A monoamine oxidase inhibitor (MAOI) is a type of antidepressant that works by blocking an enzyme in your body called monoamine oxidase. This enzyme normally breaks down brain chemicals like serotonin, norepinephrine, and dopamine. When the enzyme is blocked, levels of these mood-regulating chemicals rise, which can relieve depression. MAOIs were among the first antidepressants ever developed, and while they’re prescribed less often today than newer options, they remain effective for people who haven’t responded to other treatments.
How MAOIs Work in the Brain
Your brain naturally produces chemicals called monoamines, including serotonin, norepinephrine, and dopamine, that regulate mood, motivation, and alertness. After these chemicals do their job, an enzyme called monoamine oxidase breaks them down into waste products like hydrogen peroxide and aldehyde. This cleanup process keeps levels in check, but in depression, those levels can be too low.
MAOIs block that cleanup enzyme, so serotonin, norepinephrine, and dopamine stick around longer and in greater concentrations. The result is more of these chemicals available both inside and around nerve cells, which can lift mood and improve energy. Some MAOIs bind to the enzyme permanently by forming a strong chemical bond, meaning your body has to manufacture entirely new enzyme before normal breakdown resumes. Others bind loosely and temporarily through weaker interactions like hydrogen bonds, which makes their effects shorter-lived and easier to reverse.
Currently Approved MAOIs
The FDA has approved three oral MAOIs for treating depression:
- Isocarboxazid (Marplan)
- Phenelzine (Nardil)
- Tranylcypromine (Parnate)
A fourth option, selegiline (Emsam), is available as a skin patch. Selegiline is also used at different doses for Parkinson’s disease, where it helps preserve dopamine in areas of the brain involved in movement. The patch formulation is notable because it delivers the drug through the skin and into the bloodstream, largely bypassing the gut, which has implications for dietary restrictions (more on that below).
Why MAOIs Aren’t Prescribed First
MAOIs are typically reserved for people whose depression hasn’t improved with newer antidepressants like SSRIs or SNRIs. The main reason is practical: MAOIs come with strict food and drug interaction rules that make them harder to live with day to day. Newer antidepressants don’t carry these same restrictions and are generally easier to manage.
That said, MAOIs can be remarkably effective. Some people with treatment-resistant depression respond well to an MAOI after failing multiple other medications. For certain subtypes of depression, particularly those involving low energy, oversleeping, and sensitivity to rejection, MAOIs have a strong track record.
The Tyramine Problem
The most well-known risk with MAOIs involves a substance called tyramine, which is found naturally in many foods. Normally, monoamine oxidase in your gut and liver breaks down tyramine before it causes any trouble. But when you’re taking an MAOI, that enzyme is blocked, so tyramine builds up. High tyramine levels can trigger a sudden, dangerous spike in blood pressure, sometimes called the “cheese effect” because aged cheese is one of the most common culprits.
Foods with tyramine levels above about 6 milligrams per serving are considered risky for people on MAOIs. That threshold is surprisingly easy to hit with certain foods. The general rule is that anything aged, fermented, cured, or spoiled tends to be high in tyramine because bacteria convert an amino acid in the food into tyramine over time.
Foods to Avoid on an MAOI
- Aged cheeses: Aged cheddar, Swiss, Parmesan, blue cheeses like Stilton and Gorgonzola, and brine-aged cheeses like feta
- Cured and processed meats: Pepperoni, salami, dry sausage, bologna, bacon, corned beef, and smoked or cured fish
- Fermented foods: Sauerkraut, kimchi, pickled fish, caviar, tofu, and pickles
- Fermented sauces: Soy sauce, fish sauce, shrimp sauce, miso, Worcestershire sauce, and teriyaki sauce
- Fermented drinks: Kombucha, kefir, and draft beer
- Soy products: Soybean paste (especially fermented varieties), tofu, and soy sauce
- Spoiled or improperly stored food: Any protein-rich food that has been left out too long
Interestingly, not every food you’d expect is a problem. Research has found that most commercial chain pizzas, even those loaded with double pepperoni and double cheese, contain low amounts of tyramine. The issue is specifically with artisan and aged cheeses, not with all cheese. Similarly, while improperly stored chicken livers can develop high tyramine levels, foods like raspberries, mozzarella, and bananas don’t become dangerous even with prolonged storage. Caffeinated beverages may also contain some tyramine, so your prescriber may recommend limiting those as well.
The Selegiline Patch Exception
The selegiline patch (Emsam) offers a partial workaround to the dietary restrictions. At its lowest dose of 6 mg per 24 hours, the patch delivers the drug through the skin directly into the bloodstream. This largely avoids the gut, where monoamine oxidase normally handles tyramine from food. FDA data supports that dietary modifications are not required at this lowest dose.
At higher doses (9 mg and 12 mg per 24 hours), the dietary restrictions apply again. If you’re stepping down from a higher dose to 6 mg, or stopping the higher-dose patch entirely, you need to continue avoiding high-tyramine foods for two weeks after the change.
Drug Interactions and Serotonin Syndrome
The food restrictions get more attention, but drug interactions with MAOIs are equally serious. The biggest concern is serotonin syndrome, a potentially life-threatening condition that happens when too much serotonin accumulates in the brain. Symptoms can range from agitation and rapid heart rate to muscle rigidity, high fever, and seizures.
Combining an MAOI with an SSRI, an SNRI, or certain other antidepressants can trigger this reaction. Many over-the-counter medications are also risky, including some cough suppressants and decongestants. This is why switching between an MAOI and another antidepressant requires a washout period, typically 14 days after stopping the MAOI before starting anything new. During those two weeks, the body rebuilds its supply of monoamine oxidase enzyme so that normal serotonin regulation resumes. Cross-tapering, where you overlap the two medications, is not recommended because the risk of serotonin syndrome is too high.
The same 14-day gap applies whether you’re switching to an SSRI, an SNRI, or even a different MAOI. In practice, your prescriber may adjust the exact timing depending on which specific medications are involved, but two weeks is the standard baseline.
What Taking an MAOI Is Like Day to Day
Living with an MAOI means being consistently aware of what you eat and what other medications you take. For many people, the dietary restrictions become routine after the first few weeks, similar to managing a food allergy. You learn which restaurants and grocery items are safe and which to skip. Fresh, unprocessed foods are generally fine, and the restrictions are more about fermented, aged, and cured products than about entire food groups.
Side effects vary by person and by specific medication but can include dizziness when standing up (from blood pressure drops), trouble sleeping, weight gain, and sexual side effects. These overlap with side effects of other antidepressants, though the profile differs somewhat. The blood pressure effects go in both directions: tyramine can cause dangerous spikes, but the medication itself can sometimes cause low blood pressure, particularly when standing up quickly.
If you’re being considered for an MAOI, it’s usually because other options haven’t worked well enough. For people in that situation, the extra vigilance around food and drug interactions is often a worthwhile trade-off for an antidepressant that actually helps.