes of antidepressants, but they work in different ways.

SSRIs work by blocking only serotonin reuptake, which increases serotonin (a neurotransmitter) levels in your brain. MAOIs increase the levels of multiple neurotransmitters in your brain.

SSRIs are the most commonly prescribed antidepressant for depression, whereas healthcare providers rarely prescribe MAOIs. SSRIs can also help treat several other conditions.

How do you take MAOIs?

You can take MAOIs orally (by mouth) in tablet or capsule form. Selegiline also comes in the form of a skin patch. Your healthcare provider will prescribe a certain dose and provide instructions for taking the medication.

What are the side effects of MAOIs?

Each type and brand of MAOI has its own side effects. Be sure to talk to your healthcare provider or pharmacist about possible side effects to look out for.

In general, common side effects of MAOIs include:

• Dizziness or lightheadedness (due to low blood pressure).
• Dry mouth (xerostomia).
• Nausea.
• Diarrhea or constipation.
• Drowsiness.
• Insomnia.

What are the risks or complications of MAOIs?

Possible complications associated with MAOIs include:

• Risk of suicidal thoughts or behavior.
• Serotonin syndrome.
• Antidepressant discontinuation syndrome.
• Food interactions causing high blood pressure.

Suicidal thoughts or behavior

Children, teens and adults younger than the age of 25 may experience an increase in suicidal thoughts or behavior when taking MAOIs, especially when they first start them or when they take a different dose.

If you or your child have suicidal thoughts or behavior, call your healthcare provider who prescribed the medication immediately. You can also dial 988 on your phone to reach the Suicide and Crisis Lifeline.

Serotonin syndrome

Serotonin syndrome is a potentially life-threatening drug reaction that results from having too much serotonin in your body.

Serotonin syndrome is rare, but it can happen when you either take a new MAOI or take an increased dose. The syndrome most often happens when you take an MAOI in addition to other medications that increase your serotonin levels, such as SSRIs or opioids like tramadol and methadone.

Always tell your healthcare provider which medications and supplements you’re currently taking before starting a new medication. And always take your medications as prescribed. These steps can help prevent serotonin syndrome.

Symptoms of serotonin syndrome include:

• Nervousness.
• Nausea and vomiting.
• Diarrhea.
• Dilated pupils.
• Muscle issues, like twitching, involuntary contractions, spasms and rigidity.
• Sweating and shivering.
• Side-to-side eye movements.

Severe symptoms include:

• Confusion or delirium.
• Rapid heart rate (tachycardia).
• High blood pressure.
• Fever.
• Seizures.
• Loss of consciousness.

Get immediate medical help if you’re experiencing these symptoms. Serotonin syndrome can be fatal if it’s not treated in time.

Antidepressant discontinuation syndrome

Antidepressant discontinuation syndrome can happen if you suddenly stop taking your MAOI after you’ve taken it for at least six weeks.

Symptoms of antidepressant discontinuation syndrome include:

• Flu-like symptoms, such as fatigue, headache, achiness and sweating.
• Insomnia.
• Nausea.
• Dizziness and lightheadedness.
• Sensory issues, such as burning, tingling or shock-like sensations.
• Anxiety, irritability and agitation.

These symptoms are usually mild, but they can be unpleasant. They typically last one to two weeks.

Never stop taking your MAOI without talking to your healthcare provider first. Safely stopping antidepressants is a process. It usually takes at least four weeks to slowly reduce your dose.

Food interactions

MAOIs prevent the breakdown of tyramine in your body and in certain foods and drinks (and certain medications). If you take an MAOI and consume too much tyramine-containing foods or drinks, it causes high levels of tyramine in your blood. This can cause a sudden increase in blood pressure, called the tyramine pressor response.

A sudden increase in blood pressure is dangerous. In rare cases, a high tyramine level can trigger a cerebral hemorrhage (brain bleed), which can result in death.

Which foods should I avoid on MAOIs?

Foods that have high tyramine levels that you should avoid while taking MAOIs include:

• Aged cheese. (Unaged cheeses, such as cottage cheese, mozzarella and ricotta, are unlikely to have high tyramine levels unless you store them at a high temperature.)
• Soy sauce.
• Cured fish.
• Fermented sausages.
• Liver. (Fresh liver has no tyramine, but it can spoil quickly if you don’t refrigerate it, producing high levels of tyramine.)
• Salami.
• Overripe fruits, including avocados, bananas and figs.
• Fermented beers (including tap beer).
• Fava beans.
• Artisan sourdough bread.

Tyramine can increase with the aging of food. If you take an MAOI, you should aim to eat fresh foods instead of leftovers.

Be sure to talk to your healthcare provider and/or a registered dietitian about which foods you should avoid.

It’s important to realize that people vary significantly in their tolerance of tyramine-containing foods while taking MAOIs. If you’re starting an MAOI, your healthcare providers may have you purchase a blood pressure cuff to check your blood pressure after methodically sampling small amounts of tyramine-containing foods. This way, you can see how your body reacts and determine whether you can incorporate these foods into your eating pattern.

How long does it take MAOIs to work?

It may take two to three weeks to feel the full effect of an MAOI and notice an improvement in your symptoms. Talk to your healthcare provider if you don’t feel better after this time.

When should I call my healthcare provider?

You should have regular appointments with your healthcare provider when you’re taking an MAOI to assess how well it’s working.

Otherwise, talk to your healthcare provider:

• If you develop bothersome side effects.
• If your symptoms aren’t improving or if they’ve gotten worse.
• If you’re thinking of stopping the medication.

When should I seek emergency care?

If you have symptoms of serotonin syndrome or are having suicidal thoughts, call 911 or go to the nearest emergency room.

A note from Cleveland Clinic

While MAOIs are an uncommon prescription medication today, healthcare providers may still prescribe them in some cases. Due to the potential safety concerns and food and medication interactions with MAOIs, it’s important to notify every healthcare provider you see about your use of MAOIs to avoid any health consequences. You should also inform your MAOI prescriber of any new medications you start. Talk to your provider about any concerns or questions you have. They’re available to help.