Monoamine Oxidase Inhibitors MAOIs

Monoamine oxidase inhibitors, or MAOIs, were the first antidepressants. Iproniazid, a tuberculosis drug that lifted patients’ mood, led to the class in the 1950s. MAOIs still work well for some adults with hard-to-treat depression, but they are almost never used in children and teens. None is approved by the US Food and Drug Administration (FDA) for anyone under 18, and they come with food and drug interactions that can be dangerous. This guide explains how MAOIs work, why doctors avoid them in young people, what families must know if an MAOI is ever considered and which medicines are used first instead.

How MAOIs work

Monoamine oxidase is an enzyme that breaks down three chemical messengers in the brain: serotonin, norepinephrine and dopamine. MAOIs block this enzyme, so more of these messengers stay available. There are two forms of the enzyme. MAO-A mainly breaks down serotonin and norepinephrine, and in the gut it also breaks down tyramine from food. MAO-B mainly breaks down dopamine. The older MAOIs block both forms, which explains both their effect on mood and their diet problems.

Low doses of selective MAO-B inhibitors such as selegiline tablets and rasagiline are used for Parkinson’s disease, not depression. Moclobemide, a reversible MAO-A inhibitor with fewer diet restrictions, is used in some countries but is not sold in the US.

MAOIs used in the United States

Drug	Brand	Form	Approval
Phenelzine	Nardil	Tablet	Adults with depression
Tranylcypromine	Parnate	Tablet	Adults with major depression
Isocarboxazid	Marplan	Tablet	Adults with depression
Selegiline transdermal	Emsam	Skin patch	Adults with major depression

Why MAOIs are rarely used in children and teens

• No pediatric approval. The FDA has not approved any MAOI for anyone under 18. Use in children would be “off-label” and limited to specialist care.
• Little evidence. Very few studies have tested MAOIs in young people. A placebo-controlled trial of the selegiline patch in adolescents with major depression did not show a clear advantage over placebo.
• Diet rules are hard for kids. Pizza with aged cheese, pepperoni, soy sauce and many snacks contain tyramine. Strict rules at school, at friends’ homes and at parties are difficult to keep.
• Common children’s medicines interact. ADHD stimulants, many cough and cold products and most other antidepressants must not be combined with an MAOI.
• Safer options exist. Therapy and SSRIs have much stronger evidence in young people.

Tyramine and hypertensive crisis

Normally, MAO in the gut and liver breaks down tyramine from food. When the enzyme is blocked, tyramine reaches the bloodstream and releases norepinephrine, which can push blood pressure to dangerous levels within hours. This is called a hypertensive crisis.

Foods and drinks high in tyramine

• Aged cheeses such as cheddar, blue cheese, Parmesan and Swiss
• Cured, smoked, fermented or spoiled meats and fish, such as salami, pepperoni and dried sausage
• Soy sauce, miso, fermented tofu and some fish sauces
• Sauerkraut, kimchi and yeast extracts such as Marmite
• Tap or draft beer and some wines
• Fava (broad) bean pods and overripe fruit

Fresh foods, fresh meat and most fresh cheeses such as cottage cheese and cream cheese are generally low in tyramine. Leftovers should be refrigerated and eaten soon, because tyramine increases as food ages. On the Emsam patch, the lowest dose (6 mg per 24 hours) does not require the special diet; higher doses do.

Signs of a hypertensive crisis

Sudden severe headache, especially at the back of the head, stiff neck, pounding heartbeat, chest pain, sweating, nausea or vomiting, nosebleed and blurred vision. This is an emergency: call 911.

Dangerous drug combinations

MAOIs interact with many medicines. Two kinds of reactions are most serious: serotonin syndrome and a sharp rise in blood pressure.

• Other antidepressants: SSRIs such as sertraline, fluoxetine and escitalopram, SNRIs, tricyclics, bupropion and mirtazapine
• ADHD stimulants: methylphenidate and amphetamine products
• Cough and cold medicines: dextromethorphan and decongestants such as pseudoephedrine and phenylephrine
• Pain medicines: meperidine, tramadol, methadone and fentanyl
• Others: the antibiotic linezolid, methylene blue, triptans for migraine, St. John’s wort and some weight-loss and herbal products

Serotonin syndrome can cause agitation, confusion, fever, sweating, shivering, fast heartbeat, diarrhea, muscle twitching and stiffness. Severe cases are life-threatening and need emergency care.

Switching medicines safely: washout periods

• After stopping an MAOI, wait at least 14 days before starting another antidepressant or interacting drug.
• After stopping most SSRIs, wait about 2 weeks before starting an MAOI.
• After stopping fluoxetine, wait at least 5 weeks, because it stays in the body much longer.

The prescribing doctor sets the exact timing. Never switch or stop antidepressants on your own.

The FDA boxed warning

Since 2004, every antidepressant, including MAOIs, carries an FDA boxed warning about an increased risk of suicidal thoughts and behavior in children, teens and young adults under 25. The risk is highest in the first weeks of treatment and after dose changes. Close follow-up is essential. Read more about the safety of antidepressants in childhood depression.

What doctors use first for depression in young people

Treatment of depression in children and teens usually starts with psychotherapy, such as cognitive behavioral therapy or interpersonal therapy. For moderate to severe depression, a doctor may add a selective serotonin reuptake inhibitor (SSRI):

• Fluoxetine: FDA-approved for major depression from age 8
• Escitalopram: FDA-approved for major depression from age 12

If two or more well-dosed trials do not help, a child and adolescent psychiatrist will review the diagnosis and consider other options. An MAOI would only be considered after many other treatments have failed. See also how mental illness in children is treated.

Safety checklist for families

1. Ask why this medicine is recommended and which other options were tried.
2. Get a written list of foods, drinks and medicines to avoid, and share it with school staff and caregivers.
3. Check every new medicine, including over-the-counter products and supplements, with the pharmacist.
4. Tell every doctor, dentist and emergency department that your child takes an MAOI.
5. Know the signs of hypertensive crisis and serotonin syndrome.
6. Watch closely for changes in mood, sleep, agitation or talk of self-harm, especially in the first weeks.
7. Keep follow-up appointments and never stop the medicine suddenly.

If your child talks about suicide or self-harm, call or text 988, the Suicide and Crisis Lifeline, or call 911.

Frequently Asked Questions

Are MAOIs ever prescribed to teenagers?

Rarely. A child and adolescent psychiatrist might consider one off-label for severe depression that has not responded to several other treatments, with close monitoring.

Can a child on an MAOI take ADHD medication?

No. Stimulants such as methylphenidate and amphetamine must not be combined with an MAOI because of the risk of dangerous blood pressure increases.

Does the Emsam patch avoid diet restrictions?

Only at the lowest dose. At higher doses, the same tyramine rules apply as with MAOI tablets.

Are MAOIs more effective than newer antidepressants?

For most adults they are not more effective, but some adults with treatment-resistant or atypical depression respond to them. In young people there is too little evidence to recommend them.

This article is general information and does not replace advice from your child’s doctor or pharmacist.